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Sample records for alkaloids berberine hydrastine

  1. High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal.

    PubMed

    Abourashed, E A; Khan, I A

    2001-07-01

    Goldenseal (Hydrastis canadensis L., Ranunculaceae) is an ingredient of various dietary supplements intended for enhancing general body immunity. Many goldenseal products are currently available in the United States, either alone or in combination with echinacea. In most products, the content of the main active alkaloids of goldenseal, hydrastine and berberine, is not indicated on the label. A high-performance liquid chromatography (HPLC) method has been developed for the detection and quantification of hydrastine and berberine in a number of products obtained from the United States market. The method uses a Phenomenex Luna C(18) column, a mobile phase consisting of solvent A (100 mM sodium acetate/acetic acid, pH 4.0) and solvent B (acetonitrile/methanol; 90/10, v/v). Elution was run at a flow rate of 1.0 mL/min, with a linear gradient of 80- 40% A in B over 20 min and ultraviolet detection at 290 nm. A wide range of content variation was observed for both alkaloids in the tested samples.

  2. Determination of hydrastine and berberine in goldenseal raw materials, extracts, and dietary supplements by high-performance liquid chromatography with UV: collaborative study.

    PubMed

    Brown, Paula N; Roman, Mark C

    2008-01-01

    A multilaboratory collaborative study was conducted on a high-performance liquid chromatographic (HPLC) method utilizing UV detection, previously validated using AOAC single-laboratory validation guidelines for determination of hydrastine and berberine in goldenseal (Hydrastis canadensis L.) raw materials, extracts, and dietary supplements at levels ranging from 0.4 to 6% (w/w). Nine collaborating laboratories determined the hydrastine and berberine content in 8 blind samples. Sample materials included powdered botanical raw materials, whole root material, and 4 finished product dietary supplements containing either goldenseal powdered root material or extract. The materials were extracted with an acidified water and acetonitrile solution. HPLC analyses of the extracts were performed on a C18 column using UV detection at 230 nm. Results for powdered root material and capsule products ranged from about 0.2% (w/w) for each alkaloid to about 4% (w/w) for each alkaloid. Liquid tincture results were approximately 4000-5000 microg/mL for each alkaloid. Reproducibility relative standard deviations (RSDR) for hydrastine ranged from 2.68 to 6.65%, with HorRat values ranging from 0.77 to 1.89. RSDR for berberine ranged from 5.66 to 7.68%, with HorRat values ranging from 1.32 to 2.12. All finished products containing goldenseal extract yielded HorRat values <2.0. Based on these results, the method is recommended for Official First Action for determination of hydrastine and berberine in goldenseal raw materials and dietary supplement finished products containing powdered goldenseal and goldenseal extract.

  3. Determination of Hydrastine and Berberine in Goldenseal Raw Materials, Extracts, and Dietary Supplements by High-Performance Liquid Chromatography with UV: Collaborative Study

    PubMed Central

    Brown, Paula N.; Roman, Mark C.

    2008-01-01

    A multilaboratory collaborative study was conducted on a high-performance liquid chromatographic (HPLC) method utilizing UV detection, previously validated using AOAC single-laboratory validation guidelines for determination of hydrastine and berberine in goldenseal (Hydrastis canadensis L.) raw materials, extracts, and dietary supplements at levels ranging from 0.4 to 6% (w/w). Nine collaborating laboratories determined the hydrastine and berberine content in 8 blind samples. Sample materials included powdered botanical raw materials, whole root material, and 4 finished product dietary supplements containing either goldenseal powdered root material or extract. The materials were extracted with an acidified water and acetonitrile solution. HPLC analyses of the extracts were performed on a C18 column using UV detection at 230 nm. Results for powdered root material and capsule products ranged from about 0.2% (w/w) for each alkaloid to about 4% (w/w) for each alkaloid. Liquid tincture results were approximately 4000–5000 μg/mL for each alkaloid. Reproducibility relative standard deviations (RSDR) for hydrastine ranged from 2.68 to 6.65%, with HorRat values ranging from 0.77 to 1.89. RSDR for berberine ranged from 5.66 to 7.68%, with HorRat values ranging from 1.32 to 2.12. All finished products containing goldenseal extract yielded HorRat values <2.0. Based on these results, the method is recommended for Official First Action for determination of hydrastine and berberine in goldenseal raw materials and dietary supplement finished products containing powdered goldenseal and goldenseal extract. PMID:18727526

  4. Multicomponent Therapeutics of Berberine Alkaloids

    PubMed Central

    Luo, Jiaoyang; Yan, Dan; Yang, Meihua; Dong, Xiaoping; Xiao, Xiaohe

    2013-01-01

    Although berberine alkaloids (BAs) are reported to be with broad-spectrum antibacterial and antiviral activities, the interactions among BAs have not been elucidated. In the present study, methicillin-resistant Staphylococcus aureus (MRSA) was chosen as a model organism, and modified broth microdilution was applied for the determination of the fluorescence absorption values to calculate the anti-MRSA activity of BAs. We have initiated four steps to seek the optimal combination of BAs that are (1) determining the anti-MRSA activity of single BA, (2) investigating the two-component combination to clarify the interactions among BAs by checkerboard assay, (3) investigating the multicomponent combination to determine the optimal ratio by quadratic rotation-orthogonal combination design, and (4) in vivo and in vitro validation of the optimal combination. The results showed that the interactions among BAs are related to their concentrations. The synergetic combinations included “berberine and epiberberine,” “jatrorrhizine and palmatine” and “jatrorrhizine and coptisine”; the antagonistic combinations included “coptisine and epiberberine”. The optimal combination was berberine : coptisine : jatrorrhizine : palmatine : epiberberine = 0.702 : 0.863 : 1 : 0.491 : 0.526, and the potency of the optimal combination on cyclophosphamide-immunocompromised mouse model was better than the natural combinations of herbs containing BAs. PMID:23634170

  5. Analysis of goldenseal, Hydrastis canadensis L., and related alkaloids in urine using HPLC with UV detection.

    PubMed

    Dawes, Michelle L; Brettell, Thomas

    2012-01-01

    A screening method was developed to extract and detect berberine and hydrastine alkaloids from goldenseal root powder and urine samples using HPLC with UV detection. The isocratic method was developed to detect alkaloids in 5 mL of urine prior to drug screening. Urine samples were spiked with the alkaloids at varying concentrations and extracted twice with 3:1 chloroform:2-propanol (CHCl(3):2-propanol). The extracts were combined, concentrated using nitrogen gas and the residue was then reconstituted with a mobile phase of acetonitrile:buffer (32:68). A 17 min isocratic run time was performed with a flow rate of 2.0 mL/min, and UV detection at 230 nm using a C(18) (250 mm × 4.6 mm) column at room temperature. The method showed good linearity for berberine (r(2)=0.9990) and hydrastine (r(2)=0.9983) over a range of 11.80 ng/mL to 17.64 μg/mL. The LOD for berberine in urine was 12.74 ng/mL and the LOD for hydrastine in urine was 54.48 ng/mL. Urine samples were spiked with goldenseal root powder and liquid extract as part of a blinded study to determine whether berberine and hydrastine alkaloids could also be extracted in vitro from goldenseal and show a presence in urine samples. Out of the 37 blinded urine samples extracted the two spiked samples were correctly identified based on the presence or absence of berberine and hydrastine. The results demonstrated that this method will enable laboratories to test for the herbal supplement in submitted urine samples prior to drug testing, avoiding false negative results.

  6. Herbicidal Spectrum, Absorption and Transportation, and Physiological Effect on Bidens pilosa of the Natural Alkaloid Berberine.

    PubMed

    Wu, Jiao; Ma, Jing-Jing; Liu, Bo; Huang, Lun; Sang, Xiao-Qing; Zhou, Li-Juan

    2017-08-02

    Berberine is a natural herbicidal alkaloid from Coptis chinensis Franch. Here we characterized its herbicidal spectrum and absorption and transportation in the plant, along with the possible mechanism. Berberine showed no effect on the germination of the 10 tested plants. The IC50 values of berberine on the primary root length and fresh weight of the 10 tested plants ranged from 2.91 to 9.79 mg L(-1) and 5.76 to 35.07 mg L(-1), respectively. Berberine showed a similar herbicidal effect on Bidens pilosa as the commercial naturally derived herbicide cinmethylin. HPLC and fluorescence analysis revealed that berberine was mainly absorbed by B. pilosa root and transported through vascular bundle acropetally. Enzyme activity studies, GC-MS analysis, and SEM and TEM observations indicated that berberine might first function on the cell membrane indicated by variation of the IUFA percent and then cause POD, PPO, and SOD activity changes and cellular structure deformity, which was eventually expressed as the decrease of cell adaptation ability and abnormal cell function and may even result in cell death. Environmental safety evaluation tests revealed that berberine was low in toxicity to Brachydanio rerio. These indicate that berberine has the potential to be a bioherbicide and/or a lead molecule for new herbicides.

  7. Binding of plant alkaloids berberine and palmatine to serum albumins: a thermodynamic investigation.

    PubMed

    Khan, Asma Yasmeen; Hossain, Maidul; Kumar, Gopinatha Suresh

    2013-01-01

    The thermodynamics of the interaction of two pharmaceutically important isoquinoline alkaloids berberine and palmatine with bovine and human serum albumin was investigated using calorimetric techniques, and the data was supplemented with fluorescence and circular dichroism studies. Thermodynamic results revealed that there was only one class of binding sites for both alkaloids on BSA and HSA. The equilibrium constant was of the order of 10(4) M(-1) for both the alkaloids to serum albumins but the magnitude was slightly higher with HSA. Berberine showed higher affinity over palmatine to both proteins. The binding was enthalpy dominated and entropy favoured for both the alkaloids to BSA and HSA. Salt dependent studies suggested that electrostatic interaction had a significant role in the binding process, the binding affinity reduced as the salt concentration increased. Temperature dependent calorimetric data yielded heat capacity values that suggested the involvement of different molecular forces in the complexation of the two alkaloids with BSA and HSA. 3D fluorescence, synchronous fluorescence and circular dichroism data suggested that the binding of the alkaloids changed the conformation of proteins by reducing their helicity. Destabilization of the protein conformation was also revealed from differential scanning calorimetry studies. Overall, the alkaloids bound strongly to serum albumins, but berberine was a better binder to both serum proteins compared to palmatine.

  8. The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling.

    PubMed

    Varghese, Finny S; Thaa, Bastian; Amrun, Siti Naqiah; Simarmata, Diane; Rausalu, Kai; Nyman, Tuula A; Merits, Andres; McInerney, Gerald M; Ng, Lisa F P; Ahola, Tero

    2016-11-01

    Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase

  9. Effect of ion pairing on the fluorescence of berberine, a natural isoquinoline alkaloid

    NASA Astrophysics Data System (ADS)

    Megyesi, Mónika; Biczók, László

    2007-10-01

    Effect of association with chloride or perchlorate anions on the fluorescence properties of berberine, a cationic isoquinoline alkaloid, has been studied. Interaction with Cl - caused more efficient fluorescence quenching; it significantly accelerated the radiationless deactivation and slowed down the radiative transition. Combined analysis of spectrophotometric, steady-state and time-resolved fluorescence results provided 1.5 × 10 5 M -1 for the equilibrium constant of ion pairing with Cl - in CH 2Cl 2. Both ion pairing and enrichment of the microenvironment of berberine in ions led to excited state quenching in solvents of medium polarity, but only the latter effect was observed in the presence of perchlorates in butyronitrile.

  10. IR absorption and surface-enhanced Raman spectra of the isoquinoline alkaloid berberine

    NASA Astrophysics Data System (ADS)

    Strekal', N. D.; Motevich, I. G.; Nowicky, J. W.; Maskevich, S. A.

    2007-01-01

    We present the IR absorption and surface-enhanced Raman scattering (SERS) spectra of the isoquinoline alkaloid berberine adsorbed on a silver hydrosol and on the surface of a silver electrode for different potentials. Based on quantum chemical calculations, for the first time we have assigned the vibrations in the berberine molecule according to vibrational mode. The effect of the potential of the silver electrode on the geometry of sorption of the molecule on the surface is considered, assuming a short-range mechanism for enhancement of Raman scattering.

  11. Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro.

