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Sample records for potential mitochondria-targeted antioxidants

  1. Perspectives and potential applications of mitochondria-targeted antioxidants in cardiometabolic diseases and type 2 diabetes.

    PubMed

    Rocha, Milagros; Apostolova, Nadezda; Herance, Jose Raul; Rovira-Llopis, Susana; Hernandez-Mijares, Antonio; Victor, Victor M

    2014-01-01

    There is abundant evidence to suggest that mitochondrial dysfunction is a main cause of insulin resistance and related cardiometabolic comorbidities. On the other hand, insulin resistance is one of the main characteristics of type 2 diabetes, obesity, and metabolic syndrome. Lipid and glucose metabolism require mitochondria to generate energy, and when O2 consumption is low due to inefficient nutrient oxidation, there is an increase in reactive oxygen species, which can impair different types of molecules, including DNA, lipids, proteins, and carbohydrates, thereby inducing proinflammatory processes. Factors which contribute to mitochondrial dysfunction, such as mitochondrial biogenesis and genetics, can also lead to insulin resistance in different insulin-target tissues, and its association with mitochondrial dysfunction can culminate in the development of cardiovascular diseases. In this context, therapies that improve mitochondrial function may also improve insulin resistance. This review explains mechanisms of mitochondrial function related to the pathological effects of insulin resistance in different tissues. The pathogenesis of cardiometabolic diseases will be explained from a mitochondrial perspective and the potential beneficial effects of mitochondria-targeted antioxidants as a therapy for modulating mitochondrial function in cardiometabolic diseases, especially diabetes, will also be considered.

  2. Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy.

    PubMed

    Victor, V M; Apostolova, N; Herance, R; Hernandez-Mijares, A; Rocha, M

    2009-01-01

    Chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions forms an integral part of the development of cardiovascular diseases (CVD), and in particular atherosclerosis. These ROS are released from different sources, such as xanthine oxidase, lipoxygenase, nicotinamide adenine dinucleotide phosphate oxidase, the uncoupling of nitric oxide synthase and, in particular, mitochondria. Endothelial dysfunction, characterized by a loss of nitric oxide (NO) bioactivity, occurs early on in the development of atherosclerosis, and determines future vascular complications. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not clear, oxidative stress seems to play an important role. In general, ROS are essential to cell function, but adequate levels of antioxidant defenses are required in order to avoid the harmful effects of excessive ROS production. Mitochondrial oxidative stress damage and dysfunction contribute to a number of cell pathologies that manifest themselves through a range of conditions. This review considers the process of atherosclerosis from a mitochondrial perspective, and assesses strategies for the targeted delivery of antioxidants to mitochondria that are currently under development. We will provide a summary of the following areas: the cellular metabolism of reactive oxygen species (ROS) and its role in pathophysiological processes such as atherosclerosis; currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases; and recent developments in mitochondrially-targeted antioxidants that concentrate on the matrix-facing surface of the inner mitochondrial membrane in order to protect against mitochondrial oxidative damage, and their therapeutic potential as a treatment for atherosclerosis.

  3. Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant

    DTIC Science & Technology

    2016-06-01

    Award Number: W81XWH-12-1-0258 TITLE: Neuroprotection and Anti-Epileptogenesis with Mitochondria -Targeted Antioxidant PRINCIPAL INVESTIGATOR...SUBTITLE Neuroprotection and Anti-Epileptogenesis with Mitochondria -Targeted Antioxidant 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0258 5c

  4. Mitochondria-targeted antioxidants as highly effective antibiotics.

    PubMed

    Nazarov, Pavel A; Osterman, Ilya A; Tokarchuk, Artem V; Karakozova, Marina V; Korshunova, Galina A; Lyamzaev, Konstantin G; Skulachev, Maxim V; Kotova, Elena A; Skulachev, Vladimir P; Antonenko, Yuri N

    2017-05-03

    Mitochondria-targeted antioxidants are known to alleviate mitochondrial oxidative damage that is associated with a variety of diseases. Here, we showed that SkQ1, a decyltriphenyl phosphonium cation conjugated to a quinone moiety, exhibited strong antibacterial activity towards Gram-positive Bacillus subtilis, Mycobacterium sp. and Staphylococcus aureus and Gram-negative Photobacterium phosphoreum and Rhodobacter sphaeroides in submicromolar and micromolar concentrations. SkQ1 exhibited less antibiotic activity towards Escherichia coli due to the presence of the highly effective multidrug resistance pump AcrAB-TolC. E. coli mutants lacking AcrAB-TolC showed similar SkQ1 sensitivity, as B. subtilis. Lowering of the bacterial membrane potential by SkQ1 might be involved in the mechanism of its bactericidal action. No significant cytotoxic effect on mammalian cells was observed at bacteriotoxic concentrations of SkQ1. Therefore, SkQ1 may be effective in protection of the infected mammals by killing invading bacteria.

  5. Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes.

    PubMed

    Jin, Huajun; Kanthasamy, Arthi; Ghosh, Anamitra; Anantharam, Vellareddy; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

    2014-08-01

    Parkinson's disease is a progressive neurodegenerative disease in the elderly, and no cure or disease-modifying therapies exist. Several lines of evidence suggest that mitochondrial dysfunction and oxidative stress have a central role in the dopaminergic neurodegeneration of Parkinson's disease. In this context, mitochondria-targeted therapies that improve mitochondrial function may have great promise in the prevention and treatment of Parkinson's disease. In this review, we discuss the recent developments in mitochondria-targeted antioxidants and their potential beneficial effects as a therapy for ameliorating mitochondrial dysfunction in Parkinson's disease.

  6. MITOCHONDRIA-TARGETED ANTIOXIDANTS FOR TREATMENT OF PARKINSON’S DISEASE: PRECLINICAL AND CLINICAL OUTCOMES

    PubMed Central

    Jin, Huajun; Kanthasamy, Arthi; Ghosh, Anamitra; Anantharam, Vellareddy; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G.

    2013-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disease in the elderly, and no cure or disease-modifying therapies exist. Several lines of evidence suggest that mitochondrial dysfunction and oxidative stress have a central role in the dopaminergic neurodegeneration of PD. In this context, mitochondria-targeted therapies that improve mitochondrial function may have great promise in the prevention and treatment of PD. In this review, we discuss the recent developments in mitochondria-targeted antioxidants and their potential beneficial effects as a therapy for ameliorating mitochondrial dysfunction in PD. PMID:24060637

  7. Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole

    PubMed Central

    2010-01-01

    Background Pramipexole exists as two isomers. The S(-) enantiomer is a potent D3/D2 receptor agonist and is extensively used in the management of PD. In contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist effects. Very limited studies are available to characterize the pharmacological spectrum of the R(+) enantiomer of pramipexole. Results Using differentiated SH-SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and R(+) pramipexole are endowed with equipotent efficacy in preventing cell death induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation. Both pramipexole enantiomers prevented mitochondrial ROS generation with a potency about ten times higher then that elicited for neuroprotection. Conclusions These results support the concept of both S(-) and R(+) pramipexole enantiomers as mitochondria-targeted antioxidants and suggest that the antioxidant, neuroprotective activity of these drugs is independent of both the chiral 6-propylamino group in the pramipexole molecule and the DA receptor stimulation. PMID:20137065

  8. Design, Synthesis, and Some Aspects of the Biological Activity of Mitochondria-Targeted Antioxidants.

    PubMed

    Korshunova, G A; Shishkina, A V; Skulachev, M V

    2017-07-01

    This review summarizes for the first time data on the design and synthesis of biologically active compounds of a new generation - mitochondria-targeted antioxidants, which are natural (or synthetic) p-benzoquinones conjugated via a lipophilic linker with (triphenyl)phosphonium or ammonium cations with delocalized charge. It also describes the synthesis of mitochondria-targeted antioxidants - uncouplers of oxidative phosphorylation - based on fluorescent dyes.

  9. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    PubMed Central

    He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

    2014-01-01

    Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

  10. Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review.

    PubMed

    Ramis, M R; Esteban, S; Miralles, A; Tan, Dun-Xian; Reiter, R J

    2015-01-01

    Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenously-produced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant α-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.

  11. Mitochondria-targeted Antioxidants as a Prospective Therapeutic Strategy for Multiple Sclerosis.

    PubMed

    Fetisova, Elena; Chernyak, Boris; Korshunova, Galina; Muntyan, Maria; Skulachev, Vladimir

    2017-01-01

    Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/ remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter. In this review, we discuss a possible role of mitochondrial reactive oxygen species (mtROS) in MS pathogenesis, mechanisms of mtROS generation and effects of some mitochondria-targeted antioxidants as potential components of MS therapy. In the early phase of MS, mtROS stimulate NLRP3 inflammasomes, which is critical for the formation of local inflammatory lesions. Later, mtROS contribute to blood-brain barrier disruption induced by mediators of inflammation, followed by infiltration of leukocytes. ROS generated by leukocytes and activated microglia promote mitochondrial dysfunction and oligodendrocyte cell death. In the progressive phase, neurodegeneration also depends on excessive mtROS generation. Currently, only a few immunomodulatory drugs are approved for treatment of MS. These drugs mainly reduce the number of relapses but do not stop MS progression. Certain dietary and synthetic antioxidants have demonstrated encouraging results in animal models of MS but were ineffective in the completed clinical trials. Novel mitochondria-targeted antioxidants could be promising components of combined programs for MS therapy considering that they can be applied at extremely low doses and concurrently demonstrate anti-inflammatory and neuroprotective activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant

    DTIC Science & Technology

    2014-10-01

    efficacy of a novel, mitochondrial-targeted antioxidant SS-31, as a neuroprotective and antiepileptogenic agent in three experimental models of epilepsy ...anticonvulsant properties of SS-31 in the Tetanus Toxin (TX) model of mesial temporal lobe epilepsy . The TX model is established and run on a regular basis in

  13. Effects of the Mitochondria-Targeted Antioxidant Mitoquinone in Murine Acute Pancreatitis

    PubMed Central

    Wen, Li; Szatmary, Peter; Mukherjee, Rajarshi; Armstrong, Jane; Chvanov, Michael; Tepikin, Alexei V.; Murphy, Michael P.; Sutton, Robert; Criddle, David N.

    2015-01-01

    Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP using in vitro and in vivo approaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisation per se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease. PMID:25878403

  14. Contradictory Effects of Mitochondria- and Non-mitochondria-targeted Antioxidants on Hepatocarcinogenesis by Altering DNA Repair.

    PubMed

    Wang, Bibo; Fu, Jing; Yu, Ting; Xu, An; Qin, Wenhao; Yang, Zhishi; Chen, Yao; Wang, Hongyang

    2017-09-12

    Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, it does not fully deny antioxidants for cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants. Based on the mouse models of chemical hepatocarcinogenesis, we showed that administration of non-mitochondria-targeted antioxidants N-acetylcysteine (NAC) and the soluble vitamin E analog Trolox prevented tumorigenesis, whereas administration of mitochondria-targeted antioxidants SS-31 (the mitochondria targeted peptide) and Mito-Q (a derivative of ubiquinone) encouraged tumorigenesis. RNA sequencing revealed that NAC and SS-31 cause highly different changes in oxidation-reduction state and DNA damage response. Remarkably, in diethylnitrosamine (DEN)-treated primary hepatocytes, NAC and Trolox alleviated DNA damage by activating ATM/ATR for DNA repair while SS-31 and MitoQ aggravated damage by inactivating them. Interestingly, partial recovery of SS-31-scavengened mitochondrial ROS (mtROS) could alleviate SS-31-aggravated DNA damage. Localization of ATM between mitochondria and nuclei was changed after NAC and SS-31 treatment. Furthermore, blockage of p-ATR led to the recurrence of NAC-ameliorated DEN HCC. In contrast, reactivation of p-ATR blocked SS-31-promoted DEN HCC. These results demonstrate that the type of antioxidants plays a previously unappreciated role in hepatocarcinogenesis, and provide a mechanistic rationale for exploring the therapeutic use of antioxidants for liver cancer. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  15. Mitochondria-targeted antioxidant SkQ1 improves spermatogenesis in Immp2l mutant mice.

    PubMed

    Jiang, Yaodong; Liu, Chunlian; Lei, Bin; Xu, Xian; Lu, Baisong

    2017-07-13

    Previous studies have confirmed that spermatogenesis in homozygous Immp2l mutant male mice was normal at the age of 6 months, but was significantly abnormal at the age of 13 months. Meanwhile, oxidative stress is reported to be involved in spermatogenic impairment in old mutant mice. However, it is unclear whether antioxidant treatment is a suitable intervention for improving spermatogenesis in old mutant mice. This study sought to investigate the effect of mitochondria-targeted antioxidant SkQ1 on spermatogenesis in homozygous Immp2l mutant mice. Immp2l mutant mice were treated with the mitochondria-targeted antioxidant SkQ1 from the age of 6 weeks until 13 months. SkQ1 treatment significantly improved spermatogenesis in old Immp2 l mutant mice. Moreover, SkQ1 treatment improved the morphology of testicular seminiferous tubules, significantly reduced the apoptosis of germ cells and increased the level of GPX4 expression in old Immp2 l mutant mice. In conclusion, our data suggest that the mitochondria-targeted antioxidant SkQ1 is effective in improving spermatogenesis in Immp2 l mutant mice and might be used for the treatment of male infertility. © 2017 Blackwell Verlag GmbH.

  16. Radioprotective effects of mitochondria-targeted antioxidant SkQR1.

    PubMed

    Fetisova, Elena K; Antoschina, Margarita M; Cherepanynets, Varvara D; Izumov, Denis S; Kireev, Igor I; Kireev, Roman I; Lyamzaev, Konstantin G; Riabchenko, Nikolay I; Chernyak, Boris V; Skulachev, Vladimir P

    2015-01-01

    We show here that mitochondria-targeted antioxidant composed of plastoquinone conjugated through hydrocarbon linker with cationic rhodamine 19 (SkQR1) protected against nuclear DNA damage induced by gamma radiation in K562 erythroleukemia cells. We also demonstrate that SkQR1 prevented the early (1 h postirradiation) accumulation of phosphorylated histone H2AX (γ-H2AX) an indicator of DNA double-strand break formation, as well as the radiation-induced increase in chromosomal aberrations. These data suggested that nuclear DNA damage induced by gamma radiation may be mediated by mitochondrial reactive oxygen species (ROS) production. We show that SkQR1 suppressed delayed accumulation of ROS 32 h after irradiation probably by inhibiting mitochondrial ROS-induced ROS release mechanisms. This suggests that mitochondria-targeted antioxidants may protect cells from the late consequences of radiation exposure related to delayed oxidative stress. We have previously reported that SkQRl is the substrate of multidrug resistance pump P-glycoproten (Pgp 170) and selectively protects Pgp 170-negative cells against oxidative stress. In line with this finding, we demonstrate here that SkQR1 did not protect Pgp170-positive K562 subline against DNA damage induced by gamma radiation. The selective radioprotection of normal Pgp 170-negative cells by mitochondria-targeted antioxidants could be a promising strategy to increase the efficiency of radiotherapy for multidrug-resistant tumors.

  17. Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease.

    PubMed

    Kwon, Hyek Jin; Cha, Moon-Yong; Kim, Dokyoon; Kim, Dong Kyu; Soh, Min; Shin, Kwangsoo; Hyeon, Taeghwan; Mook-Jung, Inhee

    2016-02-23

    Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer's disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer's disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer's disease.

  18. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model.

    PubMed

    Zhang, Pengcheng; Qiang, Xiaoyan; Zhang, Miao; Ma, Dongshen; Zhao, Zheng; Zhou, Cuisong; Liu, Xie; Li, Ruiyan; Chen, Huan; Zhang, Yubin

    2015-01-01

    Excessive alcohol consumption induces oxidative stress and lipid accumulation in the liver. Mitochondria have long been recognized as the key target for alcoholic liver disease (ALD). Recently, the artificial mitochondria-targeted antioxidant MitoQ has been used to treat ALD effectively in mice. Here, we introduce the natural mitochondria-targeted antioxidant demethyleneberberine (DMB), which has been found in Chinese herb Cortex Phellodendri chinensis. The protective effect of DMB on ALD was evaluated with HepG2 cells and acutely/chronically ethanol-fed mice, mimicking two common patterns of drinking in human. The results showed that DMB, which is composed of a potential antioxidant structure, could penetrate the membrane of mitochondria and accumulate in mitochondria either in vitro or in vivo. Consequently, the acute drinking-caused oxidative stress and mitochondrial dysfunction were significantly ameliorated by DMB. Moreover, we also found that DMB suppressed CYP2E1, hypoxia inducible factor α, and inducible nitric oxide synthase, which contributed to oxidative stress and restored sirtuin 1/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ coactivator-1α pathway-associated fatty acid oxidation in chronic ethanol-fed mice, which in turn ameliorated lipid peroxidation and macrosteatosis in the liver. Taking these findings together, DMB could serve as a novel and potential therapy for ALD in human beings.

  19. [Mitochondria-targeted antioxidant SkQR1 selectively protects MDR-negative cells against ionizing radiation].

    PubMed

    Fetisova, E K; Antoshina, M M; Cherepanynets, V D; Izumov, D S; Kireev, I I; Kireev, R I; Lyamzaev, K G; Riabchenko, N I; Chernyak, B V; Skulachev, V P

    2014-01-01

    Radioprotection appeared to be an important problem of today due to atom energetic development and utilization of radiation material in the industry, science and medicine. It has been shown that mitochondrial targeted antioxidant SkQR1 could attenuate radiation injury of human erythroleukemia K562 cells. Pretreatment with SkQR1 before irradiation decreased DNA double strand breaks formation, diminished the number of chromosomal aberrations and suppressed delayed ROS production. Prevention of oxidative stress and normalization of mitochondrial function by mitochondria-targeted antioxidants may be a potential therapeutic strategy not only against immediate consequences of radiation, but, either against its late consequences such as genomic instability. SkQR1 did not protect against radiation-induced damage the K562 subline with high level of multidrug resistance (MDR) due to SkQR1 extrusion with Pgp 170 MDR pump. We suggest that mitochondria-targeted antioxidants might be used for selective protection of normal cells against radiation-induced damage without interference with radiotherapy of MDR-positive tumors.

  20. Mitochondria-targeted antioxidants as promising drugs for treatment of age-related brain diseases.

    PubMed

    Skulachev, Vladimir P

    2012-01-01

    Much experimental evidence suggests that age-related brain pathologies are most often mediated by reactive oxygen species primarily originating from mitochondria (mROS). Two papers with such evidence have been recently published in the Journal of Alzheimer's Disease (Stefanova et al., J Alzheimers Dis 21, 476-491, 2010; Lloret et al., J Alzheimers Dis, doi: 10.3233/JAD-2011-110890). In the first paper, it was shown that appearance of a typical behavioral trait of aging in rats (that old animals do not enter an open arm in a maze) was completely reversed by ten weeks treatment of the old rats with the mitochondria-targeted antioxidant SkQ1. In the second article, the authors identified molecular mechanisms by which amyloid-β-induced mROS can mediate hyperphosphorylation of the tau protein, a key event in Alzheimer's disease. Conventional antioxidants prevented such hyperphosphorylation. In this article, I will summarize the present state of the art in this field. I conclude that mitochondria-targeted rechargeable antioxidants are promising as tools to treat brain pathologies developing in elderly humans.

  1. In search of novel highly active mitochondria-targeted antioxidants: thymoquinone and its cationic derivatives.

    PubMed

    Severina, Inna I; Severin, Fedor F; Korshunova, Galina A; Sumbatyan, Natalya V; Ilyasova, Tatyana M; Simonyan, Ruben A; Rogov, Anton G; Trendeleva, Tatyana A; Zvyagilskaya, Renata A; Dugina, Vera B; Domnina, Lidia V; Fetisova, Elena K; Lyamzaev, Konstantin G; Vyssokikh, Mikhail Yu; Chernyak, Boris V; Skulachev, Maxim V; Skulachev, Vladimir P; Sadovnichii, Viktor A

    2013-06-27

    Since the times of the Bible, an extract of black cumin seeds was used as a medicine to treat many human pathologies. Thymoquinone (2-demethylplastoquinone derivative) was identified as an active antioxidant component of this extract. Recently, it was shown that conjugates of plastoquinone and penetrating cations are potent mitochondria-targeted antioxidants effective in treating a large number of age-related pathologies. This review summarizes new data on the antioxidant and some other properties of membrane-penetrating cationic compounds where 2-demethylplastoquinone substitutes for plastoquinone. It was found that such a substitution significantly increases a window between anti- and prooxidant concentrations of the conjugates. Like the original plastoquinone derivatives, the novel compounds are easily reduced by the respiratory chain, penetrate through model and natural membranes, specifically accumulate in mitochondria in an electrophoretic fashion, and strongly inhibit H2O2-induced apoptosis at pico- and nanomolar concentrations in cell cultures. At present, cationic demethylplastoquinone derivatives appear to be the most promising mitochondria-targeted drugs of the quinone series.

  2. Mitochondria-targeted antioxidant mitotempo protects mitochondrial function against amyloid beta toxicity in primary cultured mouse neurons.

    PubMed

    Hu, Hongtao; Li, Mo

    2016-09-09

    Mitochondrial defects including excess reactive oxygen species (ROS) production and compromised ATP generation are featured pathology in Alzheimer's disease (AD). Amyloid beta (Aβ)-mediated mitochondrial ROS overproduction disrupts intra-neuronal Redox balance, in turn exacerbating mitochondrial dysfunction leading to neuronal injury. Previous studies have found the beneficial effects of mitochondria-targeted antioxidants in preventing mitochondrial dysfunction and neuronal injury in AD animal and cell models, suggesting that mitochondrial ROS scavengers hold promise for the treatment of this neurological disorder. In this study, we have determined that mitotempo, a novel mitochondria-targeted antioxidant protects mitochondrial function from the toxicity of Aβ in primary cultured neurons. Our results showed that Aβ-promoted mitochondrial superoxide production and neuronal lipid oxidation were significantly suppressed by the application of mitotempo. Moreover, mitotempo also demonstrated protective effects on mitochondrial bioenergetics evidenced by preserved mitochondrial membrane potential, cytochrome c oxidase activity as well as ATP production. In addition, the Aβ-induced mitochondrial DNA (mtDNA) depletion and decreased expression levels of mtDNA replication-related DNA polymerase gamma (DNA pol γ) and Twinkle were substantially mitigated by mitotempo. Therefore, our study suggests that elimination of excess mitochondrial ROS rescues mitochondrial function in Aβ-insulted neruons; and mitotempo has the potential to be a promising therapeutic agent to protect mitochondrial and neuronal function in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice.

    PubMed

    Demyanenko, Ilya A; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Fedorov, Artem V; Manskikh, Vasily N; Zinovkin, Roman A; Pletjushkina, Olga Yu; Chernyak, Boris V; Skulachev, Vladimir P; Popova, Ekaterina N

    2017-01-01

    Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db(-)/db(-) mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.

  4. Mitochondria-targeted antioxidants protect against Abeta toxicity in Alzheimer’s disease neurons

    PubMed Central

    Manczak, Maria; Mao, Peizhong; Calkins, Marcus; Cornea, Anda; Arubala, Reddy P.; Murphy, Michael P.; Szeto, Hazel H; Park, Byung; Reddy, P. Hemachandra

    2011-01-01

    Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by progressive decline of memory and cognitive functions. Despite tremendous progress that has been made in understanding disease progression and therapeutics of AD, we still do not have drugs that are capable of slowing its progression. The purpose of our study was to investigate the effects of the mitochondria-targeted antioxidants (MTAs) MitoQ and SS31, and the anti-aging agent resveratrol on neurons from a mouse model of Alzheimer’s disease (AD) (Tg2576 line) and on mouse neuroblastoma (N2a) cells incubated with the amyloid beta (Aβ) peptide. Using electron and confocal microscopy, gene expression analysis, and biochemical methods, we studied mitochondrial structure and function, and neurite outgrowth in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Aβ. In N2a cells only incubated with the Aβ, we found increased expressions of mitochondrial fission genes and decreased expression of fusion genes, and also decreased expression of peroxiredoxins, endogenous cytoprotective antioxidant enzymes. Electron microscopy of the N2a cells incubated with Aβ revealed a significantly increased number of mitochondria, indicating that Aβ fragments mitochondria. Biochemical analysis revealed that function is defective in mitochondria. Neurite outgrowth was significantly decreased in Aβ-incubated N2a cells, indicating that Aβ affects neurite outgrowth. However, in N2a cells treated with MitoQ, SS31, and resveratrol, and then incubated with Aβ, abnormal expression of peroxiredoxins and mitochondrial structural genes were prevented and mitochondrial function was normal; intact mitochondria were present and neurite outgrowth was significantly increased. In primary neurons from amyloid beta precursor protein (AβPP) transgenic mice that were treated with MitoQ and SS31, neurite outgrowth was significantly increased and cyclophilin D expression was significantly

  5. Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity.

    PubMed

    Du, Kuo; Farhood, Anwar; Jaeschke, Hartmut

    2017-02-01

    Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria-specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients.

  6. Mito-methyl coumarin, a novel mitochondria-targeted drug with great antitumor potential was synthesized.

    PubMed

    Wang, Huanan; Xu, Wenqing

    2017-07-15

    Due to higher transmembrane potential of tumor cells, enhanced accumulation of cationic drugs in tumor mitochondria has been attributed to a higher (more negative inside) mitochondrial transmembrane potential compared with normal cells, emerging researchers are focus on developing mitochondria-targeted antitumor drugs. Coumarins showed great potential on antitumor, but mitochondria-targeted coumarin derivatives have not been reported. In the present study, we synthesized mitochondria-targeted-methyl coumarin (mito-methyl coumarin) through coupling 6-methyl coumarin to TPP. We confirmed that mito-methyl coumarin inhibited HeLa cells proliferation selectively, induced ROS generation, reduced mitochondrial membrane potential, promoted mitochondria Ca(2+) accumulation, decreased mitochondria mass and induced HeLa cells apoptosis, but methyl coumarin did not. These results demonstrate that we succeed in synthesizing a novel mitochondria-targeted drug, mito-methyl coumarin, which is effective in inhibiting HeLa cells proliferation and inducing HeLa cells apoptosis through promoting ROS generation and mitochondria Ca(2+) accumulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Mitochondrial nitric oxide synthase, mitochondrial brain dysfunction in aging, and mitochondria-targeted antioxidants.

    PubMed

    Navarro, Ana; Boveris, Alberto

    2008-01-01

    This paper reviews the current ideas on nitric oxide (NO) physiology in brain and other mammalian organs and on the subcellular distribution of nitric oxide synthases (NOS) emphasizing on the evidence of a mitochondrial NOS isoform (mtNOS) that exhibits a mean activity of 0.86+/-0.09 nmol NO/min x mg protein in 13 mouse and rat organs. Mammalian brain aging is associated with mitochondrial dysfunction, determined as decreased electron transfer and enzymatic activities and as an increased content of phospholipid oxidation products and of protein oxidation/nitration products. Brain mtNOS is the most decreased enzymatic activity upon aging; decreased levels of NO are interpreted as the cause of decreased mitochondrial biogenesis in aged brain. The beneficial effect of high doses of vitamin E on mice survival and neurological function are related to its effect as antioxidant in brain mitochondria and to the preservation of mtNOS activity. Mitochondria-targeted antioxidants, phosphonium cation derivatives and antioxidant tetrapeptides, are reviewed in terms of structures and biological effects.

  8. The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/-/ApoE-/- mice.

    PubMed

    Mercer, John R; Yu, Emma; Figg, Nichola; Cheng, Kian-Kai; Prime, Tracy A; Griffin, Julian L; Masoodi, Mojgan; Vidal-Puig, Antonio; Murphy, Michael P; Bennett, Martin R

    2012-03-01

    A number of recent studies suggest that mitochondrial oxidative damage may be associated with atherosclerosis and the metabolic syndrome. However, much of the evidence linking mitochondrial oxidative damage and excess reactive oxygen species (ROS) with these pathologies is circumstantial. Consequently the importance of mitochondrial ROS in the etiology of these disorders is unclear. Furthermore, the potential of decreasing mitochondrial ROS as a therapy for these indications is not known. We assessed the impact of decreasing mitochondrial oxidative damage and ROS with the mitochondria-targeted antioxidant MitoQ in models of atherosclerosis and the metabolic syndrome (fat-fed ApoE(-/-) mice and ATM(+/-)/ApoE(-/-) mice, which are also haploinsufficient for the protein kinase, ataxia telangiectasia mutated (ATM). MitoQ administered orally for 14weeks prevented the increased adiposity, hypercholesterolemia, and hypertriglyceridemia associated with the metabolic syndrome. MitoQ also corrected hyperglycemia and hepatic steatosis, induced changes in multiple metabolically relevant lipid species, and decreased DNA oxidative damage (8-oxo-G) in multiple organs. Although MitoQ did not affect overall atherosclerotic plaque area in fat-fed ATM(+/+)/ApoE(-/-) and ATM(+/-)/ApoE(-/-) mice, MitoQ reduced the macrophage content and cell proliferation within plaques and 8-oxo-G. MitoQ also significantly reduced mtDNA oxidative damage in the liver. Our data suggest that MitoQ inhibits the development of multiple features of the metabolic syndrome in these mice by affecting redox signaling pathways that depend on mitochondrial ROS such as hydrogen peroxide. These findings strengthen the growing view that elevated mitochondrial ROS contributes to the etiology of the metabolic syndrome and suggest a potential therapeutic role for mitochondria-targeted antioxidants. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

    PubMed

    Demyanenko, Ilya A; Popova, Ekaterina N; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Romashchenko, Valeria P; Fedorov, Artem V; Manskikh, Vasily N; Skulachev, Maxim V; Zinovkin, Roman A; Pletjushkina, Olga Yu; Skulachev, Vladimir P; Chernyak, Boris V

    2015-07-01

    The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

  10. Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing.

    PubMed

    Gruber, Jan; Fong, Sheng; Chen, Ce-Belle; Yoong, Sialee; Pastorin, Giorgia; Schaffer, Sebastian; Cheah, Irwin; Halliwell, Barry

    2013-01-01

    Populations in many nations today are rapidly ageing. This unprecedented demographic change represents one of the main challenges of our time. A defining property of the ageing process is a marked increase in the risk of mortality and morbidity with age. The incidence of cancer, cardiovascular and neurodegenerative diseases increases non-linearly, sometimes exponentially with age. One of the most important tasks in biogerontology is to develop interventions leading to an increase in healthy lifespan (health span), and a better understanding of basic mechanisms underlying the ageing process itself may lead to interventions able to delay or prevent many or even all age-dependent conditions. One of the putative basic mechanisms of ageing is age-dependent mitochondrial deterioration, closely associated with damage mediated by reactive oxygen species (ROS). Given the central role that mitochondria and mitochondrial dysfunction play not only in ageing but also in apoptosis, cancer, neurodegeneration and other age-related diseases there is great interest in approaches to protect mitochondria from ROS-mediated damage. In this review, we explore strategies of targeting mitochondria to reduce mitochondrial oxidative damage with the aim of preventing or delaying age-dependent decline in mitochondrial function and some of the resulting pathologies. We discuss mitochondria-targeted and -localized antioxidants (e.g.: MitoQ, SkQ, ergothioneine), mitochondrial metabolic modulators (e.g. dichloroacetic acid), and uncouplers (e.g.: uncoupling proteins, dinitrophenol) as well as some alternative future approaches for targeting compounds to the mitochondria, including advances from nanotechnology.

  11. Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness.

    PubMed

    Powers, Scott K; Hudson, Matthew B; Nelson, W Bradley; Talbert, Erin E; Min, Kisuk; Szeto, Hazel H; Kavazis, Andreas N; Smuder, Ashley J

    2011-07-01

    Mechanical ventilation is a life-saving intervention used to provide adequate pulmonary ventilation in patients suffering from respiratory failure. However, prolonged mechanical ventilation is associated with significant diaphragmatic weakness resulting from both myofiber atrophy and contractile dysfunction. Although several signaling pathways contribute to diaphragm weakness during mechanical ventilation, it is established that oxidative stress is required for diaphragmatic weakness to occur. Therefore, identifying the site(s) of mechanical ventilation- induced reactive oxygen species production in the diaphragm is important. These experiments tested the hypothesis that elevated mitochondrial reactive oxygen species emission is required for mechanical ventilation-induced oxidative stress, atrophy, and contractile dysfunction in the diaphragm. Cause and effect was determined by preventing mechanical ventilation-induced mitochondrial reactive oxygen species emission in the diaphragm of rats using a novel mitochondria-targeted antioxidant (SS-31). None. Compared to mechanically ventilated animals treated with saline, animals treated with SS-31 were protected against mechanical ventilation-induced mitochondrial dysfunction, oxidative stress, and protease activation in the diaphragm. Importantly, treatment of animals with the mitochondrial antioxidant also protected the diaphragm against mechanical ventilation-induced myofiber atrophy and contractile dysfunction. These results reveal that prevention of mechanical ventilation-induced increases in diaphragmatic mitochondrial reactive oxygen species emission protects the diaphragm from mechanical ventilation-induced diaphragmatic weakness. This important new finding indicates that mitochondria are a primary source of reactive oxygen species production in the diaphragm during prolonged mechanical ventilation. These results could lead to the development of a therapeutic intervention to impede mechanical ventilation

  12. Toxicity of neurons treated with herbicides and neuroprotection by mitochondria-targeted antioxidant SS31.

    PubMed

    Reddy, Tejaswini P; Manczak, Maria; Calkins, Marcus J; Mao, Peizhong; Reddy, Arubala P; Shirendeb, Ulziibat; Park, Byung; Reddy, P Hemachandra

    2011-01-01

    The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1-6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides--picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity.

  13. Toxicity of Neurons Treated with Herbicides and Neuroprotection by Mitochondria-Targeted Antioxidant SS31

    PubMed Central

    Reddy, Tejaswini P.; Manczak, Maria; Calkins, Marcus J.; Mao, Peizhong; Reddy, Arubala P.; Shirendeb, Ulziibat; Park, Byung; Reddy, P. Hemachandra

    2011-01-01

    The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1–6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides—picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity. PMID:21318024

  14. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.

    PubMed

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E; Soto Hernandez, Jessica; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-11-24

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.

  15. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E.; Hernandez, Jessica Soto; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-01-01

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle. PMID:26415224

  16. Mitochondria-Targeted Antioxidants and Uncouplers of Oxidative Phosphorylation in Treatment of the Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Zakharova, Vlada V; Pletjushkina, Olga Yu; Zinovkin, Roman A; Popova, Ekaterina N; Chernyak, Boris V

    2017-05-01

    Systemic inflammatory response syndrome (SIRS) development is accompanied by mitochondrial dysfunction and excessive ROS production. Mitochondrial dysfunctions also occur in many SIRS-related diseases and may be critical for their pathogenesis; therefore, a use of mitochondria-targeted drugs is a promising trend in SIRS research and therapy. Here, we review recent studies concerning the application of the mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation in animal models of SIRS and related diseases. We propose that a new class of uncouplers of oxidative phosphorylation, lipophilic cations could be a base for a new generation of drugs for SIRS treatment. J. Cell. Physiol. 232: 904-912, 2017. © 2016 Wiley Periodicals, Inc.

  17. Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

    PubMed Central

    2013-01-01

    Background MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. Methods Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. Results Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. Conclusion Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel

  18. Antiproliferative effects of mitochondria-targeted cationic antioxidants and analogs: Role of mitochondrial bioenergetics and energy-sensing mechanism

    PubMed Central

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna; Hardy, Micael; Ouari, Olivier; Joseph, Joy; Dwinell, Michael B.; Kalyanaraman, Balaraman

    2015-01-01

    One of the proposed mechanisms for tumor proliferation involves redox signaling mediated by reactive oxygen species such as superoxide and hydrogen peroxide generated at moderate levels. Thus, the antiproliferative and anti-tumor effects of certain antioxidants were attributed to their ability to mitigate intracellular reactive oxygen species (ROS). Recent reports support a role for mitochondrial ROS in stimulating tumor cell proliferation. In this study, we compared the antiproliferative effects and the effects on mitochondrial bioenergetic functions of a mitochondria-targeted cationic carboxyproxyl nitroxide (Mito-CP), exhibiting superoxide dismutase (SOD)-like activity and a synthetic cationic acetamide analog (Mito-CP-Ac) lacking the nitroxide moiety responsible for the SOD activity. Results indicate that both Mito-CP and Mito-CP-Ac potently inhibited tumor cell proliferation. Both compounds altered mitochondrial and glycolytic functions, and intracellular citrate levels. Both Mito-CP and Mito-CP-Ac synergized with 2-deoxy-glucose (2-DG) to deplete intracellular ATP, inhibit cell proliferation and induce apoptosis in pancreatic cancer cells. We conclude that mitochondria-targeted cationic agents inhibit tumor proliferation via modification of mitochondrial bioenergetics pathways rather than by dismutating and detoxifying mitochondrial superoxide. PMID:26004344

  19. Antiproliferative effects of mitochondria-targeted cationic antioxidants and analogs: Role of mitochondrial bioenergetics and energy-sensing mechanism.

    PubMed

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna; Hardy, Micael; Ouari, Olivier; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2015-08-28

    One of the proposed mechanisms for tumor proliferation involves redox signaling mediated by reactive oxygen species such as superoxide and hydrogen peroxide generated at moderate levels. Thus, the antiproliferative and anti-tumor effects of certain antioxidants were attributed to their ability to mitigate intracellular reactive oxygen species (ROS). Recent reports support a role for mitochondrial ROS in stimulating tumor cell proliferation. In this study, we compared the antiproliferative effects and the effects on mitochondrial bioenergetic functions of a mitochondria-targeted cationic carboxyproxyl nitroxide (Mito-CP), exhibiting superoxide dismutase (SOD)-like activity and a synthetic cationic acetamide analog (Mito-CP-Ac) lacking the nitroxide moiety responsible for the SOD activity. Results indicate that both Mito-CP and Mito-CP-Ac potently inhibited tumor cell proliferation. Both compounds altered mitochondrial and glycolytic functions, and intracellular citrate levels. Both Mito-CP and Mito-CP-Ac synergized with 2-deoxy-glucose (2-DG) to deplete intracellular ATP, inhibit cell proliferation and induce apoptosis in pancreatic cancer cells. We conclude that mitochondria-targeted cationic agents inhibit tumor proliferation via modification of mitochondrial bioenergetics pathways rather than by dismutating and detoxifying mitochondrial superoxide.

  20. The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

    PubMed Central

    McManus, Meagan J.; Murphy, Michael P.; Franklin, James L.

    2012-01-01

    Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer’s disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienlyl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψm) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD. PMID:22049413

  1. Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics.

    PubMed

    Reddy, P Hemachandra; Tripathi, Raghav; Troung, Quang; Tirumala, Karuna; Reddy, Tejaswini P; Anekonda, Vishwanath; Shirendeb, Ulziibat P; Calkins, Marcus J; Reddy, Arubala P; Mao, Peizhong; Manczak, Maria

    2012-05-01

    Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer's disease (AD) progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. Recent research on amyloid beta (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

  2. Vandetanib and cabozantinib potentiate mitochondria-targeted agents to suppress medullary thyroid carcinoma cells.

    PubMed

    Starenki, Dmytro; Hong, Seung-Keun; Wu, Pui-Kei; Park, Jong-In

    2017-07-03

    Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells. Of note, vandetanib and cabozantinib increased mitochondrial membrane potential (Δψm) in drug-naïve as well as drug-resistant cells but only drug-naïve cells exhibited substantially altered oxygen consumption and extracellular acidification rates. Therefore, these inhibitors appear to cause a bioenergetics stress to which drug-resistant MTC cells are more tolerant. Given the ability of vandetanib and cabozantinib to increase Δψm, we hypothesized that these inhibitors can augment growth inhibitory effects of mitochondria-targeted carboxy-proxyl and ubiquinone by increasing their Δψm-dependent uptake/retention in MTC cells. Indeed, our in vitro and mouse xenograft data strongly support this possibility.

  3. Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas.

    PubMed

    Reiter, Russel J; Rosales-Corral, Sergio; Tan, Dun Xian; Jou, Mei Jie; Galano, Annia; Xu, Bing

    2017-09-01

    Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin's chemical structure has never changed; thus, the melatonin present in currently living humans is identical to that present in cyanobacteria that have existed on Earth for billions of years. Melatonin in the systemic circulation of mammals quickly disappears from the blood presumably due to its uptake by cells, particularly when they are under high oxidative stress conditions. The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. Melatonin presumably enters mitochondria through oligopeptide transporters, PEPT1, and PEPT2. Thus, melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant. In addition to being taken up from the circulation, melatonin may be produced in the mitochondria as well. During evolution, mitochondria likely originated when melatonin-forming bacteria were engulfed as food by ancestral prokaryotes. Over time, engulfed bacteria evolved into mitochondria; this is known as the endosymbiotic theory of the origin of mitochondria. When they did so, the mitochondria retained the ability to synthesize melatonin. Thus, melatonin is not only taken up by mitochondria but these organelles, in addition to many other functions, also probably produce melatonin as well. Melatonin's high concentrations and multiple actions as an antioxidant provide potent antioxidant protection to these organelles which are exposed to abundant free radicals.

  4. Mitochondria-targeted antioxidant SkQ1 reduces age-related alterations in the ultrastructure of the lacrimal gland

    PubMed Central

    Bakeeva, Lora E.; Eldarov, Chupalav M.; Vangely, Irina M.; Kolosova, Nataliya G.; Vays, Valeriya B.

    2016-01-01

    Dry eye syndrome is an eye disorder affecting many people at an old age. Because dry eye syndrome is accelerated by aging, a useful approach to the prevention of this syndrome may be an intervention into the aging process. Previously, we showed that the mitochondria-targeted antioxidant SkQ1 delays manifestations of aging and inhibits the development of age-related diseases including dry eye syndrome. Nevertheless, the link between SkQ1's effects and its suppression of age-related changes in the lacrimal gland remains unclear. Here we demonstrated that dietary supplementation with SkQ1 (250 nmol/[kg body weight] daily) starting at age 1.5 months significantly alleviated the pathological changes in lacrimal glands of Wistar rats by age 24 months. By this age, lacrimal glands underwent dramatic deterioration of the ultrastructure that was indicative of irreversible disturbances in these glands' functioning. In contrast, in SkQ1-treated rats, the ultrastructure of the lacrimal gland was similar to that in much younger rats. Morphometric analysis of electron-microscopic specimens of lacrimal glands revealed the presence of numerous secretory granules in acinar cells and a significant increase in the number of operating intercalary ducts. Our results confirm that dietary supplementation with SkQ1 is a promising approach to healthy ageing and to prevention of aberrations in the lacrimal gland that underlie dry eye syndrome. PMID:27852065

  5. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    PubMed Central

    Reddy, P. Hemachandra

    2011-01-01

    Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma. PMID:21461182

  6. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.

    PubMed

    Solesio, María E; Prime, Tracy A; Logan, Angela; Murphy, Michael P; Del Mar Arroyo-Jimenez, María; Jordán, Joaquín; Galindo, María F

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder for which available treatments provide symptom relief but do not stop disease progression. Mitochondria, and in particular mitochondrial dynamics, have been postulated as plausible pharmacological targets. Mitochondria-targeted antioxidants have been developed to prevent mitochondrial oxidative damage, and to alter the involvement of reactive oxygen species (ROS) in signaling pathways. In this study, we have dissected the effect of MitoQ, which is produced by covalent attachment of ubiquinone to a triphenylphosphonium lipophilic cation by a ten carbon alkyl chain. MitoQ was tested in an in vitro PD model which involves addition of 6-hydroxydopamine (6-OHDA) to SH-SY5Y cell cultures. At sublethal concentrations of 50μM, 6-OHDA did not induce increases in protein carbonyl, mitochondrial lipid peroxidation or mitochondrial DNA damage. However, after 3h of treatment, 6-OHDA disrupts the mitochondrial morphology and activates the machinery of mitochondrial fission, but not fusion. Addition of 6-OHDA did not increase the levels of fission 1, mitofusins 1 and 2 or optic atrophy 1 proteins, but does lead to the translocation of dynamin related protein 1 from the cytosol to the mitochondria. Pre-treatment with MitoQ (50nM, 30min) results in the inhibition of the mitochondrial translocation of Drp1. Furthermore, MitoQ also inhibited the translocation of the pro-apoptotic protein Bax to the mitochondria. These findings provide mechanistic evidence for a role for redox events contributing to mitochondrial fission and suggest the potential of mitochondria-targeted therapeutics in diseases that involve mitochondrial fragmentation due to oxidative stress.

  7. Reactive Oxygen Species and the Aging Eye: Specific Role of Metabolically Active Mitochondria in Maintaining Lens Function and in the Initiation of the Oxidation-Induced Maturity Onset Cataract--A Novel Platform of Mitochondria-Targeted Antioxidants With Broad Therapeutic Potential for Redox Regulation and Detoxification of Oxidants in Eye Diseases.

    PubMed

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    The aging eye appears to be at considerable risk from oxidative stress. A great deal of research indicates that dysfunctional mitochondria are the primary site of reactive oxygen species (ROS). More than 95% of O2 produced during normal metabolism is generated by the electron transport chain in the inner mitochondrial membrane. Mitochondria are also the major target of ROS. Cataract formation, the opacification of the eye lens, is one of the leading causes of human blindness worldwide, accounting for 47.8% of all causes of blindness. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cell plasma membrane damage, which causes clouding of the lens, light scattering, and obstruction of vision. ROS-induced damage in the lens cell may consist of oxidation of proteins, DNA damage, and/or lipid peroxidation, all of which have been implicated in cataractogenesis. This article is an attempt to integrate how mitochondrial ROS are altered in the aging eye along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. As a result of the combination of weak metal chelating, OH and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid, and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biologic membranes and aqueous environments and act as the antiapoptotic natural drug compounds The authors developed and patented the new ophthalmic compositions, including N-acetylcarnosine, acting as a prodrug of naturally targeted to mitochondria L-carnosine endowed with pluripotent antioxidant activities combined with mitochondria-targeted

  8. The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells.

    PubMed

    Lowes, Damon A; Wallace, Carol; Murphy, Michael P; Webster, Nigel R; Galley, Helen F

    2009-04-01

    Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles' tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles' tendons were exposed to 0-0.3 mM antibiotic for 24 h and 7 days in the presence of 1 microM MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.

  9. Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers.

    PubMed

    Li, Yan; Fawcett, J Paul; Zhang, Hu; Tucker, Ian G

    2007-04-01

    Mitoquinone (MitoQ(10) mesylate) is a mitochondria-targeted antioxidant formulated for oral administration in the treatment of neurodegenerative diseases. We have investigated the absorption and metabolism of MitoQ(10) in Caco-2 cell monolayers. The intracellular accumulation of MitoQ(10) was 18-41% of the total amount of MitoQ(10) added. Some of the intracellular MitoQ(10) was reduced to mitoquinol and subsequently metabolized to glucuronide and sulfate conjugates. Transport of MitoQ(10) was polarized with the apparent permeability (P(app)) from basolateral (BL) to apical (AP) (P(appBL-->AP)) being >2.5-fold the P(app) from apical to basolateral (P(appAP-->BL)). In the presence of 4% bovine serum albumin on the basolateral side, the P(appAP-->BL) value increased 7-fold compared with control. The P(appBL-->AP) value decreased by 26, 31 and 61% in the presence of verapamil 100 microM, ciclosporin 10 and 30 microM, respectively, whereas the P(appAP-->BL) value increased 71% in the presence of ciclosporin 30 microM. Apical efflux of mitoquinol sulfate and mitoquinol glucuronide conjugates was significantly decreased by ciclosporin 30 microM and the breast cancer receptor protein (BCRP) inhibitor, reserpine 25 microM, respectively. These results suggested that the bioavailability of MitoQ(10) may be limited by intracellular metabolism and the action of P-glycoprotein and BCRP. However, the dramatic increase in absorptive P(app) in the presence of bovine serum albumin on the receiver side suggests these barrier functions may be less significant in-vivo.

  10. Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury.

    PubMed

    Patil, Naeem K; Parajuli, Nirmala; MacMillan-Crow, Lee Ann; Mayeux, Philip R

    2014-04-01

    Acute kidney injury (AKI) is a complication of sepsis and leads to a high mortality rate. Human and animal studies suggest that mitochondrial dysfunction plays an important role in sepsis-induced multi-organ failure; however, the specific mitochondrial targets damaged during sepsis remain elusive. We used a clinically relevant cecal ligation and puncture (CLP) murine model of sepsis and assessed renal mitochondrial function using high-resolution respirometry, renal microcirculation using intravital microscopy, and renal function. CLP caused a time-dependent decrease in mitochondrial complex I and II/III respiration and reduced ATP. By 4 h after CLP, activity of manganese superoxide dismutase (MnSOD) was decreased by 50% and inhibition was sustained through 36 h. These events were associated with increased mitochondrial superoxide generation. We then evaluated whether the mitochondria-targeted antioxidant Mito-TEMPO could reverse renal mitochondrial dysfunction and attenuate sepsis-induced AKI. Mito-TEMPO (10 mg/kg) given at 6 h post-CLP decreased mitochondrial superoxide levels, protected complex I and II/III respiration, and restored MnSOD activity by 18 h. Mito-TEMPO also improved renal microcirculation and glomerular filtration rate. Importantly, even delayed therapy with a single dose of Mito-TEMPO significantly increased 96-h survival rate from 40% in untreated septic mice to 80%. Thus, sepsis causes sustained inactivation of three mitochondrial targets that can lead to increased mitochondrial superoxide. Importantly, even delayed therapy with Mito-TEMPO alleviated kidney injury, suggesting that it may be a promising approach to treat septic AKI.

  11. The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease.

    PubMed

    Ng, Li Fang; Gruber, Jan; Cheah, Irwin K; Goo, Chong Kit; Cheong, Wei Fun; Shui, Guanghou; Sit, Kim Ping; Wenk, Markus R; Halliwell, Barry

    2014-06-01

    β-Amyloid (Aβ)-induced toxicity and oxidative stress have been postulated to play critical roles in the pathogenic mechanism of Alzheimer disease (AD). We investigated the in vivo ability of a mitochondria-targeted antioxidant, MitoQ, to protect against Aβ-induced toxicity and oxidative stress in a Caenorhabditis elegans model overexpressing human Aβ. Impairment of electron transport chain (ETC) enzymatic activity and mitochondrial dysfunction are early features of AD. We show that MitoQ extends lifespan, delays Aβ-induced paralysis, ameliorates depletion of the mitochondrial lipid cardiolipin, and protects complexes IV and I of the ETC. Despite its protective effects on lifespan, healthspan, and ETC function, we find that MitoQ does not reduce DCFDA fluorescence, protein carbonyl levels or modulate steadystate ATP levels or oxygen consumption rate. Moreover, MitoQ does not attenuate mitochondrial DNA (mtDNA) oxidative damage. In agreement with its design, the protective effects of MitoQ appear to be targeted specifically to the mitochondrial membrane and our findings suggest that MitoQ may have therapeutic potential for Aβ- and oxidative stress-associated neurodegenerative disorders, particularly AD. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Mitochondria-targeted small molecule SS31: a potential candidate for the treatment of Alzheimer's disease.

    PubMed

    Reddy, P Hemachandra; Manczak, Maria; Kandimalla, Ramesh

    2017-04-15

    The objective of our study was to better understand the protective effects of the mitochondria-targeted tetra-peptide SS31 against amyloid beta (Aβ)-induced mitochondrial and synaptic toxicities in Alzheimer's disease (AD) progression. Using intraperitoneal injections, we administered SS31 to an AD mouse model (APP) over a period of 6 weeks, beginning when the APP mice were 12 months of age. We studied their cortical tissues after SS31 treatment and determined that SS31 crosses the blood brain barrier and reaches mitochondrial sites of free radical production. We also determined: (1) plasma and brain levels of SS31, (2) mRNA levels and levels of mitochondrial dynamics, biogenesis proteins and synaptic proteins, (3) soluble Aβ levels and immunoreactivity of mutant APP and Aβ levels and (4) mitochondrial function by measuring H2O2, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. We found reduced mRNA expression and reduced protein levels of fission genes, and increased levels of mitochondrial fusion, biogenesis and synaptic genes in SS31-treated APP mice relative to SS31-untreated APP mice. Immunofluorescence analysis revealed reduced full-length mutant APP and soluble/insoluble Aβ levels in the SS31-treated APP mice. Sandwich ELISA assays revealed significantly reduced soluble Aβ levels in the SS31-treated APP mice relative to the untreated APP mice. Mitochondrial function was maintained in the SS31-treated APP mice over the 6 weeks of SS31 treatment compared with mitochondrial function in the untreated APP mice. Our findings indicate that SS31 treatment reduces Aβ production, reduces mitochondrial dysfunction, maintains mitochondrial dynamics and enhances mitochondrial biogenesis and synaptic activity in APP mice; and that SS31 may confer protective effects against mitochondrial and synaptic toxicities in APP transgenic mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email

  13. Alzheimer's disease-like pathology in senescence-accelerated OXYS rats can be partially retarded with mitochondria-targeted antioxidant SkQ1.

    PubMed

    Stefanova, Natalia A; Muraleva, Natalia A; Skulachev, Vladimir P; Kolosova, Nataliya G

    2014-01-01

    We previously showed that mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) at nanomolar concentrations is capable of preventing and slowing down some cerebral dysfunctions in accelerated-senescence OXYS rats. Here we demonstrate that OXYS rats develop behavior, learning, and memory deficits against a background of neurodegeneration signs detected by magnetic resonance tomography and amyloid-β (Aβ) pathology similar to those seen in Alzheimer's disease (AD). Long-term treatment with SkQ1 (250 nmol/kg body weight daily from the age of 1.5 to 23 months) reduced the age-related alterations in behavior and spatial memory deficit in Morris water maze in OXYS and Wistar rats. Furthermore, this is the first report that SkQ1 treatment slows down pathological accumulation of AβPP, Aβ, and hyperphosphorylation of tau-protein in OXYS rats, as well as age-dependent changes in healthy Wistar rats. Our results support the possibility of using the OXYS strain as a rat model of AD-like pathology. It seems probable that the mitochondria-targeted antioxidant SkQ1 can be a good prophylactic strategy to maintain brain health and to treat AD.

  14. Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy

    PubMed Central

    Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Khan, Nadeem; Mupparaju, S. P.; Rahme, Laurence G.; Swartz, Harold M.; Szeto, Hazel H.; Tompkins, Ronald G.; Tzika, A. Aria

    2013-01-01

    Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms.—Righi, V., Constantinou, C., Mintzopoulos, D., Khan, N., Mupparaju, S. P., Rahme, L. G., Swartz, H. M., Szeto, H. H., Tompkins, R. G., and Tzika, A. A. Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy. PMID:23482635

  15. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

    PubMed

    Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P; Nye, Gareth A; Wells, Nicola; Giakoumaki, Ifigeneia I; Griffiths, Richard D; McArdle, Anne; Jackson, Malcolm J

    2016-11-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  16. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  17. Mitochondria-targeted nutraceuticals in sports medicine: a new perspective.

    PubMed

    Ostojic, Sergej M

    2017-01-01

    Since mitochondria have been recognized as the cells' key organelles involved in the energy utilization during exercise, targeting the organelle with specifically designed compounds (mitochondria-targeted nutraceuticals, MTNs) may have a great promise in the prevention and treatment of heavy exercise-related mitochondrial dysfunction. In vitro studies suggested that MTNs have antioxidant effects at the molecular level, and might boost mitochondrial biogenesis and organelle bioenergetics, with both processes are known to positively affect exercise performance and recovery. However, while there are a number of different MTNs evaluated for a potential benefit as a therapy for mitochondria-related diseases and conditions, only few human studies evaluated the possible impact of novel MTNs in the field of sports medicine. This mini review summarizes recent research findings regarding the efficacy of different mitochondria-targeted nutritional agents, emphasizing their roles in sports medicine.

  18. Antioxidant mechanism of mitochondria-targeted plastoquinone SkQ1 is suppressed in aglycemic HepG2 cells dependent on oxidative phosphorylation.

    PubMed

    Ježek, Jan; Engstová, Hana; Ježek, Petr

    2017-09-01

    Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells. Only in glycolytic cells, SkQ1 prevented the rotenone-induced enhancement of Jm and Jc but not basal releases without rotenone. The effect ceased in glutaminolytic aglycemic cells, in which the redox parameter NAD(P)H/FAD increased after rotenone in contrast to its decrease in glycolytic cells. Autofluorescence decay indicated decreased NADPH/NADH ratios with rotenone in both metabolic modes. SkQ1 did not increase cell respiration and diminished Jm established high by antimycin or myxothiazol but not by stigmatellin. The revealed SkQ1 antioxidant modes reflect its reduction to SkQ1H2 at Complex I IQ or Complex III Qi site. Both reductions diminish electron diversions to oxygen thus attenuating superoxide formation. Resulting SkQ1H2 oxidizes back to SkQ1at the second (flavin) Complex I site, previously indicated for MitoQ10. Regeneration proceeds only at lower NAD(P)H/FAD in glycolytic cells. In contrast, cyclic SkQ1 reduction/SkQ1H2 oxidation does not substantiate antioxidant activity in intact cells in the absence of oxidative stress (neither pro-oxidant activity, representing a great advantage). A targeted delivery to oxidative-stressed tissues is suggested for the effective antioxidant therapy based on SkQ1. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. [Protective effect of mitochondria-targeted antioxidant SS31 on early brain injury following subarachnoid hemorrhage in rats].

    PubMed

    Zhou, Jian; Li, Zhengzheng; Chen, Zhenggang; Yang, Kun

    2017-09-28

    To evaluate protective effects of SS31 on early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) in rats.
 Methods: A total of 96 Sprague-Dawley rats were randomly divided into 4 groups: A sham group, an SAH group, an SAH+vehicle group (SAH+V), and an SAH+SS31 group. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological deficit scores were evaluated at 24 h after SAH. The SS31 (5 mg/kg) as well as equal volume of vehicle were administrated intraperitoneally at 2 h after SAH. The neurological scores, brain edema, blood-brain barrier (BBB) permeability, apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, superoride dismutase (SOD) activity, and the expression of cytosolic cytochrome c (Cyt C) and Bax were analyzed at 24 h after SAH.
 Results: Treatment with SS31 could significantly reduce MDA levels, and restored the activities of GPx and SOD in the cortex following SAH when compared with the SAH+V group. In addition, Bax SS31 trearment increased or decreased the levels of mitochondrial Cyt C or Bax, respectively. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH.
 Conclusion: SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibition of neuronal apoptosis.

  20. A mitochondria-targeted derivative of ascorbate: MitoC

    PubMed Central

    Finichiu, Peter G.; Larsen, David S.; Evans, Cameron; Larsen, Lesley; Bright, Thomas P.; Robb, Ellen L.; Trnka, Jan; Prime, Tracy A.; James, Andrew M.; Smith, Robin A.J.; Murphy, Michael P.

    2015-01-01

    Mitochondrial oxidative damage contributes to a wide range of pathologies. One therapeutic strategy to treat these disorders is targeting antioxidants to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation. To date only hydrophobic antioxidants have been targeted to mitochondria; however, extending this approach to hydrophilic antioxidants offers new therapeutic and research opportunities. Here we report the development and characterization of MitoC, a mitochondria-targeted version of the hydrophilic antioxidant ascorbate. We show that MitoC can be taken up by mitochondria, despite the polarity and acidity of ascorbate, by using a sufficiently hydrophobic link to the TPP moiety. MitoC reacts with a range of reactive species, and within mitochondria is rapidly recycled back to the active ascorbate moiety by the glutathione and thioredoxin systems. Because of this accumulation and recycling MitoC is an effective antioxidant against mitochondrial lipid peroxidation and also decreases aconitase inactivation by superoxide. These findings show that the incorporation of TPP function can be used to target polar and acidic compounds to mitochondria, opening up the delivery of a wide range of bioactive compounds. Furthermore, MitoC has therapeutic potential as a new mitochondria-targeted antioxidant, and is a useful tool to explore the role(s) of ascorbate within mitochondria. PMID:26453920

  1. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    PubMed Central

    Perepechaeva, M. L.; Grishanova, A. Yu.; Rudnitskaya, E. A.; Kolosova, N. G.

    2014-01-01

    The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD). The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor) and Nrf2 (nuclear factor erythroid 2-related factor 2), which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1. PMID:25132985

  2. MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

    PubMed

    Mao, Peizhong; Manczak, Maria; Shirendeb, Ulziibat P; Reddy, P Hemachandra

    2013-12-01

    Oxidative stress and mitochondrial dysfunction are involved in the progression and pathogenesis of multiple sclerosis (MS). MitoQ is a mitochondria-targeted antioxidant that has a neuroprotective role in several mitochondrial and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Here we sought to determine the possible effects of a systematic administration of MitoQ as a therapy, using an experimental autoimmune encephalomyelitis (EAE) mouse model. We studied the beneficial effects of MitoQ in EAE mice that mimic MS like symptoms by treating EAE mice with MitoQ and pretreated C57BL6 mice with MitoQ plus EAE induction. We found that pretreatment and treatment of EAE mice with MitoQ reduced neurological disabilities associated with EAE. We also found that both pretreatment and treatment of the EAE mice with MitoQ significantly suppressed inflammatory markers of EAE, including the inhibition of inflammatory cytokines and chemokines. MitoQ treatments reduced neuronal cell loss in the spinal cord, a factor underlying motor disability in EAE mice. The neuroprotective role of MitoQ was confirmed by a neuron-glia co-culture system designed to mimic the mechanism of MS and EAE in vitro. We found that axonal inflammation and oxidative stress are associated with impaired behavioral functions in the EAE mouse model and that treatment with MitoQ can exert protective effects on neurons and reduce axonal inflammation and oxidative stress. These protective effects are likely via multiple mechanisms, including the attenuation of the robust immune response. These results suggest that MitoQ may be a new candidate for the treatment of MS. © 2013.

  3. NOVEL MITOCHONDRIA-TARGETED ANTIOXIDANT PEPTIDE AMELIORATES BURN-INDUCED APOPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN THE SKELETAL MUSCLE OF MICE

    PubMed Central

    Lee, Hyung-yul; Kaneki, Masao; Andreas, Jonathan; Tompkins, Ronald G.; Martyn, J.A. Jeevendra

    2011-01-01

    This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum (ER) stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham-burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight) and the rectus abdominis muscles collected on post-burn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses. Treatment with SS-31 peptide prevented burn-induced increases in the caspase 3 activity (p < 0.05) and apoptosis (p < 0.01) on post-burn day 7. The SS-31 peptide treatment also prevented the increase in the expression levels of phosphatase and tensin homolog (PTEN) on post-burn days 3 and 7. Burn injury-induced increases in the levels of two ER stress markers, binding immunoglobulin protein (BiP) and protein disulfide isomerase (PDI), were significantly decreased by the SS-31 peptide treatments on post-burn day 7 and on day 3 for BiP as well (p < 0.05). The effects of SS-31 appear to be, in part, due to its ability to reduce oxidative stress in burned mice, evidenced by reduced expression of oxidized proteins that were clearly evident on post-burn day 7. Our results demonstrate a possible therapeutic potential of SS-31 peptide to ameliorate the adverse effects of burn injury in skeletal muscle. PMID:21937949

  4. Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis.

    PubMed

    Karnewar, Santosh; Vasamsetti, Sathish Babu; Gopoju, Raja; Kanugula, Anantha Koteswararao; Ganji, Sai Krishna; Prabhakar, Sripadi; Rangaraj, Nandini; Tupperwar, Nitin; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

    2016-04-11

    Mitochondria-targeted compounds are emerging as a new class of drugs that can potentially alter the pathophysiology of those diseases where mitochondrial dysfunction plays a critical role. We have synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE(-/-) mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2- and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. While L-NAME (NOS inhibitor) significantly abrogated Mito-Esc-mediated protective effects, Compound c (inhibitor of AMPK) significantly decreased Mito-Esc-mediated increase in NO production. Notably, Mito-Esc promoted mitochondrial biogenesis by enhancing SIRT3 expression through AMPK activation; and restored H2O2-induced inhibition of mitochondrial respiration. siSIRT3 treatment not only completely reversed Mito-Esc-mediated mitochondrial biogenetic marker expressions but also caused endothelial cell death. Furthermore, Mito-Esc administration to ApoE(-/-) mice greatly alleviated Ang-II-induced atheromatous plaque formation, monocyte infiltration and serum pro-inflammatory cytokines levels. We conclude that Mito-Esc is preferentially taken up by the mitochondria and preserves endothelial cell survival during oxidative stress by modulating NO generation via AMPK. Also, Mito-Esc-induced SIRT3 plays a pivotal role in mediating mitochondrial biogenesis and perhaps contributes to its anti-atherogenic effects.