    PubMed

    Orfila, L; Rodríguez, M; Colman, T; Hasegawa, M; Merentes, E; Arvelo, F

    2000-08-01

    The cytotoxicity of two protoberberine alkaloids: berberine and lincangenine, their 8-hydroxy-7,8-dihydro-derivatives and tetrahydroprotoberberine:thaicanine, was evaluated. The cellular responses through the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) method were measured in Hela (uterus carcinoma), SVKO3 (ovary carcinoma), Hep-2 (larynx carcinoma), primary culture from mouse embryon, and human fibroblast cells at the concentration: 10-1000 ppm (microg/ml) for 24 h. Berberine showed the highest cytotoxicity among the compounds tested, giving LC50 values for all cell lines at the concentration of 10 ppm. The results indicated that the cytotoxicity was notably decreased by structural changes, i.e. by modulation of the planarity caused by the introduction of hydroxyl group at C-8 and concomitant saturation of double bond between N-C8 in protoberberine molecules. In the case of berberine, the cytotoxic effect changed from 98.8 (berberine) to 39% for 8-hydroxydihydroberberine at the concentration of 100 ppm in Hela cells line. The same effect was observed with lincangenine and 8-OH-lincangenine (cytotoxicities 70 and 25%, respectively, at 1000 ppm in SVKO3 cells). On the other hand, these compounds showed a low selectivity for the different human cancer cell lines tested.

  12. Photochemistry and Photocytotoxicity of Alkaloids from Goldenseal (Hydrastis canadensis L.) 3. Effect on Human Lens and Retinal Pigment Epithelial Cells

    PubMed Central

    Chignell, C.F.; Sik, R.H.; Watson, M.A.; Wielgus, A.R.

    2008-01-01

    The dried root or rhizome of Goldenseal (Hydrastis canadensis L.) contains several alkaloids including berberine, hydrastine, palmatine and lesser amounts of canadine and hydrastinine. Preparations derived from Goldenseal have been used to treat skin and eye ailments. Berberine, the major alkaloid in Goldenseal root powder, has been used in eye drops to treat trachoma, a disease characterized by keratoconjunctivitis. Berberine and palmatine are also present in extracts from Berberis amurensis Ruprecht (Berberidaceae) which are used to treat ocular disorders. We have previously shown that Goldenseal alkaloids are phototoxic to keratinocytes (Chem Res Toxicol. 14, 1529, 2001; ibid 19, 739, 2006) and now report their effect on human lens and retinal pigment epithelial cells. Human lens epithelial cells (HLE-B3) were severely damaged when incubated with berberine (25 μM) and exposed to UVA (5 J/cm2). Under the same conditions palmatine was less phototoxic and hydrastine, canadine and hydrastinine were inactive. Moderate protection against berberine phototoxicity was afforded by the antioxidants ascorbate (2 mM) and N-acetylcysteine (5 mM). When exposed to UVA (5 J/cm2) both berberine (10 μM) and palmatine (10 μM) caused mild DNA damage as determined by the alkaline Comet assay which measures single strand breaks. Berberine and palmatine are the only Goldenseal alkaloids with appreciable absorption above 400 nm. Because light at wavelengths below 400 nm is cut off by the anterior portion of the human eye only berberine and palmatine were tested for phototoxicity to human retinal pigment epithelial (hRPE) cells. Although berberine did damage hRPE cells when irradiated with visible light (λ>400 nm) approximately ten times higher concentrations were required to produce the same amount of damage as seen in lens cells. Palmatine was not phototoxic to hRPE cells. Neither berberine nor palmatine photodamaged RPE DNA. Infusions of Goldenseal are estimated to contain ∼1 m

  13. An isoquinoline alkaloid, berberine, can inhibit fungal alpha amylase: enzyme kinetic and molecular modeling studies.

    PubMed

    Tintu, Ignatius; Dileep, Kalarickal V; Augustine, Anu; Sadasivan, Chittalakkottu

    2012-10-01

    Aspergillus flavus is a commonly found fungal pathogen, which produces aflatoxins, highly toxic and hepatocarcinogenic natural compounds. Inhibition of fungal alpha amylase activity has been found to limit the ability of the fungus to produce aflatoxins. Berberine, an isoquinoline alkaloid commonly found in many medicinal plants, was identified to inhibit the growth of A. flavus. The amount of berberine required to inhibit the fungal mycelial growth was determined. The compound was also found to inhibit the alpha amylase from the A. flavus. The binding affinity of the compound toward alpha amylase and the enzyme inhibitory activity have been determined by enzyme kinetic studies and Isothermal Titration Calorimetric analysis. Molecular modeling and docking studies were carried out to understand the enzyme-ligand interactions. © 2012 John Wiley & Sons A/S.

  14. Effects of isoquinoline alkaloid berberine on lipid peroxidation, antioxidant defense system, and liver damage induced by lead acetate in rats.

    PubMed

    Hasanein, Parisa; Ghafari-Vahed, Masumeh; Khodadadi, Iraj

    2017-01-01

    Liver is considered a target organ affected by lead toxicity. Oxidative stress is among the mechanisms involved in liver damage. Here we investigated the effects of the natural alkaloid berberine on oxidative stress and hepatotoxicity induced by lead in rats. Animals received an aqueous solution of lead acetate (500 mg Pb/l in the drinking water) and/or daily oral gavage of berberine (50 mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical, molecular, and histological evaluations. Lead-induced oxidative stress, shown by increasing lipid peroxidation along with a concomitant decrease in hepatic levels of thiol groups, total antioxidant capacity, the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and reduced versus oxidized glutathione ratio. Berberine corrected all the disturbances in oxidative stress markers induced by lead administration. Berberine also prevented the elevated levels of enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) and the decrease in body weight and albumin. The protective effects of berberine were comparable with silymarin. Furthermore, berberine attenuated liver damage, shown by decreased necrosis and inflammatory cell infiltration. Berberine represents a potential therapeutic option against lead-induced hepatotoxicity through inhibiting lipid peroxidation and enhancing antioxidant defenses. Berberine exerted protective effects on lead-induced oxidative stress and hepatotoxicity in rats.

  15. Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents.

    PubMed

    Zhang, Zhi-Hui; Li, Jing; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Li, Zhi-Hong; Song, Hong-Rui; Wang, Wen-Jie; Qin, Hai-Lin

    2016-06-01

    Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.

  16. Tetra­hydro­berberine, a pharmacologically active naturally occurring alkaloid

    PubMed Central

    Pingali, Subramanya; Donahue, James P.; Payton-Stewart, Florastina

    2015-01-01

    Tetra­hydro­berberine (systematic name: 9,10-dimeth­oxy-5,8,13,13a-tetra­hydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the mol­ecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The inter­molecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole –CH2⋯OCH3 and –OCH3⋯OCH3 inter­actions between neighboring mol­ecules. PMID:25836282

  17. In vitro studies of antifibrotic and cytoprotective effects elicited by proto-berberine alkaloids in human dermal fibroblasts.

    PubMed

    Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria

    2015-12-01

    The pathogenic mechanisms of skin fibrosis are still not completely understood, unlike the profibrotic role played by inflammatory cytokines and transforming growth factor-β1 (TGF-β1). Few antifibrotic drugs are available. Nevertheless, folk medicine suggests numerous treatments of fibrotic conditions. Based on information from folk medicine and literature, the hypothesis was made that proto-berberine alkaloids could act as antifibrotic and cytoprotective agents. The effects of berberine, dihydroberberine, canadine, stylopine, and coptisine were investigated on an in vitro model of fibrosis purposely set up. The study is based on the use of human dermal fibroblasts (HDF). The ability of the proto-berberine alkaloids investigated to modulate mitochondrial dehydrogenase activity, cell proliferation, collagen production, and inflammatory cytokine (IL-1β and IL-6) production was tested on HDF cells grown under standard growth conditions, in the presence of 100 μM H(2)O(2), simulating oxidative stress conditions, and in the presence of 34 ng/ml TGF-β1, simulating fibrotic conditions. Antiradical activity was assayed as well, as it could contribute to cytoprotection. Each alkaloid tested showed peculiar effects on HDF. In particular, all of the alkaloids tested, with the exception of coptisine, inhibited TGF-β1-induced collagen production. Due to its irritant effects and the lack of desired properties, coptisine has low exploitation potentialities. The other proto-berberine alkaloids investigated resulted all endowed with activities for which they can be exploited as antifibrotic and cytoprotective agents. Stylopine globally proved to be the most promising compound, being endowed with revitalizing, anti-inflammatory, antifibrotic and wound-healing promoting activities, and showing no toxic effects. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Inclusion complex formation of ionic liquids with 4-sulfonatocalixarenes studied by competitive binding of berberine alkaloid fluorescent probe

    NASA Astrophysics Data System (ADS)

    Miskolczy, Zsombor; Biczók, László

    2009-07-01

    A clinically important natural isoquinoline alkaloid, berberine, was used as a fluorescent probe to study the encapsulation of 1-alkyl-3-methylimidazolium (C nMIm +) type ionic liquids in 4-sulfonato-substituted calix[4]arene (SCX4) and calix[6]arene (SCX6) at pH 2. Addition of ionic liquids to the aqueous solution of berberine-SCXn inclusion complexes brought about considerable fluorescence intensity diminution due to the extrusion of berberine from the macrocycle into the aqueous phase by the competitive inclusion of C nMIm + cation. The lengthening of the aliphatic side chain of the imidazolium moiety diminished the equilibrium constant of complexation with SCX4, but enhanced the stability of SCX6 complexes. Larger binding strength was found for SCX4.

  19. Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on glutamate-evoked tissue transglutaminase up-regulation in astroglial cell cultures.

    PubMed

    Campisi, Agata; Acquaviva, Rosaria; Mastrojeni, Silvana; Raciti, Giuseppina; Vanella, Angelo; De Pasquale, Rita; Puglisi, Salvatore; Iauk, Liliana

    2011-06-01

    Berberis aetnensis C. Presl. is a bushy-spiny shrub common on Mount Etna (Sicily, Italy), containing various alkaloids with several pharmacological properties. This study assessed the effect of berberine and of the alkaloid extract of B. aetnensis roots on the glutamate-evoked tissue transglutaminase (TG2) up-regulation in rat astrocyte primary cultures, used as an in vitro model of excitotoxicity. The findings show that the alkaloid extract of B. aetnensis roots consists mainly of berberine. Furthermore, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. It was found that berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. Thus, it is suggested that berberine and the alkaloid extract of B. aetnensis roots, may represent a natural therapeutic strategy in the neuropathological conditions associated with excitotoxicity.

  20. Recognition of molecularly imprinted polymers for a quaternary alkaloid of berberine.

    PubMed

    Chen, Chia-Yun; Wang, Chih-Hung; Chen, Arh-Hwang

    2011-05-30

    Selective and affinitive imprinted polymers incorporating a quaternary alkaloid of berberine (BER) were prepared using a non-covalent imprinting method. The results showed that, compared to other imprinted polymers, the polymer AD-10 had not only a higher of the ratio of Q(MIP)/Q(BP) for BER adsorption, and but also a larger of the ratio of Q(MIP,B)/Q(MIP,P) for BER and palmatine (PAL) adsorptions. Spectrophotometric analysis demonstrated that a 1:1 cooperative hydrogen-bonding complex might be predominating in the pre-polymerization between the BER template and AA monomer. Adsorption experiments of BER on the polymer AD-10 were in accordance with the second-order and Langmuir adsorption models. The E value (5.70 kJ/mol) calculated from the Dubinin-Radushkevich model indicated that the adsorption followed a physisorption process. In addition, a Scatchard plot showed a single straight line with an equilibrium dissociation constant (K(D)) of 65.80 μmol/L. SPE analyses of a mixture of BER and PAL and the methanol extract from the cortices of Phellodendron wilsonii showed that AD-10 had more efficiency, and higher specificity and selectivity for SPE in the concentration and determination of BER and its extraction from natural products.

  1. Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats.

    PubMed

    Patil, Shaktipal; Tawari, Santosh; Mundhada, Dharmendra; Nadeem, Sayyed

    2015-09-01

    Memory impairment induced by ethanol in rats is a consequence of changes in the CNS that are secondary to impaired oxidative stress and cholinergic dysfunction. Treatment with antioxidants and cholinergic agonists are reported to produce beneficial effects in this model. Berberine, an isoquinoline alkaloid is reported to exhibit antioxidant effect and cholinesterase (ChE) inhibitor activity. However, no report is available on the influence of berberine on ethanol-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in ethanol-induced rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameter of oxidative stress and cholinesterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Forty five days after ethanol treated rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., once a day for 45days) improved cognitive performance, and lowered oxidative stress and ChE activity in ethanol treated rats. In another set of experiments, berberine (100mg/kg) treatment during training trials also improved learning and memory, and lowered oxidative stress and ChE activity. Chronic treatment (45days) with vitamin C, and donepezil during training trials also improved ethanol-induced memory impairment and reduced oxidative stress and/or cholinesterase activity. In conclusion, the present study demonstrates that treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in ethanol treated rats.

  2. Molecular Mechanisms of Action of Herbal Antifungal Alkaloid Berberine, in Candida albicans

    PubMed Central

    Dhamgaye, Sanjiveeni; Devaux, Frédéric; Vandeputte, Patrick; Khandelwal, Nitesh Kumar; Sanglard, Dominique; Mukhopadhyay, Gauranga; Prasad, Rajendra

    2014-01-01

    Candida albicans causes superficial to systemic infections in immuno-compromised individuals. The concomitant use of fungistatic drugs and the lack of cidal drugs frequently result in strains that could withstand commonly used antifungals, and display multidrug resistance (MDR). In search of novel fungicidals, in this study, we have explored a plant alkaloid berberine (BER) for its antifungal potential. For this, we screened an in-house transcription factor (TF) mutant library of C. albicans strains towards their susceptibility to BER. Our screen of TF mutant strains identified a heat shock factor (HSF1), which has a central role in thermal adaptation, to be most responsive to BER treatment. Interestingly, HSF1 mutant was not only highly susceptible to BER but also displayed collateral susceptibility towards drugs targeting cell wall (CW) and ergosterol biosynthesis. Notably, BER treatment alone could affect the CW integrity as was evident from the growth retardation of MAP kinase and calcineurin pathway null mutant strains and transmission electron microscopy. However, unlike BER, HSF1 effect on CW appeared to be independent of MAP kinase and Calcineurin pathway genes. Additionally, unlike hsf1 null strain, BER treatment of Candida cells resulted in dysfunctional mitochondria, which was evident from its slow growth in non-fermentative carbon source and poor labeling with mitochondrial membrane potential sensitive probe. This phenotype was reinforced with an enhanced ROS levels coinciding with the up-regulated oxidative stress genes in BER-treated cells. Together, our study not only describes the molecular mechanism of BER fungicidal activity but also unravels a new role of evolutionary conserved HSF1, in MDR of Candida. PMID:25105295

  3. Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

    PubMed Central

    Kim, Mia; Shin, Mal Soon; Lee, Jae Min; Cho, Han Sam; Kim, Chang Ju; Kim, Young Joon; Choi, Hey Ran

    2014-01-01

    Purpose Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils. Methods Gerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c. Results Our results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils. Conclusions Berberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems. PMID:25279238

  4. Binding of DNA-binding alkaloids berberine and palmatine to tRNA and comparison to ethidium: Spectroscopic and molecular modeling studies

    NASA Astrophysics Data System (ADS)

    Islam, Md. Maidul; Pandya, Prateek; Chowdhury, Sebanti Roy; Kumar, Surat; Kumar, Gopinatha Suresh

    2008-11-01

    The interaction of two natural protoberberine plant alkaloids berberine and palmatine with tRNA phe was studied using various biophysical techniques and molecular modeling and the data were compared with the binding of the classical DNA intercalator, ethidium. Circular dichroic studies revealed that the tRNA conformation was moderately perturbed on binding of the alkaloids. The cooperative binding of both the alkaloids and ethidium to tRNA was revealed from absorbance and fluorescence studies. Fluorescence quenching studies advanced a conclusion that while berberine and palmatine are partially intercalated, ethidium is fully intercalated on the tRNA molecule. The binding of the alkaloids as well as ethidium stabilized the tRNA melting, and the binding constant evaluated from the averaged optical melting temperature data was in agreement with fluorescence spectral-binding data. Differential scanning calorimetry revealed that the tRNA melting showed three close transitions that were affected on binding of these small molecules. Molecular docking calculations performed showed the preferred regions of binding of these small molecules on the tRNA. Taken together, the results suggest that the binding of the alkaloids berberine and palmatine on the tRNA structure appears to be mostly by partial intercalation while ethidium intercalates fully on the tRNA. These results further advance our knowledge on the molecular aspects on the interaction of these alkaloids to tRNA.

  5. Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis).

    PubMed

    Cecil, Chad E; Davis, Jeanine M; Cech, Nadja B; Laster, Scott M

    2011-11-01

    In this study we tested whether the isoquinoline alkaloid berberine can inhibit the growth of influenza A. Our experiments showed strong inhibition of the growth of H1N1 influenza A strains PR/8/34 or WS/33 in RAW 264.7 macrophage-like cells, A549 human lung epithelial-derived cells and murine bone marrow derived macrophages, but not MDCK canine kidney cells. Studies of the mechanism underlying this effect suggest that berberine acts post-translationally to inhibit virus protein trafficking/maturation which in turn inhibits virus growth. Berberine was also evaluated for its ability to inhibit production of TNF-α and PGE(2) from A/PR/8/34 infected-RAW 264.7 cells. Our studies revealed strong inhibition of production of both mediators and suggest that this effect is distinct from the anti-viral effect. Finally, we asked whether berberine-containing ethanol extracts of goldenseal also inhibit the growth of influenza A and production of inflammatory mediators. We found strong effectiveness at high concentrations, although upon dilution extracts were somewhat less effective than purified berberine. Taken together, our results suggest that berberine may indeed be useful for the treatment of infections with influenza A.

  6. RNA targeting by small molecule alkaloids: Studies on the binding of berberine and palmatine to polyribonucleotides and comparison to ethidium

    NASA Astrophysics Data System (ADS)

    Islam, Md. Maidul; Suresh Kumar, Gopinatha

    2008-03-01

    The binding affinity, energetics and conformational aspects of the interaction of isoquinoline alkaloids berberine and palmatine to four single stranded polyribonucleotides polyguanylic acid [poly(G)], polyinosinic acid [poly(I)], polycytidylic acid [poly(C)] and polyuridylic acid [poly(U)] were studied by absorption, fluorescence, isothermal titration calorimetry and circular dichroism spectroscopy and compared with ethidium. Berberine, palmatine and ethidium binds strongly with poly(G) and poly(I) with affinity in the order 10 5 M -1 while their binding to poly(C) and poly(U) were very weak or practically nil. The same conclusions have also emerged from isothermal titration calorimetric studies. The binding of all the three compounds to poly(C) and poly(I) was exothermic and favored by both negative enthalpy change and positive entropy change. Conformational change in the polymer associated with the binding was observed in poly(I) with all the three molecules and poly(U) with ethidium but not in poly(G) and poly(C) revealing differences in the orientation of the bound molecules in the hitherto different helical organization of these polymers. These fundamental results may be useful and serve as database for the development of futuristic RNA based small molecule therapeutics.

  7. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells.

    PubMed

    Piyanuch, Rojsanga; Sukhthankar, Mugdha; Wandee, Gritsanapan; Baek, Seung Joon

    2007-12-18

    Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple signaling pathways. Our results suggest that berberine facilitates apoptosis and that NAG-1 and ATF3 expression plays an important role in berberine-induced apoptosis.

  8. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells

    PubMed Central

    Piyanuch, Rojsanga; Sukhthankar, Mugdha; Baek, Seung Joon

    2007-01-01

    Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple signaling pathways. Our results suggest that berberine facilitates apoptosis and that NAG-1 and ATF3 expression plays an important role in berberine-induced apoptosis. PMID:17964072

  9. Resolution of Liver Fibrosis by Isoquinoline Alkaloid Berberine in CCl4-Intoxicated Mice Is Mediated by Suppression of Oxidative Stress and Upregulation of MMP-2 Expression

    PubMed Central

    Jakovac, Hrvoje; Marchesi, Vanja Vasiljev; Blažeković, Biljana

    2013-01-01

    Abstract Liver fibrosis is the result of chronic liver injury, and it represents a widespread medical problem. The aim of this study is to investigate the antifibrotic activity of isoquinoline alkaloid berberine in carbon tetrachloride (CCl4)-induced damage in mice. Hepatic fibrosis was induced by intraperitoneal (i.p.) administration of CCl4 (2 mL/kg, 20% v/v in olive oil) twice a week for 8 weeks. Berberine at the doses of 3 and 9 mg/kg and silymarin at the dose of 50 mg/kg were given i.p. once daily for the next 2 weeks. CCl4 intoxication increased the levels of serum transaminases and induced oxidative stress in the liver. Hepatic fibrosis was evidenced by a massive deposition of collagen, which coincided with increased expression of tumor necrosis factor (TNF)–α and transforming growth factor (TGF)–β1 and the activation of hepatic stellate cells. The high-dose berberine (9 mg/kg) ameliorated oxidative stress, decreased TNF-α and TGF-β1 expression, increased the levels of matrix metalloproteinase (MMP)–2, and stimulated the elimination of fibrous deposits. Berberine at the dose of 9 mg/kg exhibited stronger therapeutic activity against hepatic fibrosis than silymarin at the dose of 50 mg/kg. In vitro analyses show an important scavenging activity of berberine against oxygen and nitrogen reactive species. The results of this study suggest that berberine could ameliorate liver fibrosis through the suppression of hepatic oxidative stress and fibrogenic potential, concomitantly stimulating the degradation of collagen deposits by MMP-2. PMID:23734997

  10. [Inhibition of the respiratory chain by the alkaloids berberine sulfate, alpinigenine, and tetrahydropalmatine].

    PubMed

    Schewe; Müller, W

    1976-01-01

    The three alcaloids inhibited the NADH oxidase system of electron transfer particles from beef heart up to 90--100 percent. The concentrations of half-inhibition amounted to 50 muM for berberine sulphate and tetrahydropalmatine and 0.55 mM for alpinigenine. All three compounds showed comparable inhibitions on the succinate-cytochrome c oxidoreductase system only at concentrations 20--25 times as high. The site of action may be the iron sulphur region of the complex I of the electron transfer system. The biological importance of this respiratory inhibitions should be taken into account.

  11. Berberine alkaloid: Quantum chemical study of different forms by the DFT and MP2 methods

    NASA Astrophysics Data System (ADS)

    Danilov, V. I.; Dailidonis, V. V.; Hovorun, D. M.; Kurita, N.; Murayama, Y.; Natsume, T.; Potopalsky, A. I.; Zaika, L. A.

    2006-10-01

    The stable structures and electronic properties for the berberine cation as well as possible ammonium, carbinol and amino-aldehyde forms of protoberberine salts in the presence of hydroxyl ions were investigated by the B3LYP/6-31G(d,p) and MP2/6-31++G(d,p) methods. The geometry optimizations by both methods lead to the nonplanar propeller-twisted and buckled structure for the all forms. The obtained bond lengths and bond angles agree with the experimental values. The comparison of total energies elucidates that the amino-aldehyde form is the most preferable tautomer in gas phase, while the carbinol form is less stable. The least stable tautomer is the ammonium form.

  12. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies.

    PubMed

    Pirillo, Angela; Catapano, Alberico Luigi

    2015-12-01

    Berberine (BBR) is an isoquinoline plant alkaloid endowed with several pharmacological activities, including anti-microbial, glucose- and cholesterol-lowering, anti-tumoral and immunomodulatory properties. The main mechanism by which BBR exerts a protective role in atherosclerosis relates to its cholesterol-lowering activity. BBR significantly increases hepatic low density lipoprotein receptor (LDLR) expression and reduces the expression and secretion of the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9). In addition to this, several other atheroprotective effects have been ascribed to BBR, including anti-inflammatory and anti-oxidant properties, inhibition of vascular smooth muscle cell proliferation and improvement of endothelial dysfunction. BBR also increases glucose utilization in adipocytes and myocytes, while decreases glucose absorption in intestinal cells, resulting in a net hypoglycemic effect. In hypercholesterolemic animals, BBR significantly decreases LDL-C and total cholesterol (TC) levels and reduces aortic lesions, an effect similar to that of statins. In diabetic animals, BBR significantly reduces glucose levels, improves glucose tolerance, reduces body weight gain and adipose tissue mass. Several clinical studies have also tested the efficacy of BBR in humans. In hypercholesterolemic subjects, BBR induces a significant reduction of TC, triglycerides and LDL-C levels and a significant increase of HDL-C levels, without major adverse effects. BBR also reduces glycemia and plasma cholesterol in diabetic patients, improves lipid and glucose profile and decreases body mass index and waist circumference in subjects with metabolic syndrome. These findings, together with the good tolerability, suggest that BBR administration might be considered a potential therapeutic approach for the treatment of hypercholesterolemia or diabetes. Given the level of evidence available to date well-designed randomized controlled trials to test safety

  13. Photophysical and calorimetric studies on the binding of 9-O-substituted analogs of the plant alkaloid berberine to double stranded poly(A).