  5. Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis

    PubMed Central

    Karnewar, Santosh; Vasamsetti, Sathish Babu; Gopoju, Raja; Kanugula, Anantha Koteswararao; Ganji, Sai Krishna; Prabhakar, Sripadi; Rangaraj, Nandini; Tupperwar, Nitin; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

    2016-01-01

    Mitochondria-targeted compounds are emerging as a new class of drugs that can potentially alter the pathophysiology of those diseases where mitochondrial dysfunction plays a critical role. We have synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE−/− mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2- and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. While L-NAME (NOS inhibitor) significantly abrogated Mito-Esc-mediated protective effects, Compound c (inhibitor of AMPK) significantly decreased Mito-Esc-mediated increase in NO production. Notably, Mito-Esc promoted mitochondrial biogenesis by enhancing SIRT3 expression through AMPK activation; and restored H2O2-induced inhibition of mitochondrial respiration. siSIRT3 treatment not only completely reversed Mito-Esc-mediated mitochondrial biogenetic marker expressions but also caused endothelial cell death. Furthermore, Mito-Esc administration to ApoE−/− mice greatly alleviated Ang-II-induced atheromatous plaque formation, monocyte infiltration and serum pro-inflammatory cytokines levels. We conclude that Mito-Esc is preferentially taken up by the mitochondria and preserves endothelial cell survival during oxidative stress by modulating NO generation via AMPK. Also, Mito-Esc-induced SIRT3 plays a pivotal role in mediating mitochondrial biogenesis and perhaps contributes to its anti-atherogenic effects. PMID:27063143

  6. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease.

    PubMed

    Snow, Barry J; Rolfe, Fiona L; Lockhart, Michelle M; Frampton, Christopher M; O'Sullivan, John D; Fung, Victor; Smith, Robin A J; Murphy, Michael P; Taylor, Kenneth M

    2010-08-15

    Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD.

  7. Mitochondria targeting nano agents in cancer therapeutics

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-01-01

    Mitochondria have emerged as noteworthy therapeutic targets as their physiological functions are often altered in pathological conditions such as cancer. The electronic databases of MEDLINE, EMBASE and PubMed were searched for recent studies reporting the importance of mitochondria targeting nanoagents in cancer therapeutics. The concluding remarks of the above papers mostly confirmed the growing potential of these novel nanoagents in the area of anticancer research. Furthermore, numerous studies demonstrated the immense potential of nanocarriers in delivering mitochondria-acting compounds to their target site. Among the assemblage of nanomaterials, carbon nanotubes (CNTs) are becoming more prominent for drug delivery due to favorable attributes including their unique shape, which promotes cellular uptake, and large aspect ratio that facilitates conjugation of bioactive molecules on their surface. The present review focused on the current view of variable options available in mitochondria-targeting anticancer therapeutics. It may be concluded that improvements are essential for its establishment as a gold standard therapeutic option especially in the clinical setting. PMID:28105197

  8. The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer.

    PubMed

    Bazhin, Alexandr V; Yang, Yuhui; D'Haese, Jan G; Werner, Jens; Philippov, Pavel P; Karakhanova, Svetlana

    2016-07-01

    Our understanding in the last few years about reactive oxygen species (ROS) has changed from being harmful substances to crucial intra- and extracellular messengers as well as important regulators controlling a wide spectrum of signaling pathways, including those in cancer immunology. Therefore, these multiple essential roles of ROS and especially of mitochondria-derived ROS in malignant transformation and cancer progression make them a promising target for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. A link between ROS, antioxidants and the PDAC development and progression has been recently established. Therefore, usage of specific highly efficient antioxidants could bring an option for treatment and/or prevention of PDAC. 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) is a new antioxidant with the highest mitochondrion membrane penetrating ability and potent antioxidant capability. In this work, we investigated an impact of SkQ1 on tumor angiogenesis, immune micromilieu, and oncological parameters in the orthotopic Panc02 murine model of PDAC. We showed that in this model SkQ1 treatment leads to the elevation of pro-angiogenic factors and to building of mainly an anti-inflammatory cytokine milieu. On the cellular level we showed an increase in a percentage of memory T cells and a decrease in frequency on natural killer T (NKT) cells. At the same time, SkQ1 was ineffective in the improvement of oncological parameters of PDAC-bearing mice. New studies are needed to clarify the absence of therapeutic and/or prophylactic benefits of the antioxidant. © 2016 UICC.

  9. Inhibition of ROS production through mitochondria-targeted antioxidant and mitochondrial uncoupling increases post-thaw sperm viability in yellow catfish.

    PubMed

    Fang, Lu; Bai, Chenglian; Chen, Yuanhong; Dai, Jun; Xiang, Yang; Ji, Xiaoping; Huang, Changjiang; Dong, Qiaoxiang

    2014-12-01

    Reactive oxygen species (ROS) are one of the main causes for decreased viability in cryopreserved sperm. Many studies have reported the beneficial effect of antioxidant supplements in freezing media for post-thaw sperm quality. In the present study, we explored two new approaches of ROS inhibition in sperm cryopreservation of yellow catfish, namely mitochondrial-targeted antioxidant and metabolic modulator targeting mitochondrial uncoupling pathways. Our study revealed that addition of MitoQ, a compound designed to deliver ubiquinone into mitochondria, significantly decreased ROS production, as well as lipid peroxidation, and increased post-thaw viability. Similarly, sperm incubated with 2,4-dinitrophenol (DNP), a chemical protonophore that induces mitochondrial uncoupling, also had reduced ROS production, as well as lipid peroxidation, and increased post-thaw sperm viability. Conversely, activation of uncoupling protein (UCP2) by 4-hydroxynonenal (HNE) neither reduced ROS production nor increased post-thaw sperm viability. Our findings indicate that ROS inhibition through mitochondrial-targeted antioxidant or mild mitochondrial uncoupling is beneficial for sperm cryopreservation in yellow catfish. Our study provides novel methods to mitigate oxidative stress induced damage in cryopreserved sperm for future applications.

  10. Effects of mitochondria-targeted plastoquinone derivative antioxidant (SkQ1) on demography of free-breeding Campbell dwarf hamsters (Phodopus campbelli) kept in outdoor conditions. reproduction and lifespan: explanation in the framework of ultimate loads.

    PubMed

    Rogovin, K A; Khrushcheva, A M; Shekarova, O N; Ushakova, M V; Manskikh, V N; Sokolova, O V; Vasilieva, N Yu

    2014-10-01

    We studied demographic effects of the mitochondria-targeted antioxidant SkQ1 on free-breeding Campbell dwarf hamsters (Phodopus campbelli, Thomas, 1905, Rodentia, Cricetidae) in an outdoor vivarium with seasonally varying day length and temperatures. The animals were kept in pairs from their young age. We removed litters from parental cages at their age of 25 days. Experimental hamsters received daily 50 nmol/kg SkQ1 with water by oral dosing, whereas control animals received water. SkQ1 had no effect on the lifespan of either males or females in reproductive pairs. Mortality among females was higher than among males irrespective of SkQ1 treatment, this being related to higher costs of reproduction in females. However, SkQ1 accelerated breeding in pairs in the first half of the reproductive period of a year. Although there were no statistical differences in body mass of males and females between experimental and control animals during most of their life, SkQ1-receiving males had higher body mass at the end of their life. The opposite tendency was characteristic for old females. One-year-old males and females of the experimental and control groups showed no difference in intensity of immune response to sheep red blood cells. The dermal hypersensitivity response to phytohemagglutinin (test for T-cell immunity) was significantly higher in SkQ1-treated 1- and 1.5-year-old males. This was not true for females. There was a tendency toward increased density of the neutrophil population in blood in 1-year-old SkQ1-treated males. However, experimental males showed no difference from control males in the activity of the "peroxidase-endogenous hydrogen peroxide system" of neutrophils. The background level of stress estimated by the concentration of cortisol in blood serum was significantly lower in the SkQ1-treated males during autumn adaptive adjustment of the organism. A similar trend was also observed during the January frosts, when the background level of stress was

  11. Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury.

    PubMed

    Silachev, Denis N; Plotnikov, Egor Y; Zorova, Ljubava D; Pevzner, Irina B; Sumbatyan, Natalia V; Korshunova, Galina A; Gulyaev, Mikhail V; Pirogov, Yury A; Skulachev, Vladimir P; Zorov, Dmitry B

    2015-08-11

    We explored the neuroprotective properties of natural plant-derived antioxidants plastoquinone and thymoquinone (2-demethylplastoquinone derivative) modified to be specifically accumulated in mitochondria. The modification was performed through chemical conjugation of the quinones with penetrating cations: Rhodamine 19 or tetraphenylphosphonium. Neuroprotective properties were evaluated in a model of middle cerebral artery occlusion. We demonstrate that the mitochondria-targeted compounds, introduced immediately after reperfusion, possess various neuroprotective potencies as judged by the lower brain damage and higher neurological status. Plastoquinone derivatives conjugated with rhodamine were the most efficient, and the least efficiency was shown by antioxidants conjugated with tetraphenylphosphonium. Antioxidants were administered intraperitoneally or intranasally with the latter demonstrating a high level of penetration into the brain tissue. The therapeutic effects of both ways of administration were similar. Long-term administration of antioxidants in low doses reduced the neurological deficit, but had no effect on the volume of brain damage. At present, cationic decylrhodamine derivatives of plastoquinone appear to be the most promising anti-ischemic mitochondria-targeted drugs of the quinone family. We suggest these antioxidants could be potentially used for a stroke treatment.

  12. Mitochondria-Targeted Protective Compounds in Parkinson's and Alzheimer's Diseases

    PubMed Central

    Fernández-Moriano, Carlos; González-Burgos, Elena; Gómez-Serranillos, M. Pilar

    2015-01-01

    Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinson's disease and Alzheimer's disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinson's and Alzheimer's diseases, with particular attention to in vitro and in vivo studies on promising endogenous and exogenous mitochondria-targeted protective compounds. PMID:26064418

  13. Proteome-scale identification and characterization of mitochondria targeting proteins of Mycobacterium avium subspecies paratuberculosis: Potential virulence factors modulating host mitochondrial function.

    PubMed

    Rana, Aarti; Kumar, Devender; Rub, Abdur; Akhter, Yusuf

    2015-07-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of Johne's Disease among ruminants. During the course of infection, it expresses a number of proteins for its successful persistence inside the host that cause variety of physiological abnormalities in the host. Mitochondrion is one of the attractive targets for pathogenic bacteria. Employing a proteome-wide sequence and structural signature based approach we have identified 46 M. avium subsp. paratuberculosis proteins as potential targets for the host mitochondrial targeting. These may act as virulence factors modulating mitochondrial physiology for bacterial survival and immune evasion inside the host cells.

  14. Neuroprotection by a mitochondria-targeted drug in a Parkinson’s disease model

    PubMed Central

    Ghosh, Anamitra; Chandran, Karunakaran; Kalivendi, Shasi V.; Joseph, Joy; Antholine, William E.; Hillard, Cecilia J.; Kanthasamy, Arthi; Kanthasamy, Anumantha; Kalyanaraman, Balaraman

    2014-01-01

    The objective of this study was to assess the neuroprotective effects of a mitochondria-targeted antioxidant, Mito-Q10, the coenzyme-Q analog attached to a triphenylphosphonium cation that targets the antioxidant to mitochondria, in experimental models of Parkinson’s disease (PD). Primary mesencephalic neuronal cells and cultured dopaminergic cells were treated with 1-methyl-4-phenylpyridinium (MPP+), an active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and mice were used for testing the efficacy of Mito-Q10. MPP+ treatment caused a dose-dependent loss of tyrosine hydroxylase and membrane potential and an increase in caspase-3 activation in dopaminergic cells, which were reversed by Mito-Q10. MPTP treatment induced a loss of striatal dopamine and its metabolites, inactivation of mitochondrial aconitase in the substantia nigra, and a loss of locomotor activity in mice. Treatment with Mito-Q10 significantly inhibited both MPP+- and MPTP-induced neurotoxicity in cell culture and mouse models. Collectively, these results indicate that mitochondrial targeting of antioxidants is a promising neuroprotective strategy in this preclinical mouse model of PD. PMID:20828611

  15. A mitochondria-targeted nitroxide is reduced to its hydroxylamine by ubiquinol in mitochondria.

    PubMed

    Trnka, Jan; Blaikie, Frances H; Smith, Robin A J; Murphy, Michael P

    2008-04-01

    Piperidine nitroxides such as TEMPOL act as antioxidants in vivo due to their interconversion among nitroxide, hydroxylamine, and oxoammonium derivatives, but the mechanistic details of these reactions are unclear. As mitochondria are a significant site of piperidine nitroxide metabolism and action, we synthesized a mitochondria-targeted nitroxide, MitoTEMPOL, by conjugating TEMPOL to the lipophilic triphenylphosphonium cation. MitoTEMPOL was accumulated several hundred-fold into energized mitochondria where it was reduced to the hydroxylamine by direct reaction with ubiquinol. This reaction occurred by transfer of H() from ubiquinol to the nitroxide, with the ubisemiquinone radical product predominantly dismutating to ubiquinone and ubiquinol, together with a small amount reacting with oxygen to form superoxide. The piperidine nitroxides TEMPOL, TEMPO, and butylTEMPOL reacted similarly with ubiquinol in organic solvents but in mitochondrial membranes the rates varied in the order: MitoTEMPOL > butylTEMPOL > TEMPO > TEMPOL, which correlated with the extent of access of the nitroxide moiety to ubiquinol within the membrane. These findings suggest ways of using mitochondria-targeted compounds to modulate the coenzyme Q pool within mitochondria in vivo, and indicate that the antioxidant effects of mitochondria-targeted piperidine nitroxides can be ascribed to their corresponding hydroxylamines.

  16. Antioxidant potential of Lactuca sativa

    PubMed Central

    Garg, Munish; Garg, Chanchal; Mukherjee, Pulok K.; Suresh, B.

    2004-01-01

    The present study is based on the evaluation of antioxidant potential of a well known plant Lactuca sativa. Methanolic leaf extract was investigated for in vitro inhibition of oxidative damage induced by UV-radiations to the salmonella typhi bacteria and in vivo effect on the production of body enzymes i.e. catalase and superoxide dismutase. The lipid peroxidation masurement was also done in terms of thiobarbituric acid reactive substances (TBARS) in blood and brain of male albino wistar rats. The plant extract has shown significant antioxidant potential both in vitro and in vivo. PMID:22557144

  17. Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant

    DTIC Science & Technology

    2015-10-01

    tetanus toxin (Tx) model of epilepsy . Progress on the project has been limited throughout the grant period due to an inability to obtain a sufficient...of epilepsy . The pilocarpine-induced model of status epilepticus (PILO) will be used to test SS-31 as a neuroprotectant, the kindling model will be... epilepsy . The combination of the negative results we obtained with SS-31 treatment in the PILO and kindling models and our continued difficulty in

  18. Mitochondria-Targeting Polydopamine Nanoparticles To Deliver Doxorubicin for Overcoming Drug Resistance.

    PubMed

    Li, Wen-Qing; Wang, Zhigang; Hao, Sijie; He, Hongzhang; Wan, Yuan; Zhu, Chuandong; Sun, Li-Ping; Cheng, Gong; Zheng, Si-Yang

    2017-05-24

    Mitochondria play a critical role in diverse cellular processes, such as energy production and apoptosis regulation. The mitochondria-targeted drug delivery is becoming a potential novel strategy for overcoming drug resistance in cancer therapy. Herein, we synthesize nature-inspired dopamine-derived polydopamine (PDA) nanoparticles. Using triphenylphosphonium (TPP) as the mitochondrial penetration molecule to improve the target efficiency, we synthesize poly(ethylene glycol) (PEG)-modified PDA (PDA-PEG) and TPP-functionalized PEG-modified PDA (PDA-PEG-TPP) nanoparticles. Then anticancer drug doxorubicin (DOX) was loaded on PDA-PEG and PDA-PEG-TPP (PDA-PEG-DOX and PDA-PEG-TPP-DOX) nanoparticles, which are apt to deliver DOX to cell nuclei and mitochondria, respectively. To mimic the repeated anticancer drug treatment in clinical cases, we repeatedly treated the MDA-MD-231 cancer cells for a long time using DOX-loaded nanoparticles and find that the mitochondria targeting PDA-PEG-TPP-DOX has higher potential to overcome the drug resistance than the regular delivery nanoparticles PDA-PEG-DOX. These results indicate the promising potential of applying PDA-PEG-TPP-DOX nanoparticles in mitochondria-targeted drug delivery to overcome the drug resistance in long-time anticancer chemotherapy.

  19. Mitochondria-targeting for improved photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ngen, Ethel J.

    Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus

  20. Probiotics as potential antioxidants: a systematic review.

    PubMed

    Mishra, Vijendra; Shah, Chandni; Mokashe, Narendra; Chavan, Rupesh; Yadav, Hariom; Prajapati, Jashbhai

    2015-04-15

    Probiotics are known for their health beneficial effects and are established as dietary adjuncts. Probiotics have been known for many beneficial health effects. In this view, there is interest to find the potential probiotic strains that can exhibit antioxidant properties along with health benefits. In vitro and in vivo studies indicate that probiotics exhibit antioxidant potential. In this view, consumption of probiotics alone or foods supplemented with probiotics may reduce oxidative damage, free radical scavenging rate, and modification in activity of crucial antioxidative enzymes in human cells. Incorporation of probiotics in foods can provide a good strategy to supply dietary antioxidants, but more studies are needed to standardize methods and evaluate antioxidant properties of probiotics before they can be recommended for antioxidant potential. In this paper, the literature related to known antioxidant potential of probiotics and proposing future perspectives to conduct such studies has been reviewed.

  1. Antioxidants as Potential Therapeutics for Lung Fibrosis

    PubMed Central

    DAY, BRIAN J.

    2009-01-01

    Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non–metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans. PMID:17999627

  2. Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.

    PubMed

    Zielonka, Jacek; Joseph, Joy; Sikora, Adam; Hardy, Micael; Ouari, Olivier; Vasquez-Vivar, Jeannette; Cheng, Gang; Lopez, Marcos; Kalyanaraman, Balaraman

    2017-08-09

    Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

  3. A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.

    PubMed

    Reelfs, Olivier; Abbate, Vincenzo; Hider, Robert C; Pourzand, Charareh

    2016-08-01

    Mitochondria are the principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion. Therefore, targeted removal of mitochondrial labile iron via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria-homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, adenosine triphosphate depletion, and the ensuing necrotic cell death in skin fibroblasts, and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of the UVA component of sunlight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.

    PubMed

    Cheng, Gang; Zielonka, Jacek; Ouari, Olivier; Lopez, Marcos; McAllister, Donna; Boyle, Kathleen; Barrios, Christy S; Weber, James J; Johnson, Bryon D; Hardy, Micael; Dwinell, Michael B; Kalyanaraman, Balaraman

    2016-07-01

    Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+)). In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells. Moreover, Mito-Met10 potently triggered G1 cell-cycle phase arrest in PDAC cells, enhanced their radiosensitivity, and more potently abrogated PDAC growth in preclinical mouse models, compared with Met. Collectively, our findings show how improving the mitochondrial targeting of Met enhances its anticancer activities, including aggressive cancers like PDAC in great need of more effective therapeutic options. Cancer Res; 76(13); 3904-15. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes.

    PubMed

    Jou, Mei-Jie

    2008-01-01

    Astrocytes, in addition to passively supporting neurons, have recently been shown to be actively involved in synaptic transmission and neurovascular coupling in the central nervous system (CNS). This review summarizes briefly our previous observations using fluorescent probes coupled with laser scanning digital imaging microscopy to visualize spatio-temporal alteration of mitochondrial reactive oxygen species (mROS) generation in intact astrocytes. mROS formation is enhanced by exogenous oxidants exposure, Ca2+ stress and endogenous pathological defect of mitochondrial respiratory complexes. In addition, mROS formation can be specifically stimulated by visible light or visible laser irradiation and can be augmented further by photodynamic coupling with photosensitizers, particularly with mitochondria-targeted photosensitizers. "Severe" oxidative insult often results in massive and homogeneous augmentation of mROS formation which causes cessation of mitochondrial movement, pathological fission and irreversible swelling of mitochondria and eventually apoptosis or necrosis of cells. Mitochondria-targeted antioxidants and protectors such as MitoQ, melatonin and nanoparticle C(60) effectively prevent "severe" mROS generation. Intriguingly, "minor" oxidative insults enhance heterogeneity of mROS and mitochondrial dynamics. "Minor" mROS formation-induced fission and fusion of mitochondria relocates mitochondrial network to form a mitochondria free gap, i.e., "firewall", which may play a crucial role in mROS-mediated protective "preconditioning" by preventing propagation of mROS during oxidative insults. These mROS-targeted strategies for either enhancement or prevention of mitochondrial oxidative stress in astrocytes may provide new insights for future development of therapeutic interventions in the treatment of cancer such as astrocytomas and gliomas and astrocyte-associated neurodegeneration, mitochondrial diseases and aging.

  6. Antioxidants as potential therapeutics for neuropsychiatric disorders

    PubMed Central

    Pandya, Chirayu D; Howell, Kristy R; Pillai, Anilkumar

    2012-01-01

    Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders. PMID:23123357

  7. An Antioxidant potential of Hingot and Hadjod.

    PubMed

    Vijay, Priyanka; Vijayvergia, R

    2009-12-01

    The antioxidant activity of two plants - Hadjod i.e. Cissus quadrangularis (CQ) and Hingot i.e. Balanites aegyptiaca (BA) was determined by the thiocyanate method. The antioxidant activity of both the plants increased with increasing amount of extract (200 g-1000 g) added to the linoleic emulsion. The ethanolic extract of CQ was more effective than the other. Like antioxidant activity, the reducing power was also dependent upon the concentration. The ethanolic extract of BA shows more reducing power than the other. The result obtained in the present study indicates that the both the plants are potential source of natural antioxidants. In addition, we could suggest that although the reducing power of a substance may be an indicator of its potential antioxidant activity, there is not necessarily a linear correlation between these two activities.

  8. An Antioxidant potential of Hingot and Hadjod

    PubMed Central

    Vijay, Priyanka; Vijayvergia, R.

    2009-01-01

    The antioxidant activity of two plants - Hadjod i.e. Cissus quadrangularis (CQ) and Hingot i.e. Balanites aegyptiaca (BA) was determined by the thiocyanate method. The antioxidant activity of both the plants increased with increasing amount of extract (200 g-1000 g) added to the linoleic emulsion. The ethanolic extract of CQ was more effective than the other. Like antioxidant activity, the reducing power was also dependent upon the concentration. The ethanolic extract of BA shows more reducing power than the other. The result obtained in the present study indicates that the both the plants are potential source of natural antioxidants. In addition, we could suggest that although the reducing power of a substance may be an indicator of its potential antioxidant activity, there is not necessarily a linear correlation between these two activities. PMID:25206251

  9. Mitochondria Targeted Peptides Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity

    PubMed Central

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y.; Luo, Guoxiong; Szeto, Hazel H.

    2009-01-01

    Abstract A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD. Antioxid. Redox Signal. 11, 2095–2104. PMID:19203217

  10. Mitochondria-targeted liposomes improve the apoptotic and cytotoxic action of sclareol.

    PubMed

    Patel, Niravkumar R; Hatziantoniou, Sophia; Georgopoulos, Aristidis; Demetzos, Costas; Torchilin, Vladimir P; Weissig, Volkmar; D'Souza, Gerard G M

    2010-09-01

    Current efforts toward improving the effectiveness of drug therapy are increasingly relying on drug-targeting strategies to effectively deliver bioactive molecules to their molecular targets. Pharmaceutical nanocarriers represent a major tool toward this aim, and our efforts have been directed toward achieving nanocarrier-mediated subcellular delivery of drug molecules with mitochondria as the primary subcellular target. Meeting the need for specific subcellular delivery is essential to realizing the full potential of many poorly soluble anticancer drugs. In this article, we report that mitochondria-targeted liposomes significantly improve the apoptotic and cytotoxic action of sclareol, a poorly soluble potential anticancer drug. The results support the broad applicability of our nanocarrier-mediated subcellular targeting approach as a means to improve the effectiveness of certain anticancer therapeutics.

  11. Marine bioactive peptides as potential antioxidants.

    PubMed

    Ngo, Dai-Hung; Kim, Se-Kwon

    2013-05-01

    Bioactive peptides derived from marine organisms are the focus of current studies because of their numerous health beneficial effects. They exert various biological roles, one of the most crucial of which is the antioxidant effect. Reverse relationship between antioxidant intake and diseases has been approved through plenty of studies. Antioxidant activity of marine peptides can be attributed to in vitro and in vivo free radical scavenging activities. Antioxidant peptides isolated from marine sources may be used as functional ingredients in food formulations to promote consumer health and improve the shelf life of food products. This chapter presents an overview of the antioxidant peptides derived marine resources with the potential utilization in the food as well as pharmaceutical industries.

  12. Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer.

    PubMed

    Zhang, Shaojuan; Yang, Ling; Ling, Xiaoxi; Shao, Pin; Wang, Xiaolei; Edwards, W Barry; Bai, Mingfeng

    2015-12-01

    Photodynamic therapy (PDT) has been proven to be a minimally invasive and effective therapeutic strategy for cancer treatment. It can be used alone or as a complement to conventional cancer treatments, such as surgical debulking and chemotherapy. The mitochondrion is an attractive target for developing novel PDT agents, as it produces energy for cells and regulates apoptosis. Current strategy of mitochondria targeting is mainly focused on utilizing cationic photosensitizers that bind to the negatively charged mitochondria membrane. However, such an approach is lack of selectivity of tumor cells. To minimize the damage on healthy tissues and improve therapeutic efficacy, an alternative targeting strategy with high tumor specificity is in critical need. Herein, we report a tumor mitochondria-specific PDT agent, IR700DX-6T, which targets the 18kDa mitochondrial translocator protein (TSPO). IR700DX-6T induced apoptotic cell death in TSPO-positive breast cancer cells (MDA-MB-231) but not TSPO-negative breast cancer cells (MCF-7). In vivo PDT study suggested that IR700DX-6T-mediated PDT significantly inhibited the growth of MDA-MB-231 tumors in a target-specific manner. These combined data suggest that this new TSPO-targeted photosensitizer has great potential in cancer treatment. Photodynamic therapy (PDT) is an effective and minimally invasive therapeutic technique for treating cancers. Mitochondrion is an attractive target for developing novel PDT agents, as it produces energy to cells and regulates apoptosis. Current mitochondria targeted photosensitizers (PSs) are based on cationic molecules, which interact with the negatively charged mitochondria membrane. However, such PSs are not specific for cancerous cells, which may result in unwanted side effects. In this study, we developed a tumor mitochondria-targeted PS, IR700DX-6T, which binds to translocator protein (TSPO). This agent effectively induced apoptosis in TSPO-positive cancer cells and significantly

  13. The Use of Mitochondria-Targeted Endonucleases to Manipulate mtDNA

    PubMed Central

    Bacman, Sandra R.; Williams, Sion L.; Pinto, Milena; Moraes, Carlos T.

    2014-01-01

    For more than a decade, mitochondria-targeted nucleases have been used to promote double-strand breaks in the mitochondrial genome. This was done in mitochondrial DNA (mtDNA) homoplasmic systems, where all mtDNA molecules can be affected, to create models of mitochondrial deficiencies. Alternatively, they were also used in a heteroplasmic model, where only a subset of the mtDNA molecules were substrates for cleavage. The latter approach showed that mitochondrial-targeted nucleases can reduce mtDNA haplotype loads in affected tissues, with clear implications for the treatment of patients with mitochondrial diseases. In the last few years, designer nucleases, such as ZFN and TALEN, have been adapted to cleave mtDNA, greatly expanding the potential therapeutic use. This chapter describes the techniques and approaches used to test these designer enzymes. PMID:25416366

  14. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

    PubMed

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y; Luo, Guoxiong; Szeto, Hazel H; Beal, M Flint

    2009-09-01

    A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD.

  15. Potential Anticancer Properties of Grape Antioxidants

    PubMed Central

    Zhou, Kequan; Raffoul, Julian J.

    2012-01-01

    Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera), one of the world's largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR) and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted. PMID:22919383

  16. Mitochondria-targeted plastoquinone derivative SkQ(1) decreases ischemia-reperfusion injury during liver hypothermic storage for transplantation.

    PubMed

    Cherkashina, D V; Sosimchik, I A; Semenchenko, O A; Volina, V V; Petrenko, A Yu

    2011-09-01

    The ability of the mitochondria-targeted plastoquinone derivative 10-(6'-plastoquinonyl)decyl triphenylphosphonium (SkQ(1)) to decrease ischemia-reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4°C without or in the presence of 1 μM SkQ(1) with following reperfusion for 60 min at 37°C. The presence in the storage medium of SkQ(1) significantly decreased spontaneous production of reactive oxygen species and intensity of lipid peroxidation in the liver during HS and reperfusion. The GSH level after HS in solution with SkQ(1) was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ(1) did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ(1) to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ(1) exhibited positive effect on the liver secretory function and morphology after HS as revealed in enhanced bile flow rate during reperfusion and partial recovery of organ architectonics and state of liver sinusoids and hepatocytes. The data point to promising application of mitochondria-targeted antioxidants for correction of the ischemia-reperfusion injury of isolated liver during long-term cold storage before transplantation.

  17. In vitro antioxidant potential of dicliptera roxburghiana

    PubMed Central

    2013-01-01

    Background Stress caused by free radicals accumulation result into many hazardous diseases. A number of investigations are focusing to find out the plant oriented natural antioxidant moieties. The basic aim of this research was to investigate the antioxidant potential, total Phenolic and flavonoids contents and photochemical screening of the crude methanol extract and its derived various fractions Dicliptera roxburghiana of Acanthaceae family. Methods Crude methanol extract of aerial parts of Dicliptera roxburghiana (DRME) was partitioned in to n-hexane (DRHF), chloroform (DRCF), ethyl acetate (DREF), n-butanol (DRBF) and the remaining soluble portion as residual aqueous fraction (DRAF). We evaluated the antioxidant activities of the extract and various fractions through different analytical methods such as DPPH, superoxide anion, ABTS, H2O2, hydroxyl radical and phosphomolybdate radical inhibition. In vitro lipid peroxidation and reducing power of the plant was also analyzed. Total flavonoid and phenolic contents of the extract and all fractions were also quantified. Plant was also subjected for preliminary phytochemical screening to confirm the presence or absence of various constituents in the plant. Results Phytochemical screening confirmed the presence of flavonoids, phenolics, tannins, alkaloids, saponins, terpenoids and coumarines. Quantitative analysis revealed the maximum amount of total phenolic and flavonoid contents in DRME while lowest in DRHF. Methanol extract, DREF, DRCF and DRBF exhibited promising antioxidant potential for DPPH, ABTS, H2O2, phosphomolybdate, superoxide anion and hydroxyl radical scavenging capabilities, while these were not appreciable for DRHF and DRAF. All fractions except DRHF and DRAF possess strong reducing power ability and showed appreciable lipid peroxidation inhibition. Conclusion These research investigations revealed that Dicliptera roxburghiana is a potent source of natural antioxidants. Hence the plant can be used for

  18. A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.

    PubMed

    Boison, Daniel; Lu, Wen-Long; Xu, Qin-Mei; Yang, Huang; Huang, Tao; Chen, Qiu-Yun; Gao, Jing; Zhao, Yao

    2016-11-01

    HIF-1α and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1α and LDH-A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging.

  19. Structural modifications of mitochondria-targeted chlorambucil alter cell death mechanism but preserve MDR evasion.

    PubMed

    Jean, Sae Rin; Pereira, Mark P; Kelley, Shana O

    2014-08-04

    Multidrug resistance (MDR) remains one of the major obstacles in chemotherapy, potentially rendering a multitude of drugs ineffective. Previously, we have demonstrated that mitochondrial targeting of DNA damaging agents is a promising tool for evading a number of common resistance factors that are present in the nucleus or cytosol. In particular, mitochondria-targeted chlorambucil (mt-Cbl) has increased potency and activity against resistant cancer cells compared to the parent compound chlorambucil (Cbl). However, it was found that, due to its high reactivity, mt-Cbl induces a necrotic type of cell death via rapid nonspecific alkylation of mitochondrial proteins. Here, we demonstrate that by tuning the alkylating activity of mt-Cbl via chemical modification, the rate of generation of protein adducts can be reduced, resulting in a shift of the cell death mechanism from necrosis to a more controlled apoptotic pathway. Moreover, we demonstrate that all of the modified mt-Cbl compounds effectively evade MDR resulting from cytosolic GST-μ upregulation by rapidly accumulating in mitochondria, inducing cell death directly from within. In this study, we systematically elucidated the advantages and limitations of targeting alkylating agents with varying reactivity to mitochondria.

  20. Mitochondria-targeting photoacoustic therapy using single-walled carbon nanotubes.

    PubMed

    Zhou, Feifan; Wu, Shengnan; Yuan, Yi; Chen, Wei R; Xing, Da

    2012-05-21

    In vitro photoacoustic therapy using modified single-walled carbon nanotubes (SWNTs) as "bomb" agents is a newly reported approach for cancer. Herein, a mitochondria-targeting photoacoustic modality using unmodified SWNTs and its in vitro and in vivo antitumor effect are reported. Unmodified SWNTs can be taken up into cancer cells due to a higher mitochondrial transmembrane potential in cancerous cells than normal cells. Under the irradiation of a 1064 nm pulse laser, 79.4% of cancer cells with intracellular SWNTs die within 20 s, while 82.3% of normal cells without SWNTs remain alive. This modality kills cancer cells mainly by triggering cell apoptosis that initiates from mitochondrial damage, through the depolarization of mitochondria and the subsequent release of cytochrome c after photoacoustic therapy. It is very effective in suppressing tumor growth by selectively destroying tumor tissue without causing epidermis injury. Taken together, these discoveries provide a new method using mitochondria-localized SWNTs as photoacoustic transducers for cancer treatment.

  1. Antioxidant potential of selected Spirulina platensis preparations.

    PubMed

    Dartsch, Peter C

    2008-05-01

    Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and therapeutic properties and is also capable of acting as an antioxidant and antiinflammatory agent. In this study, a cell-free and a cell-based test assay were used to examine the antioxidant and antiinflammatory properties of four selected Spirulina platensis preparations: (1) Biospirulina, (2) SpiruComplex, a preparation with naturally bound selenium, chromium and zinc, (3) SpiruZink, a preparation with naturally bound zinc, (4) Zinkspirulina + Acerola, a preparation with naturally bound zinc and acerola powder. The cell-free test assay used potassium superoxide as a donor for superoxide radicals, whereas the cell-based test assay used the formation of intracellular superoxide radicals of functional neutrophils upon stimulation by phorbol-12-myristate-13-acetate as a model to investigate the potential of Spirulina preparations to inactivate superoxide radicals. In accordance with the recommended daily dosage, test concentrations ranging from 50 to 1000 microg/mL were chosen. The results showed a dose-dependent inactivation of free superoxide radicals (antioxidant effect) as well as an antiinflammatory effect characterized by a dose-dependent reduction of the metabolic activity of functional neutrophils and a dose-dependent inactivation of superoxide radicals generated during an oxidative burst. The results demonstrate that the tested Spirulina preparations have a high antioxidant and antiinflammatory potential. Especially SpiruZink and Zinkspirulina + Acerola might be useful as a supportive therapeutic approach for reducing oxidative stress and/or the generation of oxygen radicals in the course of inflammatory processes.

  2. Plant cell death caused by fungal, bacterial, and viral elicitors: protective effect of mitochondria-targeted quinones.

    PubMed

    Kiselevsky, D B; Frolova, O Yu; Solovyev, A G; Dorokhov, Yu L; Morozov, S Yu; Samuilov, V D

    2014-12-01

    Chitosan (partially deacetylated chitin), a component of fungal cell walls, caused epidermal cell (EC) death in the leaves of pea (Pisum sativum L.) and tobacco Nicotiana tabacum or Nicotiana benthamiana detected by destruction of cell nuclei. The mitochondria-targeted quinone SkQ1 prevented the destruction of EC nuclei induced by chitosan. Chitosan increased and SkQ1 suppressed the activity of protein kinases in N. benthamiana and P. sativum and eliminated the effect of chitosan. Chitosan induced the generation of reactive oxygen species (ROS) in the guard cells (GC) of pea plants. Treatment with chitosan or H2O2 did not cause destruction of GC nuclei; however, it resulted in disruption of the permeability barrier of the plasma membrane detected by propidium iodide fluorescence. Treatment with bacterial lipopolysaccharide but not peptidoglycan caused destruction of pea EC nuclei, which was prevented by SkQ1. Leaves of tobacco plants containing the N gene responsible for resistance to tobacco mosaic virus (TMV) were infiltrated with Agrobacterium tumefaciens cells. These cells contained a genetic construct with the gene of the helicase domain of TMV replicase (p50); its protein product p50 is a target for the N-gene product. As a result, the hypersensitive response (HR) was initiated. The HR manifested itself in the death of leaves and was suppressed by SkQ3. Treatment of tobacco epidermal peels with the A. tumefaciens cells for the p50 gene expression stimulated the destruction of EC nuclei, which was inhibited by SkQ1 or SkQ3. The p50-lacking A. tumefaciens cells did not induce the destruction of EC nuclei. The protective effect of mitochondria-targeted antioxidants SkQ1 and SkQ3 demonstrates the involvement of mitochondria and their ROS in programmed cell death caused by pathogen elicitors.

  3. Mitochondria-targeted cancer therapy using a light-up probe with aggregation-induced-emission characteristics.

    PubMed

    Hu, Qinglian; Gao, Meng; Feng, Guangxue; Liu, Bin

    2014-12-15

    Subcellular organelle-specific reagents for simultaneous tumor targeting, imaging, and treatment are of enormous interest in cancer therapy. Herein, we present a mitochondria-targeting probe (AIE-mito-TPP) by conjugating a triphenylphosphine (TPP) with a fluorogen which can undergo aggregation-induced emission (AIE). Owing to the more negative mitochondrial membrane potential of cancer cells than normal cells, the AIE-mito-TPP probe can selectively accumulate in cancer-cell mitochondria and light up its fluorescence. More importantly, the probe exhibits selective cytotoxicity for studied cancer cells over normal cells. The high potency of AIE-mito-TPP correlates with its strong ability to aggregate in mitochondria, which can efficiently decrease the mitochondria membrane potential and increase the level of intracellular reactive oxygen species (ROS) in cancer cells. The mitochondrial light-up probe provides a unique strategy for potential image-guided therapy of cancer cells.

  4. The energy blocker inside the power house: Mitochondria targeted delivery of 3-bromopyruvate.

    PubMed

    Marrache, Sean; Dhar, Shanta

    2015-03-01

    A key hallmark of many aggressive cancers is accelerated glucose metabolism. The enzymes that catalyze the first step of glucose metabolism are hexokinases. High levels of hexokinase 2 (HK2) are found in cancer cells, but only in a limited number of normal tissues. Metabolic reprogramming of cancer cells using the energy blocker, 3-bromopyruvate (3-BP) that inhibits HK2 has the potential to provide tumor-specific anticancer agents. However, the unique structural and functional characteristics of mitochondria prohibit selective subcellular targeting of 3-BP to modulate the function of this organelle for therapeutic gain. A mitochondria targeted gold nanoparticle (T-3-BP-AuNP) decorated with 3-BP and delocalized lipophilic triphenylphosphonium cations to target the mitochondrial membrane potential (Δψm) was developed for delivery of 3-BP to cancer cell mitochondria by taking advantage of higher Δψm in cancer cells compared to normal cells. In vitro studies demonstrated enhanced anticancer activity of T-3-BP-AuNPs compared to the non-targeted construct NT-3-BP-AuNP or free 3-BP. The anticancer activity of T-3-BP-AuNP was further enhanced upon laser irradiation by exciting the surface plasmon resonance band of AuNP and thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermal effects. The less toxic behavior of T-3-BPNPs in normal mesenchymal stem cells indicated that these NPs preferentially kill cancer cells. T-3-BP-AuNPs showed enhanced ability to modulate cancer cell metabolism by inhibiting glycolysis as well as demolishing mitochondrial oxidative phosphorylation. Our findings demonstrated that concerted chemo-photothermal treatment of glycolytic cancer cells with a single NP capable of targeting mitochondria mediating simultaneous release of a glycolytic inhibitor and photothermal ablation may have promise as a new anticancer therapy.

  5. Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles.

    PubMed

    Yu, Pengcheng; Yu, Haijun; Guo, Chengyue; Cui, Zhirui; Chen, Xianzhi; Yin, Qi; Zhang, Pengcheng; Yang, Xiangliang; Cui, Honggang; Li, Yaping

    2015-03-01

    Chemotherapy is an important approach for clinical cancer treatment. However, the success of chemotherapy is usually hindered by the occurrence of intrinsic or acquired multidrug resistance of cancer cells. Herein, we reported an effective approach to overcome doxorubicin (DOX) resistance in MCF-7/ADR breast cancer using DOX-loaded pH-responsive micelles. The micelles were prepared from a pH-responsive diblock copolymer, poly(ethylene glycol)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PEG-b-PDPA), and a vitamin E derivate (D-α-tocopheryl polyethylene glycol 1000 succinate, TPGS) (denoted as PDPA/TPGS micelles). At neutral pH of 7.4, DOX was loaded into the hydrophobic core of PDPA/TPGS micelles via a film sonication method. After cellular uptake, the DOX payload was released in early endosomes by acidic pH-triggered micelle dissociation. Meanwhile, the TPGS component synergistically improved the cytotoxicity of DOX by targeting mitochondrial organelles and reducing the mitochondrial transmembrane potential. In vitro cell culture experiments using DOX-resistant MCF-7/ADR cells demonstrated that PDPA/TPGS micelles reduced the IC50 of DOX by a sixfold magnitude. In vivo animal studies showed that DOX-loaded PDPA/TPGS micelles (PDPA/TPGS@DOX) inhibited tumor growth more efficiently than free DOX in a nude mouse model bearing orthotopic MCF-7/ADR tumor. All these results imply that the mitochondria-targeted pH-responsive PDPA/TPGS micelles have significant potential for efficiently combating DOX resistance in breast cancer cells. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Mitochondria-targeted molecules MitoQ and SS31 reduce mutant huntingtin-induced mitochondrial toxicity and synaptic damage in Huntington's disease.

    PubMed

    Yin, Xiangling; Manczak, Maria; Reddy, P Hemachandra

    2016-05-01

    The objective of this study was to determine the protective effects of the mitochondria-targeted molecules MitoQ and SS31 in striatal neurons that stably express mutant huntingtin (Htt) (STHDhQ111/Q111) in Huntington's disease (HD). We studied mitochondrial and synaptic activities by measuring mRNA and the protein levels of mitochondrial and synaptic genes, mitochondrial function, and ultra-structural changes in MitoQ- and SS31-treated mutant Htt neurons relative to untreated mutant Htt neurons. We used gene expression analysis, biochemical methods, transmission electron microscopy (TEM) and confocal microscopy methods. In the MitoQ- and SS31-treated mutant Htt neurons, fission genes Drp1 and Fis1 were down-regulated, and fusion genes Mfn1, Mfn2 and Opa1 were up-regulated relative to untreated neurons, suggesting that mitochondria-targeted molecules reduce fission activity. Interestingly, the mitochondrial biogenesis genes PGC1α, PGC1β, Nrf1, Nrf2 and TFAM were up-regulated in MitoQ- and SS31-treated mutant Htt neurons. The synaptic genes synaptophysin and PSD95 were up-regulated, and mitochondrial function was normal in the MitoQ- and SS31-treated mutant Htt neurons. Immunoblotting findings of mitochondrial and synaptic proteins agreed with the mRNA findings. TEM studies revealed decreased numbers of structurally intact mitochondria in MitoQ- and SS31-treated mutant Htt neurons. These findings suggest that mitochondria-targeted molecules MitoQ and SS31 are protective against mutant Htt-induced mitochondrial and synaptic damage in HD neurons, and these mitochondria-targeted molecules are potential therapeutic molecules for the treatment of HD neurons.

  7. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a ‘differential multiple cleavage-site’ model

    PubMed Central

    Bacman, SR; Williams, SL; Hernandez, D; Moraes, CT

    2009-01-01

    The ability to manipulate mitochondrial DNA (mtDNA) heteroplasmy would provide a powerful tool to treat mitochondrial diseases. Recent studies showed that mitochondria-targeted restriction endonucleases can modify mtDNA heteroplasmy in a predictable and efficient manner if it recognizes a single site in the mutant mtDNA. However, the applicability of such model is limited to mutations that create a novel cleavage site, not present in the wild-type mtDNA. We attempted to extend this approach to a ‘differential multiple cleavage site’ model, where an mtDNA mutation creates an extra restriction site to the ones normally present in the wild-type mtDNA. Taking advantage of a heteroplasmic mouse model harboring two haplotypes of mtDNA (NZB/BALB) and using adenovirus as a gene vector, we delivered a mitochondria-targeted Scal restriction endonuclease to different mouse tissues. Scal recognizes five sites in the NZB mtDNA but only three in BALB mtDNA. Our results showed that changes in mtDNA heteroplasmy were obtained by the expression of mitochondria-targeted ScaI in both liver, after intravenous injection, and in skeletal muscle, after intramuscular injection. Although mtDNA depletion was an undesirable side effect, our data suggest that under a regulated expression system, mtDNA depletion could be minimized and restriction endonucleases recognizing multiple sites could have a potential for therapeutic use. PMID:17597792

  8. Design and Synthesis of a Mitochondria-Targeted Mimic of Glutathione Peroxidase, MitoEbselen-2, as a Radiation Mitigator.

    PubMed

    Stoyanovsky, Detcho A; Jiang, Jianfei; Murphy, Michael P; Epperly, Michael; Zhang, Xiaolan; Li, Song; Greenberger, Joel; Kagan, Valerian; Bayır, Hülya

    2014-12-11

    Ionizing radiation (IR) triggers mitochondrial overproduction of H2O2 and accumulation of lipid hydroperoxides leading to the induction of apoptotic and necroptotic cell death pathways. Given the high catalytic efficiency of the seleno-enzyme glutathione peroxidase (Gpx) toward reduction of lipid hydroperoxides and H2O2, we tested the potential of mitochondria-targeted derivatives of ebselen to mitigate the deleterious effects of IR. We report that 2-[[2-[4-(3-oxo-1,2-benzoselenazol-2-yl)phenyl]acetyl]amino]ethyl-triphenyl-phosphonium chloride (MitoPeroxidase 2) was effective in reducing lipid hydroperoxides, preventing apoptotic cell death, and, when administered 24 h postirradiation, increased the survival of mice exposed to whole body γ-irradiation.

  9. Rationale for mitochondria-targeting strategies in cancer bioenergetic therapies.

    PubMed

    Jose, Caroline; Rossignol, Rodrigue

    2013-01-01

    In the 1920s, Otto Warburg first hypothesized that mitochondrial impairment is a leading cause of cancer although he recognized the existence of oxidative tumors. Likewise, Weinhouse and others in the 50s found that deficient mitochondrial respiration is not an obligatory feature of cancer and Peter Vaupel suggested in the 1990s that tumor oxygenation rather than OXPHOS capacity was the limiting factor of mitochondrial energy production in cancer. Recent studies now clearly indicate that mitochondria are highly functional in mice tumors and the field of oncobioenergetic identified MYC, Oct1 and RAS as pro-OXPHOS oncogenes. In addition, cancer cells adaptation to aglycemia, metabolic symbiosis between hypoxic and non-hypoxic tumor regions as well the reverse Warburg hypothesis support the crucial role of mitochondria in the survival of a subclass of tumors. Therefore, mitochondria are now considered as potential targets for anti-cancer therapy and tentative strategies including a bioenergetic profile characterization of the tumor and the subsequent adapted bioenergetic modulation could be considered for cancer killing. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

  10. Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

    PubMed Central

    Starenki, Dmytro

    2013-01-01

    Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

  11. Mitochondria-targeted nitroxide, Mito-CP, suppresses medullary thyroid carcinoma cell survival in vitro and in vivo.

    PubMed

    Starenki, Dmytro; Park, Jong-In

    2013-04-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP-induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy.

  12. A fluorescent carbon-dots-based mitochondria-targetable nanoprobe for peroxynitrite sensing in living cells.

    PubMed

    Wu, Xiaoxue; Sun, Shan; Wang, Yuhui; Zhu, Jiali; Jiang, Kai; Leng, Yumin; Shu, Qinghai; Lin, Hengwei

    2017-04-15

    Mitochondria, the power generators in cell, are a primary organelle of oxygen consumption and a main source of reactive oxygen/nitrogen species (ROS/RNS). Peroxynitrite (ONOO(-)), known as a kind of RNS, has been considered to be a significant factor in many cell-related biological processes, and there is great desire to develop fluorescent probes that can sensitively and selectively detect peroxynitrite in living cells. Herein, we developed a fluorescent carbon-dots (C-dots) based mitochondria-targetable nanoprobe with high sensitivity and selectivity for peroxynitrite sensing in living cells. The C-dots with its surface rich in amino groups was synthesized using o-phenylenediamine as carbon precursor, and it could be covalently conjugated with a mitochondria-targeting moiety, i.e. triphenylphosphonium (TPP). In the presence of peroxynitrite, the fluorescence of the constructed nanoprobe (C-dots-TPP) was efficiently quenched via a mechanism of photoinduced electron transfer (PET). The nanoprobe exhibited relatively high sensitivity (limit of detection: 13.5nM) and selectivity towards peroxynitrite in aqueous buffer. The performance of the nanoprobe for fluorescence imaging of peroxynitrite in mitochondria was investigated. The results demonstrated that the nanoprobe showed fine mitochondria-targeting ability and imaging contrast towards peroxynitrite in living cells. We anticipate that the proposed nanoprobe will provide a facile tool to explore the role played by peroxynitrite in cytobiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

    PubMed

    Tate, Alan D; Antonelli, Patrick J; Hannabass, Kyle R; Dirain, Carolyn O

    2017-03-01

    Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

  14. Neuroprotection and Anti-Epileptogenesis with a Mitochondria-Targeted Antioxidant

    DTIC Science & Technology

    2013-12-01

    3 days after SE, sectioned through the hippocampus and stained for: Nissl , Fluoro-jade C (FJ), NeuN and heat shock protein (HSP). Three rats from...each group died during SE. There was no significant difference in the latency to SE between the two groups. There was also no difference in Nissl , FJ...immunohistochemical stains: Nissl , Fluoro-jade C (FJ), NeuN and heat shock protein 70-72 (HSP). Nissl , FJ and NeuN stains were used to assess

  15. Ruthenium(II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents.

    PubMed

    Liu, Jiangping; Chen, Yu; Li, Guanying; Zhang, Pingyu; Jin, Chengzhi; Zeng, Leli; Ji, Liangnian; Chao, Hui

    2015-07-01

    Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1-RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74-0.81), significant TPA cross sections (124-198 GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1-RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6 μM in one-photon PDT (λirr = 450 nm, 12 J cm(-2)) and 1.9 μM in two-photon PDT (λirr = 830 nm, 800 J cm(-2)) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death.

    PubMed

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna M; Mackinnon, A Craig; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2013-06-13

    Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect.

  17. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

    PubMed Central

    2013-01-01

    Background Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. Methods In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Results Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. Conclusions We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect. PMID:23764021

  18. A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells

    PubMed Central

    He, Huan; Li, Dong-Wei; Yang, Li-Yun; Fu, Li; Zhu, Xun-Jin; Wong, Wai-Kwok; Jiang, Feng-Lei; Liu, Yi

    2015-01-01

    Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment. PMID:26337336

  19. Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Hao, Shuangying; Jia, Ming; Ji, Muhuo; Qiu, Lili; Sun, Xiaoyan; Yang, Jianjun; Li, Kuanyu

    2015-08-01

    Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice.

  20. Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases

    PubMed Central

    Ajith, Thekkuttuparambil Ananthanarayanan; Jayakumar, Thankamani Gopinathan

    2014-01-01

    Mitochondria are one of the major sites for the generation of reactive oxygen species (ROS) as an undesirable side product of oxidative energy metabolism. Damaged mitochondria can augment the generation of ROS. Dysfunction of mitochondria increase the risk for a large number of human diseases, including cardiovascular diseases (CVDs). Heart failure (HF) following ischemic heart disease, infantile cardiomyopathy and cardiac hypertrophy associated with left ventricular dilations are some of the CVDs in which the role of mitochondrial oxidative stress has been reported. Advances in mitochondrial research during the last decade focused on the preservation of its function in the myocardium, which is vital for the cellular energy production. Experimental and clinical trials have been conducted using mitochondria-targeted molecules like: MnSOD mimetics, such as EUK-8, EUK-134 and MitoSOD; choline esters of glutathione and N-acetyl-L-cysteine; triphenylphosphonium ligated vitamin E, lipoic acid, plastoquinone and mitoCoQ10; and Szeto-Schiller (SS)- peptides (SS-02 and SS-31). Although many results are inconclusive, some of the findings, especially on CoQ10, are worthwhile. This review summarizes the role of mitochondria-targeted delivery of agents and their consequences in the control of HF. PMID:25349653

  1. Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents

    PubMed Central

    Modica-Napolitano, Josephine S.; Weissig, Volkmar

    2015-01-01

    Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy. PMID:26230693

  2. Bioactive compounds and antioxidant potential fruit of Ximenia americana L.

    PubMed

    Almeida, Maria Lucilania Bezerra; Freitas, Wallace Edelky de Souza; de Morais, Patrícia Lígia Dantas; Sarmento, José Dárcio Abrantes; Alves, Ricardo Elesbão

    2016-02-01

    The caatinga ecoregion in northeast Brazil presents a wide variety in plant species. However, the potential of these species as a source of energy, carbohydrates, vitamins, minerals and bioactive properties beneficial to health is still unknown. Among these species we can find the wild plum (Ximenia americana). Due to its various phytotherapeutic properties and absence of studies on the chemical composition of the fruit this article aimed to evaluate the bioactive compounds and antioxidant potential of the X. americana in different stages of maturation. The fruits of X. americana showed considerable amounts of bioactive compounds, as well as antioxidant activity and antioxidant enzymes. The fruits at green maturity stage showed higher content of yellow flavonoids (22.07 mg/100g), anthocyanins (1.92 mg/100 g), polyphenols (3051.62 mg/100 g), starch (4.22%), antioxidant activity (489.40 g fruit/g DPPH and 198.77 μmol Trolox/g) and activity of antioxidant enzymes; the antioxidant activity allocated to the fruit was shown to be related to the contents of extractable polyphenols, yellow flavonoids, total anthocyanins and antioxidant enzymes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Antitumour and antioxidant potential of some selected Pakistani honeys.

    PubMed

    Noor, Nadia; Sarfraz, Raja Adil; Ali, Shaukat; Shahid, Muhammad

    2014-01-15

    Antitumour potential of honey is attributed to its excellent antioxidant activity which in turn depends on the geographical origin. The present study focuses on exploration of antioxidant and antitumour potential as well as total phenolic contents (TPC) of 58 Pakistani honeys involving spectrochemical techniques and potato disk assay. Agrobacterium tumefaciens was used to induce tumours in potato disks. All analysed honey samples exhibited 1.33±0.00-155.16±0.98mg/100g of TPC, 50% 2,2-diphenyl picryl hydrazyl (DPPH) inhibition, ⩾7.36±0.43-39.86±2.34mg/100g qurecitin equivalent antioxidant contents, ⩾13.69±0.91-65.50±1.37mg/100g ascorbic acid equivalent antioxidant contents, 64.65±0.43-1780.74±11.79mM ferric reducing antioxidant power and 60% peroxide inhibition. Antitumour activity observed for 43 natural and 10 commercial samples was ⩾20%. Two samples from Faisalabad region showed 87.50±5.50% and 79.00±5.56% antitumour activity which were reference standard. It was concluded that Pakistani honeys possessed excellent antioxidant and antitumour potential overall. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Antioxidant potential of spices and their active constituents.

    PubMed

    Srinivasan, K

    2014-01-01

    Excessive free radical generation overbalancing the rate of their removal leads to oxidative stress. Oxidative stress has been implicated in the etiology of cardiovascular disease, inflammatory diseases, cancer, and other chronic diseases. Antioxidants are compounds that hinder the oxidative processes and thereby delay or suppress oxidative stress. There is a growing interest in natural antioxidants found in plants. Herbs and spices are most important targets to search for natural antioxidants from the point of view of safety. A wide variety of phenolic compounds present in spices that are extensively used as food adjuncts possess potent antioxidant, anti-inflammatory, antimutagenic, and cancer preventive activities. This paper reviews a host of spice compounds as exogenous antioxidants that are experimentally evidenced to control cellular oxidative stress, both in vitro and in vivo, and their beneficial role in preventing or ameliorating oxidative-stress-mediated diseases, from atherosclerosis to diabetes to cataract to cancer. The antioxidative effects of turmeric/curcumin, clove/eugenol, red pepper/capsaicin, black pepper/piperine, ginger/gingerol, garlic, onion, and fenugreek, which have been extensively studied and evidenced as potential antioxidants, are specifically reviewed in this treatise.

  5. Antioxidant Capacity and Antimutagenic Potential of Murraya koenigii

    PubMed Central

    Husain, Fohad Mabood; Ahmad, Iqbal

    2013-01-01

    It is well known that the intake of antioxidants with increased consumption of fruits and vegetables and medicinal herbs contributes towards reduced risk of certain diseases including cancers. This study aims to evaluate the broad-spectrum antioxidant and antimutagenic activities as well as to elucidate phytochemical profile of an Indian medicinal plant Murraya koenigii (curry) leaves. Leaves of the plant were successively fractionated in various organic solvents. Benzene fraction demonstrated the highest phenolic content followed by petroleum ether. The benzene fraction showed maximum antioxidant activity in all tested assays, namely, phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, ferric reducing antioxidant power (FRAP) and cupric reducing antioxidant capacity (CUPRAC) assays. Based on the promising broad-spectrum antioxidant activity, benzene fraction was further evaluated for antimutagenic activity and showed a dose-dependent antimutagenic response in Ames Salmonella mutagenicity assay. It inhibited 72–86% mutagenicity induced by sodium azide, methyl methanesulfonate, benzo(a)pyrene, and 2-aminoflourene at the maximum tested concentration (100 μg/mL) in Salmonella typhimurium tester strains. At least 21 compounds were detected by GC/MS. The findings clearly demonstrated that phenolic-rich benzene fraction has promising broad-spectrum antioxidant and antimutagenic property and needs further evaluation to exploit its therapeutic potential. PMID:23853769

  6. Sesamol: an efficient antioxidant with potential therapeutic benefits.

    PubMed

    Geetha, Thiraviam; Rohit, Bhandari; Pal, Kaur Indu

    2009-07-01

    Sesamol has been shown earlier to exhibit antimutagenic (reactive oxygen mediated) and antiageing activity in our lab and it has also been found to exert chemopreventive effect. Here we report the in vitro antioxidant activity of sesamol. As most of the antioxidants act due to their property to auto-oxidise and the pro- or antioxidant activity would depend on the concentration of the agent used and the free radical source, at least 6 dilutions in concentration range of 5-1000 nmoles of sesamol were selected for each test system. Further the antioxidant activity was compared with a water soluble antioxidant (ascorbic acid). Eventhough some preliminary studies on the antioxidant activity of sesamol have been reported in DPPH assay & inhibition of lipid peroxidation, it is not complete. We, here in report comprehensively (both in terms of the no. of doses and also a variety of test systems being employed) on the antioxidant activity of sesamol. Furthermore, since all the data has been generated by the same workers and under same laboratory conditions, hence is scientifically significant. Also the process of dose selection as discussed earlier is more scientific; and the data treatment, i.e. calculation of IC(50) values and comparisons with ascorbic acid has been statistically validated. In conclusion, sesamol was found to be an efficient scavenger of the entire range of ROS in several test systems pointing towards the potential of sesamol to be developed as a possible therapeutic.

  7. A mitochondria-targeted ratiometric two-photon fluorescent probe for biological zinc ions detection

    PubMed Central

    Ning, Peng; Jiang, Jiacheng; Li, Longchun; Wang, Shuxin; Yu, Haizhu; Feng, Yan; Zhu, Manzhou; Zhang, Buchang; Yin, Hang; Guo, Qingxiang; Meng, Xiangming

    2015-01-01

    A mitochondria-targeted ratiometric two-photon fluorescent probe (Mito-MPVQ) for biological zinc ions detection was developed based on quinolone platform. Mito-MPVQ showed large red shifts (68nm) and selective ratiometric signal upon Zn2+ binding. The ratio of emission intensity (I488 nm/I420 nm) increases dramatically from 0.45 to 3.79 (ca. 8-fold). NMR titration and theoretical calculation confirmed the binding of Mito-MPVQ and Zn2+. Mito-MPVQ also exhibited large two-photon absorption cross sections (150GM) at nearly 720 nm and insensitivity to pH within the biologically relevant pH range. Cell imaging indicated that Mito-MPVQ could efficiently located in mitochondria and monitor mitochondrial Zn2+ under two-photon excitation with low cytotoxicity. PMID:26528806

  8. Maintaining antioxidant potential of fresh fruits and vegetables after harvest.

    PubMed

    Villa-Rodriguez, Jose A; Palafox-Carlos, H; Yahia, Elhadi M; Ayala-Zavala, J Fernando; Gonzalez-Aguilar, Gustavo A

    2015-01-01

    The consumption of fruits and vegetables has increased in the past few years, not only because of their attractive sensorial properties, but also for their nutritional and health benefits. Antioxidants are compounds found in fresh fruits and vegetables, and evidence of their role in the prevention of degenerative diseases is continuously emerging. However, the antioxidants in some fruits and vegetables can be lost during handling after harvest, even during minimal processing and storage. In this sense, postharvest treatments are needed to preserve the quality and antioxidant potential of fresh produce. Postharvest treatments and technologic strategies (including ultraviolet light, controlled and modified atmospheres, heat treatments, and application of natural compounds, such as edible coatings, active packaging, microencapsulation, and nanoemulsion) have shown positive and promising results to maintain fruit and vegetable antioxidant potential. The purpose of this review is to analyze and propose the application of postharvest strategies to maintain, or even improve, the antioxidant status of fruits and vegetables, thus offering options to maximize health benefits to consumers.

  9. How mitochondrial dysfunction affects zebrafish development and cardiovascular function: an in vivo model for testing mitochondria-targeted drugs

    PubMed Central

    Pinho, Brígida R; Santos, Miguel M; Fonseca-Silva, Anabela; Valentão, Patrícia; Andrade, Paula B; Oliveira, Jorge M A

    2013-01-01

    , it evidences zebrafish's potential for in vivo efficacy or toxicity screening of ubiquinone analogues or antiparasitic mitochondria-targeted drugs. PMID:23758163

  10. How mitochondrial dysfunction affects zebrafish development and cardiovascular function: an in vivo model for testing mitochondria-targeted drugs.

    PubMed

    Pinho, Brígida R; Santos, Miguel M; Fonseca-Silva, Anabela; Valentão, Patrícia; Andrade, Paula B; Oliveira, Jorge M A

    2013-07-01

    ubiquinone analogues or antiparasitic mitochondria-targeted drugs. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  11. A long-linker conjugate of fluorescein and triphenylphosphonium as mitochondria-targeted uncoupler and fluorescent neuro- and nephroprotector.

    PubMed

    Antonenko, Yuri N; Denisov, Stepan S; Silachev, Denis N; Khailova, Ljudmila S; Jankauskas, Stanislovas S; Rokitskaya, Tatyana I; Danilina, Tatyana I; Kotova, Elena A; Korshunova, Galina A; Plotnikov, Egor Y; Zorov, Dmitry B

    2016-11-01

    Limited uncoupling of oxidative phosphorylation is known to be beneficial in various laboratory models of diseases. Linking a triphenyl-phosphonium cation to fluorescein through a decyl (C10) spacer yields a fluorescent uncoupler, coined mitoFluo, that selectively accumulates in energized mitochondria (Denisov et al., Chem.Commun. 2014). Proton-transport activity of mitoFluo was tested in liposomes reconstituted with bacteriorhodopsin. To examine the uncoupling action on mitochondria, we monitored mitochondrial membrane potential in parallel with oxygen consumption. Neuro- and nephroprotecting activity was detected by a limb-placing test and a kidney ischemia/reperfusion protocol, respectively. We compared mitoFluo properties with those of its newly synthesized analog having a short (butyl) spacer (C4-mitoFluo). MitoFluo, but not C4-mitoFluo, caused collapse of mitochondrial membrane potential resulting in stimulation of mitochondrial respiration. The dramatic difference in the uncoupling activity of mitoFluo and C4-mitoFluo was in line with the difference in their protonophoric activity on a lipid membrane. The accumulation of mitoFluo in mitochondria was more pronounced than that of C4-mitoFluo. MitoFluo decreased the rate of ROS production in mitochondria. MitoFluo was effective in preventing consequences of brain trauma in rats: it suppressed trauma-induced brain swelling and reduced a neurological deficit. Besides, mitoFluo attenuated acute kidney injury after ischemia/reperfusion in rats. A long alkyl linker was proved mandatory for mitoFluo to be a mitochondria- targeted uncoupler. MitoFluo showed high protective efficacy in certain models of oxidative stress-related diseases. MitoFluo is a candidate for developing therapeutic and fluorescence imaging agents to treat brain and kidney pathologies. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. In vitro antioxidant potential of selected aphrodisiac medicinal plants.

    PubMed

    Riaz, M; Shahid, M; Jamil, A; Saqib, M

    2017-01-01

    The present study aimed to evaluate the antioxidant activity of six selected aphrodisiac medicinal plants. Useful parts of the selected medicinal plants were collected and extracted in methanolic solvent. The antioxidant activity of selected plant extract was determined through different antioxidant assays, namely DPPH radical scavenging assay and ferric reducing antioxidant assay. Moreover, antioxidant compounds, like total phenolics and total flavonoids contents, were also determined. Results showed that Mucuna pruriens seed extract displayed high contents of phenolic compounds with total phenolic content of 683.15±4.28 mg GAE/g dry plant material while the least phenolic content was observed in Asparagus racemosus (195.5±3.02 mg GAE/g dry plant material). Highest total flavonoids content was found in Anacyclus pyrethrum roots (156.58±4.01 μg CE/g) and the least content was found in Asparagus racemosus roots. Among the studied plant extracts, the highest radical scavenging activity was shown by Mucuna pruriens seed extract (82.05±0.55%) and the least percent scavenging activity was observed in Tribulus terrestris extract (36.40±2.01%). Vitamin C was used as positive control for antioxidant assays showing 93.54±0.9% radical scavenging activity. The plant extract also exhibited a strong reducing potential against free radicals. Therefore, the present study concluded that all the studied medicinal plants possess varying concentrations of secondary active metabolites responsible for the antioxidant properties of the tested plant extracts.

  13. The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

    PubMed Central

    Poggi, Chiara

    2014-01-01

    Abstract Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies. Antioxid. Redox Signal. 21, 1863–1880. PMID:24382101

  14. Antioxidant Potential of Bark Extracts from Boreal Forest Conifers.

    PubMed

    Legault, Jean; Girard-Lalancette, Karl; Dufour, Dominic; Pichette, André

    2013-07-11

    The bark of boreal forest conifers has been traditionally used by Native Americans to treat various ailments and diseases. Some of these diseases involve reactive oxygen species (ROS) that can be prevented by the consumption of antioxidants such as phenolic compounds that can be found in medicinal plants. In this study, ultrasonic assisted extraction has been performed under various solvent conditions (water:ethanol mixtures) on the bark of seven boreal forest conifers used by Native Americans including: Pinus strobus, Pinus resinosa, Pinus banksiana, Picea mariana, Picea glauca, Larix laricina, and Abies balsamea. The total phenolic content, as well as ORACFL potency and cellular antioxidant activity (IC50), were evaluated for all bark extracts, and compared with the standardized water extract of Pinus maritima bark (Pycnogenol), which showed clinical efficiency to prevent ROS deleterious effects. The best overall phenolic extraction yield and antioxidant potential was obtained with Picea glauca and Picea mariana. Interestingly, total phenolic content of these bark extracts was similar to Pycnogenol but their antioxidant activity were higher. Moreover, most of the extracts did not inhibit the growth of human skin fibroblasts, WS1. A significant correlation was found between the total phenolic content and the antioxidant activity for water extracts suggesting that these compounds are involved in the activity.

  15. Antioxidant Potential of Bark Extracts from Boreal Forest Conifers

    PubMed Central

    Legault, Jean; Girard-Lalancette, Karl; Dufour, Dominic; Pichette, André

    2013-01-01

    The bark of boreal forest conifers has been traditionally used by Native Americans to treat various ailments and diseases. Some of these diseases involve reactive oxygen species (ROS) that can be prevented by the consumption of antioxidants such as phenolic compounds that can be found in medicinal plants. In this study, ultrasonic assisted extraction has been performed under various solvent conditions (water:ethanol mixtures) on the bark of seven boreal forest conifers used by Native Americans including: Pinus strobus, Pinus resinosa, Pinus banksiana, Picea mariana, Picea glauca, Larix laricina, and Abies balsamea. The total phenolic content, as well as ORACFL potency and cellular antioxidant activity (IC50), were evaluated for all bark extracts, and compared with the standardized water extract of Pinus maritima bark (Pycnogenol), which showed clinical efficiency to prevent ROS deleterious effects. The best overall phenolic extraction yield and antioxidant potential was obtained with Picea glauca and Picea mariana. Interestingly, total phenolic content of these bark extracts was similar to Pycnogenol but their antioxidant activity were higher. Moreover, most of the extracts did not inhibit the growth of human skin fibroblasts, WS1. A significant correlation was found between the total phenolic content and the antioxidant activity for water extracts suggesting that these compounds are involved in the activity. PMID:26784337

  16. Novel hydrazones – antioxidant potential and stabilization via polysaccharide particles

    NASA Astrophysics Data System (ADS)

    Hristova-Avakumova, N.; Nikolova-Mladenova, B.; Yoncheva, K.; Hadjimitova, V.

    2017-01-01

    In this study, we aimed to: i) determine the impact of three new isonicotinoyl hydrazones derivatives in in vitro systems used to investigate free radical processes - radical scavenging approach (ABTS and DPPH) and iron induced peroxidation in lipid containing model systems and ii) evaluate the potential of polysaccharide-based particles to act as protective carriers preserving the antioxidant activity (AOA) of the tested compounds. The tested compounds revealed excellent antioxidant effectiveness in the ABTS system. In the DPPH radical scavenging assay the compounds exhibited very weak or absence of AOA. The data from the iron induced peroxidation methods disclosed better antioxidant properties of the derivatives in the system containing egg yolk homogenate which is more plausible compared to the lecithin containing one. The incorporation of a bromine atom on 5th position in salicylaldehyde moiety is associated with diminishment of the radical scavenging activity in the systems containing stable free radicals but its AOA reduction after encapsulation during the storage was only 9.17%. The obtained data indicate that compounds have proven themselves as promising candidates for further evaluation as antioxidant agents. Their encapsulation in chitosan-alginate particles could be a useful approach for improving the stability of their antioxidant properties.

  17. Potential antioxidant activity of the moss Bryum moravicum.

    PubMed

    Pejin, Boris; Bogdanovic-Pristov, Jelena; Pejin, Ivana; Sabovljevic, Marko

    2013-01-01

    A limited number of mosses has ever been studied regarding antioxidant activity among which only a few are European species. As a part of our ongoing screening of new promising bryophyte resources of natural antioxidants, a relevant biological activity investigation was conducted on the moss Bryum moravicum Podp. (Bryaceae) collected in Germany. The antioxidant activity of an aqueous extract of the species was evaluated in vitro by analysing its ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] cation scavenging activity and total phenolic content. The study led to the detection of a moderate antioxidant activity: 1 mg of the extract was equivalent to 84.56 ± 7.93 µg of ascorbic acid. The total phenolic content in 1 mg of the extract was equivalent to 356.44 ± 9.56 µg of ferulic acid used as a standard. These results have indicated for the first time potential importance of B. moravicum in searching for novel antioxidant agents.

  18. Antioxidant and drug detoxification potentials of Hibiscus sabdariffa anthocyanin extract.

    PubMed

    Ajiboye, Taofeek O; Salawu, Nasir A; Yakubu, Musa T; Oladiji, Adenike T; Akanji, Musbau A; Okogun, Joseph I

    2011-04-01

    The antioxidant and drug metabolizing potentials of Hibiscus anthocyanin extract in CCl(4)- induced oxidative damage of rat liver was investigated. Hibiscus anthocyanin extract effectively scavenge α-diphenyl-β-picrylhydrazyl (DPPH) radical, superoxide ion, and hydrogen peroxide. It produced a 92% scavenging effect of DPPH radical at a concentration of 2.0 mg/mL. Hibiscus anthocyanin extract produced a 69 and 90% scavenging effect on superoxide ion and hydrogen peroxide, respectively, at 1.0 mg/mL, which compared favorably with the synthetic antioxidant (butylated hydroanisole and α-tocopherol). A reducing power of this anthocyanin was examined using K(3)Fe(CN)(6). Hibiscus anthocyanin extract has reducing power that is approximately 2-fold that of the synthetic antioxidant, butylated hydroanisole. Hibiscus anthocyanin extract produced a significantly increase and completely attenuated the CCl(4)-mediated decrease in antioxidant enzymes (e.g., catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). However, the level of nonenzymic antioxidant molecules (i.e., vitamins C and E) were significant preserved by Hibiscus anthocyanin extract. There was an induction of phase II drug-detoxifying enzymes: glutathione S-transferase, NAD(H):quinone oxidoreductase, and uridyl diphosphoglucuronosyl transferase by 65, 45, and 57%, respectively. In view of these properties, Hibiscus sabdariffa anthocyanin extract can act as a prophylactic by intervening as a free radical scavenger both in vitro and in vivo as well as inducing the phase II drug detoxification enzymes.

  19. Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

    PubMed

    Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E

    2014-06-01

    Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes☆

    PubMed Central

    Pun, Pamela Boon Li; Logan, Angela; Darley-Usmar, Victor; Chacko, Balu; Johnson, Michelle S.; Huang, Guang W.; Rogatti, Sebastian; Prime, Tracy A.; Methner, Carmen; Krieg, Thomas; Fearnley, Ian M.; Larsen, Lesley; Larsen, David S.; Menger, Katja E.; Collins, Yvonne; James, Andrew M.; Kumar, G.D. Kishore; Hartley, Richard C.; Smith, Robin A.J.; Murphy, Michael P.

    2014-01-01

    The glycation of protein and nucleic acids that occurs as a consequence of hyperglycemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs after the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal, and disruption of mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear owing to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells, and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography–tandem mass spectrometry, enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycemia both in cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging. PMID:24316194

  1. Measurement of Mitochondrial Cholesterol Import Using a Mitochondria-Targeted CYP11A1 Fusion Construct.

    PubMed

    Kennedy, Barry E; Charman, Mark; Karten, Barbara

    2017-01-01

    All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease. The mechanisms of mitochondrial cholesterol import are not fully elucidated yet, and may vary in different cell types and environmental conditions. Measuring cholesterol trafficking to the mitochondrial membranes is technically challenging because of its low abundance; for example, traditional pulse-chase experiments with isotope-labeled cholesterol are not feasible. Here, we describe improvements to a method first developed by the Miller group at the University of California to measure cholesterol trafficking to the inner mitochondrial membrane (IMM) through the conversion of cholesterol to pregnenolone. This method uses a mitochondria-targeted, ectopically expressed fusion construct of CYP11A1, ferredoxin reductase and ferredoxin. Pregnenolone is formed exclusively from cholesterol at the IMM, and can be analyzed with high sensitivity and specificity through ELISA or radioimmunoassay of the medium/buffer to reflect mitochondrial cholesterol import. This assay can be used to investigate the effects of genetic or pharmacological interventions on mitochondrial cholesterol import in cultured cells or isolated mitochondria.

  2. A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes.

    PubMed

    Pun, Pamela Boon Li; Logan, Angela; Darley-Usmar, Victor; Chacko, Balu; Johnson, Michelle S; Huang, Guang W; Rogatti, Sebastian; Prime, Tracy A; Methner, Carmen; Krieg, Thomas; Fearnley, Ian M; Larsen, Lesley; Larsen, David S; Menger, Katja E; Collins, Yvonne; James, Andrew M; Kumar, G D Kishore; Hartley, Richard C; Smith, Robin A J; Murphy, Michael P

    2014-02-01

    The glycation of protein and nucleic acids that occurs as a consequence of hyperglycemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs after the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal, and disruption of mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear owing to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells, and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry, enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycemia both in cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging.

  3. Mitochondria Targeted and Intracellular Biothiol Triggered Hyperpolarized (129)Xe Magnetofluorescent Biosensor.

    PubMed

    Zeng, Qingbin; Guo, Qianni; Yuan, Yaping; Yang, Yuqi; Zhang, Bin; Ren, Lili; Zhang, Xiaoxiao; Luo, Qing; Liu, Maili; Bouchard, Louis-S; Zhou, Xin

    2017-02-21

    Biothiols such as gluthathione (GSH), cysteine (Cys), homocysteine (Hcy), and thioredoxin (Trx) play vital roles in cellular metabolism. Various diseases are associated with abnormal cellular biothiol levels. Thus, the intracellular detection of biothiol levels could be a useful diagnostic tool. A number of methods have been developed to detect intracellular thiols, but sensitivity and specificity problems have limited their applications. To address these limitations, we have designed a new biosensor based on hyperpolarized xenon magnetic resonance detection, which can be used to detect biothiol levels noninvasively. The biosensor is a multimodal probe that incorporates a cryptophane-A cage as (129)Xe NMR reporter, a naphthalimide moiety as fluorescence reporter, a disulfide bond as thiol-specific cleavable group, and a triphenylphosphonium moiety as mitochondria targeting unit. When the biosensor interacts with biothiols, disulfide bond cleavage leads to enhancements in the fluorescence intensity and changes in the (129)Xe chemical shift. Using Hyper-CEST (chemical exchange saturation transfer) NMR, our biosensor shows a low detection limit at picomolar (10(-10) M) concentration, which makes a promise to detect thiols in cells. The biosensor can detect biothiol effectively in live cells and shows good targeting ability to the mitochondria. This new approach not only offers a practical technique to detect thiols in live cells, but may also present an excellent in vivo test platform for xenon biosensors.

  4. Mito-DCA: a mitochondria targeted molecular scaffold for efficacious delivery of metabolic modulator dichloroacetate.

    PubMed

    Pathak, Rakesh K; Marrache, Sean; Harn, Donald A; Dhar, Shanta

    2014-05-16

    Tumor growth is fueled by the use of glycolysis, which normal cells use only in the scarcity of oxygen. Glycolysis makes tumor cells resistant to normal death processes. Targeting this unique tumor metabolism can provide an alternative strategy to selectively destroy the tumor, leaving normal tissue unharmed. The orphan drug dichloroacetate (DCA) is a mitochondrial kinase inhibitor that has the ability to show such characteristics. However, its molecular form shows poor uptake and bioavailability and limited ability to reach its target mitochondria. Here, we describe a targeted molecular scaffold for construction of a multiple DCA loaded compound, Mito-DCA, with three orders of magnitude enhanced potency and cancer cell specificity compared to DCA. Incorporation of a lipophilic triphenylphosphonium cation through a biodegradable linker in Mito-DCA allowed for mitochondria targeting. Mito-DCA did not show any significant metabolic effects toward normal cells but tumor cells with dysfunctional mitochondria were affected by Mito-DCA, which caused a switch from glycolysis to glucose oxidation and subsequent cell death via apoptosis. Effective delivery of DCA to the mitochondria resulted in significant reduction in lactate levels and played important roles in modulating dendritic cell (DC) phenotype evidenced by secretion of interleukin-12 from DCs upon activation with tumor antigens from Mito-DCA treated cancer cells. Targeting mitochondrial metabolic inhibitors to the mitochondria could lead to induction of an efficient antitumor immune response, thus introducing the concept of combining glycolysis inhibition with immune system to destroy tumor.

  5. Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation.

    PubMed

    Kim, Won-Serk; Kim, Ikyon; Kim, Wang-Kyun; Choi, Ju-Yeon; Kim, Doo Yeong; Moon, Sung-Guk; Min, Hyung-Keun; Song, Min-Kyu; Sung, Jong-Hyuk

    2016-05-01

    Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

  6. Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation

    PubMed Central

    Kim, Won-Serk; Kim, Ikyon; Kim, Wang-Kyun; Choi, Ju-Yeon; Kim, Doo Yeong; Moon, Sung-Guk; Min, Hyung-Keun; Song, Min-Kyu; Sung, Jong-Hyuk

    2016-01-01

    Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material. PMID:26869457

  7. Antioxidant activity and potential photoprotective from amazon native flora extracts.

    PubMed

    Martins, Francislene J; Caneschi, César A; Vieira, José L F; Barbosa, Wagner; Raposo, Nádia R B

    2016-08-01

    Plant species are sources of active compounds that can fight and/or prevent damage caused by reactive oxygen species, which enables the development of natural products that can help to prevent premature aging caused by exposure to solar radiation. This study assessed the antioxidant and photoprotective activities of six dried extracts of plants from the Brazilian Amazon biome. Plant extracts were prepared in 70% (v/v) ethanol by dynamic maceration for 72h in the dark, and then filtered, concentrated and lyophilized. The extracts were subjected to a phytochemical screening. The antioxidant activity was measured using a 2,2-diphenyl-1-picrylhydrazyl assay and the photoprotection assay was performed using the diffuse transmittance technique. The data obtained from the antioxidant activity assay was evaluated by Student's t-test for independent samples, with the aid of Statistical Package for Social Sciences v.14.0 for Windows software. The flavonoids represent a special metabolites class present in all analyzed extracts. The antioxidant activity (μgmL(-1)) decreased in the following order: Aniba canelilla (1.80±0.16), Brosimum acutifolium (2.84±0.38), Dalbergia monetaria (5.46±0.17) or Caesalpinia pyramidalis (6.45±1.18), Arrabidaea chica (15.35±0.86), and Aspidosperma nitidum (99.14±2.3). Only D. monetaria showed a considerable sun protection factor allowing for labeling (6.0±0.3). The D. monetaria extract was considered the most promising sample because it had optimal antioxidant and photoprotective activities against solar radiation, considering the limit established by regulatory agencies. These extracts with antioxidant potential can be used in photoprotective formulations, providing synergistic photoprotective effect or elevating the adeed value of the product. Additionally, these formulations are attractive to a population who searchs for products made with natural ingredients. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Vernonia kotschyana roots: therapeutic potential via antioxidant activity.

    PubMed

    Vasincu, Alexandru; Paulsen, Berit S; Diallo, Drissa; Vasincu, Ioana; Aprotosoaie, Ana C; Bild, Veronica; Charalambous, Christiana; Constantinou, Andreas I; Miron, Anca; Gavrilescu, Cristina M

    2014-11-19

    The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress.

  9. Antioxidant and antimutagenic potential of Psidium guajava leaf extracts.

    PubMed

    Zahin, Maryam; Ahmad, Iqbal; Aqil, Farrukh

    2017-04-01

    Fruits, vegetables and medicinal herbs rich in phenolics antioxidants contribute toward reduced risk of age-related diseases and cancer. In this study, Psidium guajava leaf extract was fractionated in various organic solvents viz. petroleum ether, benzene, ethyl acetate, ethanl and methanol and tested for their antioxidant and antimutagenic properties. Methanolic fraction showed maximum antioxidant activity comparable to ascorbic acid and butylated hydroxyl toluene (BHT) as tested by DPPH free radical scavenging, phosphomolybdenum, FRAP (Fe3 + reducing power) and CUPRAC (cupric ions (Cu(2+)) reducing ability) assays. The fraction was analyzed for antimutagenic activities against sodium azide (NaN3), methylmethane sulfonate (MMS), 2-aminofluorene (2AF) and benzo(a)pyrene (BP) in Ames Salmonella tester strains. The methanol extracted fraction at 80 μg/ml concentration inhibited above 70% mutagenicity. Further, phytochemical analysis of methanol fraction that was found to be most active revealed the presence of nine major compounds by gas chromatography-mass spectrometry (GC-MS). This data suggests that guava contains high amount of phenolics responsible for broad-spectrum antimutagenic and antioxidant properties in vitro and could be potential candidates to be explored as modern phytomedicine.

  10. Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia.

    PubMed

    Brown, David A; Hale, Sharon L; Baines, Christopher P; del Rio, Carlos L; Hamlin, Robert L; Yueyama, Yukie; Kijtawornrat, Anusak; Yeh, Steve T; Frasier, Chad R; Stewart, Luke M; Moukdar, Fatiha; Shaikh, Saame Raza; Fisher-Wellman, Kelsey H; Neufer, P Darrell; Kloner, Robert A

    2014-01-01

    We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia's cytoprotective property. In rabbits exposed to in vivo ischemia/reperfusion (30/180 min), Bendavia administered 20 minutes prior to reperfusion (0.05 mg/kg/h, intravenously) reduced myocardial infarct size by ∼50% when administered for either 1 or 3 hours of reperfusion. However, when Bendavia perfusion began just 10 minutes after the onset of reperfusion, the protection against infarction and no-reflow was completely lost, indicating that the mechanism of protection is occurring early in reperfusion. Experiments in isolated mouse liver mitochondria found no discernible effect of Bendavia on blocking the permeability transition pore, and studies in isolated heart mitochondria showed no effect of Bendavia on respiratory rates. As Bendavia significantly lowered reactive oxygen species (ROS) levels in isolated heart mitochondria, the ROS-scavenging capacity of Bendavia was compared to well-known ROS scavengers using in vitro (cell-free) systems that enzymatically generate ROS. Across doses ranging from 1 nmol/L to 1 mmol/L, Bendavia showed no discernible ROS-scavenging properties, clearly differentiating itself from prototypical scavengers. In conclusion, Bendavia is a promising candidate to reduce cardiac injury when present at the onset of reperfusion but not after reperfusion has already commenced. Given that both infarction and no-reflow are related to increased cellular ROS, Bendavia's protective mechanism of action likely involves reduced ROS generation (as opposed to augmented scavenging) by endothelial and myocyte mitochondria.

  11. Reduction of early reperfusion injury with the mitochondria-targeting peptide Bendavia

    PubMed Central

    Brown, David A.; Hale, Sharon L.; Baines, Christopher P.; del Rio, Carlos L.; Hamlin, Robert L.; Yueyama, Yukie; Kijtawornrat, Anusak; Yeh, Steve T.; Frasier, Chad R.; Stewart, Luke M.; Moukdar, Fatiha; Shaikh, Saame Raza; Fisher-Wellman, Kelsey H.; Neufer, P. Darrell; Kloner, Robert A.

    2014-01-01

    We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia’s cytoprotective property. In rabbits exposed to in vivo ischemia/reperfusion (30/180 min), Bendavia administered 20 min prior to reperfusion (0.05mg/kg/hr, i.v.) reduced myocardial infarct size by ~50% when administered for either 1 or 3 hours of reperfusion. However, when Bendavia perfusion began just 10 min after the onset of reperfusion, the protection against infarction and no–reflow was completely lost, indicating that the mechanism of protection is occurring early in reperfusion. Experiments in isolated mouse liver mitochondria found no discernible effect of Bendavia on blocking the permeability transition pore, and studies in isolated heart mitochondria showed no effect of Bendavia on respiratory rates. As Bendavia significantly lowered reactive oxygen species (ROS) levels in isolated heart mitochondria, the ROS-scavenging capacity of Bendavia was compared to well-known ROS scavengers using in vitro (cell-free) systems that enzymatically generate ROS. Across doses ranging from 1nM to 1mM, Bendavia showed no discernible ROS-scavenging properties, clearly differentiating itself from prototypical scavengers. In conclusion, Bendavia is a promising candidate to reduce cardiac injury when present at onset of reperfusion, but not after reperfusion has already commenced. Given that both infarction and no-reflow are related to increased cellular ROS, Bendavia’s protective mechanism of action likely involves reduced ROS generation (as opposed to augmented scavenging) by endothelial and myocyte mitochondria. PMID:24288396

  12. A Mitochondria-Targeted Nitroxide/Hemigramicidin S Conjugate Protects Mouse Embryonic Cells Against Gamma Irradiation

    SciTech Connect

    Jiang Jianfei; Belikova, Natalia A.; Hoye, Adam T.; Zhao Qing; Epperly, Michael W.; Greenberger, Joel S.; Wipf, Peter; Kagan, Valerian E.

    2008-03-01

    Purpose: To evaluate the in vitro radioprotective effect of the mitochondria-targeted hemigramicidin S-conjugated 4-amino-2,2,6,6-tetramethyl-piperidine-N-oxyl (hemi-GS-TEMPO) 5-125 in {gamma}-irradiated mouse embryonic cells and adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells BEAS-2B and explore the mechanisms involved in its radioprotective effect. Methods and Materials: Cells were incubated with 5-125 before (10 minutes) or after (1 hour) {gamma}-irradiation. Superoxide generation was determined by using dihydroethidium assay, and lipid oxidation was quantitated by using a fluorescence high-performance liquid chromatography-based Amplex Red assay. Apoptosis was characterized by evaluating the accumulation of cytochrome c in the cytosol and externalization of phosphatidylserine on the cell surface. Cell survival was measured by means of a clonogenic assay. Results: Treatment (before and after irradiation) of cells with 5-125 at low concentrations (5, 10, and 20 {mu}M) effectively suppressed {gamma}-irradiation-induced superoxide generation, cardiolipin oxidation, and delayed irradiation-induced apoptosis, evaluated by using cytochrome c release and phosphatidylserine externalization. Importantly, treatment with 5-125 increased the clonogenic survival rate of {gamma}-irradiated cells. In addition, 5-125 enhanced and prolonged {gamma}-irradiation-induced G{sub 2}/M phase arrest. Conclusions: Radioprotection/mitigation by hemi-GS-TEMPO likely is caused by its ability to act as an electron scavenger and prevent superoxide generation, attenuate cardiolipin oxidation in mitochondria, and hence prevent the release of proapoptotic factors from mitochondria. Other mechanisms, including cell-cycle arrest at the G{sub 2}/M phase, may contribute to the protection.

  13. Investigation of the Antioxidant and Hepatoprotective Potential of Hypericum mysorense

    PubMed Central

    Hariharapura, Raghu C.; Srinivasan, Ramamurthy; Ashok, Godavarthi; Dongre, Santoshkumar H.; Jagani, Hitesh V.; Vijayan, Pottekkad

    2014-01-01

    Background: Hypericum is a well-known plant genus in herbal medicine. Hypericum mysorense (Family: Hypericaceae), a plant belonging to the same genus, is well known in folklore medicine for its varied therapeutic potential. Objective: The aim of the present study was to investigate the different parts of the plant for antioxidant and hepatoprotective properties. Materials and Methods: The methanol extracts of Hypericum mysorense prepared from various parts of the plant were tested in vitro for their free radical scavenging activity against ABTS• (diammonium salt), DPPH• (1,1-diphenyl-2-picrylhydrazyl), NO•, O2•− and •OH radicals, using standard systems of assays. The total antioxidant capacity, total phenolic and total flavonoid content of the extracts were analyzed. Further, the leaf and flowering top extracts were tested for their in vivo antioxidant and hepatoprotective activities on Wistar rats using a carbon tetrachloride-induced hepatic injury model. Results: The leaf and flowering top extract showed potent antioxidant activity and also possessed highest total phenolic and flavonoid content. The antioxidant activity and the total phenolic and flavonoid content present in these extracts showed a good correlation. The leaf and flowering top extracts at 200 mg/kg restored aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (ALP), total bilirubin and protein levels significantly in CCl4-intoxicated rats. The tested extracts also showed a significant (p < 0.001) reduction in 2-thiobarbituric acid reactive substance (TBARS) levels with an increase in SOD and CAT levels. The histopathology of liver did not show any toxicity after the treatment with the extracts. The active extracts were standardized using two marker compounds, hyperoside and rutin, which were isolated from the plant by HPLC. HPLC studies revealed that the maximum concentration of hyperoside and rutin is present in the flowering top extract. PMID

  14. Investigation of the Antioxidant and Hepatoprotective Potential of Hypericum mysorense.

    PubMed

    Hariharapura, Raghu C; Srinivasan, Ramamurthy; Ashok, Godavarthi; Dongre, Santoshkumar H; Jagani, Hitesh V; Vijayan, Pottekkad

    2014-08-12

    Hypericum is a well-known plant genus in herbal medicine. Hypericum mysorense (Family: Hypericaceae), a plant belonging to the same genus, is well known in folklore medicine for its varied therapeutic potential. The aim of the present study was to investigate the different parts of the plant for antioxidant and hepatoprotective properties. The methanol extracts of Hypericum mysorense prepared from various parts of the plant were tested in vitro for their free radical scavenging activity against ABTS(•) (diammonium salt), DPPH(•) (1,1-diphenyl-2-picrylhydrazyl), NO(•), O₂(•-) and (•)OH radicals, using standard systems of assays. The total antioxidant capacity, total phenolic and total flavonoid content of the extracts were analyzed. Further, the leaf and flowering top extracts were tested for their in vivo antioxidant and hepatoprotective activities on Wistar rats using a carbon tetrachloride-induced hepatic injury model. The leaf and flowering top extract showed potent antioxidant activity and also possessed highest total phenolic and flavonoid content. The antioxidant activity and the total phenolic and flavonoid content present in these extracts showed a good correlation. The leaf and flowering top extracts at 200 mg/kg restored aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (ALP), total bilirubin and protein levels significantly in CCl₄-intoxicated rats. The tested extracts also showed a significant (p < 0.001) reduction in 2-thiobarbituric acid reactive substance (TBARS) levels with an increase in SOD and CAT levels. The histopathology of liver did not show any toxicity after the treatment with the extracts. The active extracts were standardized using two marker compounds, hyperoside and rutin, which were isolated from the plant by HPLC. HPLC studies revealed that the maximum concentration of hyperoside and rutin is present in the flowering top extract.

  15. A high-resolution mitochondria-targeting ratiometric fluorescent probe for detection of the endogenous hypochlorous acid

    NASA Astrophysics Data System (ADS)

    Zhou, Liyi; Lu, Dan-Qing; Wang, Qianqian; Hu, Shunqin; Wang, Haifei; Sun, Hongyan; Zhang, Xiaobing

    2016-09-01

    Hypochlorite anion, one of the biologically important reactive oxygen species, plays an essential role in diverse normal biochemical functions and abnormal pathological processes. Herein, an efficient high-resolution mitochondria-targeting ratiometric fluorescent probe for hypochlorous acid detection has been designed, synthesized and characterized. It is easily synthesized by the condensation reaction (Cdbnd C) of a 2-(2-hydroxyphenyl) quinazolin-4(3H)-one fluorophore and a cyanine group (mitochondria-targeting), which made the whole molecular a large Stokes shift (210 nm) and the two well-resolved emission peaks separated by 140 nm. As a result, it is considered as a good candidate for high resolution hypochlorous acid imaging in live cells. The ratiometric fluorescent probe exhibited outstanding features of high sensitivity, high selectivity, rapid response time (within 50 s), and excellent mitochondria-targeting ability. Moreover, the probe can also be successfully applied to imaging endogenously hypochlorous acid in the mitochondria of living cells with low cytotoxicity, and high resolution.

  16. Evaluation of the antioxidant and antiproliferative potential of bioflavors.

    PubMed

    Bicas, J L; Neri-Numa, I A; Ruiz, A L T G; De Carvalho, J E; Pastore, G M

    2011-07-01

    α-Terpineol is a relatively cheap and abundant aroma compound. It is widely used in food, cosmetics, and household products. Many of its monoterpene counterparts have been applied in antiproliferative assays, leading to promising results in the prevention or even treatment of cancers. However, despite its theoretic potential, no paper reports the evaluation of antiproliferative capacity of this alcohol. Thus, antioxidant potential of three monoterpenoids (carvone, perillyl alcohol, and α-terpineol) was measured using two methods: DPPH and ORAC. Also, the antiproliferative effect of these monoterpenoids against nine cancerous cell lines were performed and compared to limonene and doxorubicin. Results showed that all samples tested had very low antioxidant activity in the DPPH assay, but α-terpineol (2.72μmolTrolox equiv./μmol) could be compared to commercial antioxidants in the ORAC assay. The antiproliferative results obtained encourage future in vivo studies for α-terpineol, since this monoterpenoid presented cytostatic effect against six cell lines, especially for breast adenocarcinoma and chronic myeloid leukemia, in a range of 181-588μM.

  17. Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum.

    PubMed

    Ahmad, Hanif; Ahmad, Shujaat; Shah, Syed Adnan Ali; Latif, Abdul; Ali, Mumtaz; Khan, Farman Ali; Tahir, Muhammad Nawaz; Shaheen, Farzana; Wadood, Abdul; Ahmad, Manzoor

    2017-07-01

    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Antioxidant properties of melatonin and its potential action in diseases.

    PubMed

    Karaaslan, Cigdem; Suzen, Sibel

    2015-01-01

    In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

  19. Fulleropeptide esters as potential self-assembled antioxidants

    PubMed Central

    Kop, Tatjana J; Đorđević, Jelena

    2015-01-01

    Summary The potential use of amphiphilic fullerene derivatives as a bionanomaterial was investigated by cyclic voltammetry (CV), scanning electron microscopy (SEM), and the ferrous ion oxidation–xylenol orange (FOX) method. Despite the disrupted delocalization of the π-electronic system over the C60 sphere, its antioxidant capacity remained high for all twelve derivatives. The compounds expressed up to two-fold and 5–12-fold better peroxide quenching capacity as compared to pristine C60 and standard antioxidant vitamin C, respectively. During precipitation and slow evaporation of the solvent, all compounds underwent spontaneous self-assembly giving ordered structures. The size and morphology of the resulting particles depend primarily on the sample concentration, and somewhat on the side chain structure. PMID:26171283

  20. Mitochondria-targeted catalase reduces abnormal APP processing, amyloid β production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension.

    PubMed

    Mao, Peizhong; Manczak, Maria; Calkins, Marcus J; Truong, Quang; Reddy, Tejaswini P; Reddy, Arubala P; Shirendeb, Ulziibat; Lo, Herng-Hsiang; Rabinovitch, Peter S; Reddy, P Hemachandra

    2012-07-01

    The purpose of this study was to investigate the protective effects of the mitochondria-targeted antioxidant catalase (MCAT) and lifespan extension in mice that express amyloid beta (Aβ). Using immunoblotting and immunostaining analyses, we measured the production of full-length amyloid precursor protein (APP), soluble APPα, C-terminal fragments CTF99 and CTF83, monomeric and oligomeric Aβ, Aβ deposits and beta site amyloid precursor protein cleaving enzyme 1 (BACE1), in different stages of disease progression in MCAT/AβPP and AβPP mice. Using quantitative reverse transcriptase polymerase chain reaction and immunostaining analyses, we studied the expression of catalase, BACE1, the Alzheimer's disease (AD) markers, synaptophysin, APP, neprilysin, insulin-degrading enzyme and transthyretin in MCAT, AβPP, MCAT/AβPP and wild-type (WT) mice. Using the high pressure liquid chromatography analysis of 8-hydroxy-2-deoxyguanosine, we measured oxidative DNA damage in the cerebral cortical tissues from MCAT, AβPP, MCAT/AβPP and WT mice. We found that the AβPP transgenic mice that carried the human MCAT gene lived 5 months longer than did the AβPP mice. We also found that the overexpression of MCAT in the brain sections from the MCAT/AβPP transgenic mice significantly correlated with a reduction in the levels of full-length APP, CTF99, BACE1, Aβ levels (40 and 42), Aβ deposits and oxidative DNA damage relative to the brain sections from the AβPP mice. Interestingly, we found significantly increased levels of soluble APPα and CTF83 in the MCAT/AβPP mice, relative to the AβPP mice. These data provide direct evidence that oxidative stress plays a primary role in AD etiopathology and that in MCAT mice express Aβ, MCAT prevents abnormal APP processing, reduces Aβ levels and enhances Aβ-degrading enzymes in mice at different ages, corresponding to different stages of disease progression. These findings indicate that mitochondria-targeted molecules may be an

  1. Popular naturally occurring antioxidants as potential anticoagulant drugs.

    PubMed

    Bijak, Michal; Saluk, Joanna; Szelenberger, Rafal; Nowak, Pawel

    2016-09-25

    Blood coagulation is a physiological process whose main task is prevention of blood loss from injured vessels. This process consists of a series of zymogens proteolytic activation leading to the generation of the main coagulation enzyme - thrombin. Besides its important role in blood coagulation process, thrombin is involved in many cardiovascular diseases, which are responsible for almost half of fatalities in economically developed countries. The evidence for the increased generation and in vivo activity of thrombin was observed in the plasma of individuals at high risk for clinically significant venous and arterial thromboembolic complications. Antioxidants activity of plants extracts has been well known for many years and was confirmed by many publications. However, during the last decade many research centers presented results suggesting anticoagulant potential of various plant extracts. Many researchers have also provided evidence that polyphenol compounds are able to inhibit the activity of many enzymes, including serine proteases. All research described in this review clearly indicate that polyphenols and polyphenol-rich extracts possess not only antioxidative but also anticoagulant properties and may be useful in creation of new therapeutic agents or dietary supplements. Based on described properties polyphenols would be very helpful with both prevention and treatment of thromboembolic complications associated with multiple failures of haemostasis, because the available therapeutic agents do not offer such double-effects (antioxidant and anticoagulant).

  2. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    PubMed

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  3. Antioxidant Potential and Oil Composition of Callistemon viminalis Leaves

    PubMed Central

    Zubair, Muhammad; Hassan, Sadia; Rizwan, Komal; Rasool, Nasir; Riaz, Muhammad; Zia-Ul-Haq, M.; De Feo, Vincenzo

    2013-01-01

    The present study was designed to investigate the antioxidant potential and oil composition of Callistemon viminalis leaves. GC-MS analysis of the n-hexane extract revealed the presence of 40 compounds. Leaves contained appreciable levels of total phenolic contents (0.27–0.85 GAE mg/g) and total flavonoid contents (2.25–7.96 CE mg/g). DPPH radical scavenging IC50 and % inhibition of linoleic acid peroxidation were found to be in the ranges of 28.4–56.2 μg/ml and 40.1–70.2%, respectively. The haemolytic effect of the plant leaves was found in the range of 1.79–4.95%. The antioxidant activity of extracts was also studied using sunflower oil as an oxidative substrate and found that it stabilized the oil. The correlation between the results of different antioxidant assays and oxidation parameters of oil indicated that leaves' methanolic extract, exhibiting higher TPC and TFC and scavenging power, was also more potent for enhancing the oxidative stability of sunflower oil. PMID:23818824

  4. Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.

    PubMed

    Praschberger, Monika; Hermann, Marcela; Laggner, Christian; Jirovetz, Leopold; Exner, Markus; Kapiotis, Stylianos; Gmeiner, Bernhard M K; Laggner, Hilde

    2013-11-01

    Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.

  5. Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

    PubMed

    Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

    2016-01-01

    Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

  6. Antimicrobial, Cytotoxic, Phytotoxic and Antioxidant Potential of Heliotropium strigosum Willd.

    PubMed Central

    Khurm, Muhammad; Chaudhry, Bashir A.; Uzair, Muhammad; Janbaz, Khalid H.

    2016-01-01

    Background: Heliotropium strigosum Willd. (Chitiphal) is a medicinally important herb that belongs to the Boraginaceae family. Traditionally, this plant was used in the medication therapy of various ailments in different populations of the world. The aim of the study is to probe the therapeutic aspects of H. strigosum described in the traditional folklore history of medicines. Methods: In the present study, the dichloromethane crude extract of this plant was screened to explore the antimicrobial, cytotoxic, phytotoxic and antioxidant potential of H. strigosum. For antibacterial, antifungal and antioxidant activities, microplate alamar blue assay (MABA), agar tube dilution method and diphenyl picryl hydrazine (DPPH) radical-scavenging assay were used, respectively. The cytotoxic and phytotoxic potential were demonstrated by using brine shrimp lethality bioassay and Lemna minor assay. Results: The crude extract displayed positive cytotoxic activity in the brine shrimp lethality assay, with 23 of 30 shrimps dying at the concentration of 1000 µg/mL. It also showed moderate phytotoxic potential with percent inhibition of 50% at the concentration of 1000 µg/mL. The crude extract exhibited no significant antibacterial activity against Staphylococcus aureus, Shigella flexneri, Escherichia coli and Pseudomonas aeruginosa. Non-significant antifungal and radical scavenging activity was also shown by the dichloromethane crude extract. Conclusion: It is recommended that scientists focus on the identification and isolation of beneficial bioactive constituents with the help of advanced scientific methodologies that seems to be helpful in the synthesis of new therapeutic agents of desired interest. PMID:28930129

  7. Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology.

    PubMed

    Schreibelt, Gerty; van Horssen, Jack; van Rossum, Saskia; Dijkstra, Christine D; Drukarch, Benjamin; de Vries, Helga E

    2007-12-01

    Reactive oxygen species contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. To counteract the detrimental effects of ROS the central nervous system is endowed with a protective mechanism consisting of enzymatic and non-enzymatic antioxidants. Expression of most antioxidant enzymes is regulated through the transcription factor nuclear factor-E2-related factor (Nrf2) and antioxidant response elements (ARE) in the genes encoding enzymatic antioxidants and is induced by oxidative stress. In brain tissue of MS patients, enhanced expression of Nrf2/ARE-regulated antioxidants is suggestive of the occurrence of oxidative stress in these lesions. Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS. However, the use of exogenous antioxidants for MS treatment has drawbacks, as large amounts of antioxidants are required to achieve functional antioxidant levels in the central nervous system. Therefore, the induction of endogenous antioxidant enzymes by activators of the Nrf2/ARE pathway may be an interesting approach to obtain sufficient levels of antioxidants to interfere with pathological processes underlying MS lesion formation. In this review we summarize and discuss the biological role, regulation and potential therapeutic effects of endogenous antioxidant enzymes in MS. We propose that antioxidants may inhibit the development and progression of MS lesions and may therefore represent an attractive therapeutic target for the treatment of MS and other oxidative stress-related neurological diseases.

  8. ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source.

    PubMed

    Yue, Caixia; Yang, Yuming; Zhang, Chunlei; Alfranca, Gabriel; Cheng, Shangli; Ma, Lijun; Liu, Yanlei; Zhi, Xiao; Ni, Jian; Jiang, Weihua; Song, Jie; de la Fuente, Jesús M; Cui, Daxiang

    2016-01-01

    Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for cancer. Here we report, for the first time, synthesis of a new mitochondria-targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel compound, polyethylene glycol was functionalized with thioketal linker-modified camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL-CPT-PEG1K-TPP. The ZnPc/CPT-TPPNPs was constructed for delivery of the photosensitizer Zinc phthalocyanine (ZnPc) by blending the block copolymer TL-CPT-PEG1K-TPP with 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG).Triphenylphosphine can accumulate selectively several hundred-fold within mitochondria. The thioketal linker is ROS-responsive and CPT can be released upon ROS cleavage. We also show that the ZnPc loaded in ZnPc/CPT-TPPNPs absorbed the 633 nm laser to produce ROS, which could be utilized both in photodynamic therapy and to cleave the thioketal linker thereby releasing camptothecin for chemotherapy. Thus, the mitochondria-targeting nanoparticles could elevate photodynamic therapeutic efficacy. Our results showed that surface modification of the nanoparticles with triphenylphosphine cations facilitated efficient subcellular delivery of the photosensitizer to mitochondria. The nanoparticles had a good ROS-responsive effect to release CPT, which could transfer to the nucleus and interfere with DNA replication as a topoisomeraseⅠinhibitor. Thus, the blended nanoparticles provide a new promising approach as a mitochondria-targeting ROS-activated chemo- and photodynamic therapy with a single light source for lung cancer.

  9. ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source

    PubMed Central

    Yue, Caixia; Yang, Yuming; Zhang, Chunlei; Alfranca, Gabriel; Cheng, Shangli; Ma, Lijun; Liu, Yanlei; Zhi, Xiao; Ni, Jian; Jiang, Weihua; Song, Jie; de la Fuente, Jesús M.; Cui, Daxiang

    2016-01-01

    Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for cancer. Here we report, for the first time, synthesis of a new mitochondria-targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel compound, polyethylene glycol was functionalized with thioketal linker-modified camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL-CPT-PEG1K-TPP. The ZnPc/CPT-TPPNPs was constructed for delivery of the photosensitizer Zinc phthalocyanine (ZnPc) by blending the block copolymer TL-CPT-PEG1K-TPP with 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG).Triphenylphosphine can accumulate selectively several hundred-fold within mitochondria. The thioketal linker is ROS-responsive and CPT can be released upon ROS cleavage. We also show that the ZnPc loaded in ZnPc/CPT-TPPNPs absorbed the 633 nm laser to produce ROS, which could be utilized both in photodynamic therapy and to cleave the thioketal linker thereby releasing camptothecin for chemotherapy. Thus, the mitochondria-targeting nanoparticles could elevate photodynamic therapeutic efficacy. Our results showed that surface modification of the nanoparticles with triphenylphosphine cations facilitated efficient subcellular delivery of the photosensitizer to mitochondria. The nanoparticles had a good ROS-responsive effect to release CPT, which could transfer to the nucleus and interfere with DNA replication as a topoisomeraseⅠinhibitor. Thus, the blended nanoparticles provide a new promising approach as a mitochondria-targeting ROS-activated chemo- and photodynamic therapy with a single light source for lung cancer. PMID:27877240

  10. A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage.

    PubMed

    Brand, Rhonda M; Epperly, Michael W; Stottlemyer, J Mark; Skoda, Erin M; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E; Greenberger, Joel S; Falo, Louis D

    2017-03-01

    Skin is the largest human organ, and it provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation-induced skin damage ranges from photoaging and cutaneous carcinogenesis caused by UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation-induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species. Mitochondria are particularly susceptible to oxidative stress, and mitochondrial-dependent apoptosis plays a major role in radiation-induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent reactive oxygen species accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrially targeted antioxidant prevents and mitigates radiation-induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin's antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies.

    PubMed

    Antonenko, Y N; Avetisyan, A V; Bakeeva, L E; Chernyak, B V; Chertkov, V A; Domnina, L V; Ivanova, O Yu; Izyumov, D S; Khailova, L S; Klishin, S S; Korshunova, G A; Lyamzaev, K G; Muntyan, M S; Nepryakhina, O K; Pashkovskaya, A A; Pletjushkina, O Yu; Pustovidko, A V; Roginsky, V A; Rokitskaya, T I; Ruuge, E K; Saprunova, V B; Severina, I I; Simonyan, R A; Skulachev, I V; Skulachev, M V; Sumbatyan, N V; Sviryaeva, I V; Tashlitsky, V N; Vassiliev, J M; Vyssokikh, M Yu; Yaguzhinsky, L S; Zamyatnin, A A; Skulachev, V P

    2008-12-01

    concluded that SkQs are rechargeable, mitochondria-targeted antioxidants of very high efficiency and specificity. Therefore, they might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo.

  12. Antioxidants

    MedlinePlus

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  13. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    PubMed

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  14. Significance of Antioxidant Potential of Plants and its Relevance to Therapeutic Applications

    PubMed Central

    Kasote, Deepak M.; Katyare, Surendra S.; Hegde, Mahabaleshwar V.; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants. PMID:26157352

  15. Antioxidant potential of orientin: A combined experimental and DFT approach

    NASA Astrophysics Data System (ADS)

    Praveena, R.; Sadasivam, K.; Deepha, V.; Sivakumar, Raman

    2014-03-01

    The antioxidant activity of the bioactive fractions obtained from the leaves of Rhynchosia capitata is evaluated for its capacity to reduce ferric ions. In vitro antihemolytic analysis for the separated erythrocytes of Wistar rat blood cells exhibits maximum inhibition value for ethyl acetate (1202.55 ± 9.46) than ethanol fraction (424.57 ± 12.04). Gas and solvent phase studies of structural and molecular characteristics of C-glycosyl flavonoid, orientin present in the bioactive fraction of R. capitata is investigated through hydrogen atom transfer mechanism (HAT) using DFT/B3LYP/6-311G(d,p) level of theory. Interestingly, the intramolecular hydrogen bonding formed between 3‧-O and 4‧-H makes 3‧-OH as the active site which is supported by its bond dissociation energy values. The computed values of the adiabatic ionization potential, electron affinity, hardness, softness, electronegativity and electrophilic index indicate that orientin possess good radical scavenging activity. In this study, role of molecular electrostatic potential and electron density distribution map in predicting the importance of B-ring are analyzed and reported. Spin density distribution analysis for the radicals is formed by summing of spin on rings A, B and C. The most active system able to transfer a hydrogen atom is orientin compared to vitexin and the bond dissociation enthalpy follows the order benzene > ethyl acetate > water.

  16. Health benefits of nuts: potential role of antioxidants.

    PubMed

    Blomhoff, Rune; Carlsen, Monica H; Andersen, Lene Frost; Jacobs, David R

    2006-11-01

    A diet rich in fruits, vegetables and minimally refined cereals is associated with lower risk for chronic degenerative diseases. Since oxidative stress is common in chronic degenerative disease, it has been assumed that dietary antioxidants may explain this protective effect. Every dietary plant contains numerous types of antioxidants with different properties. Many of these antioxidants cooperate in oxidative stress reduction in plants, and we hypothesize that many different antioxidants may also be needed for the proper protection of animal cells. To test this hypothesis, it is useful to identify dietary plants with high total antioxidant content. Several nuts are among the dietary plants with the highest content of total antioxidants. Of the tree nuts, walnuts, pecans and chestnuts have the highest contents of antioxidants. Walnuts contain more than 20 mmol antioxidants per 100 g, mostly in the walnut pellicles. Peanuts (a legume) also contribute significantly to dietary intake of antioxidants. These data are in accordance with our present extended analysis of an earlier report on nut intake and death attributed to various diseases in the Iowa Women's Health Study. We observed that the hazard ratio for total death rates showed a U-shaped association with nut/peanut butter consumption. Hazard ratio was 0.89 (CI = 0.81-0.97) and 0.81 (CI = 0.75-0.88) for nut/peanut butter intake once per week and 1-4 times per week, respectively. Death attributed to cardiovascular and coronary heart diseases showed strong and consistent reductions with increasing nut/peanut butter consumption. Further studies are needed to clarify whether antioxidants contribute to this apparent beneficial health effect of nuts.

  17. Antioxidant Potential of White Oyster Culinary-Medicinal Mushroom, Pleurotus florida (Higher Basidiomycetes).

    PubMed

    Ganeshpurkar, Aditya; Pardhi, Priya; Bhadoriya, Santosh Singh; Jain, Nikhil; Rai, Gopal; Jain, Alok Pal

    2015-01-01

    The present work was focused to evaluate in vitro antioxidant of Pleurotus florida. The hydroethanolic extract was prepared by macerating basidiocarp with water:ethanol (1:1). The antioxidant potential was evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity, reducing power, chelating effects on ferrous ions, total antioxidant capacity, and lipid peroxidation inhibitory activity. Further total flavonoid and phenolic content was also estimated. The comparison between different antioxidant assays was done by correlation coefficient. The results from the antioxidant assays showed that hydroethanolic extract (HEE) might act as radical scavenger to a certain extent. The distinct scavenging activities of HEE can be due to the diverse phytochemical constituents. Being a rich source of antioxidants, P. florida can be used as an accessible source of natural antioxidants with consequential health benefits.

  18. Identification of functionally important amino acid residues in the mitochondria targeting sequence of Hepatitis B virus X protein

    SciTech Connect

    Li, Sai Kam; Ho, Sai Fan; Tsui, Kwok Wing; Fung, Kwok Pui; Waye, M.Y. Mary

    2008-11-10

    Chronic hepatitis B virus (HBV) infection has been strongly associated with hepatocellular carcinoma (HCC) and the X protein (HBx) is thought to mediate the cellular changes associated with carcinogenesis. Recently, isolation of the hepatitis B virus integrants from HCC tissue by others have established the fact that the X gene is often truncated at its C-terminus. Expression of the GFP fusion proteins of HBx and its truncation mutants with a GFP tag in human liver cell-lines in this study revealed that the C-terminus of HBx is indispensable for its specific localization in the mitochondria. A crucial region of seven amino acids at the C-terminus has been mapped out in which the cysteine residue at position 115 serves as the most important residue for the subcellular localization. When cysteine 115 of HBx is mutated to alanine the mitochondria targeting property of HBx is abrogated.

  19. Potential antioxidant response to coffee — A matter of genotype?

    PubMed Central

    Hassmann, Ute; Haupt, Larisa M.; Smith, Robert A.; Winkler, Swantje; Bytof, Gerhard; Lantz, Ingo; Griffiths, Lyn R.; Marko, Doris

    2014-01-01

    In a human intervention study, coffee combining natural green coffee bean constituents and dark roast products was identified as a genotype-dependent inducer of the Nrf2/ARE pathway, significantly affecting Nrf2 gene expression and downstream GST1A1 and UGT1A1 gene transcription. The observed transcriptional changes correlated with the presence of specific Nrf2 genotypes suggesting their influence on both Nrf2 and subsequent ARE-dependent GST1A1 and UGT1A1 transcription. While the presence of the − 653 SNP seems to be advantageous, resulting in higher Nrf2, GST1A1 and UGT1A1 gene transcription following coffee consumption, in contrast, the presence of the − 651 SNP significantly down-regulated the response to the study coffee. Furthermore, the presence of the B/B genotype in GST1A1 along with the frequency of the [TA]6/6 and [TA]7/7 polymorphisms in UGT1A1 appeared to significantly increase sensitivity toward coffee-induced gene transcription. This data suggests that when examining the role of the Nrf2/ARE pathway in the regulation of antioxidative and chemopreventive phase II efficacy, individual genotypes should be included when considering the potency of bioactive food/food constituents and their therapeutic potential. PMID:25606436

  20. New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential.

    PubMed

    Pacuła, Agata J; Kaczor, Katarzyna B; Antosiewicz, Jędrzej; Janecka, Anna; Długosz, Angelika; Janecki, Tomasz; Wojtczak, Andrzej; Ścianowski, Jacek

    2017-03-20

    New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H)-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145) and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H)-ones.

  1. Commonly Used Antioxidant Botanicals: Active Constituents and their Potential Role in Cardiovascular Illness

    PubMed Central

    Wang, Chong-Zhi; Mehendale, Sangeeta R.; Yuan, Chun-Su

    2009-01-01

    Cardiovascular disease continues to be the leading cause of death in the US. Recent studies found that reactive oxygen species (ROS) have been incriminated in the pathogenesis of both acute and chronic heart disease. Many botanicals possess antioxidant properties, and these herbal antioxidants may protect against cardiovascular diseases by contributing to the total antioxidant defense system of the human body. In this article, we reviewed the antioxidant components and properties of four putative antioxidant botanicals (i.e., grape seeds, green tea, Scutellaria baicalensis, and American ginseng), and their potential role in treating cardiovascular illness. The antioxidant activities of the herbal active constituents, and the relationship between their chemical structures and biological functions were also discussed. Further investigations are needed on the mechanisms of action of these botanicals as they affect salient cellular and molecular pathways involved in major diseases. Data obtained from future studies will have the potential for translation into practical benefits for human health. PMID:17708622

  2. Antidiabetic, Antioxidant, and Hypolipidemic Potential of Sonchus asper Hill.

    PubMed

    Khan, Rahmat Ali

    2017-02-27

    antioxidant enzymes, TBARS contents, and cholesterol profile of the diabetic rats (P < .01). In treatment, the glucose and insulin levels of the SAME rats were significantly lower than the diabetic rats on day 21 (P < .01). Conclusions • The findings suggest that the significant antidiabetic potential of the SAME in ameliorating the diabetic conditions in diabetic rats might be due to the presence of the bioactive constituents in the extract.

  3. An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

    SciTech Connect

    Pelle, E.; Maes, D.; Padulo, G.A.; Kim, E.K.; Smith, W.P. )

    1990-12-01

    Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA greater than catechin greater than BHT greater than alpha-tocopherol greater than chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation.

  4. Evaluation of antioxidant potential and reduction capacity of some plant extracts in silver nanoparticles' synthesis

    PubMed Central

    Goodarzi, Vahid; Zamani, Hajar; Bajuli, Leila; Moradshahi, Ali

    2014-01-01

    The green synthesis of metallic nanoparticles is an active research area in nanotechnology. In the present study, antioxidant potential, total reducing capacity and silver nanoparticles' (Ag NPs) synthetic potential of methanolic leaf extracts of seven plant species were evaluated and compared. Antioxidant capacity, expressed as µmol Trolox equivalents g-1 DW (µmol TE g-1 DW), ranged from 116.0 to 1.80. The plants Rosmarinus sp. and Zataria Multiflora showed highest antioxidant capacities with IC50 of 1.07 and 1.22 mg ml-1, respectively. Total reducing capacity ranged from 7.6 to 0.17 mg gallic acid equivalent to g-1 DW (mg GAE g-1 DW). Plants with high antioxidant potentials also showed higher total reducing capacity. In fact, the order of the plants' reducing capacity was similar to that of their antioxidant potential. The same two plant species, i.e., Zataria Multiflora and Rosmarinus sp, with high reducing capacities, showed higher potentials for Ag NPs synthesis. It is concluded that reducing substances in the extracts contribute significantly to the antioxidant potential of the tested plant species, and plants with a high reducing capacity are excellent sources for the green synthesis of metallic nanoparticles. In addition, synthetic antioxidants have adverse effects on human health; therefore, to benefit more from the health promoting properties of plant species, evaluating their novel natural antioxidants is recommended. PMID:27843980

  5. Comparison of phenolic acids profile and antioxidant potential of six varieties of spelt (Triticum spelta L.).

    PubMed

    Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz

    2012-05-09

    Phenolic acids profile and antioxidant activity of six diverse varieties of spelt are reported. Antioxidant activity was assessed using eight methods based on different mechanism of action. Phenolic acids composition of spelt differed significantly between varieties and ranged from 506.6 to 1257.4 μg/g DW. Ferulic and sinapinic acids were the predominant phenolic acids found in spelt. Total ferulic acid content ranged from 144.2 to 691.5 μg/g DW. All analyzed spelt varieties possessed high antioxidant potential. In spite of the fact that bound phenolic acids possessed higher antioxidant activities, analysis of antioxidant potential and their relationship with phenolic acid content showed that free phenolics were more effective. Eight antioxidant methods were integrated to obtain a total antioxidant capacity index that may be used for comparison of total antioxidant capacity of spelt varieties. Total antioxidant potential of spelt cultivars were ordered as follows: Ceralio > Spelt INZ ≈ Ostro > Oberkulmer Rotkorn > Schwabenspelz > Schwabenkorn.

  6. Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

    PubMed Central

    d'Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

    2014-01-01

    Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients. PMID:24876913

  7. The mitochondria-targeted imidazole substituted oleic acid 'TPP-IOA' affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism.

    PubMed

    Maddalena, Lucas A; Ghelfi, Mikel; Atkinson, Jeffrey; Stuart, Jeffrey A

    2017-01-01

    A variety of mitochondria-targeted small molecules have been invented to manipulate mitochondrial redox activities and improve function in certain disease states. 3-Hydroxypropyl-triphenylphosphonium-conjugated imidazole-substituted oleic acid (TPP-IOA) was developed as a specific inhibitor of cytochrome c peroxidase activity that inhibits apoptosis by preventing cardiolipin oxidation and cytochrome c release to the cytosol. Here we evaluate the effects of TPP-IOA on oxidative phosphorylation in isolated mitochondria and on mitochondrial function in live cells. We demonstrate that, at concentrations similar to those required to achieve inhibition of cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation in isolated mitochondria. In live SH-SY5Y cells, TPP-IOA partially collapsed mitochondrial membrane potential, caused extensive fragmentation of the mitochondrial network, and decreased apparent mitochondrial abundance within 3h of exposure. Many cultured cell lines rely primarily on aerobic glycolysis, potentially making them less sensitive to small molecules disrupting oxidative phosphorylation. We therefore determined the anti-apoptotic efficacy of TPP-IOA in SH-SY5Y cells growing in glucose or in galactose, the latter of which increases reliance on oxidative phosphorylation for ATP supply. The anti-apoptotic activity of TPP-IOA that was observed in glucose media was not seen in galactose media. It therefore appears that, at concentrations required to inhibit cytochrome c peroxidase activity, TPP-IOA perturbs oxidative phosphorylation. In light of these data it is predicted that potential future therapeutic applications of TPP-IOA will be restricted to highly glycolytic cell types with limited reliance on oxidative phosphorylation. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Ruthenium nitrosyl functionalized graphene quantum dots as an efficient nanoplatform for NIR-light-controlled and mitochondria-targeted delivery of nitric oxide combined with photothermal therapy.

    PubMed

    Guo, Min; Xiang, Hui-Jing; Wang, Yi; Zhang, Qian-Ling; An, Lu; Yang, Shi-Ping; Ma, Yinchu; Wang, Yucai; Liu, Jin-Gang

    2017-03-18

    A mitochondria-targeting nanoplatform for near-infrared-light-controlled release of nitric oxide accompanied by photothermal therapy was developed, which consists of ruthenium nitrosyl functionalized N-doped graphene quantum dots and a triphenylphosphonium moiety. The nanoplatform demonstrated both in vitro and in vivo anti-tumor efficacy upon irradiation with 808 nm light.

  9. Photoactivatable cytotoxic agents derived from mitochondria-targeting luminescent iridium(III) poly(ethylene glycol) complexes modified with a nitrobenzyl linkage.

    PubMed

    Tso, Karson Ka-Shun; Leung, Kam-Keung; Liu, Hua-Wei; Lo, Kenneth Kam-Wing

    2016-03-25

    Two novel photoactivatable mitochondria-targeting luminescent iridium(III) poly(ethylene glycol) (PEG) complexes incorporated with a nitrobenzyl group were designed. They showed minimal cytotoxic activity in the dark, but became significantly cytotoxic upon irradiation due to the release of the PEG pendants.

  10. The potential role of antioxidants in metabolic syndrome.

    PubMed

    Gregório, Bianca Martins; De Souza, Diogo Benchimol; de Morais Nascimento, Fernanda Amorim; Pereira, Leonardo Matta; Fernandes-Santos, Caroline

    2016-01-01

    Metabolic syndrome (MS) is a constellation of risk factors that raise the risk for heart disease and other health problems, such as obesity. The clustering of metabolic abnormality is closely related to oxidative stress and inflammation, as well as the progression of atherosclerosis. Antioxidants are reducing agents which inhibit the oxidation of other molecules and can be used not only to prevent but also to treat health complications of MS and atherosclerosis. They can be ingested in the normal diet, since they are found in many food sources, or in supplement formulations. Herein, we aim to review the literature concerning the effect of antioxidants on MS. We focus on antioxidants with some evidence of action on this condition, like flavonoids, arginine, vitamin C, vitamin E, carotenoids, resveratrol and selenium. Experimental and clinical studies show that most of the above-mentioned antioxidants exhibit a wide range of effects in protecting the human body, especially in MS patients. However, the underlying mechanisms are not fully elucidated for most of these compounds. Also, some of them should be used with caution because their excess can be toxic to the body. In general, antioxidants (especially those present in foods) can be used by MS individuals because of their direct effect on oxidative stress. Additionally, they should be encouraged as part of a nutritional lifestyle change, since this is part of the therapy for all diseases involved in metabolic disorders.

  11. Antioxidant potential of Coriandrum sativum L. seed extract.

    PubMed

    Deepa, B; Anuradha, C V

    2011-01-01

    The seeds of C. sativum are used as a traditional drug for the treatment of diabetes. The antioxidant and free-radical-scavenging property of seeds in vitro was studied and also investigated whether the administration of seeds curtails oxidative stress in the kidney of streptozotocin-induced diabetic rats. Incorporation of seed powder in the diet led to marked lowering of blood glucose and a rise in the levels of insulin in diabetic rats. A parallel beneficial effect was observed on oxidant -antioxidant balance in the kidney. Addition of coriander seed powder not only inhibited the process of peroxidative damage but also significantly reactivated the antioxidant enzymes and antioxidant levels in diabetic rats. The total polyphenolic content of the seeds was found to be 12.2 gallic acid equivalents (GAE)/g while total flavanoid content was found to be 12.6 quercetin equivalents/g. The seeds also showed scavenging activity against superoxides and hydroxyl radicals in a concentration-dependent manner. Maximum free radical-scavenging action and free radical reducing power of coriander seed extract was observed at a concentration of 50 microg GAE. Islet histology structures showed degeneration of pancreatic islets in diabetic rats which was also reduced in diabetic rats treated with seed powder. These results show that C. sativum seeds not only possess antihyperglycemic properties but antioxidative properties also. Increased dietary intake of coriander seeds decrease the oxidative burden in diabetes mellitus.