    PubMed

    Basu, Anirban; Jaisankar, Parasuraman; Kumar, Gopinatha Suresh

    2013-08-05

    This interaction of four novel 9-O-substituted analogs of the plant alkaloid berberine with double stranded poly(A) was studied using a variety of biophysical techniques. Remarkably higher binding of two 9-O-ω-amino alkyl ether analogs compared to the two 9-O-N-aryl/arylalkyl amino carbonyl methyl berberine analogs was observed. Quantum efficiency values suggested that energy was transferred from the adenine base pairs to the analogs on binding. Ferrocyanide quenching and viscosity studies revealed the binding mode to be intercalative for these analogs. Circular dichroism studies showed that these analogs induced significant conformational changes in the secondary structure of ds poly(A). Energetics of the binding suggested that 9-O-N-aryl/arylalkyl amino carbonyl methyl berberines bound very weakly to ds poly(A). The binding of 9-O-ω-amino alkyl ether analogs was entropy dominated with a smaller but favorable enthalpic contribution to the Gibbs energy. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy-entropy compensation established the involvement of multiple weak noncovalent interactions in the binding process.

  14. Berberine, an isoquinoline alkaloid in herbal plants, protects pancreatic islets and serum lipids in nonobese diabetic mice.

    PubMed

    Chueh, Wei-Han; Lin, Jin-Yuarn

    2011-07-27

    Type 1 diabetes (T1D) damages pancreatic islets, gradually causing chronic complications. This study investigated the berberine effect on T1D in vivo. Nonobese diabetic (NOD) mice were grouped and administered 50, 150, and 500 mg of berberine/kg of body weight over 14 weeks using consecutive tube feeding. Changes in pancreatic islets, serum insulin, berberine, and lipid levels were determined. The results showed that berberine supplementation significantly (P < 0.05) increased the number of decreased islets and raised serum berberine levels in dose-dependent manners in experimental mice. Berberine supplementation also increased insulin levels, but decreased the ratio of low-density lipoprotein cholesterol (LDL-C)/total cholesterol (TC). Furthermore, serum berberine levels showed a significantly positive correlation with high-density lipoprotein cholesterol (HDL-C) levels and the HDL-C/TC ratio, but a negative correlation with the LDL-C/HDL-C ratio. This study suggests that berberine administration in vivo protects pancreatic islets and serum lipids in NOD mice.

  15. Transgenic and Mutation-Based Suppression of a Berberine Bridge Enzyme-Like (BBL) Gene Family Reduces Alkaloid Content in Field-Grown Tobacco

    PubMed Central

    Lewis, Ramsey S.; Lopez, Harry O.; Bowen, Steve W.; Andres, Karen R.; Steede, William T.; Dewey, Ralph E.

    2015-01-01

    Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels. PMID:25688975

  16. Transgenic and mutation-based suppression of a berberine bridge enzyme-like (BBL) gene family reduces alkaloid content in field-grown tobacco.

    PubMed

    Lewis, Ramsey S; Lopez, Harry O; Bowen, Steve W; Andres, Karen R; Steede, William T; Dewey, Ralph E

    2015-01-01

    Motivation exists to develop tobacco cultivars with reduced nicotine content for the purpose of facilitating compliance with expected tobacco product regulations that could mandate the lowering of nicotine levels per se, or the reduction of carcinogenic alkaloid-derived tobacco specific nitrosamines (TSNAs). A berberine bridge enzyme-like (BBL) gene family was recently characterized for N. tabacum and found to catalyze one of the final steps in pyridine alkaloid synthesis for this species. Because this gene family acts downstream in the nicotine biosynthetic pathway, it may represent an attractive target for genetic strategies with the objective of reducing alkaloid content in field-grown tobacco. In this research, we produced transgenic doubled haploid lines of tobacco cultivar K326 carrying an RNAi construct designed to reduce expression of the BBL gene family. Field-grown transgenic lines carrying functional RNAi constructs exhibited average cured leaf nicotine levels of 0.684%, in comparison to 2.454% for the untransformed control. Since numerous barriers would need to be overcome to commercialize transgenic tobacco cultivars, we subsequently pursued a mutation breeding approach to identify EMS-induced mutations in the three most highly expressed isoforms of the BBL gene family. Field evaluation of individuals possessing different homozygous combinations of truncation mutations in BBLa, BBLb, and BBLc indicated that a range of alkaloid phenotypes could be produced, with the triple homozygous knockout genotype exhibiting greater than a 13-fold reduction in percent total alkaloids. The novel source of genetic variability described here may be useful in future tobacco breeding for varied alkaloid levels.

  17. Spectroscopic studies on the binding interaction of novel 13-phenylalkyl analogs of the natural alkaloid berberine to nucleic acid triplexes.

    PubMed

    Bhowmik, Debipreeta; Buzzetti, Franco; Fiorillo, Gaetano; Lombardi, Paolo; Suresh Kumar, Gopinatha

    2014-01-01

    In this study we have characterized the capability of six 13-phenylalkyl analogs of berberine to stabilize nucleic acid triplex structures, poly(rA)⋅2poly(rU) and poly(dA)⋅2poly(dT). Berberine analogs bind to the RNA and DNA triplexes non-cooperatively. As the chain length of the substitution increased beyond CH2, the affinity enhanced up to critical length of (CH2)4, there after which the binding affinity decreased for both the triplexes. A remarkably stronger intercalative binding of the analogs compared to berberine to the triplexes was confirmed from ferrocyanide fluorescence quenching, fluorescence polarization and viscosity results. Circular dichroism results had indicated strong conformational changes in the triplexes on binding of the analogs. The analogs enhanced the stability of the Hoogsteen base paired third strand of both the triplexes while no significant change in the high-temperature duplex-to-single strand transitions was observed. Energetics of the interaction revealed that as the alkyl chain length increased, the binding was more entropy driven. This study demonstrates that phenylalkyl substitution at the 13-position of berberine increased the triplex binding affinity of berberine but a threshold length of the side chain is critical for the strong intercalative binding to occur.

  18. Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection.

    PubMed

    Avula, Bharathi; Wang, Yan-Hong; Khan, Ikhlas A

    2012-01-01

    Ultra-performance liquid chromatography (UPLC) with UV detection was used for the quantification of alkaloids from roots of Hydrastis canadensis L. (goldenseal) and dietary supplements claiming to contain goldenseal. The analysis was performed on a Waters Acquity UPLC system with an Acquity UPLC BEH Shield RP18 column using gradient elution with ammonium formate and acetonitrile containing formic acid. The chromatographic run time was less than 6 min. The detection wavelength used for beta-hydrastine and canadine was 290 nm; for hydrastinine, coptisine, jatrorrhizine, palmatine, and berberine, it was 344 nm. A total of five different extraction solvents, including 100% methanol, 90% methanol, 90% methanol + 1% acetic acid, 90% acetonitrile + 0.1% phosphoric acid, and 100% acetonitrile, were tested for recovery of the major compounds. The samples extracted with the 90% methanol + 1% acetic acid displayed the best recovery (>97%). The analytical method was validated for linearity, repeatability, LOD, and LOQ. The RSDs for intraday and interday experiments were less than 3.5%, and the recovery was 98-103%. UPLC/MS with a quadrupole mass analyzer and electrospray ionization source was used to confirm the identity of seven alkaloids. The analytical method was successfully applied to confirm the identification of seven alkaloids from the roots of H. canadensis, dietary supplements that claimed to contain goldenseal, and possible adulterant species.

  19. Analysis of berberine and total alkaloid content in cortex phellodendri by near infrared spectroscopy (NIRS) compared with high-performance liquid chromatography coupled with ultra-visible spectrometric detection.

    PubMed

    Chan, Chi-On; Chu, Ching-Ching; Mok, Daniel Kam-Wah; Chau, Foo-Tim

    2007-06-05

    This paper developed a rapid method using near infrared spectroscopy (NIRS) to differentiate two species of cortex phellodendri (CP), cortex phellodendri chinensis (PCS) and cortex phellodendri amurensis (PAR), and to predict quantitatively the content of berberine and total alkaloid content in all cortex phellodendri samples. Three alkaloids, berberine, jatrorrhizine and palmatine were analyzed simultaneously with a Thermo ODS Hypersil column by gradient elution with a new mobile phase under high-performance liquid chromatography-diode array detection (HPLC-DAD). Berberine content determined by HPLC-DAD was exploited as a critical parameter for successful discrimination between them. Multiplicative scatter correction (MSC), second derivative and Savitsky-Golay (S.G.) were utilized together to correct the scattering effect and eliminate the baseline shift in all near infrared diffuse reflectance spectra as well as to enhance spectral features in order to give a better correlation with the results obtained by HPLC-DAD. With the use of principal component analysis (PCA), samples datasets were separated successfully into two different clusters corresponding to two species. Furthermore, a partial least squares (PLS) regression method was built on the correlation model. The results showed that the correlation coefficients of the prediction models were R=0.996 for the berberine and R=0.994 for total alkaloid content. The influences of water absorption bands present in the NIR spectra on the models were also investigated in order to explore the practicability of NIRS in routine use. The outcome showed that NIRS possibly acts as routine screening in the quality control of Chinese herbal medicine.

  20. Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots.

    PubMed

    Frick, Susanne; Chitty, Julie A; Kramell, Robert; Schmidt, Jürgen; Allen, Robert S; Larkin, Philip J; Kutchan, Toni M

    2004-12-01

    The berberine bridge enzyme cDNA bbe from Papaver somniferum L. was transformed in antisense orientation into seedling explants of the industrial elite line C048-6-14-64. In this way, 84 phenotypically normal To plants derived from embryogenic callus cultures were produced. The selfed progeny of these 84 plants yielded several T1 plants with an altered alkaloid profile. One of these plants T1-47, and its siblings T2-1.2 and T2-1.5 are the subject of the present work. The transformation of these plants was evaluated by PCR, and northern and Southern hybridisation. The transgenic plants contained one additional copy of the transgene. The alkaloid content in latex and roots was determined with HPLC and LC-MS. We observed an increased concentration of several pathway intermediates from all biosynthetic branches, e.g., reticuline, laudanine, laudanosine, dehydroreticuline, salutaridine and (S)-scoulerine. The transformation altered the ratio of morphinan and tetrahydrobenzylisoquinoline alkaloids in latex but not the benzophenanthridine alkaloids in roots. The altered alkaloid profile is heritable at least to the T2 generation. These results are the first example of metabolic engineering of the alkaloid pathways in opium poppy and, to our knowledge, the first time that an alkaloid biosynthetic gene has been transformed into the native species, followed by regeneration into a mature plant to enable analyses of the effect of the transgene on metabolism over several generations.

  1. Derivatives of the cationic plant alkaloids berberine and palmatine amplify protonophorous activity of fatty acids in model membranes and mitochondria.

    PubMed

    Pustovidko, Antonina V; Rokitskaya, Tatiana I; Severina, Inna I; Simonyan, Ruben A; Trendeleva, Tatiana A; Lyamzaev, Konstantin G; Antonenko, Yuri N; Rogov, Anton G; Zvyagilskaya, Renata A; Skulachev, Vladimir P; Chernyak, Boris V

    2013-09-01

    Previously it has been shown by our group that berberine and palmatine, penetrating cations of plant origin, when conjugated with plastoquinone (SkQBerb and SkQPalm), can accumulate in isolated mitochondria or in mitochondria of living cells and effectively protect them from oxidative damage. In the present work, we demonstrate that SkQBerb, SkQPalm, and their analogs lacking the plastoquinone moiety (C10Berb and C10Palm) operate as mitochondria-targeted compounds facilitating protonophorous effect of free fatty acids. These compounds induce proton transport mediated by small concentrations of added fatty acids both in planar and liposomal model lipid membranes. In mitochondria, such an effect can be carried out by endogenous fatty acids and the adenine nucleotide translocase.

  2. Berberis Vulgaris and Berberine: An Update Review.

    PubMed

    Imenshahidi, Mohsen; Hosseinzadeh, Hossein

    2016-11-01

    Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using 'berberine' and 'Berberis vulgaris' as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Role of berberine in Alzheimer’s disease

    PubMed Central

    Cai, Zhiyou; Wang, Chuanling; Yang, Wenming

    2016-01-01

    Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer’s disease (AD) by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD. This review also attempts to discuss the pharmacological basis through which berberine may retard oxidative stress and neuroinflammation to exhibit its protective role in AD. Accordingly, berberine might be considered a potential therapeutic approach to prevent or delay the process of AD. However, more detailed investigations along with a safety assessment of berberine are warranted to clarify the role of berberine in limiting these risk factors and AD-related pathologies. PMID:27757035

  4. Advances in structural modifications and biological activities of berberine: an active compound in traditional Chinese medicine.

    PubMed

    Huang, Z-J; Zeng, Y; Lan, P; Sun, P-H; Chen, W-M

    2011-11-01

    Berberine is an isoquinoline alkaloid isolated from Chinese herbs such as Coptidis Rhizome. This paper is a systematic review of the structural modifications of berberine for different biological activities such as antitumor, antimicrobial, anti-Alzheimer's disease, antihyperglycemic, anti-inflammatory and antimalaria. The current review would provide some useful information for further studies on structural modification of berberine for discovering new drug leads.

  5. Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and dietary supplements using UPLC-UV-MS

    USDA-ARS?s Scientific Manuscript database

    UPLC with UV detection was used for the quantification of alkaloids from roots of Hydrastis canadensis L. (goldenseal) and dietary supplements claiming to contain goldenseal. The chromatographic run time was less than 6 min. The detection wavelengths used were 290 and 344 nm for '-hydrastine, canadi...

  6. Advance of studies on anti-atherosclerosis mechanism of berberine.

    PubMed

    Wu, Min; Wang, Jie; Liu, Long-tao

    2010-04-01

    Coptis Chinensis is a traditional Chinese medicine herb that has the effect of clearing heat and drying dampness, purging fire to eliminate toxin. Berberine is the main alkaloid of Coptis Chinensis, and, recent researches showed that berberine had the effect of anti-atherosclerosis. This paper reviewed the anti-atherosclerosis mechanism of berberine, which may be related to regulating lipids, anti-inflammation, decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell proliferation.

  7. [Advance on study in anti-atherosclerosis mechanism of berberine].

    PubMed

    Wu, Min; Wang, Jie

    2008-09-01

    Coptis chinensis is a traditional Chinese herb that has the effect of clearing heat and drying dampness, purging fire to eliminate toxin. Berberine is the main alkaloid of C. chinensis, and researches showed recently, berberine had the effect of anti-atherosclerosis. This paper has reviewed the mechanism of berberine in anti-atherosclerosis from anti-inflammation, regulating lipid, decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell proliferation.

  8. Berberine: new perspectives for old remedies.

    PubMed

    Tillhon, Micol; Guamán Ortiz, Luis M; Lombardi, Paolo; Scovassi, A Ivana

    2012-11-15

    Chemical compounds derived from plants have been used since the origin of human beings to counteract a number of diseases. Among them, the natural isoquinoline alkaloid berberine has been employed in Ayurvedic and Chinese Medicine for hundreds of years with a wide range of pharmacological and biochemical effects. More recently, a growing body of reports supports the evidence that berberine has anticancer effects, being able to block the proliferation of and to kill cancer cells. This review addresses the properties and therapeutic use of berberine and focuses on the recent advances as promising anticancer drug lead. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Current knowledge and pharmacological profile of berberine: An update.

    PubMed

    Kumar, Anil; Ekavali; Chopra, Kanwaljit; Mukherjee, Madhurima; Pottabathini, Raghavender; Dhull, Dinesh K

    2015-08-15

    Berberine, a benzylisoquinoline alkaloid, occurs as an active constituent in numerous medicinal plants and has an array of pharmacological properties. It has been used in Ayurvedic and Chinese medicine for its antimicrobial, antiprotozoal, antidiarrheal and antitrachoma activity. Moreover, several clinical and preclinical studies demonstrate ameliorative effect of berberine against several disorders including metabolic, neurological and cardiological problems. This review provides a summary regarding the pharmacokinetic and pharmacodynamic features of berberine, with a focus on the different mechanisms underlying its multispectrum activity. Studies regarding the safety profile, drug interactions and important clinical trials of berberine have also been included. Clinical trials with respect to neurological disorders need to be undertaken to exploit the beneficiary effects of berberine against serious disorders such as Alzheimer's and Parkinson's disease. Also, clinical studies to detect rare adverse effects of berberine need to be initiated to draw a complete safety profile of berberine and strengthen its applicability. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Chiral differentiation of the noscapine and hydrastine stereoisomers by electrospray ionization tandem mass spectrometry.

    PubMed

    Nagy, Tibor; Kuki, Ákos; Antal, Borbála; Nagy, Lajos; Purgel, Mihály; Sipos, Attila; Nagy, Miklós; Zsuga, Miklós; Kéki, Sándor

    2015-01-01

    Energy-dependent collision-induced dissociation (CID) of the dimers [2 M + Cat](+) of the noscapine and hydrastine stereoisomers was studied where Cat stands for Li(+), Na(+), K(+) and Cs(+) ions. These dimers were generated 'in situ' from the electrosprayed solution. The survival yield (SY) method was used for distinguishing the noscapine and hydrastine dimers. Significant differences were found between the characteristic collision energies (CE50, i.e. the collision energy necessary to obtain 50% fragmentation) of the homo- (R,R; S,S) and heterochiral (R,S; S,R) stereoisomers. To distinguish the enantiomer pairs L-, D-tyrosine ([M + Tyr + Cat](+)) and L-, D-lysine ([M + Lys + Cat](+)) were used as chiral selectors. Furthermore, these heterodimers [M + amino acid + Cat](+) were also applied to determine the stereoisomeric composition. It was found that the characteristic collision energy (CE50) of the noscapine and hydrastine homodimers ([2 M + Cat](+)) was inversely proportional to the ionic radius of the cations. Furthermore, the structures of the dimers [2 M + Cat](+) were studied by high level quantum chemical calculations.

  11. Berberine and coptisine free bases

    NASA Astrophysics Data System (ADS)

    Dostál, Jiří; Man, Stanislav; Sečkářová, Pavlína; Hulová, Dagmar; Nečas, Marek; Potáček, Milan; Toušek, Jaromír.; Dommisse, Roger; Van Dongen, Walter; Marek, Radek

    2004-01-01

    The free bases of protoberberine alkaloids berberine and coptisine and related compounds have been examined. The 1H and 13C NMR data of 8-hydroxy-7,8-dihydroberberine (2a), 8-hydroxy-7,8-dihydrocoptisine (2b), bis(7,8-dihydroberberin-8-yl) ether (3a), 8-oxoberberine (5a), and 8-oxocoptisine (5b) as well as X-ray data of compounds 2a, 5a, and 5b are reported and discussed.

  12. Pharmacological effects of berberine and its derivatives: a patent update.

    PubMed

    Jin, Yifeng; Khadka, Daulat B; Cho, Won-Jea

    2016-01-01

    A number of plant-derived agents are used in many therapeutic areas. Berberine, an important protoberberine alkaloid, is present in a number of medicinal plants that have been widely used in traditional Chinese medicine for hundreds of years. Modern research has shown that berberine and its derivatives display several pharmacological effects through various mechanisms. This review discusses recent and mostly Chinese patents that report the synthesis of berberine, berberine derivatives and berberine salts, and methods of preparation for formulations (traditional Chinese medicine) containing herbal components rich in berberine, along with their applications. The review covers several therapeutic effects of berberine, its derivatives and pharmaceutical formulations against cancer, obesity, diabetes, inflammation, atherosclerosis, Alzheimer's disease, rheumatoid arthritis and cardiovascular diseases. In addition, the mechanisms underlying the pharmacological effects are discussed. Modification of the functional groups of berberine has a significant effect on the pharmacological activity. However, studies on altering the atoms and size of the berberine skeleton are rare. Thus, it may be beneficial to initiate a drug development program focused on inserting heterocyclic rings of different sizes into berberine. Furthermore, structural modification to improve the safety, efficacy and selectivity is necessary to promote the use of berberine-based drugs in clinical settings.

  13. A multidrug and toxic compound extrusion transporter mediates berberine accumulation into vacuoles in Coptis japonica.

    PubMed

    Takanashi, Kojiro; Yamada, Yasuyuki; Sasaki, Takayuki; Yamamoto, Yoko; Sato, Fumihiko; Yazaki, Kazufumi

    2017-06-01

    Plants produce a large variety of alkaloids, which have diverse chemical structures and biological activities. Many of these alkaloids accumulate in vacuoles. Although some membrane proteins on tonoplasts have been identified as alkaloid uptake transporters, few have been characterized to date, and relatively little is known about the mechanisms underlying alkaloid transport and accumulation in plant cells. Berberine is a model alkaloid. Although all genes involved in berberine biosynthesis, as well as the master regulator, have been identified, the gene responsible for the final accumulation of berberine at tonoplasts has not been determined. This study showed that a multidrug and toxic compound extrusion protein 1 (CjMATE1) may act as a berberine transporter in cultured Coptis japonica cells. CjMATE1 was found to localize at tonoplasts in C. japonica cells and, in intact plants, to be expressed preferentially in rhizomes, the site of abundant berberine accumulation. Cellular transport analysis using a yeast expression system showed that CjMATE1 could transport berberine. Expression analysis showed that RNAi suppression of CjbHLH1, a master transcription factor of the berberine biosynthetic pathway, markedly reduced the expression of CjMATE1 in a manner similar to the suppression of berberine biosynthetic genes. These results strongly suggest that CjMATE1 is the transporter that mediates berberine accumulation in vacuoles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Berberine exposure triggers developmental effects on planarian regeneration

    PubMed Central

    Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

    2014-01-01

    The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians. PMID:24810466

  15. Berberine exposure triggers developmental effects on planarian regeneration.

    PubMed

    Balestrini, Linda; Isolani, Maria Emilia; Pietra, Daniele; Borghini, Alice; Bianucci, Anna Maria; Deri, Paolo; Batistoni, Renata

    2014-05-09

    The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians.

  16. Berberine and Its Role in Chronic Disease.

    PubMed

    Cicero, Arrigo F G; Baggioni, Alessandra

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense ([2]) (Amur corktree), Coptis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana (prickly poppy) and Eschscholzia californica (Californian poppy). In vitro it exerts significant anti-inflammatory and antioxidant activities. In animal models berberine has neuroprotective and cardiovascular protective effects. In humans, its lipid-lowering and insulin-resistance improving actions have clearly been demonstrated in numerous randomized clinical trials. Moreover, preliminary clinical evidence suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases. Altogether the available evidences suggest a possible application of berberine use in the management of chronic cardiometabolic disorders.

  17. Effect of berberine on Staphylococcus epidermidis biofilm formation.

    PubMed

    Wang, Xiaoqing; Yao, Xiao; Zhu, Zhen'an; Tang, Tingting; Dai, Kerong; Sadovskaya, Irina; Flahaut, Sigrid; Jabbouri, Said

    2009-07-01

    Staphylococcus epidermidis is one of the main causes of medical device-related infections owing to its adhesion and biofilm-forming abilities on biomaterial surfaces. Berberine is an isoquinoline-type alkaloid isolated from Coptidis rhizoma (huang lian in Chinese) and other herbs with many activities against various disorders. Although the inhibitory effects of berberine on planktonic bacteria have been investigated in a few studies, the capacity of berberine to inhibit biofilm formation has not been reported to date. In this study, we observed that berberine is bacteriostatic for S. epidermidis and that sub-minimal inhibitory concentrations of berberine blocked the formation of S.epidermidis biofilm. Using viability assays and berberine uptake testing, berberine at a concentration of 15-30mug/mL was shown to inhibit bacterial metabolism. Data from this study also indicated that modest concentrations of berberine (30-45mug/mL) were sufficient to exhibit an antibacterial effect and to inhibit biofilm formation significantly, as shown by the tissue culture plate (TCP) method, confocal laser scanning microscopy and scanning electron microscopy for both S. epidermidis ATCC 35984 and a clinical isolate strain SE243. Although the mechanisms of bacterial killing and inhibition of biofilm formation are not fully understood, data from this investigation indicated a potential application for berberine as an adjuvant therapeutic agent for the prevention of biofilm-related infections.

  18. Membrane of Candida albicans as a target of berberine.

    PubMed

    Zorić, Nataša; Kosalec, Ivan; Tomić, Siniša; Bobnjarić, Ivan; Jug, Mario; Vlainić, Toni; Vlainić, Josipa

    2017-05-17

    We investigated the mechanisms of anti-Candida action of isoquinoline alkaloid berberine, active constituent of medically important plants of Barberry species. The effects on membrane, morphological transition, synthesis of ergosterol and the consequent changes in membrane permeability have been studied. Polarization and lipid peroxidation level of the membrane following berberine treatment have been addressed. Minimal inhibitory concentration (MIC) of berberine against C. albicans was 17.75 μg/mL. Cytotoxic effect of berberine was concentration dependent, and in sub-MIC concentrations inhibit morphological transition of C. albicans cells to its filamentous form. Results showed that berberine affects synthesis of membrane ergosterol dose-dependently and induces increased membrane permeability causing loss of intracellular material to the outer space (DNA/protein leakage). Berberine also caused membrane depolarization and lipid peroxidation of membrane constituents indicating its direct effect on the membrane. Moreover, ROS levels were also increased following berberine treatment indicating further the possibility of membrane damage. Based on the obtained results it seems that berberine achieves its anti-Candida activity by affecting the cell membrane.