  12. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

    PubMed

    Gerő, Domokos; Torregrossa, Roberta; Perry, Alexis; Waters, Alicia; Le-Trionnaire, Sophie; Whatmore, Jacqueline L; Wood, Mark; Whiteman, Matthew

    2016-11-01

    The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Centauries as underestimated food additives: antioxidant and antimicrobial potential.

    PubMed

    Siler, Branislav; Zivković, Suzana; Banjanac, Tijana; Cvetković, Jelena; Nestorović Živković, Jasmina; Cirić, Ana; Soković, Marina; Mišić, Danijela

    2014-03-15

    Methanol extracts of aerial parts and roots of five centaury species (Centaurium erythraea, C. tenuiflorum, C. littorale ssp. uliginosum, C. pulchellum, and Schenkia spicata) were analysed for their main secondary metabolites: secoiridoid glycosides, a group of monoterpenoid compounds, and phenolics (xanthones and flavonoids), and further investigated for antioxidant capacity and antimicrobial activity. The results of ABTS, DPPH, and FRAP assays showed that above ground parts generally displayed up to 13 times higher antioxidant activity compared to roots, which should be related to higher phenolics content, especially flavonoids, in green plant organs. Secoiridoid glycosides showed no antioxidant activity. All the tested extracts demonstrated appreciative antibacterial (0.05-0.5 mg ml(-1)) and strong antifungal activity (0.1-0.6 mg ml(-1)). Our results imply that above ground parts of all centaury species studied, could be recommended for human usage as a rich source of natural antioxidants and also in food industry as strong antimicrobial agents for food preservation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Antioxidants: potential antiviral agents for Japanese encephalitis virus infection.

    PubMed

    Zhang, Yu; Wang, Zehua; Chen, Huan; Chen, Zongtao; Tian, Yanping

    2014-07-01

    Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Pineapple peel wastes as a potential source of antioxidant compounds

    NASA Astrophysics Data System (ADS)

    Saraswaty, V.; Risdian, C.; Primadona, I.; Andriyani, R.; Andayani, D. G. S.; Mozef, T.

    2017-03-01

    Indonesia is a large pineapple (Ananas comosus) producing country. Food industries in Indonesia processed this fruit for new products and further resulted wastes of which cause an environmental problems. Approximately, one pineapple fruit total weight is 400 gr of which 60 g is of peel wastes. In order to reduce such pineapple peel wastes (PPW), processing to a valuable product using an environmentally friendly technique is indispensable. PPW contained phenolic compound, ferulic acid, and vitamin A and C as antioxidant. This study aimed to PPW using ethanol and water as well as to analyze its chemical properties. Both dried and fresh PPW were extracted using mixtures of ethanol and water with various concentrations ranging from 15 to 95% (v/v) at room temperature for 24 h. The chemical properties, such as antioxidant activity, total phenolic content (Gallic acid equivalent/GAE), and total sugar content were determined. The results showed that the range of Inhibition Concentration (IC)50 value as antioxidant activity of extracts from dried and fresh PPW were in the range of 0.8±0.05 to 1.3±0.09 mg.mL-1 and 0.25±0.01 to 0.59±0.01 mg.mL-1, respectively, with the highest antioxidant activity was in water extract. The highest of total phenolic content of 0.9 mg.g-1 GAE, was also found in water extract.

  16. Antioxidant and Anticholinesterase Potential of Six Thymus Species.

    PubMed

    Kindl, Marija; Blažeković, Biljana; Bucar, Franz; Vladimir-Knežević, Sanda

    2015-01-01

    The present study aimed to evaluate antioxidant and acetylcholinesterase (AChE) inhibitory activities of the ethanolic extracts of six selected Thymus species growing in Croatia (T. longicaulis, T. praecox subsp. polytrichus, T. pulegioides, T. serpyllum subsp. serpyllum, T. striatus, and T. vulgaris). Antioxidant effectiveness was assessed using six different assays, in comparison with rosmarinic acid, luteolin, and reference antioxidants. All tested Thymus extracts possessed DPPH (IC50 = 3-6 μg/mL) and nitric oxide (IC50 = 70-177 μg/mL) free radical scavenging activities, strong reducing properties (IC50 = 11-15 μg/mL), ferrous ion chelating activity (IC50 = 126-389 μg/mL), ability to inhibit lipid peroxidation (IC50 = 34-80 μg/mL), and high total antioxidant capacities (238-294 mg AAE/g). AChE inhibitory activity was examined using Ellman's colorimetric method and all tested extracts showed anti-AChE activity in a dose dependent manner. The values of 10-28%, 23-39%, and 64-86% were obtained for tested concentrations of 0.25, 0.5, and 1 mg/mL, respectively. Additionally, the contents of total hydroxycinnamic derivatives, flavonoids, and tannins in dried plant samples were determined spectrophotometrically. Our results highlighted Thymus species as a rich source of natural antioxidants and AChE inhibitors that could be useful in preventing and treating Alzheimer's disease and other neurodegenerative disorders.

  17. Antioxidant and Anticholinesterase Potential of Six Thymus Species

    PubMed Central

    Kindl, Marija; Blažeković, Biljana; Bucar, Franz; Vladimir-Knežević, Sanda

    2015-01-01

    The present study aimed to evaluate antioxidant and acetylcholinesterase (AChE) inhibitory activities of the ethanolic extracts of six selected Thymus species growing in Croatia (T. longicaulis, T. praecox subsp. polytrichus, T. pulegioides, T. serpyllum subsp. serpyllum, T. striatus, and T. vulgaris). Antioxidant effectiveness was assessed using six different assays, in comparison with rosmarinic acid, luteolin, and reference antioxidants. All tested Thymus extracts possessed DPPH (IC50 = 3–6 μg/mL) and nitric oxide (IC50 = 70–177 μg/mL) free radical scavenging activities, strong reducing properties (IC50 = 11–15 μg/mL), ferrous ion chelating activity (IC50 = 126–389 μg/mL), ability to inhibit lipid peroxidation (IC50 = 34–80 μg/mL), and high total antioxidant capacities (238–294 mg AAE/g). AChE inhibitory activity was examined using Ellman's colorimetric method and all tested extracts showed anti-AChE activity in a dose dependent manner. The values of 10–28%, 23–39%, and 64–86% were obtained for tested concentrations of 0.25, 0.5, and 1 mg/mL, respectively. Additionally, the contents of total hydroxycinnamic derivatives, flavonoids, and tannins in dried plant samples were determined spectrophotometrically. Our results highlighted Thymus species as a rich source of natural antioxidants and AChE inhibitors that could be useful in preventing and treating Alzheimer's disease and other neurodegenerative disorders. PMID:26351513

  18. Mitochondria-targeted DsRed2 protein expression during the early stage of bovine somatic cell nuclear transfer embryo development.

    PubMed

    Park, Hyo-Jin; Min, Sung-Hun; Choi, Hoonsung; Park, Junghyung; Kim, Sun-Uk; Lee, Seunghoon; Lee, Sang-Rae; Kong, Il-Keun; Chang, Kyu-Tae; Koo, Deog-Bon; Lee, Dong-Seok

    2016-09-01

    Somatic cell nuclear transfer (SCNT) has been widely used as an efficient tool in biomedical research for the generation of transgenic animals from somatic cells with genetic modifications. Although remarkable advances in SCNT techniques have been reported in a variety of mammals, the cloning efficiency in domestic animals is still low due to the developmental defects of SCNT embryos. In particular, recent evidence has revealed that mitochondrial dysfunction is detected during the early development of SCNT embryos. However, there have been relatively few or no studies regarding the development of a system for evaluating mitochondrial behavior or dynamics. For the first time, in mitochondria of bovine SCNT embryos, we developed a method for the visualization of mitochondria and expression of fluorescence proteins. To express red fluorescence in mitochondria of cloned embryos, bovine ear skin fibroblasts, nuclear donor, were stably transfected with a vector carrying mitochondria-targeting DsRed2 gene tagged with V5 epitope (mito-DsRed2-V5 tag) using lentivirus-mediated gene transfer because of its ability to integrate in the cell genome and the potential for long-term transgene expression in the transduced cells and their dividing cells. From western blotting analysis of V5 tag protein using mitochondrial fraction and confocal microscopy of red fluorescence using SCNT embryos, we found that the mitochondrial expression of the mito-DsRed2 protein was detected until the blastocyst stage. In addition, according to image analysis, it may be suggested possible use of the system for visualization of mitochondrial localization and evaluation of mitochondrial behaviors or dynamics in early development of bovine SCNT embryos.

  19. Evaluation of respiration of mitochondria in cancer cells exposed to mitochondria-targeted agents.

    PubMed

    Kluckova, Katarina; Dong, Lan-Feng; Bajzikova, Martina; Rohlena, Jakub; Neuzil, Jiri

    2015-01-01

    Respiration is one of the major functions of mitochondria, whereby these vital organelles use oxygen to produce energy. Many agents that may be of potential clinical relevance act by targeting mitochondria, where they may suppress mitochondrial respiration. It is therefore important to evaluate this process and understand how this is modulated by small molecules. Here, we describe the general methodology to assess respiration in cultured cells, followed by the evaluation of the effect of one anticancer agent targeted to mitochondria on this process, and also how to assess this in tumor tissue.

  20. Triple-responsive Expansile Nanogel for Tumor and Mitochondria Targeted Photosensitizer Delivery

    PubMed Central

    He, Huacheng; Cattran, Alexander W.; Nguyen, Tu; Nieminen, Anna-Liisa

    2014-01-01

    A pH, thermal, and redox potential triple-responsive expansile nanogel system (TRN), which swells at acidic pH, temperature higher than its transition temperature, and reducing environment, has been developed. TRN quickly expands from 108 nm to over 1200 nm (in diameter), achieving more than 1000-fold size enlargement (in volume), within 2 h in a reducing environment at body temperature. Sigma-2 receptor targeting-ligand functionalized TRN can effectively target head and neck tumor, and help Pc 4 targeting mitochondria inside cancer cells to achieve enhanced photodynamic therapy efficacy. PMID:25154666

  1. A mitochondria-targeting artemisinin derivative with sharply increased antitumor but depressed anti-yeast and anti-malaria activities

    PubMed Central

    Sun, Chen; Cao, Yu; Zhu, Pan; Zhou, Bing

    2017-01-01

    The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins’ activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa). ARTa-TPP displays far more potent anti-tumorigenic activity than its parent compound. In contrast, ARTa-TPP is much less active against yeast respiration growth and malarial parasites. Notably, ARTa-TPP is also associated with increased toxicity to other kinds of control mammalian cells. These results suggest divergent action modes for artemisinins against cancer cells and malaria or yeast cells. We conclude that mitochondrial targeting could substantially elevate the anticancer potency of artemisinins, but the accompanied increased toxicity to normal cells raises an alert. The mechanism regarding the opposing effects of TPP conjugation to ARTa on its anticancer and anti-malarial/anti-yeast potencies is discussed based on our current understandings of artemisinins’ action. PMID:28368011

  2. Phosphorescent iridium(III)-bis-N-heterocyclic carbene complexes as mitochondria-targeted theranostic and photodynamic anticancer agents.

    PubMed

    Li, Yi; Tan, Cai-Ping; Zhang, Wei; He, Liang; Ji, Liang-Nian; Mao, Zong-Wan

    2015-01-01

    Mitochondria-targeted compounds represent a promising approach to target tumors selectively and overcome resistance to current anticancer therapies. In this work, three cyclometalated iridium(III) complexes (1-3) containing bis-N-heterocyclic carbene (NHC) ligands have been explored as theranostic and photodynamic agents targeting mitochondria. These complexes display rich photophysical properties, which greatly facilitates the study of their intracellular fate. All three complexes are more cytotoxic than cisplatin against the cancer cells screened. 1-3 can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, and they can carry out theranostic functions by simultaneously inducing and monitoring the morphological changes in mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy by initiating a cascade of events related to mitochondrial dysfunction. Additionally, they display up to 3 orders of magnitude higher cytotoxicity upon irradiation at 365 nm, which is so far the highest photocytotoxic responses reported for iridium complexes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A mitochondria-targeting artemisinin derivative with sharply increased antitumor but depressed anti-yeast and anti-malaria activities.

    PubMed

    Sun, Chen; Cao, Yu; Zhu, Pan; Zhou, Bing

    2017-04-03

    The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins' activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa). ARTa-TPP displays far more potent anti-tumorigenic activity than its parent compound. In contrast, ARTa-TPP is much less active against yeast respiration growth and malarial parasites. Notably, ARTa-TPP is also associated with increased toxicity to other kinds of control mammalian cells. These results suggest divergent action modes for artemisinins against cancer cells and malaria or yeast cells. We conclude that mitochondrial targeting could substantially elevate the anticancer potency of artemisinins, but the accompanied increased toxicity to normal cells raises an alert. The mechanism regarding the opposing effects of TPP conjugation to ARTa on its anticancer and anti-malarial/anti-yeast potencies is discussed based on our current understandings of artemisinins' action.

  4. Surface plasmon resonance-induced photoactivation of gold nanoparticles as mitochondria-targeted therapeutic agents for pancreatic cancer.

    PubMed

    Mocan, Lucian; Ilie, Ioana; Tabaran, Flaviu A; Dana, Bartos; Zaharie, Florin; Zdrehus, Claudiu; Puia, Cosmin; Mocan, Teodora; Muntean, Valentin; Teodora, Pop; Ofelia, Mosteanu; Marcel, Tantau; Iancu, Cornel

    2013-12-01

    Noble metal nanoparticles such as gold nanoparticles can strongly absorb light in the visible region by inducing coherent collective oscillation of conduction band electrons in strong resonance with visible frequencies of light. This phenomenon is frequently termed as surface plasmon resonance (SPR). The main objective was to study the effects of laser photoactivated gold nanoparticles (by means of SPR) on human pancreatic cancer cells. Gold nanoparticles obtained using standard wet chemical methods (with sodium borohydride as a reducing agent) underwent photoexcitation using 2w 808 nm laser and further administered to 1.4E7 pancreatic cancer cell lines. Flow cytometry, transmission electron microscopy, phase contrast microscopy, quantitative proteomics and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo excited gold nanoparticles and pancreatic cancer cells. The study shows that phonon-phonon interactions following laser photoexcitation of gold nanoparticles exhibit increased intracellular uptake, as well as mitochondrial swelling, closely followed by mitochondrial inner membrane permeabilization and depolarization. This unique data may represent a major step in mitochondria-targeted anticancer therapies using laser-activated gold nanoparticles.

  5. Heterologous expression of mitochondria-targeted microbial nitrilase enzymes increases cyanide tolerance in Arabidopsis.

    PubMed

    Molojwane, E; Adams, N; Sweetlove, L J; Ingle, R A

    2015-07-01

    Anthropogenic activities have resulted in cyanide (CN) contamination of both soil and water in many areas of the globe. While plants possess a detoxification pathway that serves to degrade endogenously generated CN, this system is readily overwhelmed, limiting the use of plants in bioremediation. Genetic engineering of additional CN degradation pathways in plants is one potential strategy to increase their tolerance to CN. Here we show that heterologous expression of microbial nitrilase enzymes targeted to the mitochondria increases CN tolerance in Arabidopsis. Root length in seedlings expressing either a CN dihydratase from Bacillus pumilis or a CN hydratase from Neurospora crassa was increased by 45% relative in wild-type plants in the presence of 50 μm KCN. We also demonstrate that in contrast to its strong inhibitory effects on seedling establishment, seed germination of the Col-0 ecotype of Arabidopsis is unaffected by CN. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  6. Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III

    PubMed Central

    Ma, Dennis; Pignanelli, Christopher; Tarade, Daniel; Gilbert, Tyler; Noel, Megan; Mansour, Fadi; Adams, Scott; Dowhayko, Alexander; Stokes, Kyle; Vshyvenko, Sergey; Hudlicky, Tomas; McNulty, James; Pandey, Siyaram

    2017-01-01

    Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics. They disrupted mitochondrial function, activated the intrinsic apoptotic pathway, and reduced growth of tumor xenografts in vivo. Interestingly, the pro-apoptotic effects of SVTH-7 on cancer cells and mitochondria were abrogated with the inhibition of mitochondrial complex II and III, suggesting mitochondrial or metabolic vulnerabilities may be exploited by this analog. This work provides a scaffold for characterizing distinct mitochondrial and metabolic features of cancer cells and reveals several lead compounds with high therapeutic potential. PMID:28220885

  7. Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III.

    PubMed

    Ma, Dennis; Pignanelli, Christopher; Tarade, Daniel; Gilbert, Tyler; Noel, Megan; Mansour, Fadi; Adams, Scott; Dowhayko, Alexander; Stokes, Kyle; Vshyvenko, Sergey; Hudlicky, Tomas; McNulty, James; Pandey, Siyaram

    2017-02-21

    Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics. They disrupted mitochondrial function, activated the intrinsic apoptotic pathway, and reduced growth of tumor xenografts in vivo. Interestingly, the pro-apoptotic effects of SVTH-7 on cancer cells and mitochondria were abrogated with the inhibition of mitochondrial complex II and III, suggesting mitochondrial or metabolic vulnerabilities may be exploited by this analog. This work provides a scaffold for characterizing distinct mitochondrial and metabolic features of cancer cells and reveals several lead compounds with high therapeutic potential.

  8. Cyclometalated iridium(III)-guanidinium complexes as mitochondria-targeted anticancer agents.

    PubMed

    Song, Xing-Dong; Kong, Xia; He, Shu-Fen; Chen, Jia-Xi; Sun, Jing; Chen, Bing-Bing; Zhao, Jin-Wu; Mao, Zong-Wan

    2017-09-29

    Guanidinium-functionalized molecules are commonly studied for their use as pharmaceutically active compounds and drugs carriers. Herein, four cyclometalated iridium(III) complexes containing guanidinium ligands have been synthesized and characterized as potential anticancer agents. These complexes exhibit moderate antitumor activity in HeLa, MCF-7, HepG2, CNE-2, and A549 human tumor cells. Interestingly, all complexes showed higher cytotoxicity than cisplatin against a cisplatin-resistant cell line A549R, and less cytotoxicity on the nontumorigenic LO2 cells. Intracellular distribution studies suggest that these complexes are selectively localized in the mitochondria. Mechanism studies indicate that these complexes arrested the cell cycle in the G0/G1 phase and can influence mitochondrial integrity, inducing cancer cell death through reactive oxygen species (ROS)-dependent pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Antioxidant and Antimicrobial Potential of the Bifurcaria bifurcata Epiphytic Bacteria

    PubMed Central

    Horta, André; Pinteus, Susete; Alves, Celso; Fino, Nádia; Silva, Joana; Fernandez, Sara; Rodrigues, Américo; Pedrosa, Rui

    2014-01-01

    Surface-associated marine bacteria are an interesting source of new secondary metabolites. The aim of this study was the isolation and identification of epiphytic bacteria from the marine brown alga, Bifurcaria bifurcata, and the evaluation of the antioxidant and antimicrobial activity of bacteria extracts. The identification of epiphytic bacteria was determined by 16S rRNA gene sequencing. Bacteria extracts were obtained with methanol and dichloromethane (1:1) extraction. The antioxidant activity of extracts was performed by quantification of total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Saccharomyces cerevisiae and Candida albicans. A total of 39 Bifurcaria bifurcata-associated bacteria were isolated and 33 were identified as Vibrio sp. (48.72%), Alteromonas sp. (12.82%), Shewanella sp. (12.26%), Serratia sp. (2.56%), Citricoccus sp. (2.56%), Cellulophaga sp. (2.56%), Ruegeria sp. (2.56%) and Staphylococcus sp. (2.56%). Six (15.38%) of the 39 bacteria Bifurcaria bifurcata-associated bacteria presented less than a 90% Basic Local Alignment Search Tool (BLAST) match, and some of those could be new. The highest antioxidant activity and antimicrobial activity (against B. subtilis) was exhibited by strain 16 (Shewanella sp.). Several strains also presented high antimicrobial activity against S. aureus, mainly belonging to Alteromonas sp. and Vibrio sp. There were no positive results against fungi and Gram-negative bacteria. Bifurcaria bifurcata epiphytic bacteria were revealed to be excellent sources of natural antioxidant and antimicrobial compounds. PMID:24663118

  10. Antioxidant and antimicrobial potential of the Bifurcaria bifurcata epiphytic bacteria.

    PubMed

    Horta, André; Pinteus, Susete; Alves, Celso; Fino, Nádia; Silva, Joana; Fernandez, Sara; Rodrigues, Américo; Pedrosa, Rui

    2014-03-24

    Surface-associated marine bacteria are an interesting source of new secondary metabolites. The aim of this study was the isolation and identification of epiphytic bacteria from the marine brown alga, Bifurcaria bifurcata, and the evaluation of the antioxidant and antimicrobial activity of bacteria extracts. The identification of epiphytic bacteria was determined by 16S rRNA gene sequencing. Bacteria extracts were obtained with methanol and dichloromethane (1:1) extraction. The antioxidant activity of extracts was performed by quantification of total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Saccharomyces cerevisiae and Candida albicans. A total of 39 Bifurcaria bifurcata-associated bacteria were isolated and 33 were identified as Vibrio sp. (48.72%), Alteromonas sp. (12.82%), Shewanella sp. (12.26%), Serratia sp. (2.56%), Citricoccus sp. (2.56%), Cellulophaga sp. (2.56%), Ruegeria sp. (2.56%) and Staphylococcus sp. (2.56%). Six (15.38%) of the 39 bacteria Bifurcaria bifurcata-associated bacteria presented less than a 90% Basic Local Alignment Search Tool (BLAST) match, and some of those could be new. The highest antioxidant activity and antimicrobial activity (against B. subtilis) was exhibited by strain 16 (Shewanella sp.). Several strains also presented high antimicrobial activity against S. aureus, mainly belonging to Alteromonas sp. and Vibrio sp. There were no positive results against fungi and Gram-negative bacteria. Bifurcaria bifurcata epiphytic bacteria were revealed to be excellent sources of natural antioxidant and antimicrobial compounds.

  11. Comprehensive Evaluation of the Antioxidant Potential of Coastal Dune Mushroom Species from the Southwest of France.

    PubMed

    Smolskaite, Lina; Talou, Thierry; Venskutonis, Petras Rimantas

    2016-01-01

    Numerous mushroom species are used as food and for medicinal purposes; however, many species that may contain bioactive compounds remain underinvestigated. In this study, the antioxidant properties of extracts sequentially isolated with cyclohexane, dichloromethane, and methanol from 25 costal dune mushroom species collected in the southwestern region of France were evaluated based on their radical scavenging capacity, ferric-reducing antioxidant power, oxygen radical absorbance capacity, and Folin-Ciocalteu-determined total phenolic content. Overall, the antioxidant potential of dried mushrooms was assessed using integrated antioxidant scores. The highest antioxidant capacity values were demonstrated by the Cortinarius infractus, Agaricus coniferarum, A. menieri, and A. freirei species. These results may foster further studies of the selected mushroom species to valorize their nutritional and medicinal properties.

  12. Ergothioneine Antioxidant Function: From Chemistry to Cardiovascular Therapeutic Potential.

    PubMed

    Servillo, Luigi; DʼOnofrio, Nunzia; Balestrieri, Maria Luisa

    2017-04-01

    Ergothioneine (ESH), the betaine of 2-mercapto-L-histidine, is a water-soluble naturally occurring amino acid with antioxidant properties. ESH accumulates in several human and animal tissues up to millimolar concentration through its high affinity transporter, namely the organic cation transporter 1 (OCTN1). ESH, first isolated from the ergot fungus (Claviceps purpurea), is synthesized only by Actinomycetales and non-yeast-like fungi. Plants absorb ESH via symbiotic associations between their roots and soil fungi, whereas mammals acquire it solely from dietary sources. Numerous evidence demonstrated the antioxidant and cytoprotective effects of ESH, including protection against cardiovascular diseases, chronic inflammatory conditions, ultraviolet radiation damages, and neuronal injuries. Although more than a century after its discovery has gone by, our understanding on the in vivo ESH mechanism is limited and this compound still intrigues researchers. However, recent evidence about differences in chemical redox behavior between ESH and alkylthiols, such as cysteine and glutathione, has opened new perspectives on the role of ESH during oxidative damage. In this short review, we discuss the role of ESH in the complex machinery of the cellular antioxidant defense focusing on the current knowledge on its chemical mechanism of action in the protection against cardiovascular disease.

  13. Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes.

    PubMed

    Omar, Salem A E; Scattergood, Paul A; McKenzie, Luke K; Bryant, Helen E; Weinstein, Julia A; Elliott, Paul I P

    2016-10-18

    The complex [Os(btzpy)₂][PF₆]₂ (1, btzpy = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine) has been prepared and characterised. Complex 1 exhibits phosphorescence (λem = 595 nm, τ = 937 ns, φem = 9.3% in degassed acetonitrile) in contrast to its known ruthenium(II) analogue, which is non-emissive at room temperature. The complex undergoes significant oxygen-dependent quenching of emission with a 43-fold reduction in luminescence intensity between degassed and aerated acetonitrile solutions, indicating its potential to act as a singlet oxygen sensitiser. Complex 1 underwent counterion metathesis to yield [Os(btzpy)₂]Cl₂ (1(Cl)), which shows near identical optical absorption and emission spectra to those of 1. Direct measurement of the yield of singlet oxygen sensitised by 1(Cl) was carried out (φ (¹O₂) = 57%) for air equilibrated acetonitrile solutions. On the basis of these photophysical properties, preliminary cellular uptake and luminescence microscopy imaging studies were conducted. Complex 1(Cl) readily entered the cancer cell lines HeLa and U2OS with mitochondrial staining seen and intense emission allowing for imaging at concentrations as low as 1 μM. Long-term toxicity results indicate low toxicity in HeLa cells with LD50 >100 μM. Osmium(II) complexes based on 1 therefore present an excellent platform for the development of novel theranostic agents for anticancer activity.

  14. A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

    2016-02-01

    Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in

  15. Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice

    PubMed Central

    Kalinovich, A V; Mattsson, C L; Youssef, M R; Petrovic, N; Ost, M; Skulachev, V P; Shabalina, I G

    2016-01-01

    Background: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. Methods: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. Results: In mice, C12TPP (50 μmol per (day•kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. Conclusions: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation. PMID:27534841

  16. Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity.

    PubMed

    Li, Steve Po-Yam; Lau, Chris Tsan-Shing; Louie, Man-Wai; Lam, Yun-Wah; Cheng, Shuk Han; Lo, Kenneth Kam-Wing

    2013-10-01

    We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N(^)C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn) = 5272.23, weight average molecular weight (Mw) = 5317.38, polydispersity index (PDI) = 1.009; HN(^)C = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N(^)C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN(^)C = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generation of singlet oxygen ((1)O2). The quantum yields for (1)O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N(^)C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 μM); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 μM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Antioxidant potential of polyphenols and tannins from burs of Castanea mollissima Blume.

    PubMed

    Zhao, Shan; Liu, Jie Yuan; Chen, Si Yu; Shi, Ling Ling; Liu, Yu Jun; Ma, Chao

    2011-10-12

    Spiny burs of Castanea mollissima Blume (Chinese chestnut) are usually discarded as industrial waste during post-harvesting processing. The objective of this study was to establish an extraction and isolation procedure for tannins from chestnut burs, and to assess their potential antioxidant activity. Aqueous ethanol solution was used as extraction solvent, and HPD 100 macroporous resin column was applied for isolation. The influence of solvent concentration in the extraction and elution process on extraction yield, tannins and polyphenols content, as well as antioxidant potential, including DPPH and ABTS radical scavenging ability, reducing power ability and cellular antioxidant ability were assessed. In both the extraction and isolation process, 50% aqueous ethanol led to superior total tannins and polyphenols content as well as significantly higher antioxidant activity. In addition, the antioxidant activity and the total tannins content in extracts and fractions had a positive linear correlation, and the predominant components responsible for antioxidant activities were characterized as hydrolysable tannins. To the best of our knowledge, this is the first report on the enrichment of tannins from burs of C. mollissim using macroporous resin chromatography, and to assess the cellular antioxidant activity of them.

  18. In vitro Antioxidant and Antilipidperoxidative potential of Pleurotus florida

    PubMed Central

    Selvi, S.; Chinnaswamy, P.

    2007-01-01

    The ethanolic extract of Pleurotus florida was studied for its free radical scavenging property on different in vitro models like 1,1 -diphenyl-picryl hydrazyl (DPPH)Assay, Ferric Reducing Antioxidant Power (FRAP) assay and in vitro antilipidperoxidative assay using goat liver homogenate and RBC Ghost model. The in vitro Lipid peroxidation (LPO) was inhibited to a good extent by the Pleurotus florida ethanolic extract and the extent of inhibition being higher in the RBC membrane model than the liver homogenate model. The mushroom extract showed good dose-dependent free radical scavenging property in both the models. PMID:22557244

  19. Antioxidant potential of green and black tea determined using the ferric reducing power (FRAP) assay.

    PubMed

    Langley-Evans, S C

    2000-05-01

    Tea is one of the most commonly consumed beverages in the world and is rich in polyphenolic compounds collectively known as the tea flavonoids. Tea flavonoids possess antioxidant properties in vitro and have been proposed as key protective dietary components, reducing risk of coronary heart disease and some cancers. The present study aimed to evaluate the possible effects of different preparation methods on the antioxidant properties of green and black tea. Antioxidant potentials of tea infusates were assessed using an assay based upon the reduction of ferric chloride linked to a chromophore. Green tea, black leaf tea and black tea in tea bags were infused with water at 90 degrees C for time periods ranging from 0.25 to 15 min. Green tea infusates possessed approximately 2.5-fold greater antioxidant capacity than both types of black tea infusates. Both green and black teas released significant levels of antioxidants into the hot water within 2 min of infusion. Preparation of teas across a range of temperatures between 20 and 90 degrees C revealed that although antioxidants were liberated from the leaves into the water in cooler infusions, increasing the temperature could increase antioxidant potential by 4 to 9.5-fold. Black tea prepared using tea bags had significantly lower antioxidant capacity than black leaf tea at temperatures between 20 and 70 degrees C, suggesting that tea bag materials may prevent some extraction of flavonoids into the tea solution. The addition of milk appeared to diminish the antioxidant potential of black tea preparations. This effect was greatest where whole cow's milk was used and appeared to be primarily related to the fat content of the added milk. These experiments have considered the effects of commonly used domestic methods of preparation on the in vitro antioxidant potential of tea. It is concluded that maximum antioxidant capacity and hence maximal health benefit may be derived from green tea or from black leaf tea prepared by

  20. Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and antimicrobial agent

    PubMed Central

    Katanic, Jelena; Mihailovic, Vladimir; Stankovic, Nevena; Boroja, Tatjana; Mladenovic, Milan; Solujic, Slavica; Stankovic, Milan S.; Vrvic, Miroslav M.

    2015-01-01

    The aim of this study was to investigate the antioxidant activity of the methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots (FHR) and their potential in different model systems, as well as antimicrobial activity. According to this, a number of assays were employed to evaluate the antioxidant and antimicrobial potential of F. hexapetala extracts. In addition, the antioxidant activity assays in different model systems were carried out, as well as pH, thermal and gastrointestinal stability studies. The phenolic compounds contents in FHA and FHR were also determined. The results showed that F. hexapetala extracts had considerable antioxidant activity in vitro and a great stability in different conditions. The extracts exhibited antimicrobial activity against most of the tested bacterial and fungal species. Also, the extracts contain high level of phenolic compounds, especially aerial parts extract. PMID:26417349

  1. Phytochemical analysis of Andrographis paniculata and Orthosiphon stamineus leaf extracts for their antibacterial and antioxidant potential.

    PubMed

    Malahubban, M; Alimon, A R; Sazili, A Q; Fakurazi, S; Zakry, F A

    2013-09-01

    Leaves of Andrographis paniculata and Orthosiphon stamineus were extracted with water, ethanol, methanol and chloroform to assess their potential as antibacterial and antioxidant agents. High performance liquid chromatography analysis showed that the methanolic extracts of A. paniculata and O. stamineus leaves gave the highest amounts of andrographolide and rosmarinic acid, respectively. These leaf extracts exhibited antimicrobial and antioxidant activities and, at the highest concentration tested (200 mg/mL), showed greater inhibitory effects against the Gram positive bacteria Bacillus cereus and Staphylococcus aureus than 10% acetic acid. Andrographis paniculata and O. stamineus methanolic and ethanolic leaf extracts also showed the strongest antioxidant activity as compared with the other extracts tested. The bioactive compounds present in these leaf extracts have the potential to be developed into natural antibacterial and antioxidant agents that may have applications in animal and human health.

  2. Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports.

    PubMed

    Pingitore, Alessandro; Lima, Giuseppina Pace Pereira; Mastorci, Francesca; Quinones, Alfredo; Iervasi, Giorgio; Vassalle, Cristina

    2015-01-01

    Free radicals are produced during aerobic cellular metabolism and have key roles as regulatory mediators in signaling processes. Oxidative stress reflects an imbalance between production of reactive oxygen species and an adequate antioxidant defense. This adverse condition may lead to cellular and tissue damage of components, and is involved in different physiopathological states, including aging, exercise, inflammatory, cardiovascular and neurodegenerative diseases, and cancer. In particular, the relationship between exercise and oxidative stress is extremely complex, depending on the mode, intensity, and duration of exercise. Regular moderate training appears beneficial for oxidative stress and health. Conversely, acute exercise leads to increased oxidative stress, although this same stimulus is necessary to allow an up-regulation in endogenous antioxidant defenses (hormesis). Supporting endogenous defenses with additional oral antioxidant supplementation may represent a suitable noninvasive tool for preventing or reducing oxidative stress during training. However, excess of exogenous antioxidants may have detrimental effects on health and performance. Whole foods, rather than capsules, contain antioxidants in natural ratios and proportions, which may act in synergy to optimize the antioxidant effect. Thus, an adequate intake of vitamins and minerals through a varied and balanced diet remains the best approach to maintain an optimal antioxidant status. Antioxidant supplementation may be warranted in particular conditions, when athletes are exposed to high oxidative stress or fail to meet dietary antioxidant requirements. Aim of this review is to discuss the evidence on the relationship between exercise and oxidative stress, and the potential effects of dietary strategies in athletes. The differences between diet and exogenous supplementation as well as available tools to estimate effectiveness of antioxidant intake are also reported. Finally, we advocate the need

  3. Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

    PubMed Central

    2015-01-01

    Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

  4. Antimicrobial, antioxidant potential and phytochemical screening of Fagonia olivieri.

    PubMed

    Shad, Anwar Ali; Zakirudin, -; Bakht, Jehan; Jan, Saleem

    2017-05-01

    The present paper investigates antioxidant, antimicrobial and photochemical screening different extracts of Fagonia olivieri. Analysis of the data indicated that the subject plant contained a good amount of flavonoids, tannins, saponins, terpenoids and steroids. Maximum concentrations of phenolic compounds was found in methanol fraction (29.0±6.12 mg GAE/g) while minimum (22.10±6.31mg GAE/g) in methylated spirit fraction. Similarly, ethanol fraction contained higher concentration of flavonoid content (135.4±7.63mg Quercetin/g) followed by methanol fraction (138.4±2.96 mg Quercetin/g). Analysis of the data revealed that maximum antioxidant activity was recorded in mthylated spirit fraction (IC50= 10.69±1.66) followed by methanol fraction (IC50= 9.10±0.76) while no activity was noted in hexane fraction. The data indicated good antibacterial and antifungal activity against S. typhi, S. aureus, P. aeruginosa and A. flavus.

  5. Antioxidant potential of Rumex vesicarius L.: in vitro approach

    PubMed Central

    Khan, Tajdar Husain; Ganaie, Majid Ahmad; Siddiqui, Nasir Ali; Alam, Aftab; Ansari, Mohd Nazam

    2014-01-01

    Objective To assess in-vitro antioxidant activity of different fraction and perform high performance thin layer chromatography fingerprint analysis of most active fraction of Rumex vesicarius L. (R. vesicarius). Methods In the present study, acetone, ethyl acetate, n-butanol, and methanol extracts of R. vesicarius were evaluated for radical scavenging activity by studying the inhibition of the level of lipid peroxidation induced by Fe(++)/ascorbate, DNA sugar damage, scavenging of hydrogen peroxide, diphenylphosphine DPPH radical scavenging activity, total phenolic content, total flavonoids content and total proanthocyanidin. High performance thin layer chromatography finger print profiling of R. vesicarius L. was also done. Results Lipid peroxidation induced by the iron/ascorbate system, hydrogen peroxide, diphenylphosphine and DNA sugar damage were inhibited by the addition of different extract of R. vesicarius. Among them, methanolic extract showed maximum efficacy. The methanolic extract showed the highest total phenolic, total flavonoids and total proanthocyanidin contents. Conclusions The results suggest that the extracts can be a vital source of phytochemical antioxidants. PMID:25183273

  6. In vitro anti-oxidant potential of new metabolites from Hypericum oblongifolium (Guttiferae).

    PubMed

    Raziq, Naila; Saeed, Muhammad; Ali, Muhammad Shaiq; Zafar, Salman; Ali, Muhammad Imran

    2015-01-01

    Phytochemical investigations on Hypericum oblongifolium led to the isolation of a flavone named folicitin (1) and a bicyclic conjugated lactone, folenolide (2) from the ethyl acetate fraction of methanolic extract. Both metabolites were characterised as new compounds based on detailed spectroscopic analyses. In vitro anti-oxidant potential of both the compounds was evaluated by the DPPH radical scavenging assay. Compound 1 exhibited significant antioxidant activity while compound 2 was found inactive.

  7. pH-Responsive de-PEGylated nanoparticles based on triphenylphosphine-quercetin self-assemblies for mitochondria-targeted cancer therapy.

    PubMed

    Xing, Lei; Lyu, Jin-Yuan; Yang, Yue; Cui, Peng-Fei; Gu, Liu-Qing; Qiao, Jian-Bin; He, Yu-Jing; Zhang, Tian-Qi; Sun, Minjie; Lu, Jin-Jian; Xu, Xiaojun; Liu, Yu; Jiang, Hu-Lin

    2017-08-11

    We have developed mitochondria-targeted self-assembled nanoparticles (NPs) based on amphiphilic triphenylphosphine-quercetin (TPP-Que) conjugates, which were further modified by poly(ethylene glycol) via a pH-responsive coordination bond to form TQ-PEG NPs. And it is revealed that the TQ-PEG NPs were more effective therapeutic agents compared with Que in vitro and in vivo.

  8. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats.

    PubMed

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury.

  9. Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA.

    PubMed

    Arndt, Sabine; Baeza-Garza, Carlos D; Logan, Angela; Rosa, Tiziana; Wedmann, Rudolf; Prime, Tracy A; Martin, Jack L; Saeb-Parsy, Kourosh; Krieg, Thomas; Filipovic, Milos R; Hartley, Richard C; Murphy, Michael P

    2017-05-12

    Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA

    PubMed Central

    Arndt, Sabine; Baeza-Garza, Carlos D.; Logan, Angela; Rosa, Tiziana; Wedmann, Rudolf; Prime, Tracy A.; Martin, Jack L.; Saeb-Parsy, Kourosh; Krieg, Thomas; Filipovic, Milos R.; Hartley, Richard C.; Murphy, Michael P.

    2017-01-01

    Hydrogen sulfide (H2S) is produced endogenously in vivo and has multiple effects on signaling pathways and cell function. Mitochondria can be both an H2S source and sink, and many of the biological effects of H2S relate to its interactions with mitochondria. However, the significance of mitochondrial H2S is uncertain, in part due to the difficulty of assessing changes in its concentration in vivo. Although a number of fluorescent H2S probes have been developed these are best suited to cells in culture and cannot be used in vivo. To address this unmet need we have developed a mitochondria-targeted H2S probe, MitoA, which can be used to assess relative changes in mitochondrial H2S levels in vivo. MitoA comprises a lipophilic triphenylphosphonium (TPP) cation coupled to an aryl azide. The TPP cation leads to the accumulation of MitoA inside mitochondria within tissues in vivo. There, the aryl azido group reacts with H2S to form an aryl amine (MitoN). The extent of conversion of MitoA to MitoN thus gives an indication of the levels of mitochondrial H2S in vivo. Both compounds can be detected sensitively by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the tissues, and quantified relative to deuterated internal standards. Here we describe the synthesis and characterization of MitoA and show that it can be used to assess changes in mitochondrial H2S levels in vivo. As a proof of principle we used MitoA to show that H2S levels increase in vivo during myocardial ischemia. PMID:28320864

  11. Antioxidant Potential of the Polyherbal Formulation "ImmuPlus": A Nutritional Supplement for Horses.

    PubMed

    Cecchini, Stefano; Paciolla, Mariateresa; Caputo, Anna Rocchina; Bavoso, Alfonso

    2014-01-01

    In order to counteract harmful effects of oxidative stress due to pathological conditions or physical exercise, horses are often administered dietary supplements having supposed high antioxidant activities. The aim of the present study was to identify the in vitro antioxidant potential of "ImmuPlus", a polyherbal formulation (Global Herbs LTD, Chichester, West Sussex, Great Britain), containing three medicinal plants (Withania somnifera, Tinospora cordifolia, and Emblica officinalis), known in Ayurveda for their use in human disease treatment. Extracts obtained by different solvents (water, methanol, ethanol, acetone, and hexane) were tested for total antioxidant capacity, total reducing power, scavenging activity against DPPH radical, and total polyphenol and flavonoid contents. Our results showed that, except as regards hexane, all the used solvents are able to extract compounds having high antioxidant activity, even when compared to ascorbic acid. Regression analysis showed significant correlations between antioxidant properties and polyphenol/flavonoid contents, indicating the latter, known for their beneficial effects on health of human and animal beings, as major components responsible for the strong antioxidant capacities. Moreover, obtained results suggest the effective role of the polyherbal mixture as good source of antioxidants in horses.

  12. Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects.

    PubMed

    Guo, Changjiang; Wei, Jingyu; Yang, Jijun; Xu, Jing; Pang, Wei; Jiang, Yugang

    2008-02-01

    In the present study, 26 elderly subjects were recruited and randomly divided into 2 groups, that is, apple (low in antioxidant capacity) and pomegranate (high in antioxidant capacity) groups, and 250 mL of juice was consumed daily for 4 weeks. Changes in plasma antioxidant capacity, activity of antioxidant enzymes, contents of ascorbic acid, vitamin E, reduced glutathione, malondialdehyde, oxidized low-density lipoprotein and carbonyls, and the degree of DNA damage in mononuclear blood cells were measured. Urine samples were collected for determination of 8-hydroxy-2'-deoxyguanosine content. Increased plasma antioxidant capacity and decreased plasma carbonyl content were demonstrated after daily consumption of pomegranate juice. In comparison, apple juice consumption presented a less significant effect on antioxidant function in elderly subjects. It is concluded that daily consumption of pomegranate juices is potentially better than apple juice in improving antioxidant function in the elderly. Because the plasma ascorbic acid, vitamin E, and reduced glutathione contents did not differ significantly between the 2 groups in this study, the phenolics may be the functional components contained in pomegranate juice that accounted for the observations.

  13. Acidic Potassium Permanganate Chemiluminescence for the Determination of Antioxidant Potential in Three Cultivars of Ocimum basilicum.

    PubMed

    Srivastava, Shivani; Adholeya, Alok; Conlan, Xavier A; Cahill, David M

    2016-03-01

    Ocimum basilicum, a member of the family Lamiaceae, is a rich source of polyphenolics that have antioxidant properties. The present study describes the development and application of an online HPLC-coupled acidic potassium permanganate chemiluminescence assay for the qualitative and quantitative assessment of antioxidants in three cultivars of O. basilicum grown under greenhouse conditions. The chemiluminescence based assay was found to be a sensitive and efficient method for assessment of total and individual compound antioxidant potential. Leaves, flowers and roots were found to be rich reserves of the antioxidant compounds which showed intense chemiluminescence signals. The polyphenolics such as rosmarinic, chicoric, caffeic, p-coumaric, m-coumaric and ferulic acids showed antioxidant activity. Further, rosmarinic acid was found to be the major antioxidant component in water-ethanol extracts. The highest levels of rosmarinic acid was found in the leaves and roots of cultivars "holy green" (14.37; 11.52 mM/100 g DW respectively) followed by "red rubin" (10.02; 10.75 mM/100 g DW respectively) and "subja" (6.59; 4.97 mM/100 g DW respectively). The sensitivity, efficiency and ease of use of the chemiluminescence based assay should now be considered for its use as a primary method for the identification and quantification of antioxidants in plant extracts.

  14. Antimutagenic and antioxidant potentials of Teucrium ramosissimum essential oil.

    PubMed

    Sghaier, Mohamed Ben; Boubaker, Jihed; Neffati, Aicha; Limem, Ilef; Skandrani, Ines; Bhouri, Wissem; Bouhlel, Ines; Kilani, Soumaya; Chekir-Ghedira, Leila; Ghedira, Kamel

    2010-07-01

    The mutagenic and antimutagenic effects of the essential oil extracted from the aerial parts of Teucrium ramosissimum were evaluated by the bacterial reverse mutation assay in Salmonella typhimurium TA98, TA100, and TA1535, with and without exogenous metabolic activation (S9 fraction). The T. ramosissimum essential oil showed no mutagenic effect. In contrast, our results established that it possessed antimutagenic effects against sodium azide (SA), aflatoxin B1 (AFB1), benzo[a]pyrene (B[a]P), and 4-nitro-o-phenylenediamine (NOPD). The antioxidant capacity of the tested essential oil was evaluated using enzymatic, i.e., the xanthine/xanthine oxidase (X/XOD) assay, and nonenzymatic systems, i.e., the nitro-blue tetrazolium (NBT)/riboflavin and the DPPH assays. A moderate free radical-scavenging activity was observed towards DPPH(.) and O2(.-). In contrast, T. ramosissimum essential oil showed no effect for all the tested concentrations in the X/XOD assay.

  15. ANTIOXIDANT POTENTIAL OF Sida retusa, Urena lobata AND Triumfetta rhomboidea.

    PubMed

    Lissy, K P; Simon, Thara K; Lathab, M S

    2006-01-01

    The methanolic extract of Sida retusa Linn.(Malvaceae),Urena lobata Linn.(Malvaceae)and Triumfetta rhomboidea Jacq.(Teliaceae) roots were found to inhibit lipid peroxidation, scavenge hydroxyl and superoxide radicals in vitro. The quantity of S.retusa root extract required for 50% inhibition of lipid peroxidation, scavenging hydroxyl radical and superoxide radical was 1130.24 ug/ml respectively. IC 50 of root extract of U.lobata was 470.60 ug/ml, 1627.35ug/ml and 1109.24 ug/ml for superoxide radical scavenging, hydroxyl radical scavenging and lipid peroxidation respectively. T.rhomboidea root extract required for IC 50 was 336.65 ug/ml, 1346.03 ug/ml and 1004.22 ug/ml for superoxide scavenging, hydroxyl radical scavenging and lipid peroxidation respectively. The present investigation indicated that S. retusa, U.lobata and T.rhomboidea possessed significant antioxidant activity.

  16. Antiglycation, antioxidant and toxicological potential of polyphenol extracts of alligator pepper, ginger and nutmeg from Nigeria

    PubMed Central

    Kazeem, MI; Akanji, MA; Hafizur, Rahman M; Choudhary, MI

    2012-01-01

    Objective To evaluate the antioxidant and antiglycation potential of polyphenols from three spices; alligator pepper, ginger and nutmeg. Methods Polyphenol extracts of these spices were subjected to brine-shrimp lethality assay, phytotoxicity test, DPPH and superoxide anion radical scavenging as well as BSA-glucose antiglycation assay. Results Results obtained showed that polyphenol extract of ginger has the highest antioxidant potential with IC50 0.075 and 0.070 mg/mL for DPPH and superoxide anion radical scavenging assay while alligator pepper displayed highest antiglycation activity with IC50 0.125 mg/mL. However, nutmeg extract exhibited weakest cytotoxic and phytotoxic potential with LD50 4359.70 and 1490 µg/mL respectively. Conclusions It can be concluded that the polyphenol extracts of alligator pepper, ginger and nutmeg displayed good antioxidant as well as antiglycation potential and are safe for consumption. PMID:23570003

  17. Antiglycation, antioxidant and toxicological potential of polyphenol extracts of alligator pepper, ginger and nutmeg from Nigeria.

    PubMed

    Kazeem, M I; Akanji, M A; Hafizur, Rahman M; Choudhary, M I

    2012-09-01

    To evaluate the antioxidant and antiglycation potential of polyphenols from three spices; alligator pepper, ginger and nutmeg. Polyphenol extracts of these spices were subjected to brine-shrimp lethality assay, phytotoxicity test, DPPH and superoxide anion radical scavenging as well as BSA-glucose antiglycation assay. Results obtained showed that polyphenol extract of ginger has the highest antioxidant potential with IC50 0.075 and 0.070 mg/mL for DPPH and superoxide anion radical scavenging assay while alligator pepper displayed highest antiglycation activity with IC50 0.125 mg/mL. However, nutmeg extract exhibited weakest cytotoxic and phytotoxic potential with LD50 4359.70 and 1490 µg/mL respectively. It can be concluded that the polyphenol extracts of alligator pepper, ginger and nutmeg displayed good antioxidant as well as antiglycation potential and are safe for consumption.

  18. Evaluation of antioxidant activity, sugar composition, and flow packaging potential for california dried and fresh figs

    USDA-ARS?s Scientific Manuscript database

    Potential sensory perception and antioxidant capacity varied among these 20 cultivars tested that included dry and fresh traditional and recently introduced potentially dry or fresh varieties. Fructose, sweetness power and total phenolics levels were similar between the new introductions varieties a...

  19. Antioxidative and antiinflammatory potential of different functional drink concepts in vitro.

    PubMed

    Dartsch, Peter C; Kler, Adolf; Kriesl, Erwin

    2009-02-01

    The present study was undertaken to investigate the antioxidative effects of three different functional drink concepts especially designed to improve the body's performance and function and to possess high antioxidant activities. The concepts based on the mixture of various plant ingredients were: (1) eQ - equalize your nutrient balance, brain line [acerola-dragon fruit], (2) eQ - equalize your nutrient balance, beauty line [honey-pepper] and (3) Let's get red [intense]. By using a cell-based test assay, the study investigated the potential of the functional drinks to inactivate reactive superoxide anion radicals generated by inflammation-mediating cells as well as the effect on basal metabolism of these cells (antioxidant and antiinflammatory potential). In addition, by using a cell-free test assay the potential of the drinks to inactivate free exogenous superoxide anion radicals (scavenger effect) was investigated. The data presented here demonstrate the different radical scavenging, antioxidant and anti-inflammatory potential of the functional drink concepts. In particular Let's get red [intense] turned out to be the most potent drink in this respect and demonstrated marked efficacy in scavenging, antioxidant and antiinflammatory action.

  20. Cherry juice targets antioxidant potential and pain relief.

    PubMed

    Kuehl, Kerry S

    2012-01-01

    Strenuous physical activity increases the risk of musculoskeletal injury and can induce muscle damage resulting in acute inflammation and decreased performance. The human body's natural response to injury results in inflammation-induced pain, swelling, and erythema. Among sports medicine physicians and athletic trainers, the mainstays of urgent treatment of soft tissue injury are rest, ice, compression, and elevation (RICE). In order to reduce pain and inflammation, anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) act on the multiple inflammatory pathways, which, although often very effective, can have undesirable side effects such as gastric ulceration and, infrequently, myocardial infarction and stroke. For centuries, natural anti-inflammatory compounds have been used to mediate the inflammatory process and often with fewer side effects. Tart cherries appear to possess similar effectiveness in treating the inflammatory reaction seen in both acute and chronic pain syndromes encountered among athletes and non-athletes with chronic inflammatory disease. This article reviews the antioxidant and anti-inflammatory effects of tart cherries on prevention, treatment, and recovery of soft tissue injury and pain.

  1. Antioxidant potential of evening primrose oil administration in hyperlipemic rabbits.

    PubMed

    De La Cruz, J P; Quintero, L; Galvez, J; Villalobos, M A; Sánchez de la Cuesta, F

    1999-01-01

    The dietary intake of saturated fatty acids affects arteriosclerosis. We studied the effect of supplementation (15% wt/wt) of a hyperlipemic diet (1.33% cholesterol) with evening primrose oil (EPO) (Oenothera biennis) for 6 weeks in four groups of 10 rabbits each. At the end of this period we determined lipid peroxidation, glutathione content, and glutathione peroxidase, reductase and transferase activities in liver, brain, heart, aorta and platelets. The atherogenic diet increased tissue lipid peroxidation and decreased the protective antioxidant effect of glutathione. Dietary supplementation with EPO reduced tissue lipid peroxidation (61% in liver, 57% in brain, 42% in heart, 24% in aorta, 33% in platelets). Total glutathione was increased, especially in the aorta (90%) and platelets (200%); however, in all tissues the percentage of oxidised glutathione decreased. Evening primrose oil reduced glutathione peroxidase activity and increased the activities of glutathione reductase and transferase. We conclude that in rabbits made hyperlipemic with a diet rich in saturated fatty acids, EPO decreased tissue oxidative stress.

  2. Mitochondria-targeted esculetin inhibits PAI-1 levels by modulating STAT3 activation and miR-19b via SIRT3: Role in acute coronary artery syndrome.

    PubMed

    Katta, Sujana; Karnewar, Santosh; Panuganti, Devayani; Jerald, Mahesh Kumar; Sastry, B K S; Kotamraju, Srigiridhar

    2018-01-01

    In this study we explored the microRNAs responsible for the regulation of PAI-1 during LPS-stimulated inflammation in human aortic endothelial cells and subsequently studied the effect of a newly synthesized mitochondria-targeted esculetin (Mito-Esc) that was shown for its anti-atherosclerotic potential, in modulating PAI-1 levels and its targeted miRs during angiotensin-II-induced atherosclerosis in ApoE(-/-) mice. LPS-stimulated PAI-1 was accompanied with an upregulation of miR-19b and down-regulation of miR-30c. These effects of LPS on PAI-1 were reversed in the presence of both parent esculetin and Mito-Esc. However, the effect of Mito-Esc was more pronounced in the regulation of PAI-1. In addition, LPS-stimulated PAI-1 expression was significantly decreased in cells treated with Anti-miR-19b, thereby suggesting that miR-19b co-expression plays a key role in PAI-1 regulation. The results also show that incubation of cells with Stattic, an inhibitor of STAT-3, inhibited LPS-stimulated PAI-1 expression. Interestingly, knockdown of SIRT3, a mitochondrial biogenetic marker, enhanced PAI-1 levels via modulation of miR-19b and -30c. Mito-Esc treatment significantly inhibited Ang-II-induced PAI-1, possibly via altering miR-19b and 30c in ApoE(-/-) mice. The association between PAI-1, miR-19b and -30c were further confirmed in plasma and microparticles isolated from patients suffering from acute coronary syndrome of various degrees. Taken together, LPS-induced PAI-1 involves co-expression of miR-19b and down regulation of miR-30c, and Mito-Esc treatment by modulating miR-19b and miR-30c through SIRT3 activation, inhibits PAI-1 levels that, in part, contribute to its anti-atherosclerotic effects. Moreover, there exists a strong positive correlation between miR-19b and PAI-1 in patients suffering from ST-elevated myocardial infarction. © 2017 Wiley Periodicals, Inc.

  3. Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells.

    PubMed

    Kim, Seok-Jo; Cheresh, Paul; Williams, David; Cheng, Yuan; Ridge, Karen; Schumacker, Paul T; Weitzman, Sigmund; Bohr, Vilhelm A; Kamp, David W

    2014-02-28

    Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5-25 μg/cm(2)) or H2O2 (100-250 μM)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317-323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1(-/-) mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity.

  4. Potential antioxidant and lipid peroxidation inhibition of Phyllanthus acidus leaf extract in minced pork.

    PubMed

    Nguyen, Tuyen Thi Kim; Laosinwattana, Chamroon; Teerarak, Montinee; Pilasombut, Komkhae

    2017-09-01

    This study investigated the effect of extraction solvents on antioxidant bio-active compounds as well as potential antioxidant and lipid peroxidation inhibition of Phyllanthus acidus (P. acidus) leaf extract in minced pork. The effect of various solvent systems of water, 25%, 50%, 75% (v/v) ethanol in water and absolute ethanol on the extraction crude yield, total phenolic content, total flavonoid content and in vitro antioxidant activities of P. acidus leaves was determined. In addition, antioxidant activities of the addition of crude extract from P. aciuds leaves at 2.5 and 5 g/kg in minced pork on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation decolorization, reducing power and inhibition of lipid peroxidation (thiobarbituric acid reactive substances; TBARS) were determined. Moreover, sensory evaluation of the samples was undertaken by using a 7-point hedonic scale. The results showed that the highest crude yield (2.8 g/100 g dry weight) was obtained from water which also had the highest recovery yield for total phenolic content, total flavonoid content and the strongest antioxidant activity. The addition of crude water extract from P. acidus leaves was more effective in retarding lipid peroxidation and higher antioxidant activity than control and butylated hydroxytoluene in minced pork. In particular, the samples containing P. acidus extract had no significant effect on the sensory scores of overall appearance, color, odor, texture, flavor, and overall acceptability compared to the control. Water solvent was an optimally appropriate solvent for P. acidus leaf extraction because of its ability to yield the highest amount of bio-active compounds and in vitro antioxidant property. Particularly, P. acidus crude water extract also strongly expressed the capacity to retard lipid oxidation, radical scavenging, radical cation decolorization and reducing power in

  5. Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from alpha-phenyl-N-tert-butylnitrone.

    PubMed

    Murphy, Michael P; Echtay, Karim S; Blaikie, Frances H; Asin-Cayuela, Jordi; Cocheme, Helena M; Green, Katherine; Buckingham, Julie A; Taylor, Ellen R; Hurrell, Fiona; Hughes, Gillian; Miwa, Satomi; Cooper, Christopher E; Svistunenko, Dimitri A; Smith, Robin A J; Brand, Martin D

    2003-12-05

    Although the physiological role of uncoupling proteins (UCPs) 2 and 3 is uncertain, their activation by superoxide and by lipid peroxidation products suggest that UCPs are central to the mitochondrial response to reactive oxygen species. We examined whether superoxide and lipid peroxidation products such as 4-hydroxy-2-trans-nonenal act independently to activate UCPs, or if they share a common pathway, perhaps by superoxide exposure leading to the formation of lipid peroxidation products. This possibility can be tested by blocking the putative reactive oxygen species cascade with selective antioxidants and then reactivating UCPs with distal cascade components. We synthesized a mitochondria-targeted derivative of the spin trap alpha-phenyl-N-tert-butylnitrone, which reacts rapidly with carbon-centered radicals but is unreactive with superoxide and lipid peroxidation products. [4-[4-[[(1,1-Dimethylethyl)-oxidoimino]methyl]phenoxy]butyl]triphenylphosphonium bromide (MitoPBN) prevented the activation of UCPs by superoxide but did not block activation by hydroxynonenal. This was not due to MitoPBN reacting with superoxide or the hydroxyl radical or by acting as a chain-breaking antioxidant. MitoPBN did react with carbon-centered radicals and also prevented lipid peroxidation by the carbon-centered radical generator 2,2'-azobis(2-methyl propionamidine) dihydrochloride (AAPH). Furthermore, AAPH activated UCPs, and this was blocked by MitoPBN. These data suggest that superoxide and lipid peroxidation products share a common pathway for the activation of UCPs. Superoxide releases iron from iron-sulfur center proteins, which then generates carbon-centered radicals that initiate lipid peroxidation, yielding breakdown products that activate UCPs.

  6. [ANTIOXIDANT POTENTIAL OF MELIPONA BEECHEII HONEY AND ITS RELATIONSHIP TO HEALTH: A REVIEW].

    PubMed

    Cauich Kumul, Roger; Ruiz Ruiz, Jorge Carlos; Ortíz Vázquez, Elizabeth; Segura Campos, Maira Rubi

    2015-10-01

    The present article provides a literature review about the biological potential of Melipona beecheii. The objective is to project some tendecies in research about nutraceutical aspects related to the bioactive compounds presents in the honey of this stingless bee species, known for its medicinal properties traditional, in the Yucatan Peninsula. Currently, there is strong evidence that M. beecheii honey has bioactive compounds such as proteins, flavonoids and polyphenols with high antioxidant activity. The scientific evidence allows to propose to the honey of stingless bee species as a potential alternative for the obtention of bioactive compounds with antioxidant activity in the Yucatan Peninsula and natural food being proposed to reduce some diseases associated with stress oxidative physiological human cells. However, there is still information that explains such antioxidant activity, therefore, according to the literature reviewed, sees the need to address nutraceuticals and functional aspects correlated with the bioactive compounds present in this honey bee.

  7. Phenolic Extracts from Wild Olive Leaves and Their Potential as Edible Oils Antioxidants

    PubMed Central

    Lafka, Theodora-Ioanna; Lazou, Andriana E.; Sinanoglou, Vassilia J.; Lazos, Evangelos S.

    2013-01-01

    The kinetics solid-liquid extraction of phenolics from wild olive leaves was elaborated using different mathematical models (Peleg, second order, Elovich, and power law model). As solvents, methanol, ethanol, ethanol:water 1:1, n-propanol, isopropanol and ethyl acetate were used. The second order model best described the solvent extraction process, followed by the Elovich model. The most effective solvent was ethanol with optimum phenol extraction conditions 180 min, solvent to sample ratio 5:1 v/w and pH 2. Ethanol extract exhibited the highest antiradical activity among solvent and supercritical fluid extraction (SFE) extracts, which in addition showed the highest antioxidant capacity compared to synthetic and natural food antioxidants such as BHT, ascorbyl palmitate and vitamin E. Antioxidant potential of SFE extract was quite high, although its phenolic potential was not. Leaf extracts were proven to be good protectors for olive and sunflower oils at levels of 150 ppm. PMID:28239093

  8. Effect of polymerization on antioxidant and xanthine oxidase inhibitory potential of sea buckthorn (H. rhamnoides) proanthocyanidins.

    PubMed

    Arimboor, Ranjith; Arumughan, C

    2012-10-01

    Inhibitory potential of sea buckthorn (Hippophae rhamnoides L) seed proanthocyanidins against oxidative stress and xanthine oxidase activity was evaluated. Composition of antioxidant proanthocyanidins was profiled by analyzing the cleavage products obtained by the acid catalyzed hydrolysis in the presence of phloroglucinol. Catechin, epicatechin, gallocatechin, and epigallocatechin were found as the extension and terminal subunits of proanthocyanidins with an average degree of polymerization (ADP) of 14.7. Seed proanthocyanidins showed considerably high antioxidant and xanthine oxidase inhibitory potentials. Antioxidant and xanthine oxidase inhibitory capacity evaluation of proanthocyanidin fractions with varying ADP showed that proanthocyanidins with lower molecular size were more effective as superoxide anion (ADP ≤ 4.2) and hydroxyl radical (ADP ≤ 5.9) scavengers and xanthine oxidase (ADP ≤ 3.1) inhibitors. ADP of the studied proanthocyanidin fractions did not show significant influence on their DPPH and ABTS radical scavenging and ferric reduction capacities.

  9. In vivo Raman spectroscopy detects increased epidermal antioxidative potential with topically applied carotenoids

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Caspers, P. J.; van der Pol, A.; Richter, H.; Patzelt, A.; Zastrow, L.; Darvin, M.; Sterry, W.; Fluhr, J. W.

    2009-01-01

    In the present study, the distribution of the carotenoids as a marker for the complete antioxidative potential in human skin was investigated before and after the topical application of carotenoids by in vivo Raman spectroscopy with an excitation wavelength of 785 nm. The carotenoid profile was assessed after a short term topical application in 4 healthy volunteers. In the untreated skin, the highest concentration of natural carotenoids was detected in different layers of the stratum corneum (SC) close to the skin surface. After topical application of carotenoids, an increase in the antioxidative potential in the skin could be observed. Topically applied carotenoids penetrate deep into the epidermis down to approximately 24 μm. This study supports the hypothesis that antioxidative substances are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Subsequently they penetrate into the different layers of the SC.

  10. Potentiating effects of honey on antioxidant properties of lemon-flavoured black tea.

    PubMed

    Pereira, Carla; Barros, Lillian; Vilas-Boas, Miguel; Ferreira, Isabel C F R

    2013-03-01

    Health benefits including antioxidant potential of black tea (Camellia sinensis), lemon (Citrus limon) and honey bees (Apis mellifera) have been extensively reported. Nevertheless, nothing is reported about the effects of their concomitant use. Herein, those effects were evaluated in infusions of lemon-flavoured black tea with three different kinds of honey (light amber, amber and dark amber) from Lavandula stoechas, Erica sp. pl. and other indigenous floral species from north-east Portugal, a region with high amounts of this food product. Data obtained showed that the use of honey (dark amber>amber>light amber) potentiates the antioxidant activity of lemon-flavoured black tea, increasing the reducing power and lipid peroxidation inhibition properties, as also the antioxidant contents such as phenolics, flavonoids and organic acids including ascorbic acid.

  11. Antioxidant potential in non-extractable fractions of dried persimmon (Diospyros kaki Thunb.).

    PubMed

    Matsumura, Yoko; Ito, Toshihiro; Yano, Hisakazu; Kita, Eiji; Mikasa, Keiichi; Okada, Masatoshi; Furutani, Azusa; Murono, Yuka; Shibata, Mitsuru; Nishii, Yasue; Kayano, Shin-Ichi

    2016-07-01

    Dried fruits of persimmon (Diospyros kaki Thunb.) are a traditional food in Japan and contain large quantities of tannins. In this study, we investigated the in vitro and in vivo antioxidant potentials of non-extractable fractions from dried persimmons. Hydrolysed non-extractable fractions showed the highest antioxidant activities in vitro. In subsequent experiments, the plasma oxygen radical absorbance capacity (ORAC) values in rats supplemented with a 5% non-extractable fraction were approximately 1.5times higher than those in control rats after 1week in vivo. Furthermore, using an in vitro model of the gastrointestinal tract, the ORAC values of the non-extractable fraction were significantly increased with colonic fermentation in the large bowel stage. These data indicate that non-extractable fractions may possess significant antioxidant potential in vitro and in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Characterization of polyphenols and antioxidant potential of white grape pomace byproducts (Vitis vinifera L.).

    PubMed

    González-Centeno, María Reyes; Jourdes, Michael; Femenia, Antoni; Simal, Susana; Rosselló, Carmen; Teissedre, Pierre-Louis

    2013-11-27

    A detailed assessment of the total phenolic and total tannin contents, the monomeric and oligomeric flavan-3-ol composition, the proanthocyanidin profile, and the antioxidant potential of the grape pomace byproducts (considered as a whole, both skins and seeds), derived from four white grape varieties (Vitis vinifera L.), was performed. Significant differences (p < 0.05) of the total phenolic content, total tannin content, and antioxidant capacity of grape pomace byproducts were observed among the different grape varieties studied. For the first time in the literature, the particular flavan-3-ol composition of the four grape varieties investigated was described for the whole fraction of their grape pomace byproducts. The phenolic composition and antioxidant capacity of grape pomaces were compared to those of their corresponding stems. The global characterization of these white grape varieties provided a basis for an integrated exploitation of both winemaking byproducts as potential, inexpensive, and easily available sources of bioactive compounds for the pharmaceutical, cosmetic, and food industries.

  13. In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions: potential role of antioxidants.

    PubMed

    Courraud, J; Charnay, C; Cristol, J P; Berger, J; Avallone, S

    2013-12-01

    Over the last decades, oxidative stress has been described as a deleterious phenomenon contributing to numerous noncommunicable diseases such as cardiovascular disease, diabetes, and cancers. As many authors ascribed the healthy effect of fruit and vegetable consumption mainly to their antioxidant contents, it has been hypothesized that their protection could occur from the gut. Therefore, the aim of this study was to develop an original and physiological model of nanoemulsions to study lipid peroxidation within the intestine and to assess the properties of potential antioxidants in this setting. Several nanoemulsions were compared in terms of physical characteristics and reactivity to 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced oxidation. Formulations included different types of lipids, a detergent (a conjugated bile salt or sodium dodecyl sulfate) and, finally, lipophilic antioxidants. Hemin and myoglobin were also tested as relevant potential oxidants. Fatty acid (FA) peroxidation was monitored by gas chromatography while malondialdehyde and antioxidant contents were measured by HPLC. Investigated nanoemulsions were composed of spherical or cylindrical mixed micelles, the latter being the least resistant to oxidation. In the experimental conditions, AAPH was the only efficient oxidant. Alpha-tocopherol and lutein significantly slowed FA degradation from 4 to 1 μM, respectively. On the contrary, beta-carotene did not show any protective capacity at 4 μM. In conclusion, the tested nanoemulsions were appropriate to assess antioxidant capacity during the intestinal phase of digestion.

  14. Production, characterization and antioxidant potential of protease from Streptomyces sp. MAB18 using poultry wastes.

    PubMed

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2013-01-01

    Poultry waste is an abundant renewable source for the recovery of several value-added metabolites with potential industrial applications. This study describes the production of protease on poultry waste, with the subsequent use of the same poultry waste for the extraction of antioxidants. An extracellular protease-producing strain was isolated from Cuddalore coast, India, and identified as Streptomyces sp. MAB18. Its protease was purified 17.13-fold with 21.62% yield with a specific activity of 2398.36 U/mg and the molecular weight was estimated as 43 kDa. The enzyme was optimally active at pH 8-10 and temperature 50-60 ° C and it was most stable up to pH 12 and 6-12% of NaCl concentration. The enzyme activity was reduced when treated with Hg(2+), Pb(2+), and SDS and stimulated by Fe(2+), Mg(2+), Triton X-100, DMSO (dimethyl sulfoxide), sodium sulphite, and β-mercaptoethanol. Furthermore, the antioxidant activities of protease were evaluated using in vitro antioxidant assays, such as DPPH radical-scavenging activity, O2 scavenging activity, NO scavenging activity, Fe(2+) chelating activity, and reducing power. The enzyme showed important antioxidant potential with an IC50 value of 78 ± 0.28 mg/mL. Results of the present study indicate that the poultry waste-derived protease may be useful as supplementary protein and antioxidant in the animal feed formulations.

  15. Antioxidant Potential of a Polyherbal Antimalarial as an Indicator of Its Therapeutic Value

    PubMed Central

    Arrey Tarkang, Protus; Nwachiban Atchan, Achille Parfait; Kuiate, Jules-Roger; Okalebo, Faith Apoelot; Guantai, Anastasia Nkatha; Agbor, Gabriel Agbor

    2013-01-01

    Nefang is a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts, in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and ferric reducing antioxidant power (FRAP) methods and, in vivo, Nefang (100 and 500 mg kg−1) activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out. P. guajava, M. indica leaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P < 0.05) and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated with Nefang showed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants of Nefang that contribute to its in vivo antioxidant potential. This activity is a good indication of the therapeutic potential of Nefang. PMID:24454347

  16. Antioxidant potential of a polyherbal antimalarial as an indicator of its therapeutic value.

    PubMed

    Arrey Tarkang, Protus; Nwachiban Atchan, Achille Parfait; Kuiate, Jules-Roger; Okalebo, Faith Apoelot; Guantai, Anastasia Nkatha; Agbor, Gabriel Agbor

    2013-01-01

    Nefang is a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts, in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and ferric reducing antioxidant power (FRAP) methods and, in vivo, Nefang (100 and 500 mg kg(-1)) activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out. P. guajava, M. indica leaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P < 0.05) and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated with Nefang showed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants of Nefang that contribute to its in vivo antioxidant potential. This activity is a good indication of the therapeutic potential of Nefang.

  17. Amauroderma rugosum (Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties

    PubMed Central

    Chan, Pui-Mun; Kanagasabapathy, Gowri; Tan, Yee-Shin; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Amauroderma rugosum is a wild mushroom that is worn as a necklace by the indigenous communities in Malaysia to prevent fits and incessant crying by babies. The aim of this study was to investigate the nutritive composition and antioxidant potential and anti-inflammatory effects of A. rugosum extracts on LPS-stimulated RAW264.7 cells. Nutritional analysis of freeze-dried mycelia of A. rugosum (KUM 61131) from submerged culture indicated a predominant presence of carbohydrates, proteins, dietary fibre, phosphorus, potassium, and sodium. The ethanol crude extract (EE), its hexane (HF), ethyl acetate (EAF), and aqueous (AF) fractions of mycelia of A. rugosum grown in submerged culture were evaluated for antioxidant potential and anti-inflammatory effects. EAF exhibited the highest total phenolic content and the strongest antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. HF showed dose-dependent inhibition of NO production in LPS-stimulated RAW264.7 cells and NO radical scavenging activity. Gas chromatographic analysis of HF revealed the presence of ethyl linoleate and ergosterol, compounds with known anti-inflammatory properties. In conclusion, the nutritive compositions and significant antioxidant potential and anti-inflammatory effects of mycelia extracts of A. rugosum have the potential to serve as a therapeutic agent or adjuvant in the management of inflammatory disorders. PMID:24371454

  18. Amauroderma rugosum (Blume & T. Nees) Torrend: Nutritional Composition and Antioxidant and Potential Anti-Inflammatory Properties.

    PubMed

    Chan, Pui-Mun; Kanagasabapathy, Gowri; Tan, Yee-Shin; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Amauroderma rugosum is a wild mushroom that is worn as a necklace by the indigenous communities in Malaysia to prevent fits and incessant crying by babies. The aim of this study was to investigate the nutritive composition and antioxidant potential and anti-inflammatory effects of A. rugosum extracts on LPS-stimulated RAW264.7 cells. Nutritional analysis of freeze-dried mycelia of A. rugosum (KUM 61131) from submerged culture indicated a predominant presence of carbohydrates, proteins, dietary fibre, phosphorus, potassium, and sodium. The ethanol crude extract (EE), its hexane (HF), ethyl acetate (EAF), and aqueous (AF) fractions of mycelia of A. rugosum grown in submerged culture were evaluated for antioxidant potential and anti-inflammatory effects. EAF exhibited the highest total phenolic content and the strongest antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. HF showed dose-dependent inhibition of NO production in LPS-stimulated RAW264.7 cells and NO radical scavenging activity. Gas chromatographic analysis of HF revealed the presence of ethyl linoleate and ergosterol, compounds with known anti-inflammatory properties. In conclusion, the nutritive compositions and significant antioxidant potential and anti-inflammatory effects of mycelia extracts of A. rugosum have the potential to serve as a therapeutic agent or adjuvant in the management of inflammatory disorders.

  19. Anticancer potential of aloes: antioxidant, antiproliferative, and immunostimulatory attributes.

    PubMed

    Harlev, Eli; Nevo, Eviatar; Lansky, Ephraim P; Ofir, Rivka; Bishayee, Anupam

    2012-06-01

    Aloe is a genus of medicinal plants with a notable history of medical use. Basic research over the past couple of decades has begun to reveal the extent of Aloe's pharmaceutical potential, particularly against neoplastic disease. This review looks at Aloe, both the genus and the folk medicine, often being called informally "aloes", and delineates their chemistry and anticancer pharmacognosy. Structures of key compounds are provided, and their pharmacological activities reviewed. Particular attention is given to their free radical scavenging, antiproliferative, and immunostimulatory properties. This review highlights major research directions on aloes, reflecting the enormous potential of natural sources, and of the genus Aloe in particular, in preventing and treating cancer. Georg Thieme Verlag KG Stuttgart · New York.

  20. Cardioprotective Effects of Mitochondria-Targeted Peptide SBT-20 in two Different Models of Rat Ischemia/Reperfusion.

    PubMed

    Dai, Wangde; Cheung, Elissa; Alleman, Rick J; Perry, Justin B; Allen, Mitchell E; Brown, David A; Kloner, Robert A

    2016-12-01

    Dysfunctional mitochondria are considered to be the major source of intracellular reactive oxygen species and play a central role in the pathophysiology of myocardial ischemia/reperfusion. This study sought to determine effects of mitochondria-targeted cytoprotective peptide SBT-20 on myocardial infarct size in two different models of ischemia/reperfusion. For in vivo studies, anesthetized Sprague Dawley rats were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rats received saline (control), low dose SBT-20 (0.3 mg/kg/h) or high dose SBT-20 (3 mg/kg/h) treatment (n = 15 rats in each group). Saline or SBT-20 were delivered into the jugular vein starting 5 min after coronary artery occlusion and were continued for one hour post coronary artery reperfusion. Body temperature, heart rate and blood pressure were monitored during the procedure. At the end of 3 h reperfusion, the ischemic risk area, no-reflow area, and infarct size were measured. In separate in vitro studies, isolated rat hearts were exposed to 20 min global ischemia, followed by SBT-20 administration (1 μM) or no SBT-20 (control) throughout the 2 h reperfusion. In vitro studies were conducted in cells and heart mitochondria to ascertain the mitochondrial effects of SBT-20 on mitochondrial respiration and reactive oxygen species production. In the in vivo study, the ischemic risk areas (as a percentage of the left ventricle) were similar among the saline (49.5 ± 2.3 %), low dose SBT-20 (48.6 ± 2.1 %), and high dose SBT-20 groups (48.7 ± 3.0 %). Treatment with SBT-20 significantly reduced infarct size ( as a percentage of risk area) in low dose (62.1 ± 4.4 %) and high dose (64.0 ± 4.9 %) compared with saline treatment (77.6 ± 2.6 %, p = 0.001 for both doses). There was no difference in infarct size between low and high dose SBT-20 treatment. The no-reflow areas (as a percentage of the risk area) were comparable among the saline (23.9

  1. The effects of exercise load during development on oxidative stress levels and antioxidant potential in adulthood.

    PubMed

    Lee, S; Hashimoto, J; Suzuki, T; Satoh, A

    2017-02-01

    The objective of this study was to elucidate the impact of physical activity during the growth period as well as on oxidative stress and antioxidative potential in adulthood. The experimental animals used were four-week old male Wistar rats, which were randomly divided into three groups. The exercise loads were as follows: control (CON), treadmill exercise (TE), and jumping exercise (JE). The exercise was performed at the same time of day, at a frequency of five days per week, for eight weeks. Derivatives of reactive oxygen metabolites (d-ROSs) and biological antioxidant potential (BAP) were measured during periods of rest prior to commencement of the experiment and after the experiment. Analysis was conducted using a Wilcoxon signed-rank test and Schaffer's multiple comparison procedure and the significance level was set at p < 0.05. The percent increase in d-ROM levels in the JE group, which experienced short-duration intense exercise loads, was higher than that in the TE group, which experienced moderately intense exercise loads. However, BAP, which is an index of antioxidant potential, markedly decreased in adulthood in the CON group, as compared to that in the developmental period, whereas the exercise groups showed no notable changes in BAP levels. Oxidative stress levels and antioxidant potential are affected differently in adulthood, depending on the intensity of sustained exercise loads experienced during development. Results suggested that in order to increase antioxidant potential, while taking oxidative stress production into account, moderately intense exercise loads are more desirable than highly intense exercise loads.

  2. Transdermal microemulsions of Glycyrrhiza glabra L.: characterization, stability and evaluation of antioxidant potential.

    PubMed

    Mostafa, Dina M; Ammar, Nagwa M; Abd El-Alim, Sameh H; El-anssary, Amira A

    2014-03-01

    The purpose of the present study is to formulate Glycyrrhiza glabra root and rhizome aqueous ethanolic extract in microemulsion carrier systems intended for transdermal delivery of incorporated antioxidant actives, flavonoids and polyphenols. The results obtained reveal that the microemulsion system ME3 possesses optimum properties regarding drug content (flavonoids and polyphenols), viscosity, pH, particle size and polydispersity index, zeta potential, stability, permeation of actives and hence possesses high in vitro and ex vivo antioxidant efficacy. These results indicate also that this microemulsion shows approximately 13-fold higher ex vivo antioxidant capacity compared with the liquorice extract solution. In addition, the proposed microemulsion is simple to dispense, cost effective and provides high patient compliance and convenience because of simple topical application and avoidance of non-comfortable oral or parenteral administration.

  3. Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects.

    PubMed

    Oshaghi, Ebrahim Abbasi; Khodadadi, Iraj; Tavilani, Heidar; Goodarzi, Mohammad Taghi

    2016-07-01

    The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group's oxidation, amyloid cross-β and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications.

  4. Chemical, Bioactive, and Antioxidant Potential of Twenty Wild Culinary Mushroom Species.

    PubMed

    Sharma, S K; Gautam, N

    2015-01-01

    The chemical, bioactive, and antioxidant potential of twenty wild culinary mushroom species being consumed by the people of northern Himalayan regions has been evaluated for the first time in the present study. Nutrients analyzed include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides, preliminary study on the detection of toxic compounds was done on these species. Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content, carotenoids (β-carotene, lycopene), flavonoids, ascorbic acid, and anthocyanidins. Fruitbodies extract of all the species was tested for different types of antioxidant assays. Although differences were observed in the net values of individual species all the species were found to be rich in protein, and carbohydrates and low in fat. Glucose was found to be the major monosaccharide. Predominance of UFA (65-70%) over SFA (30-35%) was observed in all the species with considerable amounts of other bioactive compounds. All the species showed higher effectiveness for antioxidant capacities.

  5. Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic phenolic hydrazones. A structure-activity relationship insight.

    PubMed

    Vanucci-Bacqué, Corinne; Carayon, Chantal; Bernis, Corinne; Camare, Caroline; Nègre-Salvayre, Anne; Bedos-Belval, Florence; Baltas, Michel

    2014-08-01

    A novel series of hydrazones derived from substituted benzaldehydes have been synthesized as potential antiatherogenic agents. Several methods were used for exploring their antioxidant and cytoprotective properties, such as their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition of superoxide anion (O₂(·-)) generation and the measurement of cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS). The cytoprotective efficacy was also evaluated by measuring the cell viability (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this report, we discuss the relationship between the chemical structure of phenolic hydrazones and their antioxidant and cytoprotective activities, for subsequent application as antiatherogenic agents. This SAR study confirms that the phenolic frame is not the only prerequisite for antioxidant activity and N-methylbenzothiazole hydrazone moiety magnifies the dual required properties in two most interesting derivatives.

  6. Chemical, Bioactive, and Antioxidant Potential of Twenty Wild Culinary Mushroom Species

    PubMed Central

    Sharma, S. K.; Gautam, N.

    2015-01-01

    The chemical, bioactive, and antioxidant potential of twenty wild culinary mushroom species being consumed by the people of northern Himalayan regions has been evaluated for the first time in the present study. Nutrients analyzed include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides, preliminary study on the detection of toxic compounds was done on these species. Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content, carotenoids (β-carotene, lycopene), flavonoids, ascorbic acid, and anthocyanidins. Fruitbodies extract of all the species was tested for different types of antioxidant assays. Although differences were observed in the net values of individual species all the species were found to be rich in protein, and carbohydrates and low in fat. Glucose was found to be the major monosaccharide. Predominance of UFA (65–70%) over SFA (30–35%) was observed in all the species with considerable amounts of other bioactive compounds. All the species showed higher effectiveness for antioxidant capacities. PMID:26199938

  7. Potential efficiency of antioxidants to prevent pressure ulcers. A neglected hypothesis.

    PubMed

    Bonne, Claude

    2016-06-01

    Pressure ulcers are necrotic lesions mainly due to capillary hypoperfusion. It is well known that hypoxia and also subsequent oxygenation at reperfusion provoke the formation of reactive oxygen species (ROS) responsible for cell death. The hypothesis of their participation in the pathogenesis of pressure ulcers has already been tested; several antioxidants have the capacity to inhibit skin necrosis in animal models but their efficiency in preventing bedsores has never been demonstrated in patients. The failure of clinical trials to show the protective activity of some antioxidants does not rule out the involvement of ROS in ischemic ulcers and the potential efficacy of other antioxidants in preventing their formation remains possible. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects

    PubMed Central

    Oshaghi, Ebrahim Abbasi; Khodadadi, Iraj; Tavilani, Heidar; Goodarzi, Mohammad Taghi

    2016-01-01

    The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group’s oxidation, amyloid cross-β and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications. PMID:27365555

  9. Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

    PubMed

    McElroy, Cameron S; Day, Brian J

    2016-01-15

    The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising.

  10. Antioxidant potential of tea reduces arsenite induced oxidative stress in Swiss albino mice.

    PubMed

    Sinha, D; Roy, S; Roy, M

    2010-04-01

    Environmental arsenic (As) is a potent human carcinogen and groundwater As contamination is a major health concern in West Bengal, India. Oxidative stress has been one of the prime factors in As-induced carcinogenicity. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance cause a severe imbalance of the cellular antioxidant defence mechanism. Tea, a popular beverage has excellent chemopreventive and antioxidant properties. In this study it was investigated whether these flavonoids could ameliorate the arsenite (As III) induced oxidative stress in Swiss albino mice. Bio-monitoring with comet assay elicited that the increase in genotoxicity caused by As III was counteracted by both black tea and green tea. Elevated levels of lipid peroxides and protein carbonyl by As III were effectively reduced with green as well as black tea. They also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the tea polyphenols by virtue of their antioxidant potential may be used as an effective agent to reduce the As III induced oxidative stress in Swiss albino mice.

  11. A pilot study of antioxidant potential of endophytic fungi from some Sudanese medicinal plants.

    PubMed

    Khiralla, Afra; Mohamed, Ietidal; Thomas, Justinne; Mignard, Benoît; Spina, Rosella; Yagi, Sakina; Laurain-Mattar, Dominique

    2015-09-01

    To evaluate the total phenolic content and total antioxidant capacity of ethyl acetate extracts of 21 endophytic fungi isolated from five Sudanese medicinal plants: Calotropis procera, Catharanthus roseus, Euphorbia prostrate, Vernonia amygdalina and Trigonella foenum-graecum. Crude extracts of endophytic fungi and their host plants were tested by classical Folin-Ciocalteu colorimetric method to determine the total phenolic content, also total antioxidant capacity was estimated using 1,1-diphenyl-2-picrylhydrazyl free radical scavenging in vitro method. Among the endophytes, endophytic fungus Aspergillus sp. from Trigonella foenum-graecum seeds demonstrated the highest both total phenolic content in term of gallic acid equivalent [(89.9 ± 7.1) mg GAE/g] and antioxidant activity for 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay [IC50: (18.0 ± 0.1) μg/mL]. A high positive linear correlation (R(2) = 0.999 1) was found between total antioxidant capacity and total phenolic content of endophytic fungi isolated from Vernonia amygdalina. The present study revealed that some endophytic fungi from the five Sudanese medicinal plants could be a potential source of novel natural antioxidant compounds. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  12. Influence of extraction technique on the anti-oxidative potential of hawthorn (Crataegus monogyna) extracts in bovine muscle homogenates.

    PubMed

    Shortle, E; O'Grady, M N; Gilroy, D; Furey, A; Quinn, N; Kerry, J P

    2014-12-01

    Six extracts were prepared from hawthorn (Crataegus monogyna) leaves and flowers (HLF) and berries (HB) using solid-liquid [traditional (T) (HLFT, HBT), sonicated (S) (HLFS, HBS)] and supercritical fluid (C) extraction (HLFC, HBC) techniques. The antioxidant activities of HLF and HB extracts were characterised using in vitro antioxidant assays (TPC, DPPH, FRAP) and in 25% bovine muscle (longissimus lumborum) homogenates (lipid oxidation (TBARS), oxymyoglobin (% of total myoglobin)) after 24h storage at 4°C. Hawthorn extracts exhibited varying degrees of antioxidant potency. In vitro and muscle homogenate (TBARS) antioxidant activity followed the order: HLFS>HLFT and HBT>HBS. In supercritical fluid extracts, HLFC>HBC (in vitro antioxidant activity) and HLFC≈HBC (TBARS). All extracts (except HBS) reduced oxymyoglobin oxidation. The HLFS extract had the highest antioxidant activity in all test systems. Supercritical fluid extraction (SFE) exhibited potential as a technique for the manufacture of functional ingredients (antioxidants) from hawthorn for use in muscle foods.

  13. Influence of processing stages on antimutagenic and antioxidant potentials of rooibos tea.

    PubMed

    Standley, L; Winterton, P; Marnewick, J L; Gelderblom, W C; Joubert, E; Britz, T J

    2001-01-01

    The antimutagenic and antioxidant potentials of rooibos (Aspalathus linearis) tea samples, collected from each of its major processing stages, were evaluated according to the Salmonella typhimurium mutagenicity test and the hydrogen donating ability and superoxide anion radical scavenging assays, respectively. Ten random samples were collected before and after fermentation, as well as after sun-drying, sieving, and steam pasteurization. Results indicated that the fermented tea had a significantly (P < 0.05) lower antimutagenic and antioxidant potential than the unfermented tea. Of the different processing stages, the most significant reduction in the antimutagenic and antioxidant property of the tea was found during the "fermentation" step. Sun-drying, sieving, and steam pasteurization also reduced the antimutagenic potential of the tea, although not to the same extent as the first processing step. The hydrogen donating ability was significantly increased after steam pasteurization in comparison to those of fermented and sun-dried tea. Pasteurization did not affect superoxide anion radical scavenging in comparison to fermented tea. Differences seem to exist in the antimutagenicity and antioxidant potencies of the tea sampled at the various stages during processing. A possible role of tea polyphenols in the antimutagenic and antioxdant activities of the tea is suggested as processing caused a significant reduction in the total polyphenolic content.

  14. Mitochondrial Dysfunction during Brain Aging: Role of Oxidative Stress and Modulation by Antioxidant Supplementation

    PubMed Central

    Chakrabarti, Sasanka; Munshi, Soumyabrata; Banerjee, Kalpita; Thakurta, Ishita Guha; Sinha, Maitrayee; Bagh, Maria Bindu

    2011-01-01

    Mitochondrial dysfunction and oxidative stress are two interdependent and reinforcing damage mechanisms that play a central role in brain aging. Oxidative stress initiated and propagated by active oxyradicals and various other free radicals in the presence of catalytic metal ions not only can damage the phospholipid, protein and DNA molecules within the cell but can also modulate cell signalling pathways and gene expression pattern and all these processes may be of critical importance in the aging of brain. The present article describes the mechanism of formation of reactive oxyradicals within mitochondria and then explains how these can initiate mitochondrial biogenesis program and activate various transcriptional factors in the cytosol to boost up the antioxidative capacity of the mitochondria and the cell. However, a high level of oxidative stress finally inflicts critical damage to the oxidative phosphorylation machinery and mitochondrial DNA (mtDNA). The latter part of the article is a catalogue showing the accumulating evidence in favour of oxidative inactivation of mitochondrial functions in aged brain and the detailed reports of various studies with antioxidant supplementation claiming variable success in preventing the age-related brain mitochondrial decay and cognitive decline. The antioxidant supplementation approach may be of potential help in the management of neurodegenerative diseases like Alzheimer’s disease. The newly developed mitochondria-targeted antioxidants have brought a new direction to experimental studies related to oxidative damage and they may provide potential drugs in near future for a variety of diseases or degenerative conditions including brain aging and neurodegenerative disorders. PMID:22396876

  15. Antioxidative potential, nutritional value and sensory profiles of confectionery fortified with green and yellow tea leaves (Camellia sinensis).

    PubMed

    Gramza-Michałowska, Anna; Kobus-Cisowska, Joanna; Kmiecik, Dominik; Korczak, Józef; Helak, Barbara; Dziedzic, Krzysztof; Górecka, Danuta

    2016-11-15

    This paper presents a study on development of functional food products containing green and yellow tea leaves. The results indicated that green and yellow tea are significant tools in the creation of the nutritional value, antioxidative potential and stability of the lipid fraction of cookies. Tea-fortified cookies showed considerably higher contents of dietary fiber, especially hemicellulose and insoluble fractions, and were characterized by significantly higher antioxidant potential associated with their phenolics content. Results of ABTS, DPPH, ORACFL and PCL assay showed significantly higher antioxidant potential of tea cookies, highest for yellow tea. The antioxidative potential of applied teas was significant in terms of the inhibition of hydroperoxide content, while formation of secondary lipid oxidation products was less spectacular. It is concluded that tea leaves could be widely used as a source of polyphenols with high antioxidative potential, as well as fiber; thus introducing numerous health benefits for the consumer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Antioxidant and antifungal potential of Pleurotus ostreatus and Agrocybe cylindracea basidiocarps and mycelia.

    PubMed

    Ćilerdžić, Jasmina; Stajić, Mirjana; Vukojević, Jelena; Milovanović, Ivan; Muzgonja, Nikolina

    2015-01-01

    Basidiocarps of Pleurotus ostreatus and Agrocybe cylindracea are characterized by high nutritional value and numerous medicinal activities, though bioactivities of their mycelia have not been sufficiently studied. The aim of the study was to evaluate antioxidant and antifungal potentials of P. ostreatus and A. cylindracea basidiocarp extracts, as well as those obtained from mycelia cultivated in common synthetic medium and media enriched with various agro-industrial residues. The free radical scavenging activity of the extracts was determined spectrophotometrically, based on DPPH• reduction while antifungal potential was studied by a microdilution method. The highest level of DPPH• scavenging ability was obtained by an extract of P. ostreatus mycelium cultivated in wheat bran-enriched medium, while control medium favoured the antioxidant potential of A. cylindracea mycelium. Phenol compounds were the main carriers of antioxidant activity that was demonstrated by high coefficients for correlations between total phenol contents in extracts and level of DPPH• scavenging (0.94 for P. ostreatus extracts and 0.91 for A. cylindracea extracts). Only the extracts of A. cylindracea basidiocarp and control mycelium, at a concentration of 1.33 mg/mL, inhibited the growth of Microsporum gypseum and Aspergillus flavus, while basidiocarp extract at 1.67 mg/mL also had fungicidal effect against M. gypseum. These results revealed a considerable antioxidant potential of submergedly-cultivated mycelium which showed higher antioxidant activity than basidiocarp extracts. This is very important because significant amounts of mycelium biomass could be obtained more easily, cheaper and in a more controllable way than basidiocarps cultivation.

  17. Evaluation of anti-inflammatory and anti-oxidant potential of seed extracts of Vernonia anthelmintica.

    PubMed

    Jamil, Subia; Khan, Rafeeq Alam; Ahmed, Shadab; Fatima, Sakina

    2017-05-01

    Seeds of Vernonia anthelmintica in the form of Ethanol seed extract of Vernonia anthelmintica (EEVA), Hexane extract of Vernonia anthelmintica (HEVA) and water decoction of Vernonia anthelmintica (WDVA) were evaluated for their in-vivo anti-Inflammatory potential in carrageenan induced rat paw model. The results were compared to anti-inflammatory activity of standard drug (ibuprofen) and untreated groups. In-vitro evaluation of antioxidant potential of EEVA and HEVA were also conducted by "DPPH scavenging assay". The results of present study depicts that HEVA and EEVA in higher dose possess a strong anti-inflammatory potential as compared to standard anti-inflammatory drugs, whereas WDVA showed milder anti-inflammatory potential. DPPH assay has revealed strong anti-oxidant potential of EEVC with the percentage Radical Scavenging activity (%RSA) of 89.709 at concentrations of 500 ul as compared to standard drugs gallic acid (23.436±0.43) and acetyl salicylic acid (111.44±0.7) at concentrations of 95.95 μM. The other extract HEVC has shown to have insignificant %RSA at the concentration of 500μl. Hence the present study revealed that selected extracts of Vernonia anthelmintica exhibited significant in-vitro antioxidant and in-vivo anti-inflammatory potential.

  18. An ab initio molecular dynamics analysis of lignin as a potential antioxidant for hydrocarbons.

    PubMed

    Pan, Tongyan; Cheng, Cheng

    2015-11-01

    Lignins are complex phenolic polymers with limited industrial uses. To identify new applications of lignins, this study aims to evaluate the conifer alcohol lignin as a potential antioxidant for hydrocarbons, using the petroleum asphalt as an example. Using the ab initio molecular dynamics (AIMD) method, the evaluation is accomplished by tracking the generation of critical species in a lignin-asphalt mixture under a simulated oxidative condition. The generation of new species was detected using nuclear magnetic resonance and four analytical methods including density of states analysis, highest occupied molecular orbital and lowest unoccupied molecular orbital analyses, bonding and energy level analysis, and electrostatic potential energy analysis. Results of the analyses show that the chemical radicals of carbon, nitrogen and sulfur generated in the oxidation process could enhance the agglomeration and/or decomposition tendency of asphalt. The effectiveness of lignins as an antioxidant depends on their chemical compositions. Lignins with a HOMO-LUMO gap larger than the HOMO-LUMO gap of the hydrocarbon system to be protected, such as the conifer alcohol lignin to protect petroleum asphalt as was studied in this work, do not demonstrate beneficial anti-oxidation capacity. Lignins, however, may be effective oxidants for hydrocarbon systems with a larger HOMO-LUMO gap. In addition, lignins may contain more polar sites than the hydrocarbons to be protected; thus the lignins' hydrophobicity and compatibility with the host hydrocarbons need to be well evaluated. The developed AIMD model provides a useful tool for developing antioxidants for generic hydrocarbons.

  19. Antioxidant and antimicrobial potentials of Serbian red wines produced from international Vitis vinifera grape varieties.

    PubMed

    Radovanović, Aleksandra N; Jovančićević, Branimir S; Radovanović, Blaga C; Mihajilov-Krstev, Tatjana; Zvezdanović, Jelena B

    2012-08-15

    Antioxidant and antimicrobial potentials of Serbian red wines produced from different international Vitis vinifera grape varieties and their correlation with contents of phenolic compounds were studied by spectrophotometric and chromatographic methods. The antioxidant activity of red wines was estimated through their ability to scavenge 2,2'-diphenyl-1-picrylhydrazyl free radical (DPPH(•) ). The red wines, gallic acid, (+)-catechin and quercetin were screened in vitro for antimicrobial activity against Gram-positive and Gram-negative strains using microdilution and disc diffusion techniques. Excellent correlations between the contents of quercetin-3-glucoside (R(2) = 0.9463) and quercetin (R(2) = 0.9337) and DPPH(•) -scavenging ability of the red wines were found. Serbian red wines exhibited significant activity against Staphylococcus aureus, Listeria inocua, Micrococcus flavus, Sarcina lutea, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Shigella sonnei strains, which was in correlation with their phenolic composition and antioxidant activity. The compounds gallic acid, quercetin and (+)-catechin showed high activity against B. subtilis, S. aureus, S. lutea and M. flavus Gram-positive and S. enteritidis and P. aeruginosa Gram-negative strains. The results show that quercetin-3-glucoside and quercetin concentrations can be used as markers for the determination of antioxidant and antimicrobial potentials of red wines. Copyright © 2012 Society of Chemical Industry.

  20. Antioxidant assays – consistent findings from FRAP and ORAC reveal a negative impact of organic cultivation on antioxidant potential in spinach but not watercress or rocket leaves

    PubMed Central

    Payne, Adrienne C; Mazzer, Alice; Clarkson, Graham J J; Taylor, Gail

    2013-01-01

    Watercress (Rorippa nasturtium-aquaticum), wild rocket (Diplotaxis tenuifolia), and spinach (Spinacia oleracea) are commercial crops reported to have high concentrations of antioxidants, possibly contributing to disease prevention following human consumption. Following analysis of supermarket-purchased salad leaves, we report the antioxidant content potential of these species using two comparable techniques assessing the consistency between the assays – by the ferric reducing antioxidant power (FRAP) assay and the oxygen radical absorbance capacity (ORAC) assay. The leaves were harvested from both conventionally and organically managed crops, to investigate whether organic agriculture results in improved crop quality. Watercress had the highest FRAP and ability to scavenge free radicals, followed by spinach and rocket. For watercress and rocket, there was no significant effect of organic agriculture on FRAP and ORAC, but for spinach, the antioxidant potential was reduced and this was significant at the 5% level of probability for FRAP but not ORAC, although the trend was clear in both tests. We conclude that there is variation in salad crop antioxidant potential and that FRAP and ORAC are useful techniques for measuring antioxidants in these salad crops with similar ranking for each salad crop studied. PMID:24804054

  1. Antioxidant assays - consistent findings from FRAP and ORAC reveal a negative impact of organic cultivation on antioxidant potential in spinach but not watercress or rocket leaves.

    PubMed

    Payne, Adrienne C; Mazzer, Alice; Clarkson, Graham J J; Taylor, Gail

    2013-11-01

    Watercress (Rorippa nasturtium-aquaticum), wild rocket (Diplotaxis tenuifolia), and spinach (Spinacia oleracea) are commercial crops reported to have high concentrations of antioxidants, possibly contributing to disease prevention following human consumption. Following analysis of supermarket-purchased salad leaves, we report the antioxidant content potential of these species using two comparable techniques assessing the consistency between the assays - by the ferric reducing antioxidant power (FRAP) assay and the oxygen radical absorbance capacity (ORAC) assay. The leaves were harvested from both conventionally and organically managed crops, to investigate whether organic agriculture results in improved crop quality. Watercress had the highest FRAP and ability to scavenge free radicals, followed by spinach and rocket. For watercress and rocket, there was no significant effect of organic agriculture on FRAP and ORAC, but for spinach, the antioxidant potential was reduced and this was significant at the 5% level of probability for FRAP but not ORAC, although the trend was clear in both tests. We conclude that there is variation in salad crop antioxidant potential and that FRAP and ORAC are useful techniques for measuring antioxidants in these salad crops with similar ranking for each salad crop studied.

  2. Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity.

    PubMed

    Bansal, Seema; Biswas, Gopa; Avadhani, Narayan G

    2014-01-01

    The inducible form of Heme Oxygenase-1 (HO-1), a major endoplasmic reticulum (ER) associated heme protein, is known to play important roles in protection against oxidative and chemical stress by degrading free heme released from degradation of heme proteins. In this study we show that induced expression of HO-1 by subjecting macrophage RAW-264.7 cells to chemical or physiological hypoxia resulted in significant translocation of HO-1 protein to mitochondria. Transient transfection of COS-7 cells with cloned cDNA also resulted in mitochondrial translocation of HO-1. Deletion of N-terminal ER targeting domain increased mitochondrial translocation under the transient transfection conditions. Mitochondrial localization of both intact HO-1 and N-terminal truncated HO-1 caused loss of heme aa-3 and cytochrome c oxidase (CcO) activity in COS-7 cells. The truncated protein, which localizes to mitochondria at higher levels, induced substantially steeper loss of CcO activity and reduced heme aa3 content. Furthermore, cells expressing mitochondria targeted HO-1 also induced higher ROS production. Consistent with dysfunctional state of mitochondria induced by HO-1, the mitochondrial recruitment of autophagy markers LC-3 and Drp-1 was also increased in these cells. Chronic ethanol feeding in rats also caused an increase in mitochondrial HO-1 and decrease in CcO activity. These results show that as opposed to the protective effect of the ER associated HO-1, mitochondria targeted HO-1 under normoxic conditions induces mitochondrial dysfunction.

  3. Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity☆

    PubMed Central

    Bansal, Seema; Biswas, Gopa; Avadhani, Narayan G.

    2013-01-01

    The inducible form of Heme Oxygenase-1 (HO-1), a major endoplasmic reticulum (ER) associated heme protein, is known to play important roles in protection against oxidative and chemical stress by degrading free heme released from degradation of heme proteins. In this study we show that induced expression of HO-1 by subjecting macrophage RAW-264.7 cells to chemical or physiological hypoxia resulted in significant translocation of HO-1 protein to mitochondria. Transient transfection of COS-7 cells with cloned cDNA also resulted in mitochondrial translocation of HO-1. Deletion of N-terminal ER targeting domain increased mitochondrial translocation under the transient transfection conditions. Mitochondrial localization of both intact HO-1 and N-terminal truncated HO-1 caused loss of heme aa-3 and cytochrome c oxidase (CcO) activity in COS-7 cells. The truncated protein, which localizes to mitochondria at higher levels, induced substantially steeper loss of CcO activity and reduced heme aa3 content. Furthermore, cells expressing mitochondria targeted HO-1 also induced higher ROS production. Consistent with dysfunctional state of mitochondria induced by HO-1, the mitochondrial recruitment of autophagy markers LC-3 and Drp-1 was also increased in these cells. Chronic ethanol feeding in rats also caused an increase in mitochondrial HO-1 and decrease in CcO activity. These results show that as opposed to the protective effect of the ER associated HO-1, mitochondria targeted HO-1 under normoxic conditions induces mitochondrial dysfunction. PMID:24494190

  4. Synthesis, characterization and evaluation of the antioxidant potential of vanadium encapsulated guar gum nanoparticles.

    PubMed

    Soumya, R S; Reshmi, R; Jomon, S; Antu, K A; Riya, M P; Raghu, K G

    2014-03-01

    The present study investigated the antioxidant potential of guar gum macroparticles (GGMs), vanadium oxide sulphate (VS) encapsulated guar gum macroparticles (GVMs), guar gum nanoparticles (GGNs), VS encapsulated guar gum nanoparticles (GVNs) and VS. GGNs and GVNs prepared by nanoprecipitation were characterized by SEM (scanning electron microscopy), TEM (transmission electron microscopy) and particle size analysis to confirm the nanostructure of the particles. Particle size analysis revealed that GVNs possess a size of 239 nm, about 148 nm larger than that of GGNs. TEM imaging and EDAX data also confirmed the formation of fine spherical nanoparticles with vanadium incorporation. In addition the larger size of GVNs also confirmed the vanadium incorporation. MTT assay showed that concentrations up to 100 nM of GVNs for 24 h exposure did not induce significant toxicity when VS was toxic (16%) at 100 nM. Various in vitro antioxidant assays (total reducing power, total antioxidant capacity, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), hydroxyl radical and superoxide anion radical scavenging assays) revealed significantly high antioxidant potential of GVNs compared to GGNs, VS, GGMs and GVMs. The IC50 of GVNs was 23.21 ± 2.1 μg mL(-1), 33.0 ± 2.93 μg mL(-1), 21 ± 1.98 μg mL(-1) and 22.79 ± 2.12 μg mL(-1) for DPPH, ABTS, hydroxyl, superoxide anion scavenging activity assays respectively. The cell line based assay also proved that the GVN was more effective in reactive oxygen species (ROS) scavenging than VS against tertiary butyl hydrogen peroxide (TBHP) induced oxidative stress in H9c2 cell lines. The overall results indicated that vanadium in combination with nano guar gum exhibits significantly high antioxidant potential.

  5. Proximate composition, phytochemical analysis, and in vitro antioxidant potentials of extracts of Annona muricata (Soursop).

    PubMed

    Agu, Kingsley C; Okolie, Paulinus N

    2017-09-01

    Numerous bioactive compounds and phytochemicals have been reported to be present Annona muricata (Soursop). Some of these chemical compounds have been linked to the ethnomedicinal properties of the plant and its antioxidant properties. The aim of this study was to assess the proximate composition, phytochemical constituents and in vitro antioxidant properties of A. muricata using standard biochemical procedures. The defatted Annona muricata crude methanolic extracts of the different parts of the plant were used for the estimation of proximate composition and phytochemical screening. The crude methanolic extracts of the different parts of the plant were also fractionated using solvent-solvent partitioning. Petroleum ether, chloroform, ethyl acetate, methanol, and methanol-water (90:10) were the solvents used for the fractionation. The different fractions obtained were then used to perform in vitro antioxidant analyses including, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, ferric reducing properties, and hydroxyl radical scavenging ability. The leaf methanolic extract had a higher lipid content, whereas its chloroform fraction demonstrated a better ability to quench DPPH free radical. The root-bark methanol-water, leaf methanol, fruit pulp chloroform, and leaf petroleum ether fractions demonstrated potent ferric reducing properties. The leaf and stem-bark petroleum ether fractions demonstrated better hydroxyl-free radical scavenging abilities. The leaf and fruit pulp of Annona muricata have a very potent antioxidant ability compared to the other parts of the plant. This can be associated with the rich phytochemicals and other phytoconstituents like phenols, flavonoids, alkaloids, and essential lipids, etc. Significant correlations were observed between the antioxidant status and phytochemicals present. These results thus suggest that some of the reported ethnomedicinal properties of this plant could be due to its antioxidant potentials.

  6. Geographic origin influences the phenolic composition and antioxidant potential of wild Crataegus monogyna from Spain.

    PubMed

    Abuashwashi, M A; Palomino, O M; Gómez-Serranillos, M P

    2016-11-01

    Crataegus monogyna Jacq L. (Lind.) (Rosaceae) is used in folk medicine as a sedative, aerial parts being rich in polyphenols with antioxidant ability. To study the variation in polyphenolic composition and antioxidant ability of spontaneous samples of C. monogyna in order to assess the relationship among these variables. Aerial parts of C. monogyna were collected from nine different locations in central Spain and extracted with methanol after drying. Total polyphenols were determined by the Folin-Ciocalteu method using gallic acid (GA) as standard. Sixteen polyphenolic compounds (11 flavonoids and 5 phenolic acids) were identified and quantified by reversed-phase HPLC in one single analysis. The antioxidant ability was evaluated by the oxygen radical absorbance capacity (ORAC) and the free radical scavenging activity (DPPH) methods. Linear correlation analysis was used to explore the relationships between the studied variables. Total polyphenol content ranged between 117.729 ± 0.011 and 204.286 ± 0.015 mg GAE/g extract, depending on the geographic origin. No relationship was found between total polyphenols and antioxidant ability by the ORAC or DPPH methods. Chromatographic analysis yielded lower amounts of polyphenols (23.3-143.26 mg/kg), as only flavonoids and phenolic acids were quantified. All the samples exhibited antioxidant activity between 1.32 ± 0.08 and 2.76 ± 0.007 μmol Trolox equivalents/mg and IC50 from 0.82 ± 0.10 to 3.76 ± 0.67 μg/mL. A statistically significant relationship between flavonoids and phenolic acids content and the antioxidant potential obtained by the ORAC method for C. monogyna samples was proven.

  7. Antioxidant potential of Agrobacterium-transformed and non-transformed Physalis ixocarpa plants grown in vitro and ex vitro.

    PubMed

    Bergier, Katarzyna; Kuźniak, Elżbieta; Skłodowska, Maria

    2012-12-07

    Oxidative stress is involved in pathogenesis of a number of chronic diseases hence is an increasing interest in plant-derived natural antioxidants with respect to their potential health benefits. Plants from the genus Physalis are particularly rich in secondary metabolites and show significant antioxidant potential. Recent development in transgenic research has opened new possibilities for enhanced production of secondary metabolites with plant cell and organ cultures. The hairy root-regenerated Physalis ixocarpa plants grown in vitro and ex vitro were compared to the non-transformed plants with respect to their antioxidant potential. The total antioxidant capacity (TAC), the contents of total phenols and ascorbate were evaluated in fruits, flowers, leaves and roots of P. ixocarpa using the ferric reducing antioxidant power assay (FRAP), the Folin-Ciocalteu method and the 2,2'-dipyridyl method, respectively. The antioxidant profiles, in terms of TAC, ascorbate and phenols were organ-specific and depended on the culture conditions. Neither the total phenol content nor the ascorbate level appeared to determine the TAC of the studied plant extracts. The aqueous extracts exhibited lower antioxidant activities than the acetone ones indicating that lipophilic antioxidants made a major contribution to TAC of the plant tissues. Agrobacterium rhizogenes-mediated transformation changed the antioxidant status with respect to TAC, phenols and ascorbate and this effect was observed in the plants grown in vitro and ex vitro.

  8. Mitochondria-targeted catalase reverts the neurotoxicity of hSOD1G⁹³A astrocytes without extending the survival of ALS-linked mutant hSOD1 mice.

    PubMed

    Pehar, Mariana; Beeson, Gyda; Beeson, Craig C; Johnson, Jeffrey A; Vargas, Marcelo R

    2014-01-01

    Dominant mutations in the Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. The molecular mechanism underlying the toxic gain-of-function of mutant hSOD1s remains uncertain. Several lines of evidence suggest that toxicity to motor neurons requires damage to non-neuronal cells. In line with this observation, primary astrocytes isolated from mutant hSOD1 over-expressing rodents induce motor neuron death in co-culture. Mitochondrial alterations have been documented in both neuronal and glial cells from ALS patients as well as in ALS-animal models. In addition, mitochondrial dysfunction and increased oxidative stress have been linked to the toxicity of mutant hSOD1 in astrocytes and neurons. In mutant SOD1-linked ALS, mitochondrial alterations may be partially due to the increased association of mutant SOD1 with the outer membrane and intermembrane space of the mitochondria, where it can affect several critical aspects of mitochondrial function. We have previously shown that decreasing glutathione levels, which is crucial for peroxide detoxification in the mitochondria, significantly accelerates motor neuron death in hSOD1G93A mice. Here we employed a catalase targeted to the mitochondria to investigate the effect of increased mitochondrial peroxide detoxification capacity in models of mutant hSOD1-mediated motor neuron death. The over-expression of mitochondria-targeted catalase improved mitochondrial antioxidant defenses and mitochondrial function in hSOD1G93A astrocyte cultures. It also reverted the toxicity of hSOD1G93A-expressing astrocytes towards co-cultured motor neurons, however ALS-animals did not develop the disease later or survive longer. Hence, while increased oxidative stress and mitochondrial dysfunction have been extensively documented in ALS, these results suggest that preventing peroxide-mediated mitochondrial damage alone is not

  9. In vitro study on the antioxidant potentials of the leaves and fruits of Nauclea latifolia.

    PubMed

    Ayeleso, Ademola O; Oguntibeju, Oluwafemi O; Brooks, Nicole L

    2014-01-01

    This study was carried out to investigate the in vitro antioxidant potentials of the leaves and fruits of Nauclea latifolia, a straggling shrub or small tree, native to tropical Africa and Asia. Hot water extracts of the leaves and fruits of Nauclea latifolia were assessed for their total polyphenolic, flavanol, and flavonol contents as well as 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, ferric reducing antioxidant power (FRAP), Trolox equivalence antioxidant capacity (TEAC), and oxygen radical absorbance capacity (ORAC) assays. The aqueous extract of the leaves was found to contain higher level of total polyphenols (11.63 ± 0.023 mg GAE/g), flavanol (1.45 ± 0.10 mg CE/g), and flavonol (2.22 ± 0.37 mg QE/g) than the extract of the fruits with values of 1.75 ± 0.02 mg GAE/g (total polyphenol), 0.15 ± 0.01 mg CE/g (flavanol), and 1.00 ± 0.13 mg QE/g (flavonol). Similarly, the aqueous extract of the leaves also exhibited higher DPPH (IC50 20.64 mg/mL), FRAP (86.10 ± 3.46 μmol AAE/g), TEAC (94.83 ± 3.57 μmol TE/g), and ORAC (196.55 ± 0.073 μmol TE/g) than the extract of the fruits with DPPH (IC50 120.33 mg/mL), FRAP (12.23 ± 0.40 μmol AAE/g), TEAC (12.48 ± 0.21 μmol TE/g), and ORAC (58.88 ± 0.073 μmol TE/g). The present study showed that Nauclea latifolia has strong antioxidant potentials with the leaves demonstrating higher in vitro antioxidant activities than the fruits.

  10. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol.

    PubMed

    Zeka, Keti; Ruparelia, Ketan C; Continenza, Maria A; Stagos, Dimitrios; Vegliò, Francesco; Arroo, Randolph R J

    2015-12-01

    Saffron from the province of L'Aquila, in the Abruzzo region of Italy, is highly prized and has been awarded a formal recognition by the European Union with EU Protected Designation of Origin (PDO) status. Despite this, the saffron regions are abandoned by the younger generations because the traditional cultivation of saffron (Crocus sativus L.) is labour intensive and yields only one crop of valuable saffron stamens per year. Petals of the saffron Crocus have had additional uses in traditional medicine and may add value to the crops for local farmers. This is especially important because the plant only flowers between October and November, and farmers will need to make the best use of the flowers harvested in this period. Recently, the petals of C. sativus L., which are considered a waste material in the production of saffron spice, were identified as a potential source of natural antioxidants. The antioxidants crocin and kaempferol were purified by flash column chromatography, and identified by thin layer chromatography (TLC), HPLC-DAD, infrared (IR), and nuclear magnetic resonance ((1)H &(13)C NMR) spectroscopy. The antioxidant activity was determined with the ABTS and DPPH tests. The antioxidant activities are mainly attributed to carotenoid and flavonoid compounds, notably glycosides of crocin and kaempferol. We found in dried petals 0.6% (w/w) and 12.6 (w/w) of crocin and kaempferol, respectively. Petals of C. sativus L. have commercial potential as a source for kaempferol and crocetin glycosides, natural compounds with antioxidant activity that are considered to be the active ingredients in saffron-based herbal medicine. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats

    PubMed Central

    Ji, Linlin; Gao, Weina; Wei, Jingyu; Wu, Jianquan; Yang, Jijun; Meng, Bin; Guo, Changjiang

    2014-01-01

    Vegetables vary greatly in antioxidant capacity in vitro. This study was to investigate the actions of three vegetables different remarkably in antioxidant capacity in vitro on antioxidant function in aged rats. Sixty female aged Wistar rats were randomly assigned to the control, lotus root, rape and cucumber (high, moderate and low in antioxidant capacity, respectively) treated groups. After 6 weeks of feeding, there were no significant differences in plasma FRAP value and contents of vitamin C, vitamin E, uric acid and total phenolics among different groups, whereas the content of reduced glutathione was significantly higher in the rape and cucumber groups. Plasma superoxide dismutase activity also was significantly increased in the rape and cucumber groups. Plasma contents of malondialdehyde, carbonyls and hemolysis were decreased significantly in 3 vegetable-treated groups. Meanwhile, urinary 8-hydroxy-2'-deoxyguanosine excretion was lower significantly in the rape group and the ratio of comet tail length to total length of blood mononuclear cells was decreased significantly in 3 vegetables treated groups. These results suggest that 3 vegetables tested are effective in improving antioxidant function to some extent in aged rats and no correlation is found between antioxidant capacity in vitro and improvements of antioxidant function. The benefits observed in this study may come from additive or synergistic combinations of antioxidants contained in vegetables. PMID:24895483

  12. Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy

    PubMed Central

    Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

    2017-01-01

    Jatropha (Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C-glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products. PMID:28335473

  13. Antioxidant potential of Amorphophallus paeoniifolius in relation to their phenolic content.

    PubMed

    Angayarkanni, Jayaraman; Ramkumar, Kunga Mohan; Priyadharshini, Ulaganathan; Ravendran, Poornima

    2010-06-01

    The present study evaluates the antioxidative and radical scavenging potential of the tuber extract of Amorphophallus paeoniifolius (Dennst.) Nicolson, (Araceae). The ethanol extract of A. paeoniifolius (APE) was studied for the inhibition of lipid peroxidation estimated in terms of thiobarbituric acid reactive substances (TBARS) and the levels were reduced by 4.3% to 67.2% in a dose-dependent manner. Further, APE was analyzed for scavenging capacities based on 1,1-diphenyl-2-picrylhydrazyl-2-radical (DPPH) assay and percentage inhibition activity based on 2,2-azinobis-(-3-ethyl) benzo-thiozoline-6-sulfonate (ABTS+) and H2O2. The A. paeoniifolius extract showed a maximum of 68.6% of DPPH scavenging activity and the maximum inhibition of 74% and 67.2% in the case of ABTS and H2O2, respectively. The antioxidant efficiency and inhibition of oxidation of the extract was found to be dose-dependent at the tested concentrations of 1-50 microg/mL. High-performance thin layer liquid chromatography (HPTLC) profile of the extract suggests the presence of polyphenols such as gallic acid, resveratrol, quercetin and two unidentified compounds. The results suggest that the ethanol extract of A. paeoniifolius has a potent antioxidant activity in vitro and can be utilized as an effective and safe source of antioxidants.

  14. Recent Advances on the Neuroprotective Potential of Antioxidants in Experimental Models of Parkinson’s Disease

    PubMed Central

    Koppula, Sushruta; Kumar, Hemant; More, Sandeep Vasant; Kim, Byung Wook; Kim, In Su; Choi, Dong Kug

    2012-01-01

    Parkinson’s disease (PD), a neurodegenerative movement disorder of the central nervous system (CNS) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Although the etiology of PD is not completely understood and is believed to be multifactorial, oxidative stress and mitochondrial dysfunction are widely considered major consequences, which provide important clues to the disease mechanisms. Studies have explored the role of free radicals and oxidative stress that contributes to the cascade of events leading to dopamine cell degeneration in PD. In general, in-built protective mechanisms consisting of enzymatic and non-enzymatic antioxidants in the CNS play decisive roles in preventing neuronal cell loss due to free radicals. But the ability to produce these antioxidants decreases with aging. Therefore, antioxidant therapy alone or in combination with current treatment methods may represent an attractive strategy for treating or preventing the neurodegeneration seen in PD. Here we summarize the recent discoveries of potential antioxidant compounds for modulating free radical mediated oxidative stress leading to neurotoxicity in PD. PMID:22949883

  15. Potential Role of Selenoenzymes and Antioxidant Metabolism in relation to Autism Etiology and Pathology

    PubMed Central

    Raymond, Laura J.; Deth, Richard C.; Ralston, Nicholas V. C.

    2014-01-01

    Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain's high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology. PMID:24734177

  16. Antioxidant potential of n-butanol fraction from extract of Jasminum mesnyi Hance leaves.

    PubMed

    Borar, Sakshi; Punia, Priyanka; Kalia, A N

    2011-01-01

    Methanolic extract of Jasminum mesnyi Hance leaves having antidiabetic activity was subjected to fractionation to obtain antioxidant and antihyperglycemic rich fraction. Different concentrations of ethyl acetate and n-butanol fractions were subjected to antioxidant assay by DPPH method, nitric oxide scavenging activity and reducing power assay. The fractions showed dose dependent free radical scavenging property in all the models. IC50 values for ethyl acetate and n-butanol fractions were 153.45 +/- 6.65 and 6.22 +/- 0.25 microg/ml, respectively, as compared to L-ascorbic acid and rutin (as standards; IC50 values 6.54 +/- 0.24 and 5.43 +/- 0.21 microg/ml, respectively) in DPPH model. In nitric oxide scavenging activity, IC50 values were 141.54 +/- 9.95 microg/ml, 35.12 +/- 1.58 microg/ml, 21.06 +/- 0.95 microg/ml and 29.93 +/- 0.32 microg/ml for ethyl acetate, n-butanol fractions, L-ascorbic acid and rutin, respectively. n-Butanol fraction showed a good reducing potential and better free radical scavenging activity as compared to ethyl acetate fraction. Potent antioxidant n-butanol fraction showed better oral glucose tolerance test (antihyperglycemic) at par with metformin (standard drug), n-Butanol fraction contained secoiridoid glycosides which might be responsible for both antioxidant and antihyperglycemic activity.

  17. Nicotine alkaloids as antioxidant and potential protective agents against in vitro oxidative haemolysis.

    PubMed

    Malczewska-Jaskóła, Karolina; Jasiewicz, Beata; Mrówczyńska, Lucyna

    2016-01-05

    The capacity of eleven nicotine alkaloids to reduce oxidative stress was investigated. In order to provide a structure-activity relationships analysis, new nicotine derivatives with a substituent introduced into the pyrrolidine ring were synthesized and investigated together with nicotine and its known analogs. All newly synthesized compounds were characterized by (1)H, (13)C NMR and EI-MS technique. The antioxidant properties of nicotine, its known analogs and newly produced derivatives, were evaluated by various antioxidant assays such 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH(•)) scavenging, ferrous ions (Fe(2+)) chelating activity and total reducing ability determination by Fe(3+) → Fe(2+) transformation assay. The protective effects of all compounds tested against 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) and tert-butyl hydroperoxide (t-BuOOH)-induced oxidative haemolysis and morphological injury of human erythrocytes, were estimated in vitro. The results showed that nicotine alkaloids exhibited various antiradical efficacy and antioxidant activity in a structure- and a dose-dependent manner. In addition, the capacity of nicotine alkaloids to protect erythrocytes from AAPH- and t-BuOOH-induced oxidative haemolysis, was dependent on its incubation time with cells. Our findings showed that chemical and biological investigations conducted simultaneously can provide comprehensive knowledge concerning the antioxidant potential of nicotine alkaloids. This knowledge can be helpful in better understanding the properties of nicotine alkaloids under oxidative stress conditions.

  18. Enhancing Phenolic Contents and Antioxidant Potentials of Antidesma thwaitesianum by Supercritical Carbon Dioxide Extraction.

    PubMed

    Poontawee, Warut; Natakankitkul, Surapol; Wongmekiat, Orawan

    2015-01-01

    Supercritical fluid extraction (SFE) has increasingly gained attention as an alternative technique for extraction of natural products without leaving toxic residues in extracts. Antidesma thwaitesianum Muell. Arg. (Phyllanthaceae), or ma mao, has been reported to exhibit antioxidant health benefits due to its phenolic constituents. To determine whether SFE technique could impact on phenolic contents and associated antioxidant potentials, ripe fruits of Antidesma thwaitesianum (Phyllanthaceae) were extracted using supercritical carbon dioxide (SC-CO2) and conventional solvents (ethanol, water). The results showed that the SC-CO2 extract contained significantly higher yield, total phenolic, flavonoid, and proanthocyanidin contents than those obtained from ethanol and water. It also demonstrated the greatest antioxidant activities as assessed by ABTS radical cation decolorization, DPPH radical scavenging, and ferric reducing antioxidant power (FRAP) assays. Further analysis using high-performance liquid chromatography with diode array and mass spectrometry detectors (HPLC-DAD/MSD) revealed the presence of catechin as a major phenolic compound of Antidesma thwaitesianum (Phyllanthaceae), with the maximum amount detected in the SC-CO2 extract. These data indicate that SFE technology improves both quantity and quality of Antidesma thwaitesianum fruit extract. The findings added more reliability of using this technique to produce high added value products from this medicinal plant.

  19. Wild Mushrooms in Nepal: Some Potential Candidates as Antioxidant and ACE-Inhibition Sources

    PubMed Central

    Hai Bang, Tran; Suhara, Hiroto; Doi, Katsumi; Ishikawa, Hiroya; Fukami, Katsuya; Parajuli, Gopal Prasad; Katakura, Yoshinori; Yamashita, Shuntaro; Watanabe, Kazuo; Adhikari, Mahesh Kumar; Manandhar, Hira Kaji; Kondo, Ryuichiro; Shimizu, Kuniyoshi

    2014-01-01

    Twenty-nine mushrooms collected in the mountainous areas of Nepal were analyzed for antioxidant activity by different methods, including Folin-Ciocalteu, ORAC, ABTS, and DPPH assays. Intracellular H2O2-scavenging activity was also performed on HaCaT cells. The results showed that phenolic compounds are the main antioxidant of the mushrooms. Among studied samples, Inonotus andersonii, and Phellinus gilvus exhibited very high antioxidant activity with the phenolic contents up to 310.8 and 258.7 mg GAE/g extracts, respectively. The H2O2-scavenging assay on cells also revealed the potential of these mushrooms in the prevention of oxidative stress. In term of ACE-inhibition, results showed that Phlebia tremellosa would be a novel and promising candidate for antihypertensive studies. This mushroom exhibited even higher in vitro ACE-inhibition activity than Ganoderma lingzhi, with the IC50 values of the two mushrooms being 32 μg/mL and 2 μg/mL, respectively. This is the first time biological activities of mushrooms collected in Nepal were reported. Information from this study should be a valuable reference for future studies on antioxidant and ACE-inhibitory activities of mushrooms. PMID:24672576

  20. Antioxidant potential of chestnut (Castanea sativa L.) and almond (Prunus dulcis L.) by-products.

    PubMed

    Barreira, J C M; Ferreira, I C F R; Oliveira, M B P P; Pereira, J A

    2010-06-01

    The antioxidant properties of almond green husks (Cvs. Duro Italiano, Ferraduel, Ferranhês, Ferrastar and Orelha de Mula), chestnut skins and chestnut leaves (Cvs. Aveleira, Boa Ventura, Judia and Longal) were evaluated through several chemical and biochemical assays in order to provide a novel strategy to stimulate the application of waste products as new suppliers of useful bioactive compounds, namely antioxidants. All the assayed by-products revealed good antioxidant properties, with very low EC(50) values (lower than 380 μg/mL), particularly for lipid peroxidation inhibition (lower than 140 μg/mL). The total phenols and flavonoids contents were also determined. The correlation between these bioactive compounds and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of β-carotene bleaching and inhibition of lipid peroxidation in pig brain tissue through formation of thiobarbituric acid reactive substances, was also obtained. Although, all the assayed by-products proved to have a high potential of application in new antioxidants formulations, chestnut skins and leaves demonstrated better results.