  19. Possible therapeutic potential of berberine in diabetic osteopathy.

    PubMed

    Rahigude, A B; Kaulaskar, S V; Bhutada, P S

    2012-10-01

    Diabetic osteopathy is a complication that leads to decreased bone mineral density, bone formation and having high risk of fractures that heals slowly. Diabetic osteopathy is a result of increase in osteoclastogenesis and decrease in osteoblastogenesis. Various factors viz., oxidative stress, increased inflammatory markers, PPAR-γ activation in osteoblast, activation of apoptotic pathway, increased glucose levels and inhibitory effect on parathyroid hormone etc. are mainly responsible for decreased bone mineral density. Berberine is an isoquinoline alkaloid widely used in Asian countries as a traditional medicine. Berberine is extensively reported to be an antioxidant, anti-inflammatory, antidiabetic, and having potential to treat diabetic complications and glucocorticoid induced osteoporosis. The osteoclastogenesis decreasing property of berberine can be hypothesized for inhibiting diabetic osteopathy. In addition, chronic treatment of berberine will be helpful for increasing the osteoblastic activity and expression of the modulators that affect osteoblastic differentiation. The apoptotic pathways stimulated due to increased inflammatory markers and nucleic acid damages could be reduced due to berberine. Another important consideration that berberine is having stimulatory effect on glucagon like peptide release and insulin sensitization that will be helpful for decreasing glucose levels and therefore, may exerts osteogenesis. Thiazolidinediones show bone loss due to activation of PPAR-γ in osteoblasts, whereas berberine stimulates PPAR-γ only in adipocytes and not in osteoblasts, and therefore the decreased bone loss due to use of thiazolidinediones may not be observed in berberine treatment conditions. Berberine decreases the advanced glycation end-products (AGE) formation in diabetic condition which will be ultimately helpful to decrease the stiffness of collagen fibers due to AGE-induced cross linking. Lastly, it is also reported that berberine has

  20. Berberine improves glucose metabolism through induction of glycolysis.

    PubMed

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2008-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.

  1. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes.

    PubMed

    Li, Yun; Wang, Pengcheng; Zhuang, Yuan; Lin, Huan; Li, Yehua; Liu, Ling; Meng, Qinghang; Cui, Ting; Liu, Jing; Li, Zhen

    2011-06-23

    Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

  2. Synthesis of berberine loaded polymeric nanoparticles by central composite design

    NASA Astrophysics Data System (ADS)

    Mehra, Meenakshi; Sheorain, Jyoti; Kumari, Santosh

    2016-04-01

    Berberine is an isoquinoline alkaloid which is extracted from bark and roots of Berberis vulgaris plant. It has been used in ayurvedic medicine as it possess antimicrobial, antidiabetic, anticancer, antioxidant properties etc. But poor solubility of berberine leads to poor stability and bioavailability in medical formulations decreasing its efficacy. Hence nanoformulations of berberine can help in removing the limiting factors of alkaloid enhancing its utilization in pharmaceutical industry. Sodium alginate polymer was used to encapsulate berberine within nanoparticles by emulsion solvent evaporation method using tween 80 as a surfactant. Two factors and three level in central composite design was used to study the formulation. The optimized formulation (1% v/v of Tween 80 and 0.01% w/v of sodium alginate) of polymeric nanoparticles was taken for further evaluations. The size of synthesized nanoparticles was found to be 71.18 nm by particle size analysis (PSA). The berberine loaded polymeric nanoparticles showed better antibacterial activity compared to aqueous solution of berberine by well diffusion assay.

  3. Sensitization of Candida albicans to terbinafine by berberine and berberrubine

    PubMed Central

    LAM, PIKLING; KOK, STANTON HON LUNG; LEE, KENNETH KA HO; LAM, KIM HUNG; HAU, DESMOND KWOK PO; WONG, WAI YEUNG; BIAN, ZHAOXIANG; GAMBARI, ROBERTO; CHUI, CHUNG HIN

    2016-01-01

    Candida albicans (C. albicans) is an opportunistic fungal pathogen, particularly observed in immunocompromised patients. C. albicans accounts for 50–70% of cases of invasive candidiasis in the majority of clinical settings. Terbinafine, an allylamine antifungal drug, has been used to treat fungal infections previously. It has fungistatic activity against C. albicans. Traditional Chinese medicines can be used as complementary medicines to conventional drugs to treat a variety of ailments and diseases. Berberine is a quaternary alkaloid isolated from the traditional Chinese herb, Coptidis Rhizoma, while berberrubine is isolated from the medicinal plant Berberis vulgaris, but is also readily derived from berberine by pyrolysis. The present study demonstrates the possible complementary use of berberine and berberrubine with terbinafine against C. albicans. The experimental findings assume that the potential application of these alkaloids together with reduced dosage of the standard drug would enhance the resulting antifungal potency. PMID:27073630

  4. Induction of Apoptosis by Berberine in Hepatocellular Carcinoma HepG2 Cells via Downregulation of NF-κB.

    PubMed

    Li, Min; Zhang, Mao; Zhang, Zhi-Lang; Liu, Ning; Han, Xiao-Yu; Liu, Qin-Cheng; Deng, Wei-Jun; Liao, Cai-Xian

    2017-01-26

    Hepatocellular carcinoma (HCC) is highly resistant to traditional chemotherapeutic approaches, which causes difficulty in the development of effective drugs for the treatment of HCC. Berberine, a major ingredient of Rhizoma coptidis, is a natural alkaloid used in traditional Chinese medicine. Berberine exhibits potent antitumor activity against HCC due to its high efficiency and low toxicity. In the present study, we found that berberine sensitized HepG cells to NF-κB-mediated apoptosis. Berberine exhibited a significant antiproliferation effect on the HepG2 cells and promoted apoptosis. Both qRT-PCR and immunofluorescence staining revealed that berberine reduced the NF-κB p65 levels in HepG2 cells. Moreover, p65 overexpression rescued berberine-induced cell proliferation and prevented HepG2 cells from undergoing apoptosis. These results suggest that berberine inhibits the growth of HepG2 cells by promoting apoptosis through the NF-κB p65 pathway.

  5. Berberine attenuates depressive-like behaviors by suppressing neuro-inflammation in stressed mice.

    PubMed

    Liu, Ya-Min; Niu, Le; Wang, Lin-Lin; Bai, Li; Fang, Xiao-Yan; Li, Yu-Cheng; Yi, Li-Tao

    2017-09-01

    Berberine, the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects in rodents. However, it is still not clear the involvement of neuro-inflammation suppression in the effects of berberine. The purpose of this study was to determine whether berberine affects the neuro-inflammation system in mice induced by chronic unpredictable mild stress (CUMS). Berberine was orally administrated in normal or CUMS mice for successive four weeks. Behavioral evaluation showed that berberine prevented the depressive deficits both in sucrose preference test and novelty-suppressed feeding test. The elevation of hippocampal pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the activation of microglia were decreased by berberine. In addition, chronic berberine treatment inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway as the phosphorylated proteins of NF-κB, IκB kinase (IKK)α and IKKβ in the hippocampus were suppressed after berberine administration. Furthermore, inducible nitric oxide synthase (iNOS), one downstream target of NF-κB signaling pathway was also inhibited by berberine. In conclusion, these findings suggest that administration of berberine could prevent depressive-like behaviors in CUMS mice by suppressing neuro-inflammation in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

    PubMed

    Xu, Miao; Xiao, Yuanyuan; Yin, Jun; Hou, Wolin; Yu, Xueying; Shen, Li; Liu, Fang; Wei, Li; Jia, Weiping

    2014-01-01

    Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

  7. Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice.

    PubMed

    Wang, Jie; Guo, Tao; Peng, Qi-Sheng; Yue, Shou-Wei; Wang, Shuang-Xi

    2015-11-01

    Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic approaches abolished the berberine-induced reduction in intracellular Ca(2+) concentration in VSMCs and attenuated berberine-elicited vessel dilation in mice aortas. In deoxycorticosterone acetate (DOCA)-induced hypertensive model, treatment of mice with berberine or RN-1734, a pharmacological inhibitor of TRPV4, significantly decreased systemic blood pressure (BP) in control mice or mice infected with an adenovirus vector. However, berberine-induced effects of lowering BP were reversed by overexpressing TRPV4 in mice by infecting with adenovirus. Furthermore, long-term administration of berberine decreased mean BP and pulse BP, increased artery response to vasodilator and reduced vascular collagen content in aged mice deficient in apolipoprotein E (Apoe-KO), but not in Apoe-KO old mice with lentivirus-mediated overexpression of TRPV4 channel. In conclusion, berberine induces direct vasorelaxation to lower BP and reduces vascular stiffness in aged mice through suppression of TRPV4. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  8. Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor

    PubMed Central

    Wang, Lihong; Liu, Liping; Shi, Yan; Cao, Hanwei; Chaturvedi, Rupesh; Calcutt, M. Wade; Hu, Tianhui; Ren, Xiubao; Wilson, Keith T.; Polk, D. Brent; Yan, Fang

    2012-01-01

    Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apcmin mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth. PMID:22574158

  9. Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats.

    PubMed

    Dinesh, Palani; Rasool, MahaboobKhan

    2017-03-01

    The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264.7 macrophages upon berberine treatment. Subsequently, western blot analysis revealed that berberine decreased the protein expression of IL-1β and caspase 1 and increased Nrf2 expression in RAW 264.7 macrophages. Immunofluorescence analysis also explored increased expression of Nrf2 in MSU crystal stimulated RAW 264.7 macrophages by berberine treatment. In addition, the paw edema, pain score, pro-inflammatory cytokines (IL-1β and TNFα) and articular elastase activity were found significantly reduced in berberine (50mg/kgb·wt) administered MSU crystal-induced rats. Conclusively, our current findings suggest that berberine may represent as a potential candidate for the treatment of gouty arthritis by suppressing inflammatory mediators and activating Nrf2 anti-oxidant pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Hepatobiliary excretion of berberine.

    PubMed

    Tsai, Pi-Lo; Tsai, Tung-Hu

    2004-04-01

    Berberine is a bioactive herbal ingredient isolated from the roots and bark of Berberis aristata or Coptis chinensis. To investigate the detailed pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with high-performance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg(-1), since a proportional increase in the area under the concentration-time curve (AUC) of berberine was observed in this dosage range. Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg(-1) significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation, as identified by liquid chromatography/tandem mass spectrometry. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine was not obviously affected by probenecid under the present study design.

  11. Berberine and neurodegeneration: A review of literature.

    PubMed

    Ahmed, Touqeer; Gilani, Anwar-Ul-Hassan; Abdollahi, Mohammad; Daglia, Maria; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad

    2015-10-01

    The excessive production of reactive oxygen species in nervous tissues is considered one of the major risk factors of neurodegenerative diseases. During the last two decades, much attention has been paid to the antioxidant and anti-inflammatory activity of natural products and compounds isolated from natural products which are often characterized by high efficacy and low adverse effects. Berberine is an isoquinoline alkaloid, widely present in different medicinal herbs, especially in the genus Berberis. It is mainly used as antidiarrhoeal, antibacterial, antifungal, and antiprotozoal agent. However, current research has focused on its beneficial role in neurodegenerative diseases, mainly due to its powerful antioxidant effect. The therapeutic potential of Berberine in different neurodegenerative diseases such as Alzheimer, Parkinson and Huntington disease has been brought to evidence by numerous studies. However, a limited number of reviews focus on the beneficial role of Berberine against neurodegeneration. The main objective of this review is to discuss the role of oxidative stress in neurodegeneration and the potential role of antioxidant compounds, in particular Berberine which is analyzed in its chemical structure, source, bioavailability, therapeutic potential, with special attention to its mechanism of action at a molecular level.