  1. Antioxidant, anti-inflammatory and analgesic potential of the Citrus decumana L. peel extract.

    PubMed

    Sood, Shailja; Arora, Bhawna; Bansal, Stuti; Muthuraman, Arunachalam; Gill, Naresh Singh; Arora, Rashmi; Bali, Manoj; Sharma, Pritam Dev

    2009-10-01

    The present study was designed to investigate the antioxidant, anti-inflammatory and analgesic potential of Citrus decumana peel extract. Antioxidant activity of Citrus decumana peel extract in four solvent systems was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH(.)) and hydrogen peroxide (H(2)O(2)) radical scavenging methods. Ethyl acetate peel extract of Citrus decumana (EtCD) was studied for its anti-inflammatory and analgesic activities at a dose level of 100, 200 and 300 mg/kg. Anti-inflammatory activity was performed using carrageenan-induced paw edema in rats. Analgesic activity was evaluated for its central and peripheral pharmacological actions in mice. EtCD showed significant antioxidant activity in a dose-dependent manner when compared with ascorbic acid. EtCD at the dose of 300 mg/kg produced significant decrease in paw volume and pain when compared with reference drug diclofenac and morphine, respectively. The Citrus decumana peel extract may be useful as a natural antioxidant in the treatment of inflammation and pain.

  2. Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy.

    PubMed

    Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

    2017-03-18

    Jatropha (Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C-glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

  3. Possible potentiation by certain antioxidants of the anti-inflammatory effects of diclofenac in rats.

    PubMed

    Abbas, Samah S; Schaalan, Mona F; Bahgat, Ashraf K; El-Denshary, Ezzeddin S

    2014-01-01

    In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se.

  4. Enhancing Phenolic Contents and Antioxidant Potentials of Antidesma thwaitesianum by Supercritical Carbon Dioxide Extraction

    PubMed Central

    Poontawee, Warut; Natakankitkul, Surapol; Wongmekiat, Orawan

    2015-01-01

    Supercritical fluid extraction (SFE) has increasingly gained attention as an alternative technique for extraction of natural products without leaving toxic residues in extracts. Antidesma thwaitesianum Muell. Arg. (Phyllanthaceae), or ma mao, has been reported to exhibit antioxidant health benefits due to its phenolic constituents. To determine whether SFE technique could impact on phenolic contents and associated antioxidant potentials, ripe fruits of Antidesma thwaitesianum (Phyllanthaceae) were extracted using supercritical carbon dioxide (SC-CO2) and conventional solvents (ethanol, water). The results showed that the SC-CO2 extract contained significantly higher yield, total phenolic, flavonoid, and proanthocyanidin contents than those obtained from ethanol and water. It also demonstrated the greatest antioxidant activities as assessed by ABTS radical cation decolorization, DPPH radical scavenging, and ferric reducing antioxidant power (FRAP) assays. Further analysis using high-performance liquid chromatography with diode array and mass spectrometry detectors (HPLC-DAD/MSD) revealed the presence of catechin as a major phenolic compound of Antidesma thwaitesianum (Phyllanthaceae), with the maximum amount detected in the SC-CO2 extract. These data indicate that SFE technology improves both quantity and quality of Antidesma thwaitesianum fruit extract. The findings added more reliability of using this technique to produce high added value products from this medicinal plant. PMID:25977832

  5. Possible Potentiation by Certain Antioxidants of the Anti-Inflammatory Effects of Diclofenac in Rats

    PubMed Central

    Abbas, Samah S.; Schaalan, Mona F.; Bahgat, Ashraf K.; El-Denshary, Ezzeddin S.

    2014-01-01

    In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se. PMID:24715817

  6. In vitro antioxidant potential and free radical scavenging activity of various extracts of pollen of Typha domigensis Pers.

    PubMed

    Sardar, Andleeb Anwar; Akhan, Zaheer-ud-Din; Perveen, Anjum; Farid, Sidra; Khan, Islamullah

    2014-03-01

    Antioxidant potential of the pollen of Typha domigensis Pers. using Ferric Reducing ower, Metal Chelating Activity and Trolox Equivalent Antioxidant Capacity (TEAC) assays has been carried out in the current research work. The antioxidant components were initially extracted from the pollen in methanol and were further fractionated in solvents of different polarity such as n-Hexane, Chloroform, Ethyl Acetate and Water. Methanol extract which was found to have high reducing power, total phenolic contents with high metal chelating activity, has considerable prospective to utilize as a natural antioxidant and be capable to link with the total phenolic contents of plant.

  7. Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants.

    PubMed

    López-Frías, Gabriela; Camacho-Dávila, Alejandro A; Chávez-Flores, David; Zaragoza-Galán, Gerardo; Ramos-Sánchez, Víctor H

    2015-05-14

    A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases.

  8. Polyphenols, antioxidant potential and color of fortified wines during accelerated ageing: the Madeira Wine case study.

    PubMed

    Pereira, Vanda; Albuquerque, Francisco; Cacho, Juan; Marques, José C

    2013-03-05

    Polyphenols, antioxidant potential and color of three types of fortified Madeira wines were evaluated during the accelerated ageing, named as estufagem. The traditional estufagem process was set to 45 °C for 3 months. Overheating conditions, 1 month at 70 °C, were also examined. Total polyphenols (TP), total monomeric anthocyanins (TMA) and total flavonoids (TF) were assessed by spectrophotometric methods, while individual polyphenols and furans were simultaneously determined by HPLC-DAD. Antioxidant potential (AP) was estimated by ABTS, DPPH and FRAP assays, while color was evaluated by Glories and CIELab. Traditional estufagem decreased the TP and AP up to 20% and 26%, respectively, with final values similar to other wines. TMA of the Madeira wines from red grapes decreased during estufagem. Six hydroxybenzoic acids, three hydroxycinnamic acids, one stilbene, three flavonols and three flavan-3-ols were found in these wines. The prominent phenolics were hydroxycinnamates and hydroxybenzoates, even after estufagem. Most polyphenols decreased, with the exception of caffeic, ferulic, p-coumaric, gallic and syringic acids. Finally, both chromatic systems revealed that all wines tended to similar chromatic characteristics after estufagem. The study suggests that estufagem can be applied without high impact on polyphenols and antioxidant potential of these fortified wines.

  9. Cyclic voltammetry to evaluate the antioxidant potential in winemaking by-products.

    PubMed

    José Jara-Palacios, M; Luisa Escudero-Gilete, M; Miguel Hernández-Hierro, J; Heredia, Francisco J; Hernanz, Dolores

    2017-04-01

    Grape pomace is composed of seeds, skins and stems that are an important source of phenolic substances, which have antioxidant properties and potential benefits to human health. Cyclic voltammetry (CV) has been used to measure the total antioxidant potential of different winemaking by-products. The electrochemical behavior of pomace, seeds, skins and stems was measured by CV and lipid peroxidation inhibition by thiobarbituric acid reactive substances (TBARS) method. Differences for the electrochemical parameter were found between the by-products, pomace and seeds, which presented the greatest voltammetric peak area. Furthermore, the by-products induced inhibition of lipid peroxidation in rat liver homogenates. Pomace and seeds showed higher capacity to inhibit lipid peroxidation than stems and skins, which could be because these by-products are richer in flavanols. Simple regression analyses showed that voltammetric parameters are highly correlated to the values obtained for lipid peroxidation inhibition. CV is a promising technique to estimate the total antioxidant potential of phenolic extract from winemaking by-products. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. New seminal variety of Stevia rebaudiana: Obtaining fractions with high antioxidant potential of leaves.

    PubMed

    Milani, Paula G; Formigoni, Maysa; Dacome, Antonio S; Benossi, Livia; Costa, Cecília E M DA; Costa, Silvio C DA

    2017-08-31

    The aim of this study was to determine the composition and antioxidant potential of leaves of a new variety of Stevia rebaudiana (Stevia UEM-13). Stevia leaves of UEM-13 contain rebaudioside A as the main glycoside, while most wild Stevia plants contain stevioside. Furthermore can be multiplied by seed, which reduces the cost of plant culture techniques as other clonal varieties are multiplied by buds, requiring sophisticated and expensive seedling production systems. Ethanol and methanol were used in the extraction to determine the bioactive compounds. The methanolic extract was fractionated sequentially with hexane, chloroform, ethyl acetate and isobutanol, and the highest concentration of phenolic compounds and flavonoids was obtained in the ethyl acetate fraction (524.20 mg galic acid equivalent/g; 380.62 µg quercetin equivalent/g). The glycoside content varied greatly among the fractions (0.5% - 65.3%). Higher antioxidant potential was found in the methanol extract and the ethyl acetate fraction with 93.5% and 97.32%, respectively. In addition to being an excellent source for obtaining of extracts rich in glycoside, this new variety can also be used as raw material for the production of extracts or fractions with a significant amount of antioxidant activity and potential to be used as additives in food.

  11. Potential food additives from Carex distachya roots: identification and in vitro antioxidant properties.

    PubMed

    Fiorentino, Antonio; Ricci, Andreina; D'Abrosca, Brigida; Pacifico, Severina; Golino, Annunziata; Letizia, Marianna; Piccolella, Simona; Monaco, Pietro

    2008-09-10

    In the present study, the chemical composition and antioxidant properties of root methanol extract of Carex distachya Desf. (Cyperaceae) were assessed to use this plant as sources of food additives and nutraceuticals. The IC50 of the extract (4.2 microg/mL), derived from the DPPH radical scavenging capacity assay, was similar to those of ascorbic acid, alpha-tocopherol, and BHT. These results revealed a strong antioxidant activity because of the presence of an extraordinary quantity of bioactive phytochemicals. The phytochemical study of the root extract led to the isolation and identification of new and known polyphenols, most of them common constituents of plant foods. A total of 16 polyphenols, identified on the basis of spectroscopic data as 7 lignans, 4 phenylethanoids, 3 resveratrol derivatives, a monolignol, and a secoiridoid glucoside, were isolated. The tentative structural elucidation of the new metabolites 5'-O-beta-D-glucopyranosyloxy-3,3'-dimethoxy-7,9'-epoxylignan-4,8',9-triol and 3,5-bis-O-beta-D-glucopyranosyloxy-3'-methoxy-trans-stilben-4'-ol have been performed by a combined approach using ESI/TQ/MS techniques and 1D and 2D NMR experiments. All of the compounds have been tested for their antioxidant activity using six different antioxidant and radical scavenging tests. Interestingly, the extract contained high quantities of polyphenols, most of them reported as constituents of edible plants, such as grape and olive, suggesting that the methanol root extract of this plant could be used as a source of natural antioxidants useful as potential food additives.

  12. Antioxidant activity measurement and potential antioxidant peptides exploration from hydrolysates of novel continuous microwave-assisted enzymolysis of the Scomberomorus niphonius protein.

    PubMed

    Huang, Yipeng; Ruan, Guihua; Qin, Zhijun; Li, Haiyun; Zheng, Yanjie

    2017-05-15

    A novel continuous microwave-assisted enzymatic digestion (cMAED) method is proposed for the digestion of protein from Scomberomorus niphonius to obtain potential antioxidant peptides. In this study, bromelain was found to have a high capacity for the digestion of the Scomberomorus niphonius protein. The following cMAED conditions were investigated: protease species, microwave power, temperature, bromelain content, acidity of the substrate solution, and incubation time. At 400W, 40°C, 1500U·g(-1) bromelain, 20% substrate concentration, pH 6.0 and 5min incubation, the degree of hydrolysis and total antioxidant activity of the hydrolysates were 15.86% and 131.49μg·mL(-1), respectively. The peptide analyses showed that eight of the potential antioxidant peptide sequences, which ranged from 502.32 to 1080.55Da with 4-10 amino acid residues, had features typical of well-known antioxidant proteins. Thus, the new cMAED method can be useful to obtain potential antioxidant peptides from protein sources, such as Scomberomorus niphonius. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Modeling of the total antioxidant capacity of rooibos (Aspalathus linearis) tea infusions from chromatographic fingerprints and identification of potential antioxidant markers.

    PubMed

    Orzel, Joanna; Daszykowski, Michal; Kazura, Malgorzata; de Beer, Dalene; Joubert, Elizabeth; Schulze, Alexandra E; Beelders, Theresa; de Villiers, André; Malherbe, Christiaan J; Walczak, Beata

    2014-10-31

    Models to predict the total antioxidant capacity (TAC) of rooibos tea infusions from their chromatographic fingerprints and peak table data (content of individual phenolic compounds), obtained using HPLC with diode array detection, were developed in order to identify potential antioxidant markers. Peak table data included the content of 12 compounds, namely phenylpyruvic acid-2-O-glucoside, aspalathin, nothofagin, isoorientin, orientin, ferulic acid, quercetin-3-O-robinobioside, vitexin, hyperoside, rutin, isovitexin and isoquercitrin. The TAC values, measured using the oxygen radical absorbance capacity (ORAC) and DPPH radical scavenging assays, could be predicted from the peak table data or the chromatographic fingerprints (prediction errors 9-12%) using partial least squares (PLS) regression. Prediction models created from samples of only two production years could additionally be used to predict the TAC of samples from another production year (prediction errors<13%) indicating the robustness of the models in a quality control environment. Furthermore, the uninformative variable elimination (UVE)-PLS method was used to identify potential antioxidant markers for rooibos infusions. All individual phenolic compounds that were quantified were selected as informative variables, except vitexin, while UVE-PLS models developed from chromatographic fingerprints indicated additional antioxidant markers, namely (S)-eriodictyol-6-C-glucoside, (R)-eriodictyol-6-C-glucoside, aspalalinin and two unidentified compounds. The potential antioxidant markers should be validated prior to use in quality control of rooibos tea.

  14. Quality control and in vitro antioxidant potential of Coriandrum sativum Linn.

    PubMed Central

    Singh, Mhaveer; Tamboli, E. T.; Kamal, Y. T.; Ahmad, Wasim; Ansari, S. H.; Ahmad, Sayeed

    2015-01-01

    Background: Coriandrum sativum Linn., commonly known as coriander, is a well-known spice and drug in India. It has various health-related benefits and used in various Unani formulations. In this present study, quality assessment of coriander fruits was carried out by studying anatomical characters, physicochemical tests, and chemoprofiling using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectroscopy (GC-MS) along with in vitro antioxidant potential. Materials and Methods: Standardization was carried out as per the pharmacopeial guidelines. Estimation of heavy metals, pesticides, and aflatoxins was carried out to ascertain the presence of any contaminant in the sample. Chemoprofiling was achieved by thin layer chromatography (TLC) by optimizing the mobile phase for different extracts. The most of the pharmacological activities of coriander are based on volatile oil constituents. Hence, GC-MS profiling was also carried out using hexane-soluble fraction of hydro-alcoholic extract. The total phenolic contents and in vitro antioxidant efficacy were determined using previously established methods. Results: The quality control and anatomical studies were very valuable for the identification whereas good antioxidant potential was observed when compared to ascorbic acid. The drug was found free of contaminant when analyzed for pesticides and aflatoxins whereas heavy metals were found under reported limits. Conclusion: The work embodied in this present research can be utilized for the identification and the quality control of the coriander fruit. PMID:26681883

  15. Chemical composition, antimicrobial and antioxidant potential of the essential oil of Guarea kunthiana A. Juss.

    PubMed

    Pandini, J A; Pinto, F G S; Scur, M C; Santana, C B; Costa, W F; Temponi, L G

    2017-07-27

    The essential oils are extracted from plant compounds and can present activities antimicrobial and antioxidant properties. The goals of the present study were: (a) to determine the chemical composition of the essential oil of Guarea kunthiana A. Juss using the method of gas chromatography coupled to mass spectrometry (GC-MS); (b) to evaluate the antimicrobial potential of this oil using the broth microdilution method against different microorganisms: five Gram-negative bacteria, four Gram-positive bacteria and a yeast and (c) to determine the antioxidant activity of the oil using the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical assay. The GC-MS analyses allowed identifying 13 constituents, representing 96.52% of the essencial oil composition. The main compounds identified were α-zingiberene (34.48%), β-sesquiphellandrene (22.90%), and α-curcumene (16.17%). With respect to the antimicrobial activity, the essential oil was effective against all the microorganisms tested, except for the bacteria E. coli and K. pneumoniae, which were resistant to the action of the oil. From a general point of view, Gram-positive bacteria were more susceptible to the action of the essential oil than Gram-negative bacteria. The essential oil exhibited antioxidant potential.

  16. Influence of gamma irradiation in the antioxidant potential of chestnuts (Castanea sativa Mill.) fruits and skins.

    PubMed

    Antonio, Amilcar L; Fernandes, Angela; Barreira, João C M; Bento, Albino; Botelho, M Luisa; Ferreira, Isabel C F R

    2011-09-01

    As seasonal products chestnuts have to be post-harvest treated to increase their shelf-life. The most common preservation method for chestnuts is the chemical fumigation with methyl bromide, a toxic agent that is under strictly Montreal Protocol due to its adverse effects on human health and environment. Food irradiation is a possible feasible alternative to substitute the traditional quarantine chemical fumigation treatment. This preliminary study evaluated the influence of gamma irradiation in the antioxidant potential of chestnut fruits and skins, through several chemical and biochemical parameters. The bioactive compounds (phenolics and flavonoids) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity, reducing power and inhibition of β-carotene bleaching capacity were determined. The obtained results seem to indicate that the storage favoured chestnuts antioxidant potential. Furthermore, the application of gamma irradiation also seems to be advantageous for antioxidant activity, independently of the dose used (0.27 ± 0.04 kGy or 0.54 ± 0.04 kGy).

  17. Antioxidant Potential of Momordica Charantia in Ammonium Chloride-Induced Hyperammonemic Rats

    PubMed Central

    Thenmozhi, A. Justin; Subramanian, P.

    2011-01-01

    The present study was aimed to investigate the antioxidant potential of Momordica charantia fruit extract (MCE) in ammonium chloride-induced (AC) hyperammonemic rats. Experimental hyperammonemia was induced in adult male Wistar rats (180–200 g) by intraperitoneal injections of ammonium chloride (100 mg kg−1 body weight) thrice a week. The effect of oral administration (thrice a week for 8 consecutive weeks) of MCE (300 mg kg−1 body weight) on blood ammonia, plasma urea, serum liver marker enzymes and oxidative stress biomarkers in normal and experimental animals was analyzed. Hyperammonemic rats showed a significant increase in the activities of thiobarbituric acid reactive substances, hydroperoxides and liver markers (alanine transaminase, aspartate transaminase and alkaline phosphatase), and the levels of glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione were decreased in the liver and brain tissues. Treatment with MCE normalized the above-mentioned changes in hyperammonemic rats by reversing the oxidant-antioxidant imbalance during AC-induced hyperammonemia, and offered protection against hyperammonemia. Our results indicate that MCE exerting the antioxidant potentials and maintaining the cellular integrity of the liver tissue could offer protection against AC-induced hyperammonemia. However, the exact underlying mechanism is yet to be investigated, and examination of the efficacy of the active constituents of the M. charantia on hyperammonemia is desirable. PMID:20047891

  18. Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer's disease.

    PubMed

    Choi, Dong-Young; Lee, Young-Jung; Hong, Jin Tae; Lee, Hwa-Jeong

    2012-02-10

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and most common cause of dementia. However, there is no known way to halt or cure the neurodegenerative disease. Oxidative stress is a cardinal hallmark of the disease and has been considered as therapeutic target for AD treatment. Several factors may contribute to oxidative stress in AD brains. First, mitochondrion is a key player that produces reactive oxygen species (ROS). Mitochondrial dysfunction found in AD patients may exaggerate generation of ROS and oxidative stress. Second, amyloid-beta peptide generates ROS in the presence of metal ions such as Fe(2+) and Cu(2+). Third, activated glial cells in AD brains may produce excessive amount of superoxide and nitric oxide through NADPH oxidase and inducible nitric oxide synthase, respectively. Increased ROS can cause damage to protein, lipid and nucleic acids. Numerous studies demonstrated that natural polyphenolic compounds protect against various neurotoxic insults in vitro and in vivo AD models. In these studies, dietary polyphenolic compounds exhibit neuroprotective effects through scavenging free radicals and increasing antioxidant capacity. Furthermore, they could facilitate the endogenous antioxidant system by stimulating transcription. Some epidemiological and clinical studies highlighted their therapeutic potential for AD treatment. In this review, we will briefly discuss causes of oxidative stress in AD brains, and describe antioxidant neuroprotective effects and therapeutic potential for AD of selected natural polyphenolic compounds.

  19. Investigation of Antioxidative and Anticancer Potentials of Streptomyces sp. MUM256 Isolated from Malaysia Mangrove Soil

    PubMed Central

    Tan, Loh Teng-Hern; Ser, Hooi-Leng; Yin, Wai-Fong; Chan, Kok-Gan; Lee, Learn-Han; Goh, Bey-Hing

    2015-01-01

    A Streptomyces strain, MUM256 was isolated from Tanjung Lumpur mangrove soil in Malaysia. Characterization of the strain showed that it has properties consistent with those of the members of the genus Streptomyces. In order to explore the potential bioactivities, extract of the fermented broth culture of MUM256 was prepared with organic solvent extraction method. DPPH and SOD activity were utilized to examine the antioxidant capacity and the results have revealed the potency of MUM256 in superoxide anion scavenging activity in dose-dependent manner. The cytotoxicity of MUM256 extract was determined using cell viability assay against 8 different panels of human cancer cell lines. Among all the tested cancer cells, HCT116 was the most sensitive toward the extract treatment. At the highest concentration of tested extract, the result showed 2.3-, 2.0-, and 1.8-folds higher inhibitory effect against HCT116, HT29, and Caco-2 respectively when compared to normal cell line. This result has demonstrated that MUM256 extract was selectively cytotoxic toward colon cancer cell lines. In order to determine the constituents responsible for its bioactivities, the extract was then subjected to chemical analysis using GC-MS. The analysis resulted in the identification of chemical constituents including phenolic and pyrrolopyrazine compounds which may responsible for antioxidant and anticancer activities observed. Based on the findings of this study, the presence of bioactive constituents in MUM256 extract could be a potential source for the development of antioxidative and chemopreventive agents. PMID:26635777

  20. Potential antioxidant capacity of sulfated polysaccharides from the edible marine brown seaweed Fucus vesiculosus.

    PubMed

    Rupérez, Pilar; Ahrazem, Oussama; Leal, J Antonio

    2002-02-13

    Fucus vesiculosus was sequentially extracted with water at 22 degrees C (fraction 1 (F1)) and 60 degrees C (F2), and with 0.1 M HCl (F3) and 2 M KOH (F4) at 37 degrees C. Soluble fractions (42.3% yield) were composed of neutral sugars (18.9-48 g/100 g), uronic acids (8.8-52.8 g/100 g), sulfate (2.4-11.5 g/100 g), small amounts of protein (< 1-6.1 g/100 g), and nondialyzable polyphenols (0.1-2.7 g/100 g). The main neutral sugars were fucose, glucose, galactose, and xylose. Infrared (IR) spectra of the fractions showed absorption bands at 820-850 and 1225-1250 cm(-1) for sulfate. F1, F2, and F4 also exhibited an absorption band at 1425 cm(-1), due to uronic acids, and their IR spectra resembled that of alginate. F3 had an IR spectrum similar to that of fucoidan with an average molecular weight of 1.6 x 10(6) Da, calculated by molecular exclusion high-performance liquid chromatography. The presence of fucose in this polysaccharide was confirmed by (1)H NMR spectroscopy. This fraction showed the highest potential to be antioxidant by the ferric reducing antioxidant power (FRAP) assay, followed by the alkali- and water-soluble fractions. Sulfated polysaccharides from edible seaweeds potentially could be used as natural antioxidants by the food industry.

  1. Phytochemical Characterization, Antimicrobial Activity, and Antioxidant Potential of Equisetum hyemale L. (Equisetaceae) Extracts.

    PubMed

    de Queiroz, Geisiany M; Politi, Flávio A S; Rodrigues, Edvânio R; Souza-Moreira, Tatiana M; Moreira, Raquel R D; Cardoso, Cássia R P; Santos, Lourdes C; Pietro, Rosemeire C L R

    2015-07-01

    Equisetum hyemale species is considered a medicinal plant used in the form of infusions to combat infectious or inflammation diseases and also diuretic effects, presenting several compounds related to these actions. In previous studies different species of Equisetum showed several phenolic compounds. The objective of this study was, for the first time, based on phytochemistry analysis to evaluate the antioxidant and antimicrobial activity. The 70% ethanolic and methanolic extracts of E. hyemale were characterized by spectrophotometric and high-performance liquid chromatography with pulsed amperometric detector analyses, as well as its antioxidant potential based on the scavenger activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition was verified the antimicrobial activity by broth microdilution technique against bacteria and fungi. The extracts showed phytochemical similarity, which demonstrated the presence of phenolic compounds, the scavenging activity for free radicals was about 30% and was observed better antifungal activity against dermatophyte fungi, with minimum inhibitory concentration and minimum fungicidal concentration of 0.62 mg/mL to Trichophyton rubrum and Microsporum canis. The extracts exhibits great potential to therapeutic applications or product development, since both possess antifungal activity and antioxidant action associated with little difference in their phytochemical composition.

  2. Chemical Characterization and Antioxidant Potential of Wild Ganoderma Species from Ghana.

    PubMed

    Obodai, Mary; Mensah, Deborah L Narh; Fernandes, Ângela; Kortei, Nii Korley; Dzomeku, Matilda; Teegarden, Matthew; Schwartz, Steven J; Barros, Lillian; Prempeh, Juanita; Takli, Richard K; Ferreira, Isabel C F R

    2017-01-25

    The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1-LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty acids, phenolic and other organic compounds and some vitamins and vitamin precursors. Antioxidant potential was evaluated by investigating reducing power, radical scavenging activity and lipid peroxidation inhibition using five in vitro assays. Protein, carbohydrate, fat, ash and energy contents ranged between 15.7-24.5 g/100 g·dw, 73.31-81.90 g/100 g, 0.48-1.40 g/100 g, 0.68-2.12 g/100 g ash and 396.1-402.02 kcal/100 g, respectively. Fatty acids such as linoleic, oleic and palmitic acids were relatively abundant. Free sugars included rhamnose, fructose, mannitol, sucrose and trehalose. Total tocopherols, organic acids and phenolic compounds' content ranged between 741-3191 µg/100 g, 77-1003 mg/100 g and 7.6-489 µg/100 g, respectively. There were variations in the β-glucans, ergosterol and vitamin D₂ contents. The three major minerals in decreasing order were K > P > S. Ganoderma sp. strain AM1 showed the highest antioxidant activity. This study reveals, for the first time, chemical characteristics of Ganoderma spp. which grew simultaneously on the same tree.

  3. Quality control and in vitro antioxidant potential of Coriandrum sativum Linn.

    PubMed

    Singh, Mhaveer; Tamboli, E T; Kamal, Y T; Ahmad, Wasim; Ansari, S H; Ahmad, Sayeed

    2015-01-01

    Coriandrum sativum Linn., commonly known as coriander, is a well-known spice and drug in India. It has various health-related benefits and used in various Unani formulations. In this present study, quality assessment of coriander fruits was carried out by studying anatomical characters, physicochemical tests, and chemoprofiling using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectroscopy (GC-MS) along with in vitro antioxidant potential. Standardization was carried out as per the pharmacopeial guidelines. Estimation of heavy metals, pesticides, and aflatoxins was carried out to ascertain the presence of any contaminant in the sample. Chemoprofiling was achieved by thin layer chromatography (TLC) by optimizing the mobile phase for different extracts. The most of the pharmacological activities of coriander are based on volatile oil constituents. Hence, GC-MS profiling was also carried out using hexane-soluble fraction of hydro-alcoholic extract. The total phenolic contents and in vitro antioxidant efficacy were determined using previously established methods. The quality control and anatomical studies were very valuable for the identification whereas good antioxidant potential was observed when compared to ascorbic acid. The drug was found free of contaminant when analyzed for pesticides and aflatoxins whereas heavy metals were found under reported limits. The work embodied in this present research can be utilized for the identification and the quality control of the coriander fruit.

  4. Optimization of Antioxidant Potential of Penicillium granulatum Bainier by Statistical Approaches

    PubMed Central

    Chandra, Priyanka; Arora, Daljit Singh

    2012-01-01

    A three-step optimization strategy which includes one-factor-at-a-time classical method and different statistical approaches (Plackett-Burman design and response surface methodology) that were applied to optimize the antioxidant potential of Penicillium granulatum. Antioxidant activity was assayed by different procedures and compared with total phenolic content. Primarily, different carbon and nitrogen sources were screened by classical methods, which revealed sucrose and NaNO3 to be the most suitable. In second step, Plackett-Burman design also supported sucrose and NaNO3 to be the most significant. In third step, response surface analysis showed 4.5% sucrose, 0.1% NaNO3, and incubation temperature of 25°C to be the optimal conditions. Under these conditions, the antioxidant potential assayed through different procedures was 78.2%, 70.1%, and 78.9% scavenging effect for DPPH radical, ferrous ion, and nitric oxide ion, respectively. The reducing power showed an absorbance of 1.6 with 68.5% activity for FRAP assay. PMID:23724323

  5. Antioxidant potential of indigenous cyanobacterial strains in relation with their phenolic and flavonoid contents.

    PubMed

    Ijaz, Saadia; Hasnain, Shahida

    2016-06-01

    Antioxidant activities of eight indigenous cyanobacterial strains belonging to the genera Oscillatoria, Chroococcidiopsis, Leptolyngbya, Calothrix, Nostoc and Phormidium were studied in relation with their phenolic and flavonoid contents, ranging 3.9-12.6 mg GAE g(-1) and 1.7-3.44 mg RE g(-1). The highest activities were shown by Leptolyngbya sp. SI-SM (EC50 = 63.45 and 67.49 μg mL(-1)) and Calothrix sp. SI-SV (EC50 = 65.79 and 69.38 μg mL(-1)) calculated with ABTS and DPPH assays. Significant negative correlations were seen between total phenolic and flavonoid contents and the antioxidant activities in terms of EC50 values. Furthermore, HPLC detected 15 phenolic compounds with total concentrations ranging from 277.3 to 829.7 μg g(-1). The prevalent compounds in most of the strains were rutin, tannic acid, orcinol, phloroglucinol and protocatechuic acid. Cyanobacterial strains showed high potential as a good source of phenolic compounds with potent antioxidative potential which could be beneficial for food, cosmetic and pharmaceutical industries.

  6. Angiotensin Mediated Oxidative Stress and Neuroprotective Potential of Antioxidants and AT1 Receptor Blockers.

    PubMed

    Prusty, Shakti Ketan; Sahu, Pratap Kumar; Subudhi, Bharat Bhusan

    2017-01-01

    Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central renin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration. Although it has shown promise, clinical efficacy is limited to few drugs including telmisartan mainly due to the poor brain availability of others. In this review we aim to analyze the potential of antioxidants to reduce oxidative stress in brain. We have given critical analysis of the approaches for re-purposing of AT1 blockers against oxidative stress induced neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires

    NASA Astrophysics Data System (ADS)

    Vernekar, Amit A.; Sinha, Devanjan; Srivastava, Shubhi; Paramasivam, Prasath U.; D'Silva, Patrick; Mugesh, Govindasamy

    2014-11-01

    Nanomaterials with enzyme-like properties has attracted significant interest, although limited information is available on their biological activities in cells. Here we show that V2O5 nanowires (Vn) functionally mimic the antioxidant enzyme glutathione peroxidase by using cellular glutathione. Although bulk V2O5 is known to be toxic to the cells, the property is altered when converted into a nanomaterial form. The Vn nanozymes readily internalize into mammalian cells of multiple origin (kidney, neuronal, prostate, cervical) and exhibit robust enzyme-like activity by scavenging the reactive oxygen species when challenged against intrinsic and extrinsic oxidative stress. The Vn nanozymes fully restore the redox balance without perturbing the cellular antioxidant defense, thus providing an important cytoprotection for biomolecules against harmful oxidative damage. Based on our findings, we envision that biocompatible Vn nanowires can provide future therapeutic potential to prevent ageing, cardiac disorders and several neurological conditions, including Parkinson’s and Alzheimer’s disease.

  8. Antioxidant potential of silk protein sericin against hydrogen peroxide-induced oxidative stress in skin fibroblasts.

    PubMed

    Dash, Rupesh; Acharya, Chitrangada; Bindu, P C; Kundu, S C

    2008-03-31

    The antioxidant potential of silk protein sericin from the non-mulberry tropical tasar silkworm Antheraea mylitta cocoon has been assessed and compared with that of the mulberry silkworm, Bombyx mori. Skin fibroblast cell line (AH927) challenged with hydrogen peroxide served as the positive control for the experiment. Our results showed that the sericin obtained from tasar cocoons offers protection against oxidative stress and cell viability is restored to that of control on pre-incubation with the sericin. Fibroblasts pre-incubated with non-mulberry sericin had significantly lower levels of catalase; lactate dehydrogenase and malondialdehyde activity when compared to untreated ones. This report indicates that the silk protein sericin from the non-mulberry tropical tasar silkworm, A. mylitta can serve as a valuable antioxidant.

  9. Antioxidant, total phenolic contents and antinociceptive potential of Teucrium stocksianum methanolic extract in different animal models

    PubMed Central

    2014-01-01

    Background Oxidative stress and analgesia are connected with different pathological conditions. The drug candidates from synthetic sources are associated with various side effects; therefore, researchers are giving priority to find novel, effective and safe phytomedicines. Teucrium species possesses antioxidant, analgesic, anti-inflammatory and hepatoprotective activities. The essential oils of Teucrium stocksianum have shown strong antinociceptive potential. Our current study is designed to embark total phenolic content (TPC), antioxidant and antinociceptive potential of the methanolic extract of Teucrium stocksianum (METS). Method Phytochemical composition was determined by using standard methods. Free radical scavenging potential and TPC of METS were assessed by using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) and Folin-Ciocalteu Reagent (FCR) respectively. Antinociceptive potential was determined by acetic acid induced abdominal writhing, formalin induced paw licking and tail immersion tests. Different test dose 50, 100 and 150 mg/kg body weight of METS were administered intra peritonealy (i.p) to various groups of mice for the evaluation of analgesic potential. Results Phytochemical screening confirmed the presence of flavonoids, tannins, saponins, anthraquinone, steroid, phlobatannin, terpenoid, glycoside and reducing sugars. METS was found safe at a dose of 1000 mg/kg body weight. A concentration dependent free radical scavenging effect was observed with methanolic aerial parts extract of Teucrium stocksianum (MAPETS) and methanolic roots extracts of Teucrium stocksianum (MRETS). MAPETS and MRETS have shown highest antioxidant activity 91.72% and 86.19% respectively at 100 μg/ml. MAPETS was found more rich (115.32 mg of GAE/g of dry material) in TPC as compared to MAPETS (105.41 mg of GAE/g). METS demonstrated a dose dependent antinociceptive potential in different pain models, like in acetic acid, formalin and tail immersion showing 83.103%, 80.872% and 67

  10. Antioxidant Potential of Vespa affinis L., a Traditional Edible Insect Species of North East India

    PubMed Central

    Dutta, Prachurjya; Dey, Tapan; Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Introduction Elevated oxidative stress plays an important role in the pathogenesis of health disorders, like arthritis. Traditionally, Vespa affinis L., a common edible insect among many tribes in North-East India, is believed to have a beneficial role in extenuating health disorders, such as arthritis. The present study investigated the molecular mechanism underlying medicinal benefit of the Aqueous Extract of Vespa affinis L. (AEVA) against oxidative stress pathophysiology. Methods The free radical scavenging activities of AEVA were examined against DPPH, hydroxyl, and superoxide radicals and the effect on the activities of antioxidant enzyme (GST and CAT) was determined using both recombinant proteins and human plasma. The antioxidant potential of AEVA was again investigated using THP-1 monocytes. Results AEVA possesses a significant free radical scavenging activity as evident from the DPPH, superoxide, and hydroxyl radical scavenging assay. Incubation of AEVA (2.5, 5, 7.5, and 10 μg/μL) with the recombinant antioxidant enzymes, rGST and rCAT significantly increased the enzyme activities compared to those observed in corresponding enzyme alone or AEVA itself. AEVA supplementation (5, 7.5, and 10 μg/μL) also stimulates the activities of GST and CAT when incubated with human plasma. A cell culture study also confirmed the beneficial role of AEVA (0.8 and 1.2 μg/μL) which enhances the activities of GST and CAT, and also reduces the intercellular ROS production in monocytes treated with or without H2O2 and the effects are at par with what is observed in N-acetyl cysteine-treated cells. Conclusion The antioxidant potential of the aqueous extract of Vespa affinis L. may mediate its therapeutic activities in oxidative stress-associated health disorders. PMID:27195807

  11. [Inhibitory effect of human mitochondria-targeted MPG recombinant on proliferation of human non-small cell lung cancer multidrug-resistant cell line A549/DDP].

    PubMed

    Yu, Shi-Cang; Qian, Gui-Sheng; Li, Yu-Ying; Lu, Wei-Zhong; Li, Jin; Huang, Gui-Jun

    2006-04-01

    Multidrug resistance is the key obstacle to the improvement of chemotherapy effect of lung cancer. This study was to construct eukaryotic expression vector of human mitochondria-targeted N-methylpurine DNA glycosylase (MPG), and explore its inhibitory effect on proliferation of human non-small cell lung cancer multidrug-resistant cell line A549/DDP. Manganese-superoxide dismutase mitochondria-targeted sequence-MPG fusion gene (mito-MPG) was constructed through splicing by overlap extension (SOE). Recombinant eukaryotic expression vector pCMV-Script/mito-MPG was constructed by molecule-cloning technique, and then transfected into A549/DDP cells. In the stably transfected cells which were screened out by G418, the expression of mito-MPG mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR); its expression in separated and purified mitochondria was detected by Western blot. The proliferation of A549/DDP cells was detected by trypan blue exclusion trial. Cell cycle distribution was analyzed by flow cytometry. The mito-MPG fusion gene was confirmed by DNA sequencing,the recombinant pCMV-Script/mito-MPG was confirmed by restrictive endonuclease digestion and DNA sequencing. mito-MPG mRNA and protein were detected in the cells transfected with pCMV-Script/mito-MPG (MPG group), but not in the cells transfected with pCMV-Script (P group) and untransfected cells (C group). The cell double time were 72.6 h in C group, 73.5 h in P group, and 98.9 h in MPG group. Cell cycle blockage and subdiploid peak were found in MPG group. The proliferation indexes were 51.3% in C group, 54.3% in P group, and 26.1% in MPG group. pCMV-Script/mito-MPG could be constructed and transfected into mitochondria of A549/DDP cells successfully, and inhibit proliferation and induce apoptosis of A549/DDP cells.

  12. Total phenols, antioxidant potential and antimicrobial activity of walnut (Juglans regia L.) green husks.

    PubMed

    Oliveira, Ivo; Sousa, Anabela; Ferreira, Isabel C F R; Bento, Albino; Estevinho, Letícia; Pereira, José Alberto

    2008-07-01

    The total phenols content and antioxidant and antimicrobial activities were studied in walnut (Juglans regia L.) green husks aqueous extracts of five different cultivars (Franquette, Mayette, Marbot, Mellanaise and Parisienne). Total phenols content was determined by colorimetric assay and their amount ranged from 32.61 mg/g of GAE (cv. Mellanaise) to 74.08 mg/g of GAE t (cv. Franquette). The antioxidant capacity of aqueous extracts was assessed through reducing power assay, scavenging effects on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and beta-carotene linoleate model system. A concentration-dependent antioxidative capacity was verified in reducing power and DPPH assays, with EC50 values lower than 1 mg/mL for all the tested extracts. The antimicrobial capacity was screened against Gram positive and Gram negative bacteria, and fungi. All the extracts inhibited the growth of Gram positive bacteria, being Staphylococcus aureus the most susceptible one with MIC of 0.1 mg/mL for all the extracts. The results obtained indicate that walnut green husks may become important in the obtainment of a noticeable source of compounds with health protective potential and antimicrobial activity.

  13. A potential link among antioxidant enzymes, histopathology and trace elements in canine visceral leishmaniasis

    PubMed Central

    Souza, Carolina C; Barreto, Tatiane de O; da Silva, Sydnei M; Pinto, Aldair W J; Figueiredo, Maria M; Ferreira Rocha, Olguita G; Cangussú, Silvia D; Tafuri, Wagner L

    2014-01-01

    Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu-Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL. PMID:24766461

  14. Evaluation of in vitro antioxidant potential of aqueous extract of Trapa natans L. fruits.

    PubMed

    Malviya, Neelesh; Jain, Sanjay; Jain, Avnish; Jain, Sourabh; Gurjar, Rajenda

    2010-01-01

    In the present study, the in vitro antioxidant potential of aqueous extract of Trapa natans L. fruits rind was investigated. The extract was found to contain a large amount of polyphenols and also exhibited an immense reducing ability. The total content of phenolic, flavonoid and tannin compounds was estimated as 63.81 mg of gallic acid equivalents/g of dry material, 21.34 mg of rutin equivalents/g of dry material and 17.11 mg of total tannin equivalent /g of dry material, respectively. IC50 values for different antioxidant model were calculated as 128.86 microg/mL for DPPH radicals, 97.65 microg/mL for O2*-, 148.32 microg/mL for H2O2 and 123.01 microg/mL for NO, respectively. Reducing power and inhibition of *OH radical-induced BSA oxidation were also determined. The data obtained in the present study suggest that the aqueous extract of Trapa natans L. fruit rind have significant antioxidant activity against free radicals.

  15. Nutritional values and antioxidant potential of some edible mushrooms of Kashmir valley.

    PubMed

    Boda, Rouf Hamza; Wani, Abdul Hamid; Zargar, Mohammad Afzal; Ganie, Bashir Ahmad; Wani, Bilal Ahmad; Ganie, Showkat Ahmad

    2012-07-01

    Mushrooms are considered rich in proteins, carbohydrates and other nutrients. The present study was carried out to evaluate some edible mushrooms of Kashmir valley for their protein, carbohydrate and lipid contents. The highest protein content was found in Boletus edulis (2.20g) followed by Agaricus bisporus (1.80g), Pleurotus ostreatus (1.68g), Morchella esculenta (1.62g) and Pleurotus sajor caju (1.6g). Carbohydrate content also showed variation in all the five tested edible mushroom species, the highest carbohydrate content observed in Boletus edulis (6.0g) followed by Agaricus bisporus (4.85g), Pleurotus ostreatus (4.30g), Morchella esculenta (4.25g) and Pleurotus sajor caju (3.35g) respectively. Similar results were observed for lipid content. The present study was also investigated for the antioxidant potential of aqueous extract of mushroom species by the methods of DPPH radical scavenging activity, hydroxyl radical scavenging activity and superoxide radical scavenging activity. All these in vitro antioxidant activities were concentration dependent, which were compared with standard antioxidant Catechin.

  16. Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants.

    PubMed

    Chakraborty, Kajal; Joseph, Deepu; Joy, Minju; Raola, Vamshi Krishna

    2016-12-01

    The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2'-diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7μM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6μM, respectively), followed by 3 (IC50 231.2 and 667.9μM, respectively), and 2 (IC50 322.4 and 5115.3μM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries.

  17. Polyphenol, antioxidant and antimicrobial potential of six different white and red wine grape processing leftovers.

    PubMed

    Trošt, Kajetan; Klančnik, Anja; Mozetič Vodopivec, Branka; Sternad Lemut, Melita; Jug Novšak, Katja; Raspor, Peter; Smole Možina, Sonja

    2016-11-01

    During winemaking, grape polyphenols are only partly extracted, and consequently unexploited. The main aim was to characterize the phenolic content of freeze-dried grape skin and seed (FDSS) extracts obtained from Slovenian and international grape varieties and to evaluate their antioxidant, antimicrobial and anti-adhesive activities. FDSS of six Vitis vinifera L. grapevine cultivars from Vipava Valley region (Slovenia) underwent extraction and sonification under different conditions. Flavonols were the predominant content of extracts from white 'Zelen' and 'Sauvignon Blanc' grape varieties, with strong antimicrobial activities against Gram-negative bacteria. 'Pinot Noir' FDSS extracted with 50% aqueous ethanol extraction produced a high phenolic content in the final extract, which was further associated with strong antioxidant and antimicrobial activities against all tested bacteria. Bacterial adhesion to stainless steel surfaces with minimal and maximal surface roughness was significantly inhibited (up to 60%) across a wide FDSS concentration range, with lower concentrations also effective with two types of stainless steel surfaces. FDSS extracts from winery by-products show interesting phenolic profiles that include flavonols, catechins, anthocyanins and hydroxycinnamic acids, with yields influenced by grapevine cultivar and extraction conditions. The antioxidant, antimicrobial and anti-adhesive activities of 50% aqueous ethanol 'Pinot Noir' FDSS extract reveals potential applications in food, pharmaceutical and cosmetic industries for these bioactive residues. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma.

    PubMed

    Zaknun, Daniela; Schroecksnadel, Sebastian; Kurz, Katharina; Fuchs, Dietmar

    2012-01-01

    A significant increase in the incidence of allergy and asthma has been observed during the past decades. The background of this phenomenon has not been well explained, but changes in lifestyle and habits are heavily discussed as contributing factors. Among these is a too clean environment, which may predispose individuals to increased sensitivity to allergic responses. Also the increase in dietary supplements including preservatives and colorants may contribute to this. In vitro, we and others have shown in freshly isolated human peripheral blood mononuclear cells that antioxidant compounds like vitamins C and E as well as food preservatives and colorants exert significant suppressive effects on the Th1 immune activation cascade. The effects observed may be based on the interaction of antioxidant compounds with proinflammatory cascades involving important signal transduction elements such as nuclear factor-κB. Although only obtained in vitro, these results show an anti-inflammatory property of compounds which could shift the Th1-Th2-type immune balance towards Th2-type immunity. This review article discusses the potential role of increased use of antioxidant food supplements as well as preservatives and colorants in the increase in allergy and asthma in the Western world.

  19. Potential Role of Carotenoids as Antioxidants in Human Health and Disease

    PubMed Central

    Fiedor, Joanna; Burda, Květoslava

    2014-01-01

    Carotenoids constitute a ubiquitous group of isoprenoid pigments. They are very efficient physical quenchers of singlet oxygen and scavengers of other reactive oxygen species. Carotenoids can also act as chemical quenchers undergoing irreversible oxygenation. The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids, which, although not synthesized by humans and animals, are also present in their blood and tissues, contributing to a number of biochemical processes. The antioxidant potential of carotenoids is of particular significance to human health, due to the fact that losing antioxidant-reactive oxygen species balance results in “oxidative stress”, a critical factor of the pathogenic processes of various chronic disorders. Data coming from epidemiological studies and clinical trials strongly support the observation that adequate carotenoid supplementation may significantly reduce the risk of several disorders mediated by reactive oxygen species. Here, we would like to highlight the beneficial (protective) effects of dietary carotenoid intake in exemplary widespread modern civilization diseases, i.e., cancer, cardiovascular or photosensitivity disorders, in the context of carotenoids’ unique antioxidative properties. PMID:24473231

  20. IN VITRO AND IN VIVO EVALUATION OF ANTIMICROBIAL AND ANTIOXIDANT POTENTIAL OF STEVIA EXTRACT.

    PubMed

    Moselhy, Said S; Ghoneim, Magdy A; Khan, Jehan A

    2016-01-01

    The current trend globally is the utilization of natural products as therapeutic agents given its minimum side effects. The leaves of Stevia contain several active ingredient compounds such as rebaudioside. Stevia extract have been used for many purposes. Active oxygen radicals can induce base modifications, DNA breakage, and intracellular protein crosslink's. This study was done to evaluate the potential of stevia extract as antibacterial and antioxidants actions. Antibacterial activity of different extracts of stevia was tested in vitro against different species of bacteria and hepato-protective efficacy was testes in rats injected with CCl4 as hepatotoxic. Acetone extract exhibited antibacterial activity against selected five bacteria species. The acetone extract suppressed the elevation of serum ALT (p <0.05) and AST (p <0.001) activities induced by CCl4. Animals given stevia extract showed prevention against deleterious effects of CCl4 by lowering lipid peroxidation and enhancement of antioxidant activities as SOD and CAT. The protection trial is better than treatment trial. Total phenolic content of aqueous and acetone extracts were found 30 mg and 85 mg gallic /gm extract respectively. While the total flavonoids were 40 mg and 80 mg quercetin/g respectively. The GC-MS analysis showed that monoterpene and indole are the main components. Aqueous extract don't show any antibacterial activity against the tested strains. The antioxidant properties were attributable to its phenolic content to scavenge free radicals. Acetone extract possess a potent antimicrobial and activity against deleterious effect of CCl4-caused liver damage.

  1. Relationship between total phenolic content, antioxidant potential, and antiglycation abilities of common culinary herbs and spices.

    PubMed

    Ramkissoon, Jugjeet S; Mahomoodally, Mohamad Fawzi; Ahmed, Nessar; Subratty, Anwar H

    2012-12-01

    Advanced glycation endproducts and oxidative stress contribute to the pathogenesis of diabetic complications. The total phenolic content (TPC), antioxidant, and antiglycation properties of crude ethanolic extracts of 10 common culinary herbs and spices from Mauritius were investigated in vitro. Fluorescence at 370 nm/440 nm was used as an index of albumin glycation. Allium sativum had the highest TPC (3.1 mg GAE/mL), whereas Allium cepa L. showed the highest radical scavenging capacity (72%) and Zingiber officinale had the most potent ferric-reducing antioxidant power (FRAP; 2.99 mg AAE/mL). In contrast, Thymus vulgaris and Petroselinum crispum had the most potent antiglycation activity with IC(50) values of 21.8 and 200 mg/mL, respectively. There was no significant correlation between TPC (r=0.001), FRAP (r=0.161), and the antiglycation activity (r=0.034) for the extracts studied. Therefore, the results showed that antiglycation properties of plant-derived extracts cannot always be attributed to their phenolic content or antioxidant potential.

  2. Copper complexes bearing 2-aminobenzothiazole derivatives as potential antioxidant: Synthesis, characterization.

    PubMed

    Joseph, J; Janaki, G Boomadevi

    2016-09-01

    Novel copper complexes of Schiff base ligands of 2-aminobenzothiazole derivatives were synthesized by the condensation of Knoevenagel condensate of acetoacetanilide (obtained from substituted benzaldehydes and acetoacetanilide) and 2-aminobenzothiazole. They were characterized by elemental analysis, IR, (1)H NMR, UV-Vis., molar conductance, magnetic susceptibility measurements and electrochemical studies. Based on the magnetic moment and electronic spectral data, square planar geometry has been suggested for all the complexes. Antibacterial and antifungal screening of the ligands and their complexes reveal that all the complexes show higher activities than the ligands. The binding behaviour of the complexes with calf thymus DNA has been investigated by electronic absorption spectra, viscosity measurements and cyclic voltammetry. The DNA binding constants reveal that all these complexes interact with DNA through intercalation binding mode. Superoxide dismutase and antioxidant activities of the copper complexes have also been studied. The antioxidant activities of the complexes showed higher activities. Thermal denaturation studies suggested the nature binding affinity of copper complexes with CT-DNA. All complexes exhibit suitable Cu(II)/Cu(I) redox potential to act as antioxidant enzymes mimic. Further, the copper complexes also showed catalase activity. It is hope that copper complexes were capable of decrease ROS levels or reduce oxidative stress in Alzheimer's patients.

  3. Pro-oxidant and antioxidant potential of catecholestrogens against ferrylmyoglobin-induced oxidative stress.

    PubMed

    Martínez, Rosa; Quintana, Kristina; Navarro, Rosaura; Martín, César; Hernández, M Luisa; Aurrekoetxea, Igor; Ruiz-Sanz, José Ignacio; Lacort, Mercedes; Ruiz-Larrea, M Begoña

    2002-07-11

    Ferryl heme proteins may play a major role in vivo under certain pathological conditions. Catecholestrogens, the estradiol-derived metabolites, can act either as antioxidants or pro-oxidants in iron-dependent systems. The aim of the present work was (1) to determine the effects of ferrylmyoglobin on hepatocyte cytotoxicity, and (2) to assess the pro/antioxidant potential of a series of estrogens (phenolic, catecholic and stilbene-derived) against ferrylmyoglobin induced lipid peroxidation in rat hepatocytes. Cells were exposed to metmyoglobin plus hydrogen peroxide to form ferrylmyoglobin in the presence of the transition metal chelator diethylentriaminepentaacetic acid. Results showed that ferrylmyoglobin induced an initial oxidative stress, mainly reflected in an early lipid peroxidation and further decrease in GSH and ATP. However, cells gradually adapted to this situation, by recovering the endogenous ATP and GSH levels at longer incubation times. Phenolic and stilbene-derived estrogens inhibited ferrylmyoglobin-induced lipid peroxidation to different degrees: diethylstilbestrol>estradiol>resveratrol. Catecholestrogens at concentrations higher than 1 microM also inhibited lipid peroxidation with similar efficacy. The ability of estrogens to reduce ferrylmyoglobin to metmyoglobin may account for their antioxidant activity. In contrast, physiological concentrations (100 pM-100 nM) of the catecholestrogens exerted pro-oxidant activities, 4-hydroxyestradiol being more potent than 2-hydroxyestradiol. The implications of these interactions should be considered in situations where local myoglobin or hemoglobin microbleeding takes place.

  4. A potential link among antioxidant enzymes, histopathology and trace elements in canine visceral leishmaniasis.

    PubMed

    Souza, Carolina C; Barreto, Tatiane de O; da Silva, Sydnei M; Pinto, Aldair W J; Figueiredo, Maria M; Rocha, Olguita G Ferreira; Cangussú, Silvia D; Tafuri, Wagner L

    2014-08-01

    Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu-Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL.

  5. Assessment of rosmarinic acid content in six Lamiaceae species extracts and their antioxidant and antimicrobial potential.

    PubMed

    Benedec, Daniela; Hanganu, Daniela; Oniga, Ilioara; Tiperciuc, Brindusa; Olah, Neli-Kinga; Raita, Oana; Bischin, Cristina; Silaghi-Dumitrescu, Radu; Vlase, Laurian

    2015-11-01

    In the present study, six indigenous species of Lamiaceae family (Origanum vulgare L., Melissa officinalis L., Rosmarinus officinalis L., Ocimum basilicum L., Salvia officinalis L. and Hyssopus officinalis L.), have been analyzed to assess the rosmarinic acid, phenyl propane derivatives and polyphenolic contents and their antioxidant and antimicrobial potential. HPLC-MS method has been used for the analysis ofrosmarinicacid. The phenyl propane derivatives and total phenolic contents were determined using spectrophotometric method. The ethanolic extracts were screened for antioxidant activities by DPPH radical scavenging, HAPX (hemoglobin ascorbate per oxidase activity inhibition), and EPR (electron paramagnetic resonance) methods. The ethanolic extracts revealed the presence of rosmarinic acid in the largest amount in O. vulgare (12.40mg/g) and in the lowest in R. officinalis (1.33 mg/g). O. vulgare extracts exhibited the highest antioxidant capacity, in line with the rosmarinic acid and polyphenolic contents. The antimicrobial testing showed a significant activity against L. monocytogenes, S. aureus and C. albicans for all six extracts.

  6. Impact of Elicitation on Antioxidant and Potential Antihypertensive Properties of Lentil Sprouts.

    PubMed

    Peñas, Elena; Limón, Rocío I; Martínez-Villaluenga, Cristina; Restani, Patrizia; Pihlanto, Anne; Frias, Juana

    2015-12-01

    The aim of this study was to investigate the application of elicitors (500 μM ascorbic acid, 50 μM folic acid, 5 mM glutamic acid and 50 ppm chitosan in 5 mM glutamic acid) during lentil germination up to 8 days as a strategy to increase germination rate and to enhance the accumulation of γ-aminobutyric acid (GABA) and phenolic compounds. The effect of elicitation on the protein profile and antioxidant and angiotensin I converting enzyme (ACE) inhibitory activities of sprouted lentils was also evaluated. The application of elicitors did not negatively affect the germination yield of lentils and no significant changes on the protein pattern of lentils germinated in the presence of elicitors were observed. Chitosan/glutamic acid increased by 1.6-fold the GABA content in lentil sprouts, whilst ascorbic and folic acids as well as chitosan/glutamic acid were highly effective to enhance the total content of phenolic compounds and the antioxidant activity of sprouted lentils. All elicited lentil sprouts showed ability to inhibit ACE activity (IC50: 9.5-11.9 μg peptides/mL). Therefore, elicitation can be considered a promising approach to improve the content of compounds with antioxidant and potential antihypertensive activities in lentil sprouts.

  7. Identification of potential antioxidant indices by biogenic gold nanoparticles in hyperglycemic Wistar rats.

    PubMed

    Sengani, Manimegalai; V, Devi Rajeswari

    2017-03-01

    Oxidative stress is a crucial factor in diabetes, where the abnormal metabolic ambience leads to hyperglycemia resulting in the onset of several vascular complications. Under homeostasis, innate antioxidants efficiently inhibit the oxidative stress, thereby restrain further progression of diabetes. In the present study, a potential antioxidant marker was identified from hepatic tissue of diabetic Wistar rats after oral administration of biogenic gold nanoparticles (GNPs). Diabetic animals treated with GNPs showed increase in insulin level and subsequently reduced the concentration of blood glucose level to normal. Further, GNPs favoured to retain the hepatic enzymatic markers, serum lipid levels and followed by renal biochemical profile in the rats. In addition, GNPs treated rats displayed an elevated level of lipid peroxidation, superoxide dismutase, glutathione peroxidase, and catalase enzymatic activity. Consequently, GNPs treated rats showed diminished level of histological injury in the hepatic, renal, and pancreatic tissues. Taken together, these results suggested that among the several antioxidant enzymes, catalase elucidated the highest area under curve (AUC) with 0.80 accomplished by receiver operating characteristic (ROC) curve. Collectively, our findings enlighten that GNPs treated rat able to alleviate the hyperglycemic condition due to the enzymatic activity of catalase.

  8. Evaluation of antioxidant potential of Lavandula x intermedia Emeric ex Loisel. 'Budrovka': a comparative study with L. angustifolia Mill.

    PubMed

    Blazeković, Biljana; Vladimir-Knezević, Sanda; Brantner, Adelheid; Stefan, Maja Bival

    2010-08-30

    A Croatian indigenous cultivar of lavandin, Lavandula x intermedia 'Budrovka' (Lamiaceae) was studied for the phenolic acids, flavonoids, anthocyanins, procyanidins and total tannins, as well as total polyphenols content, in the flower, inflorescence stalk and leaf ethanolic extracts. Antioxidant potentials on these plant part extracts were assessed by the DPPH free radical scavenging activity, iron chelating activity, reducing power, lipid peroxidation inhibition properties and total antioxidant capacity assays. All results were compared with those of Lavandula angustifolia, the only member of the Lavandula genus officially used in modern phytotherapy. Based on the results of our parallel study, we may suggest that Lavandula x intermedia 'Budrovka' is as potent an antioxidant as Lavandula angustifolia and the antioxidant activity of the Lavandula extracts is mainly due to the presence of rosmarinic acid. A good correlation was found between the polyphenol contents and antioxidant activities of the extracts.

  9. Seagrass as a potential source of natural antioxidant and anti-inflammatory agents.

    PubMed

    Yuvaraj, N; Kanmani, P; Satishkumar, R; Paari, A; Pattukumar, V; Arul, V

    2012-04-01

    Halophila spp. is a strong medicine against malaria and skin diseases and is found to be very effective in early stages of leprosy. Seagrasses are nutraceutical in nature and therefore of importance as food supplements. The antibacterial, antioxidant, and anti-inflammatory activities of Halophila ovalis R. Br. Hooke (Hydrocharitaceae) methanol extract were investigated and the chemical constituents of purified fractions were analyzed. Plant materials were collected from Pondicherry coastal line, and antimicrobial screening of crude extract, and purified fractions was carried out by the disc diffusion method and the minimum inhibitory concentration (MICs) of the purified fractions and reference antibiotics were determined by microdilution method. Antioxidant and anti-inflammatory activities were investigated in vitro. Chemical constituents of purified fractions V and VI were analyzed by gas chromatography-mass spectrometry (GC-MS), and the phytochemicals were quantitatively determined. Methanol extract inhibited the growth of Bacillus cereus at a minimum inhibitory concentration of 50 µg/mL and other Gram-negative pathogens at 75 µg/ml, except Vibrio vulnificus. Reducing power and total antioxidant level increased with increasing extract concentration. H. ovalis exhibited strong scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals at IC(50) of 0.13 and 0.65 mg/mL, respectively. Methanol extract of H. ovalis showed noticeable anti-inflammatory activity at IC(50) of 78.72 µg/mL. The GC-MS analysis of H. ovalis revealed the presence of triacylglycerols as major components in purified fractions. Quantitative analysis of phytochemicals revealed that phenols are rich in seagrass H. ovalis. These findings demonstrated that the methanol extract of H. ovalis exhibited appreciable antibacterial, noticeable antioxidant, and anti-inflammatory activities, and thus could be use as a potential source for natural health products.

  10. Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

    PubMed Central

    Engwa, Godwill Azeh; Ayuk, Eugene Lekem; Igbojekwe, Benardeth Ujunwa; Unaegbu, Marcellus

    2016-01-01

    The global increase in oxidative stress related diseases such as cancer, cardiovascular, and inflammatory diseases caused by overwhelming level of free radicals in the body has encouraged the search for new antioxidant agents. Based on the ability of newly synthesized phenothiazine derivatives (6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one) to oxidize H2O2, a known free radical to sulfoxide, this study assessed the in vitro and in vivo antioxidant activity. The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe3+ to Fe2+ and high ability to scavenge H2O2 free radical in vitro. These activities were comparable to ascorbic acid, a standard antioxidant. The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo. The malondialdehyde level in groups 1 and 2 animals was lower than that in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent suggesting the ability of the phenothiazine derivatives to prevent lipid membrane damage. AST and bilirubin levels were higher in group 2 animals which received 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one compared to group 3, the positive control. The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic. This activity may be due to the presence of electron donors such as sulfur as well as the richness of hydrogen in the additional benzene rings for substitution. Further study is needed to identify tolerable doses for possible therapeutic purposes. PMID:27127652

  11. Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes.

    PubMed

    Phang, Chung-Weng; Malek, Sri Nurestri Abd; Ibrahim, Halijah

    2013-10-01

    lines with IC₅₀ of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters. The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer.

  12. Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes

    PubMed Central

    2013-01-01

    effect against KB, Ca Ski and HCT 116 cell lines with IC50 of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters. Conclusions The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer. PMID:24083445

  13. Effect of antioxidant potential of tropical fruit juices on antioxidant enzyme profiles and lipid peroxidation in rats.

    PubMed

    Pereira, Ana Carolina da Silva; Dionísio, Ana Paula; Wurlitzer, Nedio Jair; Alves, Ricardo Elesbão; de Brito, Edy Souza; e Silva, Ana Mara de Oliveira; Brasil, Isabella Montenegro; Mancini Filho, Jorge

    2014-08-15

    Fruits are a rich source of a variety of biologically active compounds that can have complementary and overlapping mechanisms of action, including detoxification, enzyme modulation and antioxidant effects. Although the effects of tropical fruits have been examined individually, the interactive antioxidant capacity of the bioactive compounds in these formulations has not been sufficiently explored. For this reason, this study investigated the effect of two tropical fruit juices (FA and FB) on lipid peroxidation and antioxidant enzymes in rats. Seven groups, with eight rats each, were fed a normal diet for 4 weeks, and were force-fed daily either water (control), 100, 200, or 400 mg of FA or FB per kg. The results showed that the liver superoxide dismutase and catalase activities (FA200), erythrocytes glutathione peroxidase (FB400) and thiobarbituric acid-reactive substances (FB100, FA400, FB200, FB400) were efficiently reduced by fruit juices when compared with control; whereas HDL-c increased (FB400).