  12. Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine

    PubMed Central

    Boberek, Jaroslaw M.; Stach, Jem; Good, Liam

    2010-01-01

    Background Berberine is a plant alkaloid that is widely used as an anti-infective in traditional medicine. Escherichia coli exposed to berberine form filaments, suggesting an antibacterial mechanism that involves inhibition of cell division. Berberine is a DNA ligand and may induce filamentation through induction of the SOS response. Also, there is biochemical evidence for berberine inhibition of the cell division protein FtsZ. Here we aimed to assess possible berberine mechanism(s) of action in growing bacteria using genetics tools. Methodology/Principal Findings First, we tested whether berberine inhibits bacterial growth through DNA damage and induction of the SOS response. The SOS response induced by berberine was much lower compared to that induced by mitomycin C in an SOS response reporter strain. Also, cell filamentation was observed in an SOS-negative E. coli strain. To test whether berberine inhibits FtsZ, we assessed its effects on formation of the cell division Z-rings, and observed a dramatic reduction in Z-rings in the presence of berberine. We next used two different strategies for RNA silencing of ftsZ and both resulted in sensitisation of bacteria to berberine, visible as a drop in the Minimum Inhibitory Concentration (MIC). Furthermore, Fractional Inhibitory Concentration Indices (FICIs) showed a high level of synergy between ftsZ silencing and berberine treatment (FICI values of 0.23 and 0.25 for peptide nucleic acid- and expressed antisense RNA-based silencing of ftsZ, respectively). Finally, over-expression of ftsZ led to a mild rescue effect in berberine-treated cells. Conclusions The results argue against DNA binding as the primary mechanism of action of berberine and support the hypothesis that its antibacterial properties are due to inhibition of the cell division protein FtsZ. In addition, the genetic approach used here provides a means to rapidly test the activity of other putative FtsZ inhibitors. PMID:21060782

  13. Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling

    PubMed Central

    Xu, Li-Hui; Liang, Yi-Dan; Wei, Hong-Xia; Hu, Bo; Pan, Hao; Zha, Qing-Bing; Ouyang, Dong-Yun; He, Xian-Hui

    2017-01-01

    The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKα expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1β release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1β levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling. PMID:27980220

  14. Investigation of the interaction between berberine and nucleosomes in solution: Spectroscopic and equilibrium dialysis approach

    NASA Astrophysics Data System (ADS)

    Rabbani-Chadegani, Azra; Mollaei, Hossein; Sargolzaei, Javad

    2017-02-01

    Berberine is a natural plant alkaloid with high pharmacological potential. Although its interaction with free DNA has been the subject of several reports, to date there is no work concerning the effect of berberine on nucleoprotein structure of DNA, the nucleosomes. The present study focuses on the binding affinity of berberine to nucleosomes and histone H1 employing various spectroscopic techniques, fluorescence, circular dichroism, thermal denaturation as well as equilibrium dialysis. The results showed that the binding of berberine to nucleosomes is positive cooperative with Ka = 5.57 × 103 M- 1. Berberine quenched with the chromophores of protein moiety of nucleosomes and reduced fluorescence emission intensity at 335 nm with Ksv value of 0.135. Binding of berberine to nucleosomes decreased the absorbance at 210 and 260 nm, produced hypochromicity in thermal denaturation profiles and its affinity to nucleoprotein structure of nucleosomes was much higher than to free DNA. Berberine also exhibited high affinity to histone H1 in solution and the binding was positive cooperative with. Ka = 3.61 × 103 M- 1. Moreover berberine decreased fluorescence emission intensity of H1 by quenching with tyrosine residue in its globular core domain. The circular dichroism profiles demonstrated that the binding of drug induced secondary structural changes in both DNA stacking and histone H1. It is concluded that berberine is genotoxic drug, interacts with nucleosomes and in this process histone H1 is involved to exert its anticancer activity.

  15. Berberine suppresses migration of MCF-7 breast cancer cells through down-regulation of chemokine receptors

    PubMed Central

    Ahmadiankia, Naghmeh; Moghaddam, Hamid Kalalian; Mishan, Mohammad Amir; Bahrami, Ahmad Reza; Naderi-Meshkin, Hojjat; Bidkhori, Hamid Reza; Moghaddam, Maryam; Mirfeyzi, Seyed Jamal Aldin

    2016-01-01

    Objective(s): Berberine is one of the main alkaloids and it has been proven to have different pharmacological effects including inhibition of cell cycle and progression of apoptosis in various cancerous cells; however, its effects on cancer metastasis are not well known. Cancer cells obtain the ability to change their chemokine system and convert into metastatic cells. In this study, we examined the effect of berberine on breast cancer cell migration and its probable interaction with the chemokine system in cancer cells. Materials and Methods: The MCF-7 breast cancer cell line was cultured, and then, treated with berberine (10, 20, 40 and 80 μg/ml) for 24 hr. MTT assay was used in order to determine the cytotoxic effect of berberine on MCF-7 breast cancer cells. Wound healing assay was applied to determine the inhibitory effect of berberine on cell migration. Moreover, real-time quantitative PCR analysis of selected chemokine receptors was performed to determine the probable molecular mechanism underlying the effect of berberine on breast cancer cell migration. Results: The results of wound healing assay revealed that berberine decreases cell migration. Moreover, we found that the mRNA levels of some chemokine receptors were reduced after berberine treatment, and this may be the underlying mechanism for decreased cell migration. Conclusion: Our results indicate that berberine might be a potential preventive biofactor for human breast cancer metastasis by targeting chemokine receptor genes. PMID:27081456

  16. Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin.

    PubMed

    Hao, Gang; Yu, Yunli; Gu, Bingren; Xing, Yiwen; Xue, Man

    2015-01-01

    1. The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin. 2. Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats. 3. Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin. 4. Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart. 5. These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.

  17. Protective effect of berberine on serum glucose levels in non-obese diabetic mice.

    PubMed

    Chueh, Wei-Han; Lin, Jin-Yuarn

    2012-03-01

    Among the active components in traditional anti-diabetic herbal plants, berberine which is an isoquinoline alkaloid exhibits promising potential for its potent anti-inflammatory and hypoglycemic effects. However, the berberine effect on serum glucose levels in type 1 diabetes (T1D) subjects still remains unknown. This study investigated berberine's effects on serum glucose levels using non-obese diabetic (NOD) mice that spontaneously develop T1D. The NOD mice were randomly divided into four groups, administered water with 50, 150, and 500 mg berberine/kg bw, respectively, through 14 weeks. ICR mice were also selected as a species control group to compare with the NOD mice. Changes in body weight, oral glucose challenge, and serum glucose levels were determined to identify the protective effect of berberine on T1D. After the 14-week oral supplementation, berberine decreased fasting serum glucose levels in NOD mice close to the levels in normal ICR mice in a dose dependent manner. Serum berberine levels showed a significantly (P<0.05) negative and non-linear correlation with fasting glucose levels in berberine-administered NOD mice. Our results suggested that berberine supplemented at appropriate doses for 14 weeks did not cause toxic side effects, but improved hyperglycemia in NOD mice.

  18. Radiolysis of berberine or palmatine in aqueous solution

    NASA Astrophysics Data System (ADS)

    Marszalek, Milena; Wolszczak, Marian

    2011-01-01

    The reactions of hydrated electron (eaq-), hydrogen atom (H rad ) (reducing species) and Cl2•-, Br2•-, N,O•H radicals (oxidizing species) with berberine or palmatine in aqueous solution have been studied by steady-state and pulse radiolysis. The spectra of transient intermediates, leading to the final products, are presented. The rate constants of the reaction of eaq- and rad OH radical with both alkaloids in the homogenous solution and in the presence of DNA are reported. It is demonstrated that the primary products of the reaction of berberine and palmatine with eaq- and radicals generated during radiolysis are unstable and undergo further reactions.

  19. Effects of berberine in the gastrointestinal tract - a review of actions and therapeutic implications.

    PubMed

    Chen, Chunqiu; Yu, Zhen; Li, Yongyu; Fichna, Jakub; Storr, Martin

    2014-01-01

    Berberine is an isoquinoline alkaloid present in several plant species, including Coptis sp. and Berberis sp. In traditional medicine, extracts of berberine are used in the treatment of diarrhea of different origins. Recent studies have shown that berberine and its derivatives have significant biological effects on gastrointestinal (GI) and other functions and may become therapeutics for the treatment of diarrhea, gastroenteritis, diabetes, hyperlipidemia, cardiovascular diseases and inflammatory conditions. This paper summarizes the current knowledge on the actions of berberine in the GI tract. Binding and target sites, activated intracellular pathways, as well as the absorption and metabolism of berberine are discussed. Effects that may be useful in future clinical treatment, like antidiarrheal, anti-inflammatory and antitumor effects are critically reviewed and potential clinical applications are presented in detail.

  20. Antiurolithic effect of berberine is mediated through multiple pathways.

    PubMed

    Bashir, Samra; Gilani, Anwar H

    2011-01-25

    Berberine is an isoquinoline alkaloid, occurring in nature as the main constituent of several plants with medicinal use in kidney stone disease. This work was undertaken to evaluate its antiurolithic potential and explore the possible underlying mechanism(s). Berberine was tested in vitro for the antioxidant effect and in vivo for diuretic and antiurolithic effects on an animal model of calcium oxalate urolithiasis. Berberine exhibited concentration-dependent (50-150μg/ml) antioxidant effect against ferrous-ascorbate induced lipid peroxidation in rat kidney homogenate with potency slightly higher than the reference antioxidant, butylated hydroxytoluene. In Wistar rats, berberine (5-20mg/kg) increased urine output accompanied by increased pH and Na(+) and K(+) excretion and decreased Ca(2+) excretion, similar to hydrochlorothiazide. In an animal model of calcium oxalate urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water, berberine (10mg/kg) prevented as well as eliminated calcium oxalate crystal deposition in renal tubules and protected against deleterious effects of lithogenic treatment including weight loss, impaired renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted GSH and decreased antioxidant enzyme activities of the kidneys. In naïve rats, berberine (10mg/kg) increased urine volume and pH and decreased Ca(2+) excretion. Results of this study suggest the presence of antiurolithic effects in berberine against calcium oxalate stones mediated through a combination of antioxidant, diuretic, urinary alkalinizing and hypocalciuric effects. These data invite future studies on berberine to establish its efficacy for clinical use.

  1. [Metabolism, transformation and distribution of Coptis chinensis total alkaloids in rat].

    PubMed

    Wang, Liang; Ye, Xiaoli; Li, Xuegang; Chen, Zhu; Chen, Xiaodan; Gao, Ying; Zhao, Zhongqi; Huang, Wenwen; Chen, Xin; Yi, Jun

    2010-08-01

    To determine the pharmacokinetics, distribution and mutual transformation of the total alkaloids, jatrorrhizine, coptisine, berberine and palmatine from Coptis chinensis in rats. After the total alkaloids and berberine were fed into rats, their contents in plasma, tissues and gastrointestinal tract were determined by reversed-phase HPLC. The peak times of berberine in blood were 2.0 h (Cmax 3.7 mg x L(-1)) and 5.0 h Cmax 2.8 mg x L(-1)), respectively. Berberine in rat blood can be transformed into jatrorrhizine. After the rats were fed with the total alkaloids by gavage, the content of berberine was decreased monotonously, while coptisine, palmatine and jatrorrhizine contents were increased gradually in the stomach, it speculated that berberine may be transformed into jatrorrhizine in the stomach. Animal experiments showed that berberine and palmatine were mainly distributed in the lungs of animals, followed by the distribution in the liver, while jatrorrhizine and coptisine was mainly in the liver, then in the lungs. Berberine could transform into jatrorrhizine. The mechanism on the appearance of two maximum blood concentration of berberine in blood could be explained with the propulsion of the gastrointestinal tract partly.

  2. Inhibitory effect and transcriptional impact of berberine and evodiamine on human white preadipocyte differentiation.

    PubMed

    Hu, Yueshan; Fahmy, Hesham; Zjawiony, Jordan K; Davies, Gareth E

    2010-06-01

    It has been reported that the botanical alkaloids, berberine and evodiamine inhibit mouse preadipocyte 3T3-L1 differentiation. The aim of this study was to investigate the effect and transcriptional impact of berberine and evodiamine individually and in combination on human white preadipocyte (HWP) differentiation. We have shown that treatment with 8 microM berberine or 4 microM evodiamine resulted in a major inhibition of HWP differentiation accompanied by up-regulation of both GATA binding protein 2 and 3 (GATA-2 and GATA-3) mRNA and protein expression, suggesting that both compounds may have excellent potential as agents to prevent obesity.

  3. The actions of benzophenanthridine alkaloids, piperonyl butoxide and (S)-methoprene at the G-protein coupled cannabinoid CB₁ receptor in vitro.