  14. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions

    PubMed Central

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  15. Phenolic profile and antioxidant potential of wild watercress (Nasturtium officinale L.).

    PubMed

    Zeb, Alam

    2015-01-01

    Phenolic profile, antioxidant potential and pigment contents of wild watercress (Nasturtium officinale L.) were studied to assess the potential for future studies and its applications in neutraceuticals and bioactive functional ingredients. Different extracts of watercress (roots, stem and leaves) were analysed for pigment composition, total phenolic contents, and radical scavenging activity. The phenolic profile of the leaves and roots was studied using reversed phase HPLC-DAD. Results showed that total phenolic compounds in all samples were higher in the methanolic extracts than its corresponding aqueous extracts. The RSA of methanolic extracts was higher than aqueous extracts. Fourteen phenolic compounds were identified in the leaves, where coumaric acid and its derivatives, caftaric acid and quercetin derivatives were present in higher amounts. In roots, a total of 20 compounds was tentatively identified, with coumaric acid and its derivatives, sinapic acid, caftaric acid and quercetin derivatives were the major phenolic compounds. In conclusion, watercress has significant antioxidant activity and contains important phenolic compounds, which could be of potential biological interest.

  16. Antioxidant Potential of the Giant Mushroom, Macrocybe gigantea (Agaricomycetes), from India in Different Drying Methods.

    PubMed

    Gaur, Tanvi; Rao, P B

    2016-01-01

    Free radicals are responsible for several diseases like cancer, atherosclerosis, gastric ulcers, and several others. Studies have shown that mushrooms possess antioxidant activity and Macrocybe gigantea was recently added to the list of mushrooms under cultivation in India. The methanolic extracts were prepared from lyophilized and oven-dried samples of MA1 and MA2 strains of M. gigantea and their antioxidant properties were studied. MA2 showed comparatively higher total antioxidant activity (111.88 µg/mg) than MA1 (97.00 µg/mg). The scavenging activity on 2,2'-diphenyl picryl hydrazyl free radical (74.41%), ferrous chelating (83.74%), reducing power (0.371), and superoxide anion radical (72.05%) was significantly higher in freeze-dried MA2 than MA1 at 200 µg/mL. Correspondingly, the EC50 values were lower in freeze-dried states (96.03 µg/mL, 95.00 µg/mL, and 68.12 µg/mL in MA2 and 105.12 µg/mL, 109.8 µg/mL, and 74.60 µg/mL in MA1) than in oven-dried states (97.97 µg/mL, 120.2 µg/mL, and 125.33 µg/mL in MA2 and 108.3 µg/mL, 131.2 µg/mL, and 147.5 µg/mL in MA1, respectively). In addition, total phenolic, total flavonoid, and ortho-dihydroxy phenol content was examined and their values were comparatively higher in freeze-dried MA2 (18.00 mg/g of gallic acid equivalents, 1.67 mg/g of quercetin equivalents, and 1.10 mg/g of catechol equivalents, respectively) than in MA1 and oven-dried states in both strains. Further, MA2 showed lower EC50 values in freeze-dried samples than MA1 and oven-dried states in both strains. These results suggested that MA2 contains higher antioxidant potential than MA1 and freeze-drying by lyophilization retains higher antioxidants than heat drying by a hot air oven in both the strains; thus, they can be a good source of nutraceuticals.

  17. Microwave assisted extraction, antioxidant potential and chromatographic studies of some Rasayana drugs.

    PubMed

    Mishra, Ashish; Mishra, Shilpi; Bhargav, Shilpi; Bhargava, Cs; Thakur, Mayank

    2015-07-01

    To study and compare the conventional extraction procedure with microwave assisted extraction (MAE) for some Ayurvedic Rasayana drugs and to evaluate their antioxidant potential and carry out the characterization of extracts by thin layer chromatography. Three Ayurvedic rasayana plants Allium sativum Linn., Bombax ceiba Linn. and Inula racemosa Hook. were evaluated for an improved MAE methodology by determining the effects of grinding degree, extraction solvent, effect of dielectric constant and duration of time on the extractive value. Antioxidant potential of all three drugs was evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power was determined by using Gallic acid as standard. Further thin layer chromatographic (TLC) analysis was performed on pre-activated Silica Gel G plates and Rf value were compared with those reported for the important biomarkers. The total extractive value for Allium sativum Linn. was 36.95% (w/w) and 49.95% (w/w) for ethanol extraction respectively. In case of Bombax ceiba Linn. the yield of aqueous extract by MAE was 50% (w/w) compared to 42% (w/w) in ethanol (50% v/v). Percent yield of Inula racemosa Hook. in aqueous extract was found to be 27.55% (w/w) which was better than ethanol extract (50%) where the yield was 25.95% (w/w). Upon antioxidant activity evaluation. sativum extract showed an absorbance of 0.980±0.92 at concentration of 500 μg with maximum reducing capacity. This was followed by. ceiba Linn. 0.825±0.98 and. racemosa Hook. with 0.799±2.01 at a concentration of 500 μg. TLC based standardization of. sativum Linn. extract shows single spot with Rf value of 0.38, B. ceiba Linn. extract shows Rf values were 0.23, 0.58, 0.77, 0.92 and I. racemosa Hook. extract spot had a Rf value of 0.72. A significant improvement in extractive values was observed as a factor of time and other advantages by using MAE technology. All three drugs have high antioxidant potential and a TLC

  18. Thermal and photo-stability of the antioxidant potential of Spirulina platensis powder.

    PubMed

    Colla, L M; Bertol, C D; Ferreira, D J; Bavaresco, J; Costa, J A V; Bertolin, T E

    2016-09-26

    This work aimed to evaluate the thermal and photo stability of the antioxidant potential (AP) of the Spirulina platensis biomass. Thermal stability was established at 25ºC, 40ºC and 50ºC for 60 days, in the dark, protected from light. Photo stability was evaluated using UV (15 W, λ = 265 nm) and fluorescent (20 W, 0.16 A, power factor FP > 0.5, 50/60 Hz, 60 lm/w, 1200 lm) light for 90 days in capsules, glass and Petri dishes, at room temperature. The AP of the biomass in these conditions was determined at intervals (every 7 and 30 days in the studies of thermal and photo stability, respectively) using the induction of the oxidation of a lipid system by heat and aeration. In this lipid system, the biomass submitted to degradation was used as an antioxidant. The kinetics of the reaction was determined by the Arrhenius method. Thermal degradation was found to follow zero order kinetics, whereas photo degradation followed first order kinetics. The AP decreased 50% after 50 days at 25°C. At 40°C and 50°C, the AP decreased more than 50% after 35 and 21 days of exposition, respectively. The decrease of the AP of Spirulina was more sensible to UV and fluorescence light. After 30 days of exposition, the AP decreased more than 50% in all storage conditions tested. The antioxidant potential of Spirulina platensis is easily degraded when the biomass is exposed to heat and light, indicating the need for care to be taken in its storage.

  19. Preparation, characterization and in vitro antioxidative potential of synbiotic fermented dairy products.

    PubMed

    Shah, C; Mokashe, N; Mishra, V

    2016-04-01

    The present study, evaluates the antioxidative potential of two synbiotic dairy products viz. synbiotic lassi with honey and whey based synbiotic drink with inulin and orange juice, along with their physicochemical and microbiological activity during storage period. Antioxidative potential of raw ingredients and probiotic cultures used to prepare synbiotic products was also evaluated. Synbiotic lassi with honey was prepared using Streptococcus thermophilus MTCC 5460 (MD2) and Lactobacillus helveticus MTCC 5463 (V3) as probiotics and honey as prebiotic. For preparation of whey based synbiotic drink, Lactobacillus helveticus MTCC 5463 and inulin were used as probiotic and prebiotic, respectively and orange juice was also incorporated. Titratable acidity and pH of both synbiotic products followed a similar pattern of increase or decrease during storage. Furthermore, no major changes were observed in viability of probiotic cultures under storage conditions adapted. The hydroxyl radical scavenging activity of synbiotic lassi with honey was found to significantly decrease from 107.76 to 79.41 % at the end of storage whereas, the activity of whey based synbiotic drink was 100.32 % which declined sharply to 79.21 % on 7th day but further increased to 102.59 % on 14th day. The DPPH (α, α-Diphenyl-β-Picrylhydrazyl) radical scavenging activity of freshly prepared synbiotic lassi with honey was 28.43 % which decreased to 23.03 % on 7th day while for whey based synbiotic drink decreased from 26.85 % (0 day) to 17.12 % (7th day) and continued to decline. Moreover, probiotic strains used for synbiotic preparation also demonstrated good antioxidative activity.

  20. Effect of Long-Term Treatment with Antioxidant SkQ1 Added to Drinking Water on Cytochromes P450 Level in Rat Liver.

    PubMed

    Myasoedova, K N; Silachev, D N

    2015-12-01

    Mitochondria-targeted cationic antioxidant plastoquinonyl decyltriphenylphosphonium (SkQ1) added to drinking water in therapeutic doses (250 nmol/kg per day) for a long time (up to 24 months) does not induce cytochromes P450 in rat liver.

  1. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine

    PubMed Central

    2010-01-01

    . wallichii and H. antidysenterica - showed moderate antioxidant activity. Finally, potentially significant oxidative DNA damage preventive activity and antioxidant activity were noted in three plant extracts: C. icosandra, R. damascena and C. scariosus. These three plant extracts showed no cytotoxic activity against U937 cells. Conclusions The 50% methanolic extracts obtained from different plant parts contained significant amounts of polyphenols with superior antioxidant activity as evidenced by the scavenging of DPPH·, ABTS·+, NO, ·OH, O2.- and ONOO-. C. icosandra, R. damascena and C. scariosus showed significant potential for preventing oxidative DNA damage and radical scavenging activity, and the G. gummifera, A. pindrow, V. wallichii, H. antidysenterica, A. pyrethrum, A. tenuifolius and O. mascula extracts showed moderate activity. The extracts of C. icosandra, R. damascena and C. scariosus showed no cytotoxicity against U937 cells. In conclusion, these routinely used Unani plants, especially C. icosandra, R. damascena and C. scariosus, which are reported to have significant activity against several human ailments, could be exploited as potential sources of natural antioxidants for plant-based pharmaceutical industries. PMID:21159207

  2. Oxidative DNA damage preventive activity and antioxidant potential of plants used in Unani system of medicine.

    PubMed

    Kalim, Mehar Darukhshan; Bhattacharyya, Dipto; Banerjee, Anindita; Chattopadhyay, Sharmila

    2010-12-16

    . pindrow, V. wallichii and H. antidysenterica - showed moderate antioxidant activity. Finally, potentially significant oxidative DNA damage preventive activity and antioxidant activity were noted in three plant extracts: C. icosandra, R. damascena and C. scariosus. These three plant extracts showed no cytotoxic activity against U937 cells. The 50% methanolic extracts obtained from different plant parts contained significant amounts of polyphenols with superior antioxidant activity as evidenced by the scavenging of DPPH(·), ABTS(·+), NO, (·)OH, O₂(·⁻) and ONOO(⁻). C. icosandra, R. damascena and C. scariosus showed significant potential for preventing oxidative DNA damage and radical scavenging activity, and the G. gummifera, A. pindrow, V. wallichii, H. antidysenterica, A. pyrethrum, A. tenuifolius and O. mascula extracts showed moderate activity. The extracts of C. icosandra, R. damascena and C. scariosus showed no cytotoxicity against U937 cells. In conclusion, these routinely used Unani plants, especially C. icosandra, R. damascena and C. scariosus, which are reported to have significant activity against several human ailments, could be exploited as potential sources of natural antioxidants for plant-based pharmaceutical industries.

  3. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme-A Potential Selective Radioprotector.

    PubMed

    Pan, Jianru; He, Huocong; Su, Ying; Zheng, Guangjin; Wu, Junxin; Liu, Shutao; Rao, Pingfan

    2016-01-01

    Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent.

  4. The effect of industrial food processing on potentially health-beneficial tomato antioxidants.

    PubMed

    Capanoglu, Esra; Beekwilder, Jules; Boyacioglu, Dilek; De Vos, Ric C H; Hall, Robert D

    2010-11-01

    Increasing desires from both consumers and producers to understand better which nutritive components are present in our food and how these are influenced by industrial processing strategies is resulting in extra research involving the use of state-of-the-art technologies to generate novel biochemical information. In this review, attention has been focused on tomato as this is a product eaten right across the world both as fresh produce and after having been processed in a wide variety of ways. There is a particular interest in tomato as it is a major component in the so-called "Mediterranean diet" which has recently been associated with a healthier lifestyle. Tomatoes are rich sources of a variety of nutritional compounds and especially some key antioxidant components such as the carotenoid lycopene, vitamin C, and a range of polyphenols. The potentially protective properties of these antioxidants are of great interest and the consumer has already become aware of their potential importance. Surveying the literature has revealed that much research has been done on the biochemical composition of tomato and its products. However, it remains difficult to make clear conclusions on optimizing the processing strategy. Many, apparently conflicting, findings have been reported and consequently, in this review, we have drawn attention to these and have attempted to clarify their cause. Finally, a range of recommendations has been made as to how future research might be performed in order to generate more concrete conclusions enabling recommendations towards more optimized processing strategies.

  5. Exploring the antioxidant potential of lignin isolated from black liquor of oil palm waste.

    PubMed

    Bhat, Rajeev; Khalil, H P S A; Karim, A A

    2009-09-01

    This study was conducted to evaluate the potential antioxidant activity of lignin obtained from black liquor, a hazardous waste product generated during the extraction of palm oil. Antioxidant potential of the extracted lignin was evaluated by dissolving the extracted samples in 2 different solvent systems, namely, 2-methoxy ethanol and DMSO. Results revealed high percent inhibition of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical in the lignin sample dissolved in 2-methoxy ethanol over DMSO (concentration range of 1-100 microg/ml). Lignin extracted in 2-methoxy ethanol exhibited higher inhibition percentage (at 50 microg/ml, 84.2%), whereas a concentration of 100 microg/ml was found to be effective in the case of the DMSO solvent (69.8%). Fourier transform infrared (FTIR) spectrometry revealed that the functional groups from the extracted lignin and commercial lignin were highly similar, indicating the purity of the lignin extracted from black liquor. These results provide a strong basis for further applications of lignin in the food industry and also illustrate an eco-friendly approach to utilize oil palm black liquor.

  6. THIOCYANATE: A potentially useful therapeutic agent with host defense and antioxidant properties✩

    PubMed Central

    Chandler, Joshua D.; Day, Brian J.

    2014-01-01

    Thiocyanate (SCN) functions in host defense as part of the secreted lactoperoxidase (LPO) microbicidal pathway. SCN is the preferred substrate for LPO-driven catalytic reduction of hydrogen peroxide (H2O2) forming hypothiocyanous acid (HOSCN). HOSCN is selectively generated by many peroxidase enzymes that can utilize SCN including: eosinophil peroxidase (EPO), gastric peroxidase (GPO), myeloperoxidase (MPO), salivary peroxidase (SPO), and thyroid peroxidase (TPO). These enzymes generate HOSCN through a two-electron halogenation reaction. HOSCN is a potent microbicidal agent that kills or nullifies invading pathogens but is better tolerated by host tissue. Some controversy exists as to whether physiologic levels of HOSCN are non-toxic to host tissue, but the disagreement appears to be based on results of enzymatic generation (yielding moderate steady-state exposure) versus direct high level acute exposure in mammalian cell lines. This apparent duality is also true of other endogenous oxidants such as hydrogen peroxide and relates to the difference between physiologically relevant oxidant production versus supra-physiologic bolus dosing approaches. SCN has antioxidant properties that include the ability to protect cells against oxidizing agents such as hypochlorous acid (HOCl) and repair protein chloramines. SCN is an important endogenous molecule that has the potential to interact in complex and elegant ways with its host environment and foreign organisms. SCN’s diverse properties as both host defense and antioxidant agent make it a potentially useful therapeutic. PMID:22968041

  7. Antimicrobial, antioxidant and cytotoxicity potential of Manihot multifida (L.) Crantz (Euphorbiaceae).

    PubMed

    Fabri, Rodrigo L; De Sá, Daniel S; Pereira, Ana Patrícia O; Scio, Elita; Pimenta, Daniel S; Chedier, Luciana M

    2015-03-01

    Manihot multifida (L.) Crantz (Euphorbiaceae) is widely used in popular medicine for the treatment of infected wounds. This study evaluated the in vitro antioxidant and antimicrobial potential of this species against strains of Gram-positive and Gram-negative bacteria and fungi, known to cause infections in humans. The extracts showed minimal inhibitory concentration (MIC) varying from 39 to 2500 µg/mL for antimicrobial activity. The methanolic extract of fruits, aqueous and hexane extracts of leaves showed a very strong activity against Candida albicans (ATCC 18804) with MIC of 39 µg/mL. Furthermore, the methanolic extract of M. multifida leaves exhibited DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging potential with inhibitory concentration (IC50) values of 46.9 μg/mL, followed by hexane extract of leaves with IC50 values of 59.2 μg/mL. The cytotoxic activity against brine shrimp was stronger for the methanolic extract of leaves (lethal concentration - LC50 of 15.6 µg/mL). These results suggest that M. multifida has interesting antimicrobial and antioxidant activities. Moreover, these results corroborate the popular use of this specie in treating fungal infections since it demonstrates significant activity against C. albicans.

  8. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme—A Potential Selective Radioprotector

    PubMed Central

    Pan, Jianru; He, Huocong; Su, Ying; Zheng, Guangjin; Wu, Junxin; Liu, Shutao; Rao, Pingfan

    2016-01-01

    Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent. PMID:27313832

  9. Genetic Transformation and Hairy Root Induction Enhance the Antioxidant Potential of Lactuca serriola L.

    PubMed Central

    Elkelish, Amr; Elansary, Hosam O.; Ali, Hayssam M.; Elshikh, Mohamed; Witczak, Jacques; Ahmad, Margaret

    2017-01-01

    Lactuca serriola L. is a herbaceous species, used for human nutrition and medicinal purposes. The high antioxidant capacity of L. serriola indicates the possibility of enhancing its edible and health potential by increasing the flavonoid and phenolic contents. The present study aimed at enhancing the production of phenolics and flavonoids by hairy root cultures in Lactuca serriola transformed with Agrobacterium rhizogenes strain AR15834 harbouring the rolB gene. The genetic transformation of rolB in transformed roots was validated, and rolB expression level was evaluated using real-time qPCR analysis. Expression levels of flavonoid biosynthesis genes (CHI, PAL, FLS, and CHS) were assessed in the hairy and nontransformed roots. Results showed higher expression levels in the transgenic roots than in the nontransformed ones (p < 0.01). Transgenic hairy roots exhibited a 54.8–96.7% increase in the total phenolic content, 38.1–76.2% increase in the total flavonoid content, and 56.7–96.7% increase in the total reducing power when compared with the nontransgenic roots (p < 0.01). DPPH results also revealed that the transgenic hairy roots exhibited a 31.6–50% increase in antioxidant potential, when compared to normal roots. This study addressed the enhancement of secondary metabolite biosynthesis by hairy root induction in L. serriola. PMID:28835782

  10. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats.

    PubMed

    Asdaq, Syed Mohammed Basheeruddin; Inamdar, Mohammed Naseeruddin

    2010-09-01

    The aim of the present study was to evaluate the hypolipidemic and antioxidant potential of saffron and its active constituent, crocin, in hyperlipidemic rats. The animals fed either with normal fat diet or high fat diet were administered orally saffron (25, 50, and 100 mg/kg) or crocin (4.84, 9.69, and 19.38 mg/kg) in their respective groups for five consecutive days. Biochemical estimations of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione peroxidase enzyme activity (GSHPx), total glutathione (GSH), and oxidized glutathione (GSSG) in serum and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive species (TBARS), ferric reducing/antioxidant power (FRAP), and total sulfhydryl (SH) groups in liver tissue homogenate were carried out. Both saffron and crocin were effective in decreasing the elevated levels of TG, TC, ALP, AST, ALT, MDA, GSHPx, GSH, and GSSG in serum and increasing SOD, CAT, FRAP, and SH values in liver tissue with reduction in TBARS. The saffron was found to be superior to crocin indicating the involvement of other potential constituents of saffron apart from crocin for its synergistic behavior of quenching the free radicals and ameliorating the damages of hyperlipidemia.

  11. Antioxidant potential and its relationship with polyphenol content and degree of polymerization in Opuntia elatior Mill. fruits

    PubMed Central

    Itankar, Prakash R.; Sontakke, Varsha A.; Tauqeer, Mohd.; Charde, Sonal S.

    2014-01-01

    Background: Opuntia elatior Mill. (Nagaphani) fruits are traditionally recommended as an expectorant, remedy for whooping cough, asthma, gonorrhea, ulcers, tumors, in the treatment of diarrhea and syphilis. Many of these diseases are allied with oxidative stress caused by free radicals. Thus, current research is directed towards finding naturally-occurring antioxidants of plant origin. Aim: To evaluate antioxidant potential of hydro-alcoholic extract of the O. elatior fruits (HAOE) and its fractions. Materials and Methods: Using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assay, total polyphenolic, flavonoid (FA), flavanone (FO) contents and degree of polymerization in relation with its antioxidant activity were examined. Results: The experimental data indicated that the HAOE, ethyl acetate (EAOE) and butanol (BFOE) soluble fractions have shown significant antioxidant activity. The highest polyphenolic, FA, FO contents and degree of polymerization were found in EAOE. The scavenging potential was in the order of Ascorbic Acid > EAOE > BFOE > HAOE > BIOE, where ascorbic acid was used as a positive control. The increased antioxidant potential of EAOE and BFOE fractions over HAOE extract may be attributed to the purification achieved by fractionation of the extract which in turn resulted in an increase in the degree of polymerization and segregation of secondary metabolites. Conclusion: The fruit of O. elatior can be used as the best alternative for synthetic antioxidants. PMID:26195906

  12. Assessment of the antioxidant potential of selected plant extracts--in vitro and in vivo experiments on pork.

    PubMed

    Lahucky, Rudolf; Nuernberg, Karin; Kovac, Lubomir; Bucko, Ondrej; Nuernberg, Gerd

    2010-08-01

    The antioxidant potential of selected plant extracts was assessed in vitro and in vivo experiments on pork. In the in vitro experiment, the anti-oxidative capacity of ethanol-water extract of Melissa officinalis (MW), ethanol-propylene-glycol extracts of M. officinalis (MP), Origanum vulgaris (O) and Salvia officinalis (S) at different dilutions was analysed. Furthermore a 2% essential oil concentrate was added to Origanum (OSi) and Salvia (SSi). In the two in vivo experiments in total 104 Slovak White Meaty pigs were fed with plant extracts (MW and O) at different doses with/without additional vitamin E. In the in vitro experiment Melissa (MW) showed a higher antioxidant potential compared to Origanum and Salvia assessed by TEAC assay. Addition of essential oil to Origanum improved substantially the anti-oxidative capacity. In the in vivo experiment the highest muscle anti-oxidative effect was obtained by feeding 60 ml Origanum. Small improvement in muscle antioxidant potential was observed by feeding Melissa or Origanum in combination with vitamin E. By feeding 10 ml Melissa, Origanum or Salvia the meat quality parameters such as pH(1) and pH(24), drip loss and shear force was not affected. After 5 days storage of meat the redness value was positively affected. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  13. Phytochemicals from Kigelia pinnata leaves show antioxidant and anticancer potential on human cancer cell line.

    PubMed

    Atolani, Olubunmi; Olatunji, Gabriel A; Fabiyi, Oluwatoyin Adenike; Adeniji, Adekunle J; Ogbole, Omonike O

    2013-10-01

    Studies suggest that the traditional applications of Kigelia pinnata leaves have beneficial effects against oxidative stress-mediated diseases and cancers. The pulverized dried leaves of K. pinnata were extracted with hexane, ethyl acetate, and methanol sequentially, and the crude extracts were fractionated by silica gel column chromatography with solvent gradient of increasing polarity. 3-hydro-4,8-phytene, trans-phytol, (9Z,12Z)-methyl octadeca-9,12-dienoate, and two oil fractions were obtained. The chemical compositions of chromatographic fractions were determined using gas chromatography-mass spectroscopy. The structure elucidations of the isolated compounds were based on FTIR, MS, and NMR spectral data analyses. These along with the crude extracts were examined for their antioxidant activities using ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) assays. Total phenolic contents were also determined. The crude extracts and purified compounds were evaluated on the rhabdomyosarcoma human cancer cell for their cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays. The methanol extract was richer in phenolics and was most potent as antioxidant and cytotoxic agent among all the substances tested. Among the fractions and pure compounds, the two oil fractions showed more cytotoxicity potency, with IC50s of 143.4±0.5 and 147.9±1.3 ng/mL, which is more significant than the reference standard, cyclophosphamide (165.6±1.0 ng/mL). 3-hydro-4,8-phytene showed lower antioxidant and cytotoxicity potential (IC50=1818±5.2 μg/mL and 171.7±0.8 ng/mL, respectively). Trans-phytol did not show a high cytotoxic power (IC50=769.8±4.3 ng/mL). The comparatively high cytotoxicity index of (9Z, 12Z)-methyl octadeca-9,12-dienoate (IC50=153.3±0.1 ng/mL) indicated that it may be one of the principal cytotoxic agent in

  14. Antioxidant and Antibacterial Potential of Silver Nanoparticles: Biogenic Synthesis Utilizing Apple Extract

    PubMed Central

    Gulati, Neha

    2016-01-01

    The advancement of the biological production of nanoparticles using herbal extracts performs a significant role in nanotechnology discipline as it is green and does not engage harsh chemicals. The objective of the present investigation was to extract flavonoids in the mode of apple extract and synthesize its silver nanoparticles and ultimately nanoparticles loading into hydrogels. The presence of flavonoids in apple extract was characterized by preliminary testing like dil. ammonia test and confirmatory test by magnesium ribbon test. The synthesized silver nanoparticles were characterized using UV spectroscopy, particle size and surface morphology, and zeta potential. Silver nanoparticles loaded hydrogels were evaluated for physical appearance, pH, viscosity, spreadability, porosity, in vitro release, ex vivo permeation, and antibacterial (E. coli and S. aureus) and antioxidant studies (DPPH radical scavenging assay). Well dispersed silver nanoparticles below were observed in scanning electron microscope image. Hydrogels displayed in vitro release of 98.01%  ±  0.37% up to 24 h and ex vivo permeation of 98.81  ±  0.24% up to 24 h. Hydrogel effectively inhibited the growth of both microorganism indicating good antibacterial properties. The value of percent radical inhibition was 75.16%  ±  0.04 revealing its high antioxidant properties. As an outcome, it can be concluded that antioxidant and antiageing traits of flavonoids in apple extract plus biocidal feature of silver nanoparticles can be synergistically and successfully utilized in the form of hydrogel. PMID:28018705

  15. Antioxidant Potential, DNA Protection, and HPLC-DAD Analysis of Neglected Medicinal Jurinea dolomiaea Roots

    PubMed Central

    Shah, Naseer Ali; Khan, Muhammad Rashid; Naz, Kiran; Khan, Mubarak Ali

    2014-01-01

    Jurinea dolomiaea Boiss., family Compositae, is a medicinally important plant of alpine region. Its tuberous roots are used in various ailments in folk medicine. This study was undertaken to estimate total phenolic (TPC) and total flavonoid contents (TFC) and to determine anti-free radical potential by diverse in vitro antioxidant assays. Crude methanol extract (JDME) was fractionated into n-hexane (JDHE), chloroform (JDCE), ethyl acetate (JDEE), n-butanol (JDBE), and aqueous (JDAE) fractions. The results indicated that JDEE and JDCE constituted the highest amount of TFC (807 ± 7.2 mg rutin equivalent/g sample) and TPC (757 ± 9.4 mg gallic acid equivalent/g sample), respectively. Significant correlation of TFC with IC50 values was recorded for •OH (R 2 = 0.91), H2O2 (R 2 = 0.82), and ABTS (R 2 = 0.82) assay. It could be made clear that JDEE was the most potent in antioxidant activity as compared to others, with generally lower IC50 values for DPPH (41.1 ± 1.0 μg/mL), ABTS (46.7 ± 0.6 μg/mL), H2O2 (42.2 ± 0.9 μg/mL), •OH (61.1 ± 1.1 μg/mL), O2 − (152 ± 1.1 μg/mL), and antilipid peroxidation (54.3 ± 1.6 μg/mL). HPLC chromatogram of JDEE revealed the presence of catechin, caffeic acid, and rutin. The results indicated the antioxidant activities of J. dolomiaea roots and merit further investigations for their use in oxidative stress related disorders. PMID:24982907

  16. Antioxidant and Antibacterial Potential of Silver Nanoparticles: Biogenic Synthesis Utilizing Apple Extract.

    PubMed

    Nagaich, Upendra; Gulati, Neha; Chauhan, Swati

    2016-01-01

    The advancement of the biological production of nanoparticles using herbal extracts performs a significant role in nanotechnology discipline as it is green and does not engage harsh chemicals. The objective of the present investigation was to extract flavonoids in the mode of apple extract and synthesize its silver nanoparticles and ultimately nanoparticles loading into hydrogels. The presence of flavonoids in apple extract was characterized by preliminary testing like dil. ammonia test and confirmatory test by magnesium ribbon test. The synthesized silver nanoparticles were characterized using UV spectroscopy, particle size and surface morphology, and zeta potential. Silver nanoparticles loaded hydrogels were evaluated for physical appearance, pH, viscosity, spreadability, porosity, in vitro release, ex vivo permeation, and antibacterial (E. coli and S. aureus) and antioxidant studies (DPPH radical scavenging assay). Well dispersed silver nanoparticles below were observed in scanning electron microscope image. Hydrogels displayed in vitro release of 98.01%  ±  0.37% up to 24 h and ex vivo permeation of 98.81  ±  0.24% up to 24 h. Hydrogel effectively inhibited the growth of both microorganism indicating good antibacterial properties. The value of percent radical inhibition was 75.16%  ±  0.04 revealing its high antioxidant properties. As an outcome, it can be concluded that antioxidant and antiageing traits of flavonoids in apple extract plus biocidal feature of silver nanoparticles can be synergistically and successfully utilized in the form of hydrogel.

  17. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals.

    PubMed

    Neroev, V V; Archipova, M M; Bakeeva, L E; Fursova, A Zh; Grigorian, E N; Grishanova, A Yu; Iomdina, E N; Ivashchenko, Zh N; Katargina, L A; Khoroshilova-Maslova, I P; Kilina, O V; Kolosova, N G; Kopenkin, E P; Korshunov, S S; Kovaleva, N A; Novikova, Yu P; Philippov, P P; Pilipenko, D I; Robustova, O V; Saprunova, V B; Senin, I I; Skulachev, M V; Sotnikova, L F; Stefanova, N A; Tikhomirova, N K; Tsapenko, I V; Shchipanova, A I; Zinovkin, R A; Skulachev, V P

    2008-12-01

    Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age-induced cataract and retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 microM SkQ1 (one drop daily). SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular diseases.

  18. The Antioxidant Potential of Azadirachta indica Ameliorates Cardioprotection Following Diabetic Mellitus-Induced Microangiopathy

    PubMed Central

    Gupta, Naveen Kumar; Srivastva, Nidhi; Bubber, Parvesh; Puri, Sanjeev

    2016-01-01

    /kg body weight) post-STZ treatment significantly reversed the adverse effects witnessed by normalized blood glucose levels, improvement in reduced body weight and stabilized lipid profilesFurther, ALE treatment also significantly reduced the LPO indices, improvement in GSH content and restoration of antioxidant enzyme activities, suggesting antioxidatant potential of ALEThe microangiopathic changes in the heart tissue consequent to induction of diabetes and oxidative stress by STZ as reiterated through light microscopy and transmission electron microscopy were found to be reversed by ALE treatment. These observations pointed toward cardiopreventive effects of ALE following microangiopathic changes as seen following induction of diabetes mellitus. Abbreviations used: AI: Azadirachta indica, ALE: Azadirachta indica Leaves Extract. STZ: Streptozotocin, LPO Lipid per oxidation, GSH: Glutathione, GSSG: Glutathione disulphide, SOD: Superoxide dismutase, GP: Glutathione peroxidase, GR: Glutathione reductase. PMID:27563227

  19. Fluorescence spectroscopy and principal component analysis of soy protein hydrolysate fractions and the potential to assess their antioxidant capacity characteristics.

    PubMed

    Ranamukhaarachchi, Sahan A; Peiris, Ramila H; Moresoli, Christine

    2017-02-15

    The potential of intrinsic fluorescence and principal component analysis (PCA) to characterize the antioxidant capacity of soy protein hydrolysates (SPH) during sequential ultrafiltration (UF) and nanofiltration (NF) was evaluated. SPH was obtained by enzymatic hydrolysis of soy protein isolate. Antioxidant capacity was measured by Oxygen Radical Absorbance Capacity (ORAC) and Folin Ciocalteau Reagent (FCR) assays together with fluorescence excitation-emission matrices (EEM). PCA of the fluorescence EEMs revealed two principal components (PC1-tryptophan, PC2-tyrosine) that captured significant variance in the fluorescence spectra. Regression models between antioxidant capacity and PC1 and PC2 displayed strong linear correlations for NF fractions and a weak linear correlation for UF fractions. Clustering of UF and NF fractions according to ORACFPCA and FCRFPCA was observed. The ability of this method to extract information on contributions by tryptophan and tyrosine amino acid residues to the antioxidant capacity of SPH fractions was demonstrated. Copyright © 2016. Published by Elsevier Ltd.

  20. Comparative effects of gamma and electron beam irradiation on the antioxidant potential of Portuguese chestnuts (Castanea sativa Mill.).

    PubMed

    Carocho, Márcio; Antonio, Amilcar L; Barros, Lillian; Bento, Albino; Botelho, M Luisa; Kaluska, Iwona; Ferreira, Isabel C F R

    2012-10-01

    Chestnuts (Castanea sativa Mill.) are widely consumed all over the world, and have been recently studied for their antioxidant potential. The present study reports the effect of e-beam and gamma radiation (doses of 0, 0.5, 1 and 3 kGy) on the antioxidant potential of Portuguese chestnuts. Irradiation might be an alternative preservation method, since Methyl Bromide, a widely used fumigant, was banished by the European Union in 2010 due to its toxicity. The antioxidant activity was evaluated through 2,2-diphenyl-1-pycrylhydrazyl (DPPH) free radical scavenging activity assay, reducing power by the Ferricyanide/Prussian blue assay, and lipid peroxidation inhibition by β-carotene/linoleate and thiobarbituric acid reactive substances (TBARS) assays. The analysis of total phenolics and flavonoids was performed by spectrophotometric assays. Irradiated samples preserved total phenolics content (but not flavonoids) and revealed higher antioxidant activity (lower EC50 values) than the control samples. The most indicated doses to maintain antioxidants content, and to increase antioxidant activity were 1 and 3 kGy for electron beam and gamma radiation, respectively.

  1. Assessment of Antioxidant Potential, Total Phenolics and Flavonoids of Different Solvent Fractions of Monotheca Buxifolia Fruit

    PubMed Central

    Jan, Shumaila; Khan, Muhammad Rashid; Rashid, Umbreen; Bokhari, Jasia

    2013-01-01

    Objectives This study was conducted to investigate the antioxidant potential of methanol extract and its derived fractions (hexane, ethyl acetate, butanol, and aqueous) of fruits of Monotheca buxifolia (Falc.) Dc., a locally used fruit in Pakistan. Methods Dried powder of the fruit of M. buxifolia was extracted with methanol and the resultant was fractionated with solvents having escalating polarity; n-hexane, chloroform, ethyl acetate, n-butanol and the residual soluble aqueous fraction. Total phenolic and total flavonoid contents were estimated for the methanol and various fractions. These fractions were also subjected to various in vitro assays to estimate the scavenging activity for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide, hydroxyl, hydrogen peroxide and reductive ability for ferric ions and phosphomolybdate assay. Results The n-butanol, aqueous and methanol fractions possessed high amount of phenolics and flavonoids compared with other fractions, and subsequently showed a pronounced scavenging activity on DPPH, ABTS, superoxide, hydroxyl and hydrogen peroxide radicals and had a potent reductive ability on ferric ion and phosphomolybdate assay. There was a found significant correlation between total phenolic and flavonoid contents and EC50 of DPPH, superoxide, hydrogen peroxide radical and phosphomolybdate assays, whereas a nonsignificant correlation was found with the hydroxyl radical and ABTS radical assay. Conclusion M. buxifolia fruit can be used as natural antioxidant source to prevent damage associated with free radicals. PMID:24298440

  2. Potential natural antioxidants: adjuvant effect of green tea polyphenols in periodontal infections.

    PubMed

    Ramasamy, Chidambaram

    2015-01-01

    Polyphenols constitute the major component in green tea, which represent a cluster known as catechins. The presence of polyphenols, especially the amino acid theanine and catechins with its antioxidant properties in green tea make them ideal for medicinal- dental applications. The objective of the paper is to delineate the role of green tea polyphenols in periodontal disease. The Pub med data base was searched for human clinical studies, reviews pertinent to application of green tea polyphenols in periodontal health dating from Sep 1980- Sep 2014. The retrieved inference from the epidemiological surveys, in vitro studies and overviews of polyphenols, postulate green tea as potential natural antioxidant. Green tea mouthwashes possess limitations, which make them ineffective during the chronic stages of periodontitis. Human studies reveal that the prognosis of periodontal disease is better when the green tea catechins are used via local drug delivery. The maintenance of periodontal health could be enhanced by emphasizing the habit of drinking green tea in periodontitis patients. The future scope of the research demands the analysis of polyphenols at molecular level to have a better understanding of its overwhelming applications.

  3. Potential antioxidant, antiinflammatory, and proapoptotic anticancer activities of Kakadu plum and Illawarra plum polyphenolic fractions.

    PubMed

    Tan, Aaron C; Konczak, Izabela; Ramzan, Iqbal; Zabaras, Dimitrios; Sze, Daniel M-Y

    2011-01-01

    Kakadu plum (Terminalia ferdinandiana Exell, Combretaceae) and Illawarra plum (Podocarpus elatus Endl., Podocarpaceae) extracts were fractionated, using a bioassay-guided approach and screened for antioxidant activity [oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays] and antiinflammatory activity (nitrite concentration and prostaglandin E(2) release in lipopolysaccharide (LPS)-activated murine macrophages). Among 8 fractions obtained from KP and 5 fractions obtained from IP, fraction KPF5 from KP exhibited superior activity in all assays, with an ORAC value of 3,776 ± 603 μmol Trolox/g DW and a CAA value of 52.2 ± 8.6 μmol quercetin equivalents/g DW. In addition, KPF5 further demonstrated an upregulation of the Nrf2/Keap1 ratio in Hep G2 cells. KPF5 also inhibited the expression of COX-2 and iNOS in LPS-activated murine macrophages, potentially through the NF-κB, p44/42 mitogen activated protein kinase and Akt pathways. KPF5 also induced apoptosis and DNA damage in HT-29 cells, as determined by the cytokinesis block micronucleus cytome assay.

  4. Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera.

    PubMed

    Singh, Brahma N; Singh, B R; Singh, R L; Prakash, D; Dhakarey, R; Upadhyay, G; Singh, H B

    2009-06-01

    The aqueous extract of leaf (LE), fruit (FE) and seed (SE) of Moringa oleifera was assessed to examine the ability to inhibit the oxidative DNA damage, antioxidant and anti-quorum sensing (QS) potentials. It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA and also inhibit synergistically with trolox, with an activity sequence of LE > FE > SE. HPLC and MS/MS analysis was carried out, which showed the presence of gallic acid, chlorogenic acid, ellagic acid, ferulic acid, kaempferol, quercetin and vanillin. The LE was with comparatively higher total phenolics content (105.04 mg gallic acid equivalents (GAE)/g), total flavonoids content (31.28 mg quercetin equivalents (QE)/g), and ascorbic acid content (106.95 mg/100 g) and showed better antioxidant activity (85.77%), anti-radical power (74.3), reducing power (1.1 ascorbic acid equivalents (ASE)/ml), inhibition of lipid peroxidation, protein oxidation, OH-induced deoxyribose degradation, and scavenging power of superoxide anion and nitric oxide radicals than did the FE, SE and standard alpha-tocopherol. Eventually, LE and FE were found to inhibit violacein production, a QS-regulated behavior in Chromobacterium violaceum 12472.

  5. ANTIOXIDANT ACTIVITY AND A-AMYLASE INHIBITORY POTENTIAL OF ROSA CANINA L.

    PubMed

    Jemaa, Houda Ben; Jemia, Amani Ben; Khlifi, Sarra; Ahmed, Halima Ben; Slama, Fethi Ben; Benzarti, Anis; Elati, Jalila; Aouidet, Abdallah

    2017-01-01

    Diabetes mellitus is one of the most common endocrinal disorders and medicinal plants continue to play an important role in the management of this disease. In this study, Rosa canina was investigated for the antioxidant and α-amylase inhibition activities. Methanolic extract of Rosa canina was investigated for its potential antioxidant activity. The extracts' total phenolic and flavonoid contents and scavenging capacity for free radicals were evaluated. The α-amylase inhibition assay was also carried. Rosa canina extract exhibits a total Phenolic and flavonoid levels respectively (21.918 mg GAE/g and 2.647mg ER/g). The free radical scavenging activity was found to be prominent against DPPH with an IC50 of 0.668 mg/ml and against ABTS with an IC50 of 0.467 mg/ml. Extract showed a significant ferric ion reducing activities with an IC50 of4.962 mg/ml. Rosa canina exerted a higher inhibitory activity against α-amylase. The obtained results support the antidiabetic use of rosa canina.

  6. Phytochemical screening, antioxidants and antimicrobial potential of Lantana camara in different solvents

    PubMed Central

    Naz, Rabia; Bano, Asghari

    2013-01-01

    Objective To evaluate the antioxidant activity, hydrogen peroxide radicals scavenging activity, reducing power, the total phenolic and flavonoids contents, and antimicrobial and antifungal activities of methanol, ethanol and water extracts of leaves of Lantana camara (L. camara). Methods Methanol, ethanol and water extracts were evaluated against four Gram positive and Gram negative bacterial isolates (Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus subtilis) and two fungal strains (Aspergillus fumigatus and Aspergillus flavus). Methanol extract at different concentrations was tested for antioxidant potential and phytochemicals were determined by using spectrophotometric method. Results The total phenolic content was (40.859±0.017) mg gallic acid/g in the leaves of L. camara, while the total flavonoids was (53.112±0.199) mg/g dry weight. Methanol leaf extract of L. camara showed maximum antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa and was also effective against other bacterial strains as compared to ethanol and aqueous extracts of leaves. The methanol leaf extract of L. camara exhibited significant inhibition (71%) and (66%) against Aspergillus fumigatus and Aspergillus flavus respectively. Conclusions The methanol extract of the L. camara leaves is effective against selected bacterial and fungal strains. Its phytochemical contents have broad antimicrobial properties and the plant might be a novel source of antimicrobial drug.

  7. Wild Mushrooms: A Potential Source of Nutritional and Antioxidant Attributes with Acceptable Toxicity

    PubMed Central

    Sharif, Sumaira; Shahid, Muhammad; Mushtaq, Muhammad; Akram, Sumia; Rashid, Ayoub

    2017-01-01

    This paper describes in detail proximate composition, nutritional profile, phytochemical constituents, antioxidant activities, antimicrobial potential, and antihemolytic activity (towards human erythrocytes) of various fractions of wild Ganoderma lucidum. Proximate analysis established that wild G. lucidum comprises about 87.02±5.45% of moisture, and the remaining part is a rich source of proteins (8.59±0.37%), crude fiber (54.21±1.2%), and carbohydrate (35.16%) with smaller fat content (3.33 %). Similarly, phytochemical screening revealed the presence of flavonoids (217.51±0.30 mg/g), ascorbic acid (116±7.32 mg/g), phenolics (360.72±34.07 mg/g), β-carotenes (0.42±0.04 μg/g), and lycopene (0.05±0.00 μg/g). Extracts of wild G. lucidum in various solvents provided first line protection against Escherichia coli and Pasteurella multocida in the order of ethyl acetate> ethanol> methanol> n-hexane> water. Furthermore, aqueous and methanolic extracts of wild G. lucidum were found to be safe towards human erythrocytes. Overall, wild mushroom (G. lucidum) was found to be a good source of dietary supplements, antimicrobial and antioxidant agents in the pursuance of its commercial utilization in food and pharmaceutical industries. PMID:28702429

  8. Major Phenolic Compounds, Antioxidant Capacity and Antidiabetic Potential of Rice Bean (Vigna umbellata L.) in China

    PubMed Central

    Yao, Yang; Cheng, Xu-Zhen; Wang, Li-Xia; Wang, Su-Hua; Ren, Guixing

    2012-01-01

    Interest in edible beans as nutraceuticals is increasing. In the present study, the individual phenolic acids, the total phenolic content (TPC), the total flavonoid content (TFC), and the antioxidant and antidiabetic potential of 13 varieties of rice beans from China were investigated. Eight phenolic compounds (catechin, epicatechin, p-coumaric acid, ferulic acid, vitexin, isovitexin, sinapic acid, quercetin) were analyzed on an ultra-performance liquid chromatography (UPLC) mass spectrometry (MS) system. The rice bean varieties had significant differences in total phenolic compounds (ranging from 123.09 ± 10.35 to 843.75 ± 30.15 μg/g), in TPC (ranging from 3.27 ± 0.04 to 6.43 ± 0.25 mg gallic acid equivalents (GAE)/g), in TFC (ranging from 55.95 ± 11.16 to 320.39 ± 31.77 mg catechin (CE)/g), in antioxidant activity (ranging from 39.87 ± 1.37 to 46.40 ± 2.18 μM·TE/g), in α-glucosidase inhibition activity (ranging from 44.32 ± 2.12 to 68.71 ± 2.19) and in advanced glycation end products formation inhibition activity (ranging from 34.11 ± 0.59 to 75.75 ± 0.33). This study is the first report on phytochemistry and biological activities in rice beans. PMID:22489119

  9. Encapsulation of catechin and epicatechin on BSA NPS improved their stability and antioxidant potential

    PubMed Central

    Yadav, Ramdhan; Kumar, Dharmesh; Kumari, Avnesh; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of antioxidant molecules on protein nanoparticles (NPs) could be an advanced approach for providing stable, better food nutraceuticals and anticancer drugs. The bioavailability and stability of catechin (CAT) and epicatechin (ECAT) were very poor. In the present study, the CAT and ECAT were loaded on bovine serum albumin (BSA) NPs following desolvation method. The transmission electron microscope (TEM) and atomic force microscope (AFM) recorded size of CAT-BSA NPs and ECAT-BSA NPs were 45 ± 5 nm and 48 ± 5 nm respectively. The encapsulation efficiency of CAT and ECAT on BSA NPs was found to be 60.5 and 54.5 % respectively. CAT-BSA NPs and ECAT-BSA NPs show slow and sustained in vitro release. The CAT-BSA NPs and ECAT-BSA NPs were stable in solution at various temperatures 37 °C, 47 °C and 57 °C. DPPH assay revealed that CAT and ECAT maintained their functional activity even after encapsulation on BSA NPs. Furthermore, the efficacy of CAT-BSA NPs and ECAT-BSA NPs determined against A549 cell lines was found to be improved. CAT and ECAT aptly encapsulated in BSA NPs, showed satisfactory sustained release, maintained antioxidant potential and found improved efficacy. This has thus suggested their more effective use in food and nutraceuticals as well as in medical field. PMID:26417264

  10. Potential mechanisms behind the antioxidant actions of prolactin in the retina.

    PubMed

    Thébault, Stéphanie

    2017-07-01

    Causes for age-related retinal diseases are numerous and complex, and they are intertwined with the natural vision decline that accompanies aging. The elucidation of endogenous mechanisms that help maintain retinal function under conditions that are threatening for the eye and happen during natural aging is therefore critical in developing new prevention and therapeutic strategies against age-related retinal degeneration. Our lab recently reported that the hormone of lactation, prolactin, helps the retinal pigment epithelium to survive via antioxidant actions that result in the inhibition of sirtuin2-dependent cell death (EbioMedicine issue of May). The mechanism behind the antioxidant activity of prolactin remains elusive. The main purposes of my commentary are to discuss mechanisms that could explain this effect in the context of previously identified defense mechanisms against oxidative stress and focus particularly on the potential regulation of reduced glutathione levels by prolactin. I also briefly comment on how our study contributes to cell biology, which as the foundational science for understanding neurodegeneration, may accelerate progress in disease prevention and cures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. ANTIOXIDANT ACTIVITY AND A-AMYLASE INHIBITORY POTENTIAL OF ROSA CANINA L

    PubMed Central

    Jemaa, Houda Ben; Jemia, Amani Ben; Khlifi, Sarra; Ahmed, Halima Ben; Slama, Fethi Ben; Benzarti, Anis; Elati, Jalila; Aouidet, Abdallah

    2017-01-01

    Background: Diabetes mellitus is one of the most common endocrinal disorders and medicinal plants continue to play an important role in the management of this disease. In this study, Rosa canina was investigated for the antioxidant and α-amylase inhibition activities. Materials and Methods: Methanolic extract of Rosa canina was investigated for its potential antioxidant activity. The extracts’ total phenolic and flavonoid contents and scavenging capacity for free radicals were evaluated. The α-amylase inhibition assay was also carried. Results: Rosa canina extract exhibits a total Phenolic and flavonoid levels respectively (21.918 mg GAE/g and 2.647mg ER/g). The free radical scavenging activity was found to be prominent against DPPH with an IC50 of 0.668 mg/ml and against ABTS with an IC50 of 0.467 mg/ml. Extract showed a significant ferric ion reducing activities with an IC50 of4.962 mg/ml. Conclusion: Rosa canina exerted a higher inhibitory activity against α-amylase. The obtained results support the antidiabetic use of rosa canina. PMID:28573216

  12. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders.

    PubMed

    Ribas, Graziela S; Vargas, Carmen R; Wajner, Moacir

    2014-01-10

    In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.

  13. Mechanisms underlying the wound healing potential of propolis based on its in vitro antioxidant activity.

    PubMed

    Cao, Xue-Ping; Chen, Yi-Fan; Zhang, Jiang-Lin; You, Meng-Meng; Wang, Kai; Hu, Fu-Liang

    2017-10-15

    Propolis is a resinous substance collected by honeybees, Apis mellifera, from various plant sources. Having various pharmacological and biological activities, it has been used in folk medicine and complementary therapies since ancient times. To evaluate the effects and underlying mechanism of the protective effects of the ethanol extract of Chinese propolis (EECP) on L929 cells injured by hydrogen peroxide (H2O2). The wound healing activities of EECP in L929 cells with H2O2-induced damage were investigated. The main components of EECP were analyzed by RP-HPLC, and the free radical scavenging capacity and reducing power were also measured. The effects of EECP on the expression of antioxidant-related genes in fibroblast L929 cells were determined using qRT-PCR and western blotting. EECP had significant protective effects against cell death induced by H2O2 and significantly inhibited the decline of collagen mRNA expression caused by H2O2 in L929 cells. EECP induced the expression of antioxidant-related genes, such as HO-1, GCLM, and GCLC, which has great implications for the potential of propolis to alleviate oxidative stress in wound tissues. The protective effects of propolis have great implications for using propolis as a wound healing regent. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. A novel class of mitochondria-targeted soft electrophiles modifies mitochondrial proteins and inhibits mitochondrial metabolism in breast cancer cells through redox mechanisms.

    PubMed

    Vayalil, Praveen K; Oh, Joo-Yeun; Zhou, Fen; Diers, Anne R; Smith, M Ryan; Golzarian, Hafez; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2015-01-01

    Despite advances in screening and treatment over the past several years, breast cancer remains a leading cause of cancer-related death among women in the United States. A major goal in breast cancer treatment is to develop safe and clinically useful therapeutic agents that will prevent the recurrence of breast cancers after front-line therapeutics have failed. Ideally, these agents would have relatively low toxicity against normal cells, and will specifically inhibit the growth and proliferation of cancer cells. Our group and others have previously demonstrated that breast cancer cells exhibit increased mitochondrial oxygen consumption compared with non-tumorigenic breast epithelial cells. This suggests that it may be possible to deliver redox active compounds to the mitochondria to selectively inhibit cancer cell metabolism. To demonstrate proof-of-principle, a series of mitochondria-targeted soft electrophiles (MTSEs) has been designed which selectively accumulate within the mitochondria of highly energetic breast cancer cells and modify mitochondrial proteins. A prototype MTSE, IBTP, significantly inhibits mitochondrial oxidative phosphorylation, resulting in decreased breast cancer cell proliferation, cell attachment, and migration in vitro. These results suggest MTSEs may represent a novel class of anti-cancer agents that prevent cancer cell growth by modification of specific mitochondrial proteins.

  15. Chloroplast- or Mitochondria-Targeted DEAD-Box RNA Helicases Play Essential Roles in Organellar RNA Metabolism and Abiotic Stress Responses

    PubMed Central

    Nawaz, Ghazala; Kang, Hunseung

    2017-01-01

    The yields and productivity of crops are greatly diminished by various abiotic stresses, including drought, cold, heat, and high salinity. Chloroplasts and mitochondria are cellular organelles that can sense diverse environmental stimuli and alter gene expression to cope with adverse environmental stresses. Organellar gene expression is mainly regulated at posttranscriptional levels, including RNA processing, intron splicing, RNA editing, RNA turnover, and translational control, during which a variety of nucleus-encoded RNA-binding proteins (RBPs) are targeted to chloroplasts or mitochondria where they play essential roles in organellar RNA metabolism. DEAD-box RNA helicases (RHs) are enzymes that can alter RNA structures and affect RNA metabolism in all living organisms. Although a number of DEAD-box RHs have been found to play important roles in RNA metabolism in the nucleus and cytoplasm, our understanding on the roles of DEAD-box RHs in the regulation of RNA metabolism in chloroplasts and mitochondria is only at the beginning. Considering that organellar RNA metabolism and gene expression are tightly regulated by anterograde signaling from the nucleus, it is imperative to determine the functions of nucleus-encoded organellar RBPs. In this review, we summarize the emerging roles of nucleus-encoded chloroplast- or mitochondria-targeted DEAD-box RHs in organellar RNA metabolism and plant response to diverse abiotic stresses. PMID:28596782

  16. Chloroplast- or Mitochondria-Targeted DEAD-Box RNA Helicases Play Essential Roles in Organellar RNA Metabolism and Abiotic Stress Responses.

    PubMed

    Nawaz, Ghazala; Kang, Hunseung

    2017-01-01

    The yields and productivity of crops are greatly diminished by various abiotic stresses, including drought, cold, heat, and high salinity. Chloroplasts and mitochondria are cellular organelles that can sense diverse environmental stimuli and alter gene expression to cope with adverse environmental stresses. Organellar gene expression is mainly regulated at posttranscriptional levels, including RNA processing, intron splicing, RNA editing, RNA turnover, and translational control, during which a variety of nucleus-encoded RNA-binding proteins (RBPs) are targeted to chloroplasts or mitochondria where they play essential roles in organellar RNA metabolism. DEAD-box RNA helicases (RHs) are enzymes that can alter RNA structures and affect RNA metabolism in all living organisms. Although a number of DEAD-box RHs have been found to play important roles in RNA metabolism in the nucleus and cytoplasm, our understanding on the roles of DEAD-box RHs in the regulation of RNA metabolism in chloroplasts and mitochondria is only at the beginning. Considering that organellar RNA metabolism and gene expression are tightly regulated by anterograde signaling from the nucleus, it is imperative to determine the functions of nucleus-encoded organellar RBPs. In this review, we summarize the emerging roles of nucleus-encoded chloroplast- or mitochondria-targeted DEAD-box RHs in organellar RNA metabolism and plant response to diverse abiotic stresses.

  17. A Novel Class of Mitochondria-Targeted Soft Electrophiles Modifies Mitochondrial Proteins and Inhibits Mitochondrial Metabolism in Breast Cancer Cells through Redox Mechanisms

    PubMed Central

    Vayalil, Praveen K.; Oh, Joo-Yeun; Zhou, Fen; Diers, Anne R.; Smith, M. Ryan; Golzarian, Hafez; Oliver, Patsy G.; Smith, Robin A. J.; Murphy, Michael P.; Velu, Sadanandan E.; Landar, Aimee

    2015-01-01

    Despite advances in screening and treatment over the past several years, breast cancer remains a leading cause of cancer-related death among women in the United States. A major goal in breast cancer treatment is to develop safe and clinically useful therapeutic agents that will prevent the recurrence of breast cancers after front-line therapeutics have failed. Ideally, these agents would have relatively low toxicity against normal cells, and will specifically inhibit the growth and proliferation of cancer cells. Our group and others have previously demonstrated that breast cancer cells exhibit increased mitochondrial oxygen consumption compared with non-tumorigenic breast epithelial cells. This suggests that it may be possible to deliver redox active compounds to the mitochondria to selectively inhibit cancer cell metabolism. To demonstrate proof-of-principle, a series of mitochondria-targeted soft electrophiles (MTSEs) has been designed which selectively accumulate within the mitochondria of highly energetic breast cancer cells and modify mitochondrial proteins. A prototype MTSE, IBTP, significantly inhibits mitochondrial oxidative phosphorylation, resulting in decreased breast cancer cell proliferation, cell attachment, and migration in vitro. These results suggest MTSEs may represent a novel class of anti-cancer agents that prevent cancer cell growth by modification of specific mitochondrial proteins. PMID:25785718

  18. Phytochemical Screening, Alpha-Glucosidase Inhibition, Antibacterial and Antioxidant Potential of Ajuga bracteosa Extracts.

    PubMed

    Hafeez, Kokab; Andleeb, Saiqa; Ghousa, Tahseen; Mustafa, Rozina G; Naseer, Anum; Shafique, Irsa; Akhter, Kalsoom

    2017-01-01

    Ajuga bracteosa, a medicinal herb, is used by local community to cure a number of diseases such as inflammation, jaundice bronchial asthma, cancer and diabetes. The aim of present work was to evaluate the antioxidant potential, in vitro antidiabetic and antimicrobial effects of A. bracteosa. n-hexane, ethyl acetate, chloroform, acetone, methanol and aqueous extracts of Ajuga bracteosa roots, were prepared via maceration. Antibacterial activity was carried out by agar well diffusion method. Quantitative and qualitative phytochemical screening was done. The antioxidant activity was determined by iron (II) chelating activity, iron reducing power, DPPH, and ABTS free radical scavenging methods, Antidiabetic activity was evaluated through inhibition of α-glucosidase assay. Phytochemical analysis showed the presence of phenols, flavonoids, tannins, saponins, quinines, terpenoids, xanthoproteins, glycosides, carbohydrates, steroids, phytosterols and amino acids. DPPH and ABTS potential values were recorded as 61.92% to 88.84% and 0.11% to 38.82%, respectively. Total phenolic and total flavonoid contents were expressed as gallic acid and rutin equivalents. Total iron content was expressed as FeSO4 equivalents. Chloroform and n-hexane extracts showed significant enzyme inhibition potential with IC50 values of 29.92 μg/ml and 131.7 μg/ml respectively. Aqueous extract showed maximum inhibition of E. coli, S. typhimurium, E. amnigenus, S. pyogenes, and S. aureus, (18.0±1.0 mm, 12.5±0.7 mm, 17.0±0.0 mm, 11.0±0.0 mm and 15.3±2.0 mm mm), respectively. Similarly, n-hexane extract showed maximum inhibition of E. coli, E. amnigenus, S. aureus (11.6±1.5 mm; 11.3±1.5 mm; 13.3±0.5 mm). This study also shows that n-hexane, chloroform, ethyl acetate and aqueous extracts of A. bracteosa root possess α-glucosidase inhibitory activities and therefore it may be used as hypoglycemic agents in the management of postprandial hyperglycemia. Ajuga bracteosa root extracts may provide a

  19. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    PubMed

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  20. [Studies of several analytical methods for antioxidant potential evaluation in food].

    PubMed

    Marc, Françoise; Davin, André; Deglène-Benbrahim, Laurence; Ferrand, Carine; Baccaunaud, Michel; Fritsch, Pierre

    2004-04-01

    Oxidation control is necessary to manage the evolution of complex biological system, particularly in food whose degradation could have consequences on food security. After description of context and oxidation mechanisms, several analytical methods to evaluate the additive antioxidant potential are presented. This evaluation is performed either by quantification of products (in particular hydroperoxydes) using direct or indirect photometric techniques and chemical titration with suitable reactants or on the effectiveness to trap free radicals with modelized systems that can generate them. Methods based on the comparison of radical trapping ability between an additive and Trolox (particularly Trolox(R) equivalent antioxydant capacity, TEAC) can be applied to many products whatever the hydrophily or the hydrophobia of the medium.

  1. Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal, antiaflatoxigenic and antioxidant activity.

    PubMed

    Kumar, Rajesh; Mishra, Ajay Kumar; Dubey, N K; Tripathi, Y B

    2007-04-10

    Essential oil extracted from the leaves of Chenopodium ambrosioides Linn. (Chenopodiaceae) was tested against the aflatoxigenic strain of test fungus Aspergillus flavus Link. The oil completely inhibited the mycelial growth at 100 microg/ml. The oil exhibited broad fungitoxic spectrum against Aspergillus niger, Aspergillus fumigatus, Botryodiplodia theobromae, Fusarium oxysporum, Sclerotium rolfsii, Macrophomina phaseolina, Cladosporium cladosporioides, Helminthosporium oryzae and Pythium debaryanum at 100 microg/ml. The oil showed significant efficacy in inhibiting the aflatoxin B1 production by the aflatoxigenic strain of A. flavus. During in vivo investigation it protected stored wheat from different storage fungi for one year. Chenopodium oil also exhibited potent antioxidant activity when tested by ABTS method. All these observations suggest the possible exploitation of the Chenopodium oil as potential botanical fungitoxicant in ecofriendly control of post harvest biodeterioration of food commodities from storage fungi.

  2. Structure-Guided Design and Synthesis of a Mitochondria-Targeting Near-Infrared Fluorophore with Multimodal Therapeutic Activities.

    PubMed

    Tan, Xu; Luo, Shenglin; Long, Lei; Wang, Yu; Wang, Dechun; Fang, Shengtao; Ouyang, Qin; Su, Yongping; Cheng, Tianmin; Shi, Chunmeng

    2017-10-05

    An urgent challenge for imaging-guided disease-targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N-alkyl side chains to indocyanine green (ICG) (the only FDA-approved NIR contrast agent) are introduced, and a new analog, IR-DBI, is developed with simultaneous cancer-cell mitochondrial targeting, NIR imaging, and chemo-/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR-DBI a close binding to albumin protein site II to form a drug-protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR-DBI dye is further actively taken up by cancer cells through organic-anion-transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin-binding affinity, IR-DBI is modified into human serum albumin (HSA) via self-assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Anticancer, antioxidant potential and profiling of polyphenolic compounds of Wrightia tinctoria Roxb. (R.Br.) bark

    PubMed Central

    Fatima, Nishat; Ahmad, Mohammad Kaleem; Ansari, Jamal Akhtar; Ali, Zulfiqar; Khan, Abdul Rahman; Mahdi, Abbas Ali

    2016-01-01

    Wrightia tinctoria Roxb. (R.Br.) is an Ayurvedic remedy, ethnomedically used in the treatment of various ailments. The present work was carried out to evaluate the anticancer and antioxidant activity as well as total phenolic and phytochemical contents of W. tinctoria bark methanolic extract (WTBM) by high-performance liquid chromatography (HPLC)-diode array detector. Antiproliferative activity of WTBM was evaluated against MDA-MB-231 and MCF-7 cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation, and Hoechst staining. In addition, the antioxidant potential was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and 2,2- azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation decolorization assay. Total phenolic content was assessed by Folin–Ciocalteu method. The results demonstrated that WTBM exhibited significant antiproliferative effect against MDA-MB-231 (IC50 = 88.9 ± 1.27 μg/ml) and MCF-7 (IC50 = 45.71 ± 7.74 μg/ml) cancer cells in time- and dose-dependent manner. WTBM significantly suppresses colony formation and induces apoptosis in both MDA-MB-231 and MCF-7 cells as evident by morphological assessment, clonogenic assay, and Hoechst staining. The total phenolic content of WTBM was found to be 30.3 gallic acid equivalent mg/g dry weight of bark extract while IC50 value for DPPH and ABTS radical scavenging activity was 72.2 ± 2.8 μg/ml and 45.16 ± 1.95 μg/ml, respectively. HPLC analysis showed the presence of gallic acid, rutin, and quercetin in WTBM. These findings demonstrated that WTBM significantly inhibited proliferation of breast cancer cells and induced apoptosis, suggesting the potential chemopreventive activity of W. tinctoria bark. PMID:27833897

  4. A comparative study of the antioxidant, antimicrobial, cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

    PubMed Central

    Islam, Shawkat Md. Aminul; Ahmed, Kh Tanvir; Manik, Mohammad Kawsar; Wahid, Md. Arif; Kamal, Chowdhury Shafayat Ibne

    2013-01-01

    Objective To investigate the antioxidant, antimicrobial, cytotoxic and thrombolytic property of the fruits and leaves of Spondias dulcis (S. dulcis). Methods Methanolic extracts of fruits and leaves of S. dulcis were partitioned with chloroform and dichloromethane. The antioxidant potential of the crude extract and partitioned fractions were evaluated in terms of total phenolic content, total flavonoid content, DPPH radical scavenging potential, reducing potential and total antioxidant capacity by specific standard procedures. The antimicrobial activity was evaluated using disc diffusion method. The cytotoxicity was evaluated by using brine shrimp lethality bioassay and compared with vincristine sulfate. The thrombolytic activity was compared with streptokinase. Results The methanolic fruit extract exhibited the highest phenolic content, flavonoid content and antioxidant capacity, among the other extracts, with the highest DPPH radical scavenging activity at a concentration of 10 µg/mL (IC50: 1.91 µg/mL) and maximum reducing power at a concentration of 100 µg/mL (EC50: 3.58 µg/mL). Though all extract showed moderate antimicrobial activity against the bacterial strains, weak or no activity against fungus. The range of LC50 value of all extracts was 1.335-14.057 µg/mL which was far lower than the cut off index for cytotoxicity. All extracts exhibited statistically significant (P<0.001) thrombolytic activity. Conclusions Our study suggested that S. dulcis exhibits antimicrobial activities against a wide variety of strains while it possesses significant antioxidant, cytotoxic and thrombolytic activity. PMID:23998007

  5. Integrating Enzymatic Self-Assembly and Mitochondria Targeting for Selectively Killing Cancer Cells without Acquired Drug Resistance.

    PubMed

    Wang, Huaimin; Feng, Zhaoqianqi; Wang, Youzhi; Zhou, Rong; Yang, Zhimou; Xu, Bing

    2016-12-14

    Targeting organelles by modulating the redox potential of mitochondria is a promising approach to kill cancer cells that minimizes acquired drug resistance. However, it lacks selectivity because mitochondria perform essential functions for (almost) all cells. We show that enzyme-instructed self-assembly (EISA), a bioinspired molecular process, selectively generates the assemblies of redox modulators (e.g., triphenyl phosphinium (TPP)) in the pericellular space of cancer cells for uptake, which allows selectively targeting the mitochondria of cancer cells. The attachment of TPP to a pair of enantiomeric, phosphorylated tetrapeptides produces the precursors (L-1P or D-1P) that form oligomers. Upon dephosphorylation catalyzed by ectophosphatases (e.g., alkaline phosphatase (ALP)) overexpressed on cancer cells (e.g., Saos2), the oligomers self-assemble to form nanoscale assemblies only on the surface of the cancer cells. The cancer cells thus uptake these assemblies of TPP via endocytosis, mainly via a caveolae/raft-dependent pathway. Inside the cells, the assemblies of TPP-peptide conjugates escape from the lysosome, induce dysfunction of mitochondria to release cytochrome c, and result in cell death, while the controls (i.e., omitting TPP motif, inhibiting ALP, or removing phosphate trigger) hardly kill the Saos2 cells. Most importantly, the repeated stimulation of the cancers by the precursors, unexpectedly, sensitizes the cancer cells to the precursors. As the first example of the integration of subcellular targeting with cell targeting, this study validates the spatial control of the assemblies of nonspecific cytotoxic agents by EISA as a promising molecular process for selectively killing cancer cells without inducing acquired drug resistance.

  6. Evaluation of free radical scavenging activity of morel mushroom, Morchella esculenta mycelia: a potential source of therapeutically useful antioxidants.

    PubMed

    Nitha, B; De, Strayo; Adhikari, S K; Devasagayam, T P A; Janardhanan, K K

    2010-04-01

    Cellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases and antioxidants are known to protect the body from this damage. Antioxidants thus, have gained significant importance in human health. The search for effective, non-toxic natural compounds with antioxidant activity has intensified in recent years. Mycelia of a number mushrooms have recently been successfully used for the development of novel pharmaceutical products. We examined the aqueous-ethanol extract of cultured mycelia of the morel mushroom, Morchella esculenta (L.) Pers. (Morchellaceae) for its ability to scavenge super oxide, hydroxyl, nitric oxide, 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals as well as for inhibition of lipid peroxidation. The extract efficiently scavenged all these radicals and also inhibited lipid peroxidation. Ferric reducing antioxidant power (FRAP) assay indicated the hydrogen donating capacity of the extract. The pulse radiolysis studies using ABTS and carbonate radical (CO(3)(*-)) showed that the extract significantly carried out the decay of these radicals in a concentration-dependent manner. In conclusion, the investigation showed that the morel mushroom mycelium is an excellent source of antioxidants which are capable of imparting protection at different levels. The findings suggest the potential therapeutic use of morel mushroom, M. esculenta mycelia as an efficient antioxidant.

  7. In vitro and in vivo antioxidant potential of milks, yoghurts, fermented milks and cheeses: a narrative review of evidence.

    PubMed

    Fardet, Anthony; Rock, Edmond

    2017-10-02

    The antioxidant potential (AP) is an important nutritional property of foods, as increased oxidative stress is involved in most diet-related chronic diseases. In dairy products, the protein fraction contains antioxidant activity, especially casein. Other antioxidants include: antioxidant enzymes; lactoferrin; conjugated linoleic acid; coenzyme Q10; vitamins C, E, A and D3; equol; uric acid; carotenoids; and mineral activators of antioxidant enzymes. The AP of dairy products has been extensively studied in vitro, with few studies in animals and human subjects. Available in vivo studies greatly differ in their design and objectives. Overall, on a 100 g fresh weight-basis, AP of dairy products is close to that of grain-based foods and vegetable or fruit juices. Among dairy products, cheeses present the highest AP due to their higher protein content. AP of milk increases during digestion by up to 2·5 times because of released antioxidant peptides. AP of casein is linked to specific amino acids, whereas β-lactoglobulin thiol groups play a major role in the AP of whey. Thermal treatments such as ultra-high temperature processing have no clear effect on the AP of milk. Raw fat-rich milks have higher AP than less fat-rich milk, because of lipophilic antioxidants. Probiotic yoghurts and fermented milks have higher AP than conventional yoghurt and milk because proteolysis by probiotics releases antioxidant peptides. Among the probiotics, Lactobacillus casei/acidophilus leads to the highest AP. The data are insufficient for cheese, but fermentation-based changes appear to make a positive impact on AP. In conclusion, AP might participate in the reported dairy product-protective effects against some chronic diseases.

  8. Differentiation between stoichiometric and anticatalytic antioxidant properties of benzoic acid analogues: a structure/redox potential relationship study.

    PubMed

    Franck, Thierry; Mouithys-Mickalad, Ange; Robert, Thierry; Ghitti, Gianangelo; Deby-Dupont, Ginette; Neven, Philippe; Serteyn, Didier

    2013-11-25

    We investigated the antioxidant activities of some phenolic acid derivatives on a cell free system and on cellular and enzymatic models involved in inflammation. The stoichiometric antioxidant activities of phenolic acid derivatives were studied by measuring their capacity to scavenge the radical cation 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS(+)) and reactive oxygen species (ROS) produced by stimulated neutrophils. The anticatalytic antioxidant capacity of the molecules was evaluated on the activity of myeloperoxidase (MPO), an oxidant enzyme present in and released by the primary granules of neutrophils. The ROS produced by PMA-stimulated neutrophils were measured by lucigenin-enhanced chemiluminescence (CL) and the potential interaction of the molecules with MPO was investigated without interferences due to medium by Specific Immuno-Extraction Followed by Enzyme Detection (SIEFED). The antioxidant activities of the phenolic compounds were correlated to their redox potentials measured by differential pulse voltammetry (DPV), and discussed in relation to their molecular structure. The ability of the phenolic molecules to scavenge ABTS radicals and ROS derived from neutrophils was inversely correlated to their increased redox potential. The number of hydroxyl groups (three) and their position (catechol) were essential for their efficacy as stoichiometric antioxidants or scavengers. On MPO activity, the inhibitory capacity of the molecules was not really correlated with their redox potential. Likewise, for the inhibition of MPO activity the number of OH groups and mainly the elongation of the carboxylic group were essential, probably by facilitating the interaction with the active site or the structure of the enzyme. The redox potential measurement, combined with ABTS and CL techniques, seems to be a good technique to select stoichiometric antioxidants but not anticatalytic ones, as seen for MPO, what rather involves a direct interaction with

  9. In vitro antioxidant activity potential of lantadene A, a pentacyclic triterpenoid of Lantana plants.

    PubMed

    Grace-Lynn, Chong; Darah, Ibrahim; Chen, Yeng; Latha, Lachimanan Yoga; Jothy, Subramanion L; Sasidharan, Sreenivasan

    2012-09-19

    Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), hydroxyl radical (OH•), nitric oxide radical (NO•), superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.

  10. Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

    PubMed Central

    Carvalho-Queiroz, Claudia; Nyakundi, Ruth; Ogongo, Paul; Rikoi, Hitler; Egilmez, Nejat K.; Farah, Idle O.; Kariuki, Thomas M.; LoVerde, Philip T.

    2015-01-01

    produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. All together, these data demonstrate the potential of antioxidants as a vaccine in a non-human primate model. PMID:26082781

  11. Oxidative stability, phenolic compounds and antioxidant potential of a virgin olive oil enriched with natural bioactive compounds.

    PubMed

    Delgado-Adámez, Jonathan; Baltasar, M Nieves Franco; Yuste, María Concepción Ayuso; Martín-Vertedor, Daniel

    2014-01-01

    The aim of this research was to evaluate strategies for the development of a virgin olive oil (VOO) enriched with aqueous extracts of olive leaf and cake to increase the necessary dose in the diet of phenolic compounds with a natural product, as phenolic compounds are involved on the healthy properties of olive oil. Different extraction procedures were evaluated with the aim of increasing the phenol content and antioxidant potential of extracts of olive leaf and cake. As leaves extract presented a higher total phenolic content, it was characterized in order to determine its phenolic profile, and was employed to enrich VOO. Diverse procedures were used to prepare enriched VOO with the leaves extract, and finally the effects of phenol enrichment were evaluated based on the antioxidant potential and oxidative stability of the prepared phenol-enriched virgin olive oils. These enriched VOOs increased significantly the content in phenolic compounds, antioxidant potential and oxidative stability 40, 4 and 1.5 fold more, respectively, than the Control oil. Furthermore, the addition of lecithin had a positive effect both on the phenolic compounds content, and on the antioxidant potential of the oils. Besides, the use of the olive leaves extract, with and without lecithin respectively, supposes a strategy potential for reducing the harmful effects that inflicts long-term preservation of VOOs and its possible deterioration.

  12. Epigenetic and antioxidant effects of dietary isothiocyanates and selenium: potential implications for cancer chemoprevention.

    PubMed

    Barrera, Lawrence N; Cassidy, Aedin; Johnson, Ian T; Bao, Yongping; Belshaw, Nigel J

    2012-05-01

    There is evidence from epidemiological studies suggesting that increased consumption of cruciferous vegetables may protect against specific cancers more effectively than total fruit and vegetable intake. These beneficial effects are attributed to the glucosinolate breakdown products, isothiocyanates (ITC). Similarly, selenium (Se) consumption has also been inversely associated with cancer risk and as an integral part of many selenoproteins may influence multiple pathways in the development of cancer. This paper will briefly review the current state of knowledge concerning the effect of Se and ITC in cancer development with a particular emphasis on its antioxidant properties, and will also address whether alterations in DNA methylation may be a potential mechanism whereby these dietary constituents protect against the carcinogenic process. Furthermore, we will discuss the advantages of combining ITC and Se to benefit from their complementary mechanisms of action to potentially protect against the alterations leading to neoplasia. Based on this review it may be concluded that an understanding of the impact of ITC and Se on aberrant DNA methylation in relation to factors modulating gene-specific and global methylation patterns, in addition to the effect of these food constituents as modulators of key selenoenzymes, such as gastrointestinal glutathione peroxidase-2 (GPx2) and thioredoxin reductase-1 (TrxR1), may provide insights into the potential synergy among various components of a plant-based diet that may counteract the genetic and epigenetic alterations that initiate and sustain neoplasia.

  13. Cumulative role of bioinoculants on growth, antioxidant potential and artemisinin content in Artemisia annua L. under organic field conditions.

    PubMed

    Gupta, Rupali; Singh, Akanksha; Gupta, M M; Pandey, Rakesh

    2016-10-01

    Artemisia annua L. is mostly known for a bioactive metabolite, artemisinin, an effective sesquiterpene lactone used against malaria without any reputed cases of resistance. In this experiment, bioinoculants viz., Streptomyces sp. MTN14, Bacillus megaterium MTN2RP and Trichoderma harzianum Thu were applied as growth promoting substances to exploit full genetic potential of crops in terms of growth, yield, nutrient uptake and particularly artemisinin content. Further, multi-use of the bioinoculants singly and in combinations for the enhancement of antioxidant potential and therapeutic value was also undertaken which to our knowledge has never been investigated in context with microbial application. The results demonstrated that a significant (P < 0.05) increase in growth, nutrient uptake, total phenolic, flavonoid, free radical scavenging activity, ferric reducing antioxidant power, reducing power and total antioxidant capacity were observed in the A. annua treated with a combination of bioinoculants in comparison to control. Most importantly, an increase in artemisinin content and yield by 34 and 72 % respectively in the treatment having all the three microbes was observed. These results were further authenticated by the PCA analysis which showed positive correlation between plant macronutrients and antioxidant content with plant growth and artemisinin yield of A. annua. The present study thus highlights a possible new application of compatible bioinoculants for enhancing the growth along with antioxidant and therapeutic value of A. annua.

  14. Antioxidant potential of commercially available cumin (Cuminum cyminuml inn) in Pakistan.

    PubMed

    Bukhari, S Birjees; Iqbal, Shahid; Bhanger, M I

    2009-05-01

    Owing to increased safety concerns about synthetic antioxidants, exploitation of safer antioxidants based on natural origin is the focus of research nowadays. Cumin is a common spice and is used as a routine supportive cooking agent. Extracts of cumin were prepared in methanol, ethanol, dichloromethane and hexane by employing Soxhlet extraction apparatus. Determination of the total phenolic content, chelating activity, reducing power and free radical scavenging activity were taken as parameters for the assessment of antioxidant properties. The findings of this study suggest cumin to be a potent source of antioxidants. Results from the different parameters were in agreement with one another.

  15. Cabbage (Brassica oleracea L. var. capitata) phytochemicals with antioxidant and anti-inflammatory potential.

    PubMed

    Rokayya, Sami; Li, Chun-Juan; Zhao, Yan; Li, Ying; Sun, Chang-Hao

    2014-01-01

    The objective of this study was to investigate antioxidant and anti-inflammatory activity of cabbage phytochemicals. Color coordinates were evaluated by colorimetry, and the antioxidant and anti-inflammatory activities were analyzed by spectrophotometer for some common cabbage varieties. Red heads had the highest total antioxidant contents followed by Savoy, Chinese and green heads. The Chinese variety had the highest ABTS (2,2-azino-di-(3-ethylbenzthiazoline-sulfonic acid) antioxidant activity, was 5.72 μmol TE/g fw (Trolox equivalent). The green variety had the highest DPPH (free radical scavenging activity) antioxidant activity, which was 91.2 μmol TE/g fw. The red variety had the highest FRAP (ferric reducing antioxidant power) antioxidant activity, which was 80.8 μmol TE/g fw. The total phenol amounts were 17.2-32.6 mM trolox equivalent antioxidant capacity (TEAC) and the total flavonoid amounts were 40.0-74.2 mg quercetin per gram. Methanolic extracts of different cabbage heads showed different anti-inflammatory activity values. Chinese, Savoy and green heads had the highest anti-inflammatory activity, while red heads had the lowest. The results suggest that these varieties of cabbage heads could contribute as sources of important antioxidant and anti-inflammatory related to the prevention of chronic diseases associated to oxidative stress, such as in cancer and coronary artery disease.

  16. Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes: Herbal medicines as a case study.

    PubMed

    Yang, Xing-Xin; Xu, Feng; Wang, Dan; Yang, Zhi-Wei; Tan, Huan-Ran; Shang, Ming-Ying; Wang, Xuan; Cai, Shao-Qing

    2015-09-25

    Mitochondria are an important intracellular pharmacological target because damage to this organelle results in a variety of human disorders and because mitochondria are involved in complex processes such as energy generation, apoptosis and lipid metabolism. To expedite the search for natural bioactive compounds targeting mitochondria, we initially developed an efficient mitochondria-based screening method by combining centrifugal ultrafiltration (CU) with liquid chromatography/mass spectrometry (LC/MS), which is called screening method for mitochondria-targeted bioactive constituents (SM-MBC) and is compatible with the search of mitochondria-targeted compounds from complex matrixes such as herbal medicines extracts. Functionally active, structurally intact and pure mitochondria were obtained from rat myocardium using an optimized protocol for mitochondrial isolation comprising organelle release followed by differential and Nycodenz density gradient centrifugation. After evaluating the reliability of the method using thiabendazole (TZ), rotenone (RN), amiodarone (AR) and trimetazidine (TD) as positive controls, this method was successfully applied to screen bioactive constituents from extracts of Polygoni Cuspidati Rhizoma et Radix (PCRR) and Scutellariae Radix (SR). Nineteen active compounds were detected and identified by LC/MS, of which 17 were new mitochondria-targeted compounds. The activity of 9 of the 19 hit compounds was confirmed by in vitro pharmacological trials. These results demonstrate that SM-MBC can be used for the efficient screening of mitochondria-targeted constituents in complex preparations used to treat mitochondrial disorders, such as PCRR and SR. The results may be meaningful for an in-depth understanding of drug mechanism of action and drug discovery from medicinal herbs.

  17. Respective contribution of mitochondrial superoxide and pH to mitochondria-targeted circularly permuted yellow fluorescent protein (mt-cpYFP) flash activity.

    PubMed

    Wei-LaPierre, Lan; Gong, Guohua; Gerstner, Brent J; Ducreux, Sylvie; Yule, David I; Pouvreau, Sandrine; Wang, Xianhua; Sheu, Shey-Shing; Cheng, Heping; Dirksen, Robert T; Wang, Wang

    2013-04-12

    Superoxide flashes are transient bursts of superoxide production within the mitochondrial matrix that are detected using the superoxide-sensitive biosensor, mitochondria-targeted circularly permuted YFP (mt-cpYFP). However, due to the pH sensitivity of mt-cpYFP, flashes were suggested to reflect transient events of mitochondrial alkalinization. Here, we simultaneously monitored flashes with mt-cpYFP and mitochondrial pH with carboxy-SNARF-1. In intact cardiac myocytes and purified skeletal muscle mitochondria, robust mt-cpYFP flashes were accompanied by only a modest increase in SNARF-1 ratio (corresponding to a pH increase of <0.1), indicating that matrix alkalinization is minimal during an mt-cpYFP flash. Individual flashes were also accompanied by stepwise increases of MitoSOX signal and decreases of NADH autofluorescence, supporting the superoxide origin of mt-cpYFP flashes. Transient matrix alkalinization induced by NH4Cl only minimally influenced flash frequency and failed to alter flash amplitude. However, matrix acidification modulated superoxide flash frequency in a bimodal manner. Low concentrations of nigericin (< 100 nM) that resulted in a mild dissipation of the mitochondrial pH gradient increased flash frequency, whereas a maximal concentration of nigericin (5 μm) collapsed the pH gradient and abolished flash activity. These results indicate that mt-cpYFP flash events reflect a burst in electron transport chain-dependent superoxide production that is coincident with a modest increase in matrix pH. Furthermore, flash activity depends strongly on a combination of mitochondrial oxidation and pH gradient.

  18. Respective Contribution of Mitochondrial Superoxide and pH to Mitochondria-targeted Circularly Permuted Yellow Fluorescent Protein (mt-cpYFP) Flash Activity*

    PubMed Central

    Wei-LaPierre, Lan; Gong, Guohua; Gerstner, Brent J.; Ducreux, Sylvie; Yule, David I.; Pouvreau, Sandrine; Wang, Xianhua; Sheu, Shey-Shing; Cheng, Heping; Dirksen, Robert T.; Wang, Wang

    2013-01-01

    Superoxide flashes are transient bursts of superoxide production within the mitochondrial matrix that are detected using the superoxide-sensitive biosensor, mitochondria-targeted circularly permuted YFP (mt-cpYFP). However, due to the pH sensitivity of mt-cpYFP, flashes were suggested to reflect transient events of mitochondrial alkalinization. Here, we simultaneously monitored flashes with mt-cpYFP and mitochondrial pH with carboxy-SNARF-1. In intact cardiac myocytes and purified skeletal muscle mitochondria, robust mt-cpYFP flashes were accompanied by only a modest increase in SNARF-1 ratio (corresponding to a pH increase of <0.1), indicating that matrix alkalinization is minimal during an mt-cpYFP flash. Individual flashes were also accompanied by stepwise increases of MitoSOX signal and decreases of NADH autofluorescence, supporting the superoxide origin of mt-cpYFP flashes. Transient matrix alkalinization induced by NH4Cl only minimally influenced flash frequency and failed to alter flash amplitude. However, matrix acidification modulated superoxide flash frequency in a bimodal manner. Low concentrations of nigericin (< 100 nm) that resulted in a mild dissipation of the mitochondrial pH gradient increased flash frequency, whereas a maximal concentration of nigericin (5 μm) collapsed the pH gradient and abolished flash activity. These results indicate that mt-cpYFP flash events reflect a burst in electron transport chain-dependent superoxide production that is coincident with a modest increase in matrix pH. Furthermore, flash activity depends strongly on a combination of mitochondrial oxidation and pH gradient. PMID:23457298

  19. Potential use of the plant antioxidant network for environmental exposure assessment of heavy metals in soils.

    PubMed

    Meers, E; Ruttens, A; Geebelen, W; Vangronsveld, J; Samson, R; Vanbroekhoven, K; Vandegehuchte, M; Diels, L; Tack, F M G

    2006-09-01

    In recent years, awareness has risen that the total soil content of pollutants by itself does not suffice to fully assess the potential ecotoxicological risks involved. Chemical analysis will require to be complemented with biological assays in a multidisciplinary approach towards site specific ecological risk assessment (SS-ERA). This paper evaluates the potential use of the plants' antioxidant response to metal-induced oxidative stress to provide a sensitive biological assay in SS-ERA. To this end, plants of Phaseolus vulgaris were grown for two weeks on 15 soils varying in contamination level. Morphological parameters and enzymatic plant responses were measured upon harvest. Foliar concentrations of the (heavy) metals Al, Cu, Cd, Cr, Fe, Mn, Ni, Pb, Zn were also determined. Metal mobility in the soil was further assessed by determining soil solution and NH4OAc extractable levels. In general more significant correlations were observed between plant responses and foliar metal concentrations or exchangeable/soluble levels than between plant responses and the total soil content. The study demonstrates the potential use of the plants' antioxidant defence mechanisms to assess substrate phytotoxicity for application in SS-ERA protocols. However, the system, based on calculation of a soil Phytotoxicity Index (PI), will require adaptation and fine-tuning to meet the specific needs for this type of environmental monitoring. Large variation was observed in phytotoxicity classification based on the various test parameters. The thresholds for classification of the various morphological and enzymatic response parameters may require adaptation according to parameter stress sensitivity in order to decrease the observed variation. The use of partial PI's (leaves and roots separately) may in addition increase the sensitivity of the system since some metals show specific effects in one of both organs only. Loss of biological functionality of enzymes, as was observed for ICDH in

  20. Potential antidiabetic and antioxidant activities of Morus indica and Asystasia gangetica in alloxan-induced diabetes mellitus.

    PubMed

    Kumar, R Pradeep; Sujatha, D; Saleem, Ts Mohamed; Chetty, C Madhusudhana; Ranganayakulu, D

    2010-01-01

    Herbal drugs are frequently considered to be less toxic and also free from side effects, than synthetic ones. Hence, the present study was designed to investigate one such combination of herbal drugs, Asystasia gangetica and Morus indica for their antidiabetic and antioxidant potential against alloxan-induced diabetes in albino rats. The effect of both individual and a combination of Asystasia gangetica and Morus indica on blood glucose and liver glycogen were studied in the diabetic rats. The study also assessed for the effect of selected plant extracts for their effect on Superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and Lipid peroxidation (LPO) in the homogenates of the pancreas. The results of the present study attests significant antidiabetic and antioxidant potential for the selected plants individually and also in combination as a prominent decrease in blood glucose and liver glycogen was observed in the rats treated with the extracts of the selected plants. Similarly, the levels of the protective antioxidant enzymes like SOD, CAT and GSH were increased along with decrease in the LPO levels. The present study provides a scientific evidence for antidiabetic and antioxidant potential of Asystasia gangetica and Morus indica. Further studies to isolate bioactive compounds will pave the way to identify potential lead compounds for developing safe and efficacious antidiabetic agents.

  1. Evaluation of in vitro antioxidant capacity and reducing potential of polyherbal drug- Bhāraṅgyādi

    PubMed Central

    Kajaria, Divya Kumari; Gangwar, Mayank; Sharma, Amit Kumar; Tripathi, Yamini Bhusan; Tripathi, Jyoti Shankar; Tiwari, Shrikant

    2012-01-01

    Background: Present work was designed to investigate antioxidant activity of polyherbal formulation in search for new, safe and inexpensive antioxidant. Clerodendrum serratum, Hedychium spicatum and Inula racemosa, were extensively used in ayurvedic medicine and were investigated together in the form of polyherbal compound (Bhāraṅgyādi) for their antioxidant potential. Materials and Methods: Hydroalcoholic extract was prepared from the above samples and was tested for total reducing power and in vitro antioxidant activity by ABTS+ assay, Superoxide anion scavenging activity assay and lipid per-oxidation assay. Result: Reducing power shows dose depended increase in concentration maximum absorption of 0.677 ± 0.017 at 1000 μg/ml compared with standard Quercetin 0.856±0.020. ABTS+ assay shows maximum inhibition of 64.2 ± 0.86 with EC50 675.31 ± 4.24. Superoxide free radical shows maximum scavenging activity of 62.45 ± 1.86 with EC50 774.70 ± 5.45. Anti-lipidperoxidation free radicals scavenge maximum absorption of 67.25± 1.89 with EC50 is 700.08 ± 6.81. Ascorbic acid was used as standard with IC50 value is 4.6 μg/ml. The result suggests polyherbal formulation to be a good potential for antioxidant activity. Oxidative stress results from imbalance between free radical-generation and radical scavenging systems. This will lead to tissue damage and oxidative stress. Conclusion: In conclusion, we strongly suggest that Polyherbal compounds are source of potential antioxidant for radical scavenging. The highly positive correlation of antiradical scavenging activity and total polyphenolic content in Polyherbal compounds indicates that polyphenols are important components which could be used for the free radical scavenging activity. Further study is needed for isolation and characterization of the active moiety responsible for biological activity and to treat in various stress condition. PMID:23929990

  2. Biopeptides with antioxidant and anti-inflammatory potential in the prevention and treatment of diabesity disease.

    PubMed

    Martínez Leo, Edwin Enrique; Acevedo Fernández, Juan José; Segura Campos, Maira Rubi

    2016-10-01

    Diabesity is the leading cause of modern, chronic disease. In 2012, diabetes killed 1.2 million people worldwide and its global prevalence exceeded 347 million people, and it is expected that it will increase to 540 million by 2030. Because of this health imperative, it is also linked to increasing obesity. The role of the inflammatory process and oxidative stress in the pathophysiology of these diseases is widely documented. This paper review, using data from major databases, the role of biopeptides with antioxidant and anti-inflammatory activity as a potential aid for the prevention and treatment of diabesity, since the mechanisms of action mentioned directly affect oxidative stress and the characteristic imbalance of the inflammatory process of this disease. Some of these studies have demonstrated beneficial results in relation to oxidative stress and proinflammatory markers. However, the role of biopeptides, in relation to oxidative stress and inflammatory biomarkers, remains unclear and represents a potentially fruitful area for further research in the health area.

  3. Investigation into the antioxidant and antidiabetic potential of Moringa stenopetala: identification of the active principles.

    PubMed

    Habtemariam, Solomon

    2015-03-01

    The fresh leaves of Moringa stenopetala (family, Moringaceae) are commonly eaten as cabbage while dried leaves are used as nutritional supplement and for treating a variety of disease conditions including diabetes. The present investigation into the therapeutic potential of the leaves and seeds of the plant revealed no inhibitory effect against α-glucosidase enzyme up to the concentration of 200 μg/mL but the leaves extract displayed potent DPPH (1,1-diphenyl-2- picrylhydrazyl) radical scavenging effect (IC50, 59.5 ± 4.1 μg/mL). An activity directed fractionation and isolation procedure resulted in the identification of the major antioxidant compound as rutin and minor active component, neochlorogenic acid. Both the crude extract (0.8-200 μg/mL) and rutin (0.8-200 μM) but not neochlorogenic acid displayed a concentration-dependent protection of human pancreatic β-cells (1.4E7 cells) from oxidant-induced cell death. The identification of these compounds along with their potential role in the nutritional and medicinal significance of the plant is discussed.

  4. Nutritional and Antioxidant Potential of Lentil Sprouts Affected by Elicitation with Temperature Stress.

    PubMed

    Swieca, Michał; Baraniak, Barbara

    2014-03-28

    The influences of temperature stress on antioxidant potential and nutritional quality of lentil sprouts were studied. Temperature treatments (TC, 1 h at 4 °C; TH, 1 h at 40 °C) significantly improved the nutraceutical potential without any negative effect on nutritional quality. In comparison to control, elicited sprouts were characterized by elevated content of condensed tannins, flavonoids, and total phenolics. The highest content of total phenolics and flavonoids was determined for 6-day-old TH sprouts -23.7 ± 0.87 and 2.50 ± 0.07 mg/(g of dry weight (DW)), respectively. The general trend of antiradical, lipid preventing, and reducing properties in elicited sprouts indicates a significantly improvement of these activities. The highest reducing power was determined for 6-day-old sprouts induced at TH (0.43 ± 0.02 mmol of Trolox/(g of DW)), while the lowest for 3-day-old sprouts elicited at TC (0.29 ± 0.02 mmol of Trolox/(g of DW)). Both modifications effectively elevated the ability to prevent lipids against oxidation (in 3-day-old sprouts a 3.3- and 4-fold increase for TC and TH, respectively).

  5. In vitro evaluation of the antioxidant potential, phenolic and flavonoid contents of the stem bark ethanol extract of Anogeissus leiocarpus

    PubMed Central

    Olugbami, JO; Gbadegesin, MA

    2015-01-01

    Plant-derived antioxidants with free radical scavenging activities can be relevant as chemopreventive agents against the numerous diseases associated with free radicals and reactive oxygen species. Some phytoconstituents possess antioxidant activities in biological systems. On this basis, we evaluated the antioxidant potential, and determined the total phenolic and flavonoid contents of the ethanol extract of the stem bark of Anogeissus leiocarpus [EESAL]. Antioxidant assays carried out include: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phosphomolybdate, β-carotene bleaching, ferric reducing, and hydroxyl radical scavenging activities. Results of DPPH assay showed no significant difference (p < 0.001) between EESAL and butylated hydroxyanisole [BHA], while EESAL exhibited a significantly (p < 0.001) higher activity than BHT [butylated hydroxytoluene]. Phosphomolybdate method recorded a total antioxidant capacity of 190.00 ± 70.53 µg butylated hydroxytoluene equivalents [BHTE]/mg dry extract, while β-carotene bleaching assay gave percent antioxidant activities of both EESAL and BHT as 81.46±1.62 and 80.90±1.39 respectively. Ferric reducing abilities of both EESAL and ascorbic acid increased in a concentration-dependent manner with EESAL displaying a significantly (p < 0.001) higher reductive activity than vitamin C. EESAL displayed a significantly higher hydroxyl radical scavenging activity as compared with BHT at the lowest concentration with no significant difference at the highest concentration. Total phenolic and flavonoid contents of EESAL were obtained as 608.10 ± 2.12 µg GAE/mg and 78.96 ± 3.37 µg QE/mg respectively. Taken together, the free radical scavenging and antioxidant activity of EESAL is likely due to its high phenolic content with complementary effects of the flavonoid components. PMID:26681826

  6. UV-visible spectroscopy method for screening the chemical stability of potential antioxidants for proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Banham, Dustin; Ye, Siyu; Knights, Shanna; Stewart, S. Michael; Wilson, Mahlon; Garzon, Fernando

    2015-05-01

    A novel method based on UV-visible spectroscopy is reported for screening the chemical stability of potential antioxidant additives for proton exchange membrane fuel cells, and the chemical stabilities of three CeOx samples of varying crystallite sizes (6, 13, or 25 nm) are examined. The chemical stabilities predicted by this new screening method are compared to in-situ membrane electrode assembly (MEA) accelerated stress testing, with the results confirming that this rapid and inexpensive method can be used to accurately predict performance impacts of antioxidants.

  7. A Simple Electrochemical Method for the Rapid Estimation of Antioxidant Potentials of Some Selected Medicinal Plants

    PubMed Central

    Amidi, Salimeh; Mojab, Faraz; Bayandori Moghaddam, Abdolmajid; Tabib, Kimia; Kobarfard, Farzad

    2012-01-01

    Clinical and Epidemiological studies have shown that a diet rich in fruits and vegetables is associated with a decreased risk of cardiovascular diseases, cancers and other related disorders. These beneficial health effects have been attributed in part to the presence of antioxidants in dietary plants. Therefore screening for antioxidant properties of plant extracts has been one of the interests of scientists in this field. Different screening methods have been reported for the evaluation of antioxidant properties of plant extracts in the literature. In the present research a rapid screening method has been introduced based on cyclic voltammetry for antioxidant screening of some selected medicinal plant extracts. Cyclic Voltammetry of methanolic extracts of seven medicinal plants: Buxus hyrcana, Rumex crispus, Achillea millefolium, Zataria multiflora, Ginkgo biloba, Lippia citriodora and Heptaptera anisoptera was carried out at different scan rates. Based on the interpretation of voltammograms, Rumex crispus, Achillea millefolium and Ginkgo biloba showed higher antioxidant capability than the others while Lippia citriodora contained the highest amount of antioxidants. Cyclic voltammetry is expected to be a simple method for screening antioxidants and estimating the antioxidant activity of foods and medicinal plants. PMID:25317192

  8. A simple electrochemical method for the rapid estimation of antioxidant potentials of some selected medicinal plants.

    PubMed

    Amidi, Salimeh; Mojab, Faraz; Bayandori Moghaddam, Abdolmajid; Tabib, Kimia; Kobarfard, Farzad

    2012-01-01

    Clinical and Epidemiological studies have shown that a diet rich in fruits and vegetables is associated with a decreased risk of cardiovascular diseases, cancers and other related disorders. These beneficial health effects have been attributed in part to the presence of antioxidants in dietary plants. Therefore screening for antioxidant properties of plant extracts has been one of the interests of scientists in this field. Different screening methods have been reported for the evaluation of antioxidant properties of plant extracts in the literature. In the present research a rapid screening method has been introduced based on cyclic voltammetry for antioxidant screening of some selected medicinal plant extracts. CYCLIC VOLTAMMETRY OF METHANOLIC EXTRACTS OF SEVEN MEDICINAL PLANTS: Buxus hyrcana, Rumex crispus, Achillea millefolium, Zataria multiflora, Ginkgo biloba, Lippia citriodora and Heptaptera anisoptera was carried out at different scan rates. Based on the interpretation of voltammograms, Rumex crispus, Achillea millefolium and Ginkgo biloba showed higher antioxidant capability than the others while Lippia citriodora contained the highest amount of antioxidants. Cyclic voltammetry is expected to be a simple method for screening antioxidants and estimating the antioxidant activity of foods and medicinal plants.

  9. The effect of ripening stages on the antioxidant potential of melon (Cucumis melo L.) cultivar Hikapel

    NASA Astrophysics Data System (ADS)

    Wulandari, Puji; Daryono, Budi Setiadi; Supriyadi

    2017-06-01

    Melon (Cucumis melo L.) cultivar Hikapel, a new cultivar of melon, is one of non-netted orange-fleshed melon. Non-netted orange-fleshed melon is known as source of several phytochemicals such as phenolics, flavonoids, ascorbic acid, and carotenoids. During the ripening stages there are chemical changes of the fruit including antioxidant properties. The aims of this research were to study the changes of antioxidant activity and antioxidant compound during ripening stages of melon cv. Hikapel. Melon with three ripening stages (27 DAA, 29 DAA, and 32 DAA) were harvested and analyzed their antioxidant activity, ascorbic acid, total-phenolic, -flavonoid, and -carotenoid content. The results showed that ascorbic acid and carotenoid content increased during ripening stages, whereas total phenolic and antioxidant activity decreased. The ripening stages affected antioxidant activity of Cucumis melo L. cv. Hikapel. Antioxidant activity positively correlated with ascorbic acid, total-phenolic, and -flavonoid content. On the other hand, total carotenoid negatively correlated with antioxidant activity.

  10. Schizandrin ameliorates ovariectomy-induced memory impairment, potentiates neurotransmission and exhibits antioxidant properties

    PubMed Central

    Jiang, Zhong-Jiao; Wang, Chun-Yang; Xie, Xun; Yang, Jing-Fang; Huang, Jun-Ni; Cao, Zhi-Ping; Xiao, Peng; Li, Chu-Hua

    2015-01-01

    Background and Purpose Schizandrin (SCH) has been reported to prevent or reduce learning and memory defects. However, it is not known whether SCH ameliorates cognitive impairments induced by oestrogen deficiency. In the present study, we investigated the effect of SCH on memory in ovariectomized (OVX) and non-OVX rats. Experimental Approach A passive avoidance test was used to evaluate the effect of SCH on memory. Field EPSPs were recorded in hippocampal slices using an electrophysiological method. In OVX rats, biochemical parameters in the bilateral hippocampus were measured; these included superoxide dismutase (SOD), malondialdehyde (MDA) and AChE. Also, the number of NADPH-diaphorase (NADPH-d) positive neurons was counted by NADPH-d histochemistry staining technique. Key Results Oral SCH improved the memory and facilitated the induction of long-term potentiation in non-OVX and OVX rats; this effect was more obvious in OVX rats. Similarly, SCH perfusion enhanced synaptic transmission in hippocampal slices from both non-OVX and OVX rats. However, SCH perfusion reduced the ratio of paired-pulse facilitation only in OVX but not in non-OVX rats. In addition, SCH decreased AChE activity and MDA level and increased SOD activity and the number of NADPH-d-positive neurons in OVX rats. Conclusions and Implications SCH improves memory in OVX rats and its potential mechanisms may include a reduction in the loss of hippocampal NADPH-d positive neurons, an increase of antioxidant properties and a potentiation of synaptic transmission that possibly involves to enhance cholinergic function. Overall, our findings indicate that SCH has potential as a therapeutic strategy for the cognitive dysfunctions associated with the menopause. PMID:25573619

  11. Antioxidant potential of hydro-methanolic extract of Prasium majus L: an in vitro study.

    PubMed

    Chaouche, T M; Haddouchi, F; Ksouri, R; Medini, F; El-Haci, I A; Boucherit, Z; Sekkal, F Z; Atik-Bekara, F

    2013-11-01

    Phytochemicals are extensively found at different levels in many medicinal plants. To investigate the phenolic compound content and in vitro antioxidant activity of hydro-methanolic extract from Prasium majus L. (Lamiaceae). The present investigation comprises, estimation of total polyphenol, flavonoid, tannin, in vitro antioxidant assays such as total antioxidant capacity, DPPH, ABTS, beta-carotene and ferric reducing power. P. majus exhibited 64.25 mg GAE g(-1) extract of polyphenol phenol content and better scavenging activity of DPPH (IC50 = 7.95 microg mL(-1)), ABTS*+ (IC50 = 373.78 microg mL(-1)) and beta-carotene (IC50 = 122.56 microg mL(-1)). Our results clearly demonstrated that hydro-methanolic extract P. majus has antioxidant capacity. Therefore is a valuable source of natural antioxidants.

  12. Chemoprotective potentials of homoisoflavonoids and chalcones of Dracaena cinnabari: modulations of drug-metabolizing enzymes and antioxidant activity.

    PubMed

    Machala, M; Kubínová, R; Horavová, P; Suchý, V

    2001-03-01

    A series of homoisoflavonoids and chalcones, isolated from the endemic tropical plant Dracaena cinnabari Balf. (Agavaceae), were tested for their potential to inhibit cytochrome P4501A (CYP1A) enzymes and Fe-enhanced in vitro peroxidation of microsomal lipids in C57B1/6 mouse liver. The effects of the polyphenolic compounds were compared with those of prototypal flavonoid modulators of CYP1A and the well-known antioxidant, butylated hydroxytoluene. 2-Hydroxychalcone and partly 4,6-dihydroxychalcone were found to be strong inhibitors of CYP1A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity in vitro comparable to the effects of quercetin and chrysin. The first screening of flavonoids and chalcones of Dracaena cinnabari for antioxidant activity was done in an in vitro microsomal peroxidation assay. While chalcones were shown to be poor antioxidants, 7,8-methylenedioxy-3(4-hydroxybenzyl) chromane, as one of the tested homoisoflavonoids, exhibited a strong antioxidant activity comparable to that of the strongest flavonol antioxidant, quercetin.

  13. Anti-adenovirus activity, antioxidant potential, and phenolic content of black tea (Camellia sinensis Kuntze) extract.

    PubMed

    Karimi, Ali; Moradi, Mohammad-Taghi; Alidadi, Somayeh; Hashemi, Leila

    2016-12-01

    BackgroundAdenovirus (ADV) causes a number of diseases in human, and to date, no specific antiviral therapy is approved against this virus. Thus, searching for effective anti-ADV agents seems to be an urgent requirement. Many studies have shown that components derived from medicinal plants have antiviral activity. Therefore, the present study was aimed to evaluate in vitro anti-ADV activity and also antioxidant potential and total phenolic compounds of black tea (Camellia sinensis) crude extract. MethodsIn this study, the hydroalchoholic extract of black tea was prepared and its anti-ADV activity was evaluated on HEp2 cell line using MTT [3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. The 50 % inhibitory concentration (IC50) and 50 % cytotoxicity concentration (CC50) of the extract were determined using regression analysis. Its inhibitory effect on adsorption and/or post-adsorption stages of the virus replication cycle was evaluated. To determine antioxidant activity, total phenol content, and flavonoids content of the extract, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method were used, respectively. ResultsThe CC50 and the IC50 of the extract were 165.95±12.7 and 6.62±1.4 µg/mL, respectively, with the selectivity index (SI) of 25.06. This extract inhibited ADV replication in post-adsorption stage. The IC50 of DPPH radical was 8±1.41 μg/mL, compared with butylated hydroxytoluene, with IC50 of 25.41±1.89 μg/mL. The total phenol and flavonoid contents of the extract were 341.8±4.41 mg gallic acid equivalent per gram and 21.1±2.11 mg/g, respectively. ConclusionsHaving SI value of 25.06 with inhibitory effect on ADV replication, particularly during the post-adsorption period, black tea extract could be considered as a potential anti-ADV agent. The antiviral activity of this extract could be attributed to its phenolic compounds.

  14. Enzyme inhibitory and antioxidant activities of traditional medicinal plants: Potential application in the management of hyperglycemia

    PubMed Central

    2012-01-01

    Background Traditional Indian and Australian medicinal plant extracts were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of hyperglycemia and type 2 diabetes. The antioxidant activities were also assessed. Methods The evaluation of enzyme inhibitory activity of seven Australian aboriginal medicinal plants and five Indian Ayurvedic plants was carried out against α-amylase and α-glucosidase. Antioxidant activity was determined by measuring (i) the scavenging effect of plant extracts against 2, 2-diphenyl-1-picryl hydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) and (ii) ferric reducing power. Total phenolic and total flavonoid contents were also determined. Results Of the twelve plant extracts evaluated, the highest inhibitory activity against both α-amylase and α-glucosidase enzymes was exerted by Santalum spicatum and Pterocarpus marsupium with IC50 values of 5.43 μg/ml and 0.9 μg/ml, respectively, and 5.16 μg/ml and 1.06 μg/ml, respectively. However, the extracts of Acacia ligulata (IC50 = 1.01 μg/ml), Beyeria leshnaultii (0.39 μg/ml), Mucuna pruriens (0.8 μg/ml) and Boerhaavia diffusa (1.72 μg/ml) exhibited considerable activity against α-glucosidase enzyme only. The free radical scavenging activity was found to be prominent in extracts of Acacia kempeana, Acacia ligulata followed by Euphorbia drummondii against both DPPH and ABTS. The reducing power was more pronounced in Euphorbia drummondii and Pterocarpus marsupium extracts. The phenolic and flavonoid contents ranged from 0.42 to 30.27 μg/mg equivalent of gallic acid and 0.51 to 32.94 μg/mg equivalent of quercetin, respectively, in all plant extracts. Pearson’s correlation coefficient between total flavonoids and total phenolics was 0.796. Conclusion The results obtained in this study showed that most of the plant extracts have good potential

  15. Antioxidant potential of Juglans nigra, black walnut, husks extracted using supercritical carbon dioxide with an ethanol modifier.

    PubMed

    Wenzel, Jonathan; Storer Samaniego, Cheryl; Wang, Lihua; Burrows, Laron; Tucker, Evan; Dwarshuis, Nathan; Ammerman, Michelle; Zand, Ali

    2017-03-01

    The black walnut, Junglas nigra, is indigenous to eastern North America, and abscission of its fruit occurs around October. The fruit consists of a husk, a hard shell, and kernel. The husk is commonly discarded in processing, though it contains phenolic compounds that exhibit antioxidant and antimicrobial properties. For this study, black walnut husks were extracted using supercritical carbon dioxide with an ethanol modifier. The effects of temperature, ethanol concentration, and drying of walnut husks prior to extraction upon antioxidant potential were evaluated using a factorial design of experiments. The solvent density was held constant at 0.75 g/mL. The optimal extraction conditions were found to be 68°C and 20 wt-% ethanol in supercritical carbon dioxide. At these conditions, the antioxidant potential as measured by the ferric reducing ability of plasma (FRAP) assay was 0.027 mmol trolox equivalent/g (mmol TE/g) for dried walnut husk and 0.054 mmol TE/g for walnut husks that were not dried. Antioxidant potential was also evaluated using the total phenolic content (TPC) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assays and the FRAP assay was found to linearly correlate to the TPC assay.

  16. Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent.

    PubMed

    Ooi, Der Jiun; Chan, Kim Wei; Sarega, Nadarajan; Alitheen, Noorjahan Banu; Ithnin, Hairuszah; Ismail, Maznah

    2016-06-17

    Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF) isolated from M. latifolia rhizome methanolic extract (RME) contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction) contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

  17. Iron (FeII) Chelation, Ferric Reducing Antioxidant Power, and Immune Modulating Potential of Arisaema jacquemontii (Himalayan Cobra Lily)

    PubMed Central

    Sudan, Rasleen; Bhagat, Madhulika; Singh, Jasvinder; Koul, Anupurna

    2014-01-01

    This study explored the antioxidant and immunomodulatory potential of ethnomedicinally valuable species, namely, Arisaema jacquemontii of north-western Himalayan region. The tubers, leaves, and fruits of this plant were subjected to extraction using different solvents. In vitro antioxidant studies were performed in terms of chelation power on ferrous ions and FRAP assay. The crude methanol extract of leaves was found to harbour better chelating capacity (58% at 100 μg/mL) and reducing power (FRAP value 1085.4 ± 0.11 μMFe3+/g dry wt.) than all the other extracts. The crude methanol extract was thus further partitioned with solvents to yield five fractions. Antioxidant study of fractions suggested that the methanol fraction possessed significant chelation capacity (49.7% at 100 μg/mL) and reducing power with FRAP value of 1435.4 μM/g dry wt. The fractions were also studied for immune modulating potential where it was observed that hexane fraction had significant suppressive effect on mitogen induced T-cell and B-cell proliferation and remarkable stimulating effect on humoral response by 141% and on DTH response by 168% in immune suppressed mice as compared to the controls. Therefore, it can be concluded that A. jacquemontii leaves hold considerable antioxidant and immunomodulating potential and they can be explored further for the identification of their chemical composition for a better understanding of their biological activities. PMID:24895548

  18. Evaluation of the proximate composition, antioxidant potential, and antimicrobial activity of mango seed kernel extracts.

    PubMed

    Mutua, Jane K; Imathiu, Samuel; Owino, Willis

    2017-03-01

    After pulp extraction in fruit processing industry, a significant quantity of mango seed kernels are discarded as solid wastes. These seed kernels can be ideal raw materials for obtaining extracts rich in bioactive compounds with good antioxidant properties. The conversion of these wastes into utilizable food ingredients would help in reducing environmental problems associated with processing waste disposal. In order to determine their potential use, this study evaluated some of the biochemical characteristics and antimicrobial potential of mango seed kernel extracts on medically important human bacterial and fungal pathogens. Four mango varieties (Apple, Ngowe, Kent and Sabine) from Makueni and Embu counties in Kenya were used for this study. The analyzed mango seed kernel powders were found to contain on average, 6.74-9.20% protein content. Apple and Ngowe mango seed kernels had significantly higher fat content of 13.04 and 13.08, respectively, while Sabine from Makueni had the least fat content of 9.84%. The ash, fiber, and carbohydrate contents ranged from 1.78 to 2.87%, 2.64 to 3.71% and 72.86 to 75.92%, respectively. The mean percentage scavenging ability of mango kernel extracts at the concentration of 20 mg/mL was 92.22%. Apple and Sabine mango kernel extracts had significantly high inhibition zones of 1.93 and 1.73 compared to Kent and Ngowe with 1.13 and 1.10, respectively, against E. coli. For C. albicans, the inhibition of Kent mango kernel extract, 1.63, was significantly lower than that of Ngowe, Apple, and Sabine with 2.23, 2.13, and 1.83, respectively. This study demonstrates that mango seed powder is an abundant and cost-effective potential natural antibiotic and antifungal that can be utilized in addressing the challenge of food poisoning and infections caused by pathogenic microorganisms in the food industry.

  19. Alkaline extractive crude polysaccharide from Russula senecis possesses antioxidant potential and stimulates innate immunity response.

    PubMed

    Khatua, Somanjana; Acharya, Krishnendu

    2017-09-05

    Over past decades, investigation on bioactive polysaccharides extracted from mushroom by heated water reflux has been an emerging field of biomedicine especially in the area of immune stimulation. While studies with macromolecules isolated from remainder residue of aqueous extraction are scarce. In this context, crude polysaccharide from a traditionally edible macrofungus, Russula senecis, was prepared (RuseCap) by alkaline solvent using leftover residue of that conventional process and its structural along with therapeutic properties were evaluated. Investigation by FT-IR, HPTLC, GC-MS and spectrophotometry showed that the fraction was mainly consisted of carbohydrate with backbone of xylose, rhamnose, mannose and glucose (mostly β-glucan). Besides, RuseCap exhibited strong antioxidant activity evident by radical scavenging (superoxide, hydroxyl, DPPH, ABTS), chelating ability and reduction power where EC50 values ranged from 257 to 4068 μg/ml concentration. In addition, it also exhibited immune-boosting potentiality as the treatment effectively induced proliferation, phagocytosis, nitric oxide production, intracellular reactive oxygen species generation, morphological changes and increased transcription level of iNOS, COX-2, TNF-α, IL-6 genes in macrophage cells. Overall, the study provided blueprint for extended utilization of R. senecis basidiocarps beyond hot water process and defined use of RuseCap as potent therapeutic agent against free radicals as well as deprived immunity. © 2017 Royal Pharmaceutical Society.

  20. Antioxidant potential of Aesculus hippocastanum extract and escin against reactive oxygen and nitrogen species.

    PubMed

    Vašková, J; Fejerčáková, A; Mojžišová, G; Vaško, L; Patlevič, P

    2015-01-01

    Antioxidant, anti-inflammatory and venoconstrictor properties have been attributed to extracts from Aesculus hippocastanum. These unusual and diverse properties may be possibly basically linked with ability to scavenge free radicals. The scavenging capacity of dry horse chestnut extract of and escin have been investigated in vitro against superoxide anion radicals, hydroxyl radicals, nitrites and peroxynitrite. In general, the activity of the whole extract against superoxide radicals did not exceed 15% at pH 7.4, but the highest inhibition (46.11%) was recorded against hydroxyl radicals at a concentration of 100 µg.ml-1; however, the activity against other radicals was lower. Escin demonstrated a better ability to counteract nitric oxide oxidation products, nitrites. However, the efficiency of the whole extract completely disappeared as the concentration increased. Both extracts showed very low activity towards peroxynitrite. Escin was even able to induce peroxynitrite formation at the lower concentrations used. Whole extract showed better antiradical properties compared to its main active ingredient, escin, probably due to potential synergistic interaction with a mixture of compounds present in the plant extract. These findings can be the basis of both the presentation of side-effects and the persistence of disease in spite of ongoing treatment.

  1. Biological Activity of Conventional and Organic Pomegranate Juices: Antioxidant and Antimutagenic Potential.

    PubMed

    Cano-Lamadrid, M; Marhuenda-Egea, F C; Hernández, F; Rosas-Burgos, E C; Burgos-Hernández, A; Carbonell-Barrachina, A A

    2016-12-01

    None of the health claims about pomegranate juices has been approved yet by European Food Safety Authority (EFSA). There is a general perception among consumers that organic foods are healthier, tastier, and more nutritive than the conventional products. The aim of this research was to study the differences in the biological activity between ready-for-consumption juices obtained from pomegranates fruits grown under conventional and organic agricultural practices. Antioxidant activity has been evaluated by three methods (DPPH(•), ABTS(+), and FRAP), together with the total contents of phenolics and punicalagin (HPLC-DAD); besides, the Ames test was used to evaluate the antimutagenic potential of the juices. Pomegranate juice, either from conventionally or organically grown fruits, was antimutagenic (mean of 51 and 90 % for Salmonella typhimurium TA100 and TA98, respectively) and it was capable of protecting DNA from both, base-pair or frame-shift type of mutations. In fact, the antimutagenicity of conventional pomegranate juice was higher than that achieved by the organic sample; this finding was linked to a higher punicalagin content (201 and 104 mg L(-1) for conventional and organic juices, respectively).

  2. Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener.

    PubMed

    Ghanta, Srijani; Banerjee, Anindita; Poddar, Avijit; Chattopadhyay, Sharmila

    2007-12-26

    At 0.1 mg/mL, the ethyl acetate extract (EAE) of the crude 85% methanolic extract (CAE) of Stevia rebaudiana leaves exhibited preventive activity against DNA strand scission by *OH generated in Fenton's reaction on pBluescript II SK (-) DNA. Its efficacy is better than that of quercetin. The radical scavenging capacity of CAE was evaluated by the DPPH test (IC50=47.66+/-1.04 microg/mL). EAE was derived from CAE scavenged DPPH (IC50=9.26+/-0.04 microg/mL), ABTS+ (IC50=3.04+/-0.22 microg/mL) and *OH (IC50=3.08+/-0.19 microg/mL). Additionally, inhibition of lipid peroxidation induced with 25 mM FeSO 4 on rat liver homogenate as a lipid source was noted with CAE (IC50=2.1+/-1.07 mg/mL). The total polyphenols and total flavonoids of EAE were 0.86 mg gallic acid equivalents/mg and 0.83 mg of quercetin equivalents/mg, respectively. Flavonoids, isolated from EAE, were characterized as quercetin-3-O-arabinoside, quercitrin, apigenin, apigenin-4-O-glucoside, luteolin, and kaempferol-3-O-rhamnoside by LC-MS and NMR analysis. These results indicate that Stevia rebaudiana may be useful as a potential source of natural antioxidants.

  3. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

    PubMed Central

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  4. Antioxidant enzymes in ringed seal tissues: potential protection against dive-associated ischemia/reperfusion.

    PubMed

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Elsner, Robert

    2006-01-01

    Diving seals experience heart rate reduction and preferential distribution of the oxygenated blood flow to the heart and brain, widespread peripheral vasoconstriction, and selective ischemia in the most hypoxia-tolerant tissues. The first breath after the dive restores the oxygenated blood flow to all tissues and raises the potential for the production of reactive oxygen species (ROS). We hypothesized that in order to counteract the damaging effects of ROS and to tolerate repetitive cycles of ischemia/reperfusion associated with diving, ringed seal (Phoca hispida) tissues have elevated activities of antioxidant enzymes. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were measured by spectrophotometric techniques in heart, kidney, liver, lung, and muscle extracts of ringed seals and domestic pigs (Sus scrofa). The results suggest that in ringed seal heart SOD, GPx and GST activities are an efficient protective mechanism for counteracting ROS production and its deleterious effects. Apparently CAT activity in seal liver and GPx activity in seal muscle participate in the removal of hydroperoxides, while seal lung appears to be protected from oxidative damage by SOD and GPx activities.

  5. Antioxidant, Anti-inflammatory, and Antiulcer Potential of Manuka Honey against Gastric Ulcer in Rats

    PubMed Central

    Almasaudi, Saad B.; El-Shitany, Nagla A.; Abbas, Aymn T.; Abdel-dayem, Umama A.; Ali, Soad S.; Al Jaouni, Soad K.

    2016-01-01

    Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels. PMID:26770649

  6. Biochemical Constituents and in Vitro Antioxidant and Anticholinesterase Potential of Seeds from Native Korean Persimmon Genotypes.

    PubMed

    Bilal, Saqib; Khan, Abdul Latif; Waqas, Muhammad; Shahzad, Raheem; Kim, Il-Doo; Lee, In-Jung; Shin, Dong-Hyun

    2016-07-08

    In the current study, the functional and biochemical potential of the seeds of four persimmon cultivars (PC1, PC2, PC3 and PC4) and their role against oxidative stress and acetylcholinesterase (AChE) inhibition were evaluated. In terms of biochemical compositions, free amino acids, fatty acids and organic acids analysis was performed. The free amino acids ranged from 2617.31 (PC2) to 3773.01 μg∙g(-1) dry weight (PC4). Oleic acid and linoleic acid were the principal fatty acids, which were significantly higher in PC4 and PC1, respectively. PC4 presented the highest amount of organic acid content (4212 mg∙kg(-1)), whereas PC2 presented the lowest (2498 mg∙kg(-1)). PC2 contained higher total phenolic content and flavonoid content, whereas PC3 had the lowest amount as compared to other cultivars. The in vitro DPPH, ABTS and superoxide anion radicals scavenging activity increased in a dose-dependent manner, whereas PC2 showed significantly higher scavenging activities as compared to PC1, PC2 and PC4 types. In the case of AChE inhibition, PC4 showed a moderate activity (67.34% ± 1.8%). In conclusion, the current findings reveal that the studied persimmon seeds cultivars are a source of bioactive natural antioxidants and AChE inhibitors. Such natural products could be employed in pharmaceutical and food industries, whilst can also be considered for the treatment of neurodegenerative diseases such as Alzheimer's.

  7. A new total antioxidant potential measurements using RP-HPLC assay with fluorescence detection.

    PubMed

    Głód, Bronisław K; Piszcz, Paweł; Czajka, Katarzyna; Zarzycki, Paweł K

    2011-05-01

    In this paper, an improved total antioxidant potential (TAP) estimation using high-performance liquid chromatographic (HPLC) assay with fluorometric detection has been described. The principle of this method is based on the hydroxyl radicals generated in the Fenton-like reaction and subsequently detected using hydroxyterephthalic acid (HTPA), which is a reaction product of hydroxyl radicals and terephthalic acid (TPA), working as a sensing compound. HTPA quantity in the samples was measured by fluorescence detector working at excitation and emission wavelengths equal to 312 and 428 nm, respectively. A number of key experimental conditions including the influence of the reaction (incubation) time on the surface areas of HTPA peaks, concentration of Fe(II) ions as well as the influence of concentration of TPA on the surface area of the chromatographic peak of HTPA were optimized to the characteristic feature of TAP measurements. The elaborated assay has been used to evaluate TAP values of selected low-molecular mass compounds like pyrogallol, tryptamine, and n-alcohols (methanol, ethanol, and n-propanol) as well as chlorogenic and ascorbic acids and benzoic acid derivatives, which are commonly present in the food samples.

  8. Antioxidant, Anti-inflammatory, and Antiulcer Potential of Manuka Honey against Gastric Ulcer in Rats.

    PubMed

    Almasaudi, Saad B; El-Shitany, Nagla A; Abbas, Aymn T; Abdel-dayem, Umama A; Ali, Soad S; Al Jaouni, Soad K; Harakeh, Steve

    2016-01-01

    Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.

  9. Phytochemical analysis and antioxidant potential of the leaves of Garcinia travancorica Bedd.

    PubMed

    Aravind, A P Anu; Asha, K R T; Rameshkumar, K B

    2016-01-01

    Phytochemical analysis of the leaves of Garcinia travancorica, a hitherto uninvestigated endemic species to the Western Ghats of south India, resulted in isolation and characterisation of the polyisoprenylated benzophenones 7-epi-nemorosone (1) and garcinol (2) along with biflavonoids GB-1a (3), GB-1 (4), GB-2 (5), morelloflavone (6) and morelloflavone-7″-O-β-D-glycoside or fukugiside (7). The compounds were identified using various spectroscopic techniques, mainly through NMR and MS. The methanol extract and the biflavonoids 3, 4, 5 and 7 showed potential in vitro antioxidant activities. The IC50 value of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of compound 7 was 8.34 ± 2.12 μg/mL, comparable to that of standard ascorbic acid (3.2 ± 0.50 μg/mL). In the superoxide radical scavenging assay, compound 7 gave IC50 value of 6.95 ± 1.33 μg/mL close to standard ascorbic acid with IC50 value of 5.8 ± 0.25 μg/mL. Validated HPTLC estimation revealed G. travancorica as a rich source of morelloflavone-7″-O-β-D-glycoside (7.12% dry wt. leaves).

  10. Interdependence of antioxidants and micronutrients in oral cancer and potentially malignant oral disorders: a serum and saliva study.

    PubMed

    Shetty, Shishir Ram; Babu, Subhas G; Rao, Prasanna Kumar; Kishor, Sham Kannepady; Rao, Kumuda Arvind; Castelino, Renita

    2014-11-01

    In our previous studies we have evaluated the role of antioxidants and trace elements in potentially malignant disorders and cancers of the oral cavity, taking into consideration the importance of antioxidants as biomarkers in cancer detection. We felt that other than evaluation, the correlation and interdependence that existed among antioxidants and trace elements require further evaluation in order to develop a better understanding. Serum and salivary zinc, glutathione, and superoxide dismutase levels were evaluated in 65 healthy controls, 115 subjects with potentially malignant oral disorders, and 50 subjects with oral squamous cell carcinoma, using the atom absorption photometry, [5, 5-Dithiobis (2 nitrobenzoic acid)], and nitroblue tetrazolium methods, respectively. Serum zinc and serum glutathione showed significant positive correlation (r=0.76, P=0.01). Similarly, salivary glutathione and salivary zinc levels had a positive correlation (r=0.68, P=0.01). Serum superoxide dismutase showed a strong positive correlation with serum zinc (r=0.64, P=0.01). Similarly, there was a moderate positive correlation between salivary superoxide dismutase and salivary zinc (r=0.67, P=0.01). Our findings showed that trace elements and antioxidants exhibited interdependence in serum, as well as in saliva, in both physiologic and pathologic states such as oral cancer.

  11. Evaluation of the potential of squash pumpkin by-products (seeds and shell) as sources of antioxidant and bioactive compounds.

    PubMed

    Saaved