    PubMed

    Dhopeshwarkar, Amey S; Jain, Saurabh; Liao, Chengyong; Ghose, Sudip K; Bisset, Kathleen M; Nicholson, Russell A

    2011-03-01

    This investigation focused primarily on the interaction of two benzophenanthridine alkaloids (chelerythrine and sanguinarine), piperonyl butoxide and (S)-methoprene with G-protein-coupled cannabinoid CB(1) receptors of mouse brain in vitro. Chelerythrine and sanguinarine inhibited the binding of the CB(1) receptor agonist [(3)H]CP-55940 to mouse whole brain membranes at low micromolar concentrations (IC(50)s: chelerythrine 2.20 μM; sanguinarine 1.10 μM). The structurally related isoquinoline alkaloids (berberine and papaverine) and the phthalide isoquinoline ((-)-β-hydrastine) were either inactive or considerably below IC(50) at 30 μM. Chelerythrine and sanguinarine antagonized CP-55940-stimulated binding of [(35)S] GTPγS to the G-protein (IC(50)s: chelerythrine 2.09 μM; sanguinarine 1.22 μM). In contrast to AM251, both compounds strongly inhibited basal binding of [(35)S]GTPγS (IC(50)s: chelerythrine 10.06 μM; sanguinarine 5.19μM). Piperonyl butoxide and S-methoprene inhibited the binding of [(3)H]CP-55940 (IC(50)s: piperonyl butoxide 8.2 μM; methoprene 16.4 μM), and also inhibited agonist-stimulated (but not basal) binding of [(35)S]GTPγS to brain membranes (IC(50)s: piperonyl butoxide 22.5 μM; (S)-methoprene 19.31 μM). PMSF did not modify the inhibitory effect of (S)-methoprene on [(3)H]CP-55940 binding. Our data suggest that chelerythrine and sanguinarine are efficacious antagonists of G-protein-coupled CB(1) receptors. They exhibit lower potencies compared to many conventional CB(1) receptor blockers but act differently to AM251. Reverse modulation of CB(1) receptor agonist binding resulting from benzophenanthridines engaging with the G-protein component may explain this difference. Piperonyl butoxide and (S)-methoprene are efficacious, low potency, neutral antagonists of CB(1) receptors. Certain of the study compounds may represent useful starting structures for development of novel/more potent G-protein-coupled CB(1) receptor blocking drugs.

  4. Multiple Effects of Berberine Derivatives on Colon Cancer Cells

    PubMed Central

    Guamán Ortiz, Luis Miguel; Dutto, Ilaria; Arcamone, Andrea G.; Buzzetti, Franco

    2014-01-01

    The pharmacological use of the plant alkaloid berberine is based on its antibacterial and anti-inflammatory properties; recently, anticancer activity has been attributed to this compound. To exploit this interesting feature, we synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and we tested their effects on two human colon carcinoma cell lines, that is, HCT116 and SW613-B3, which are characterized by wt and mutated p53, respectively. We observed that cell proliferation is more affected by cell treatment with the derivatives than with the lead compound; moreover, the derivatives proved to induce cell cycle arrest and cell death through apoptosis, thus suggesting that they could be promising anticancer drugs. Finally, we detected typical signs of autophagy in cells treated with berberine derivatives. PMID:25045712

  5. The mechanism of guanine specific photooxidation in the presence of berberine and palmatine: activation of photosensitized singlet oxygen generation through DNA-binding interaction.

    PubMed

    Hirakawa, Kazutaka; Kawanishi, Shosuke; Hirano, Toru

    2005-10-01

    The mechanism of DNA damage by photoexcited alkaloids, berberine and palmatine, was examined using 32P-labeled DNA fragments obtained from human genes. Berberine and palmatine easily bind to DNA, leading to the formation of strong fluorescent complexes. The binding constants of berberine and palmatine to DNA, estimated from an analysis of their fluorescence enhancements, indicate the formation of stable complexes. Photoexcited berberine and palmatine caused DNA cleavage, specifically at almost all guanine residues, under the aerobic condition after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment, suggesting the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidized product of 2'-deoxyguanosine, and further oxidized products. The formation of 8-oxodGuo was confirmed by HPLC measurement. The quantum yield of 8-oxodGuo formation by berberine was almost the same as that induced by palmatine. Berberine and palmatine did not cause DNA photodamage under anaerobic conditions. Scavengers of singlet oxygen (1O2), such as sodium azide and methional, inhibited DNA damage. These findings suggest that photoexcited berberine and palmatine give rise to 8-oxodGuo through 1O2 generation. The photosensitized 1O2 generation from these alkaloids was examined using near-infrared luminescence measurements. Emission at ca. 1270 nm was observed during photoexcitation of the DNA-alkaloid complexes. This emission was quenched by sodium azide, a scavenger of 1O2. In the absence of DNA, berberine and palmatine could not show the emission. This spectroscopic study has shown that photoexcited alkaloids can generate 1O2 only when the DNA-alkaloid complexes are formed. In conclusion, berberine and palmatine easily bind to DNA and induce guanine specific photooxidation via 1O2 formation. The present study suggests that berberine and palmatine can act as functional photosensitizers enabling a switch in phototoxicity via 1O2 formation by the interaction

  6. In vitro cytotoxicity of the protoberberine-type alkaloids.

    PubMed

    Iwasa, K; Moriyasu, M; Yamori, T; Turuo, T; Lee, D U; Wiegrebe, W

    2001-07-01

    In vitro cytotoxic activities of 24 quaternary protoberberine alkaloids related to berberine have been evaluated using a human cancer cell line panel coupled with a drug sensitivity database. Extending the alkyl chain at position 8 or 13 strongly influenced the cytotoxic activity, that is, relative lipophilicity as well as the size of the substituent affects cytotoxicity. The highest level of activity was observed in 8- or 13-hexyl-substituted derivatives of berberine. Structure-activity relationships are described.

  7. Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities.

    PubMed

    Chang, Wenguang

    2017-01-15

    Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D. Previous studies have primarily focused on a diverse array of efficacy end points of berberine in the pathogenesis of metabolic syndromes and inflammation or oxidative stress. Currently, an increasing number of studies have revealed the importance of non-coding RNAs as regulators of the anti-diabetic effects of berberine. The regulation of non-coding RNAs has been associated with several therapeutic actions of berberine in T2D progression. Thus, this review summarizes the anti-diabetic mechanisms of berberine by focusing on its role in regulating non-coding RNA, thus demonstrating that berberine exerts global anti-diabetic effects by targeting non-coding RNAs and that these effects involve several miRNAs, lncRNAs and multiple signal pathways, which may enhance the current understanding of the anti-diabetic mechanism actions of berberine and provide new pathological targets for the development of berberine-related drugs.

  8. Inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine.

    PubMed

    Shin, Han-Bo; Choi, Myung-Soo; Yi, Chae-Min; Lee, Jun; Kim, Nam-Jung; Inn, Kyung-Soo

    2015-07-01

    Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection and poses a major public health threat worldwide. No effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. Recent studies have shown that p38 mitogen-activated protein kinase (MAPK) activity is implicated in infection by and replication of viruses such as RSV and the influenza virus. Because berberine has previously been implicated in modulating the activity of p38 MAPK, its effects on RSV infection and RSV-mediated p38 MAPK activation were examined. Replication of RSV in epithelial cells was significantly reduced by treatment with berberine. Berberine treatment caused decrease in viral protein and mRNA syntheses. Similar to previously reported findings, RSV infection caused phosphorylation of p38 MAPK at a very early time point of infection, and phosphorylation was dramatically reduced by berberine treatment. In addition, production of interleukin-6 mRNA upon RSV infection was significantly suppressed by treatment with berberine, suggesting the anti-inflammatory role of berberine during RSV infection. Taken together, we showed that berberine, a natural compound already proven to be safe for human consumption, suppresses the replication of RSV. In addition, the current study suggests that inhibition of RSV-mediated early p38 MAPK activation, which has been implicated as an early step in viral infection, as a potential molecular mechanism. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Berberine promotes axonal regeneration in injured nerves of the peripheral nervous system.

    PubMed

    Han, Ah Mi; Heo, Hwon; Kwon, Yunhee Kim

    2012-04-01

    Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH-SY5Y cells at concentrations of 0.25-3 μg/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS.

  10. Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation

    PubMed Central

    Xiao, Yuanyuan; Hou, Wolin; Yu, Xueying; Shen, Li; Liu, Fang; Wei, Li; Jia, Weiping

    2014-01-01

    Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine’s action. This study aimed to examine whether AMPK activation was necessary for berberine’s glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation. PMID:25072399

  11. Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice.

    PubMed

    Li, Weidong; Hua, Baojin; Saud, Shakir M; Lin, Hongsheng; Hou, Wei; Matter, Matthias S; Jia, Libin; Colburn, Nancy H; Young, Matthew R

    2015-10-01

    Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P = 0.009), a 48% reduction in tumors <2 mm, (P = 0.05); 94% reduction in tumors 2-4 mm, (P = 0.001), and 100% reduction in tumors >4 mm (P = 0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB.

  12. Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice

    PubMed Central

    Li, Weidong; Hua, Baojin; Saud, Shakir M.; Lin, Hongsheng; Hou, Wei; Matter, Matthias S.; Jia, Libin; Colburn, Nancy H.; Young, Matthew R.

    2015-01-01

    Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P=0.009), a 48% reduction in tumors <2 mm, (P=0.05); 94% reduction in tumors 2-4 mm, (P=0.001) and 100% reduction in tumors >4 mm (P=0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB. PMID:24838344

  13. Antidiabetic properties of berberine: from cellular pharmacology to clinical effects.

    PubMed

    Cicero, Arrigo F G; Tartagni, Elisa

    2012-04-01

    Berberine is an alkaloid that is highly concentrated in the roots, rhizomes, and stem bark of various plants. It affects glucose metabolism, increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1) levels. On GLP-1 receptor activation, adenylyl cyclase is activated, and cyclic adenosine monophosphate is generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarization, and calcium influx through the voltage-dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose-consuming tissues, such as adipose, or liver or muscle cells, berberine affects both GLUT-4 and retinol-binding protein-4 in favor of glucose uptake into cells; stimulates glycolysis by AMPK activation; and has effects on the peroxisome proliferator-activated receptor γ molecular targets and on the phosphorylation of insulin receptor substrate-1, finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small, short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing to be associated with use of high dosages.

  14. Berberine attenuates doxorubicin-induced cardiotoxicity in mice.

    PubMed

    Zhao, X; Zhang, J; Tong, N; Liao, X; Wang, E; Li, Z; Luo, Y; Zuo, H

    2011-01-01

    This study investigated the effects of berberine, a natural alkaloid, on doxorubicin-induced cardiotoxicity in mice. Mice were injected intraperitoneally with saline 10 ml/kg (n = 10), doxorubicin 2.5 mg/kg (n = 10), 60 mg/kg berberine 1 h before doxorubicin 2.5 mg/kg (n = 10), or 60 mg/kg berberine alone (n = 10) every other day for 14 days. Body weight, general condition and mortality were recorded over the 14-day study period. Electro cardiography was performed before the start of treatment and after 14 days and plasma lactate dehydrogenase (LDH) activity was measured after 14 days. At the end of the study period the heart was excised and examined histologically. An increase in mortality, an initial decrease in body weight, increased LDH activity, prolongation of QRS duration and increased myocardial injury were seen in the doxorubicin-treated group compared with the saline control group. These changes were significantly attenuated by pretreatment with berberine. The study suggests that berberine may have a potential protective role against doxorubicin-induced cardiotoxicity in mice.

  15. Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses.

    PubMed

    Kawano, Masaaki; Takagi, Rie; Kaneko, Atsushi; Matsushita, Sho

    2015-12-15

    Berberine is an herbal alkaloid with various biological activities, including anti-inflammatory and antidepressant effects. Here, we examined the effects of berberine on dopamine receptors and the ensuing anti-inflammatory responses. Berberine was found to be an antagonist at both dopamine D1- and D2-like receptors and ameliorates the development of experimentally induced colitis in mice. In lipopolysaccharide-stimulated immune cells, berberine treatment modified cytokine levels, consistent with the effects of the dopamine receptor specific antagonists SCH23390 and L750667. Our findings indicate that dopamine receptor antagonists suppress innate and adaptive immune responses, providing a foundation for their use in combatting inflammatory diseases.

  16. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes.

    PubMed

    Kim, So Hui; Shin, Eun-Jung; Kim, Eun-Do; Bayaraa, Tsenguun; Frost, Susan Cooke; Hyun, Chang-Kee

    2007-11-01

    It has recently been known that berberine, an alkaloid of medicinal plants, has anti-hyperglycemic effects. To explore the mechanism underlying this effect, we used 3T3-L1 adipocytes for analyzing the signaling pathways that contribute to glucose transport. Treatment of berberine to 3T3-L1 adipocytes for 6 h enhanced basal glucose uptake both in normal and in insulin-resistant state, but the insulin-stimulated glucose uptake was not augmented significantly. Inhibition of phosphatidylinositol 3-kinase (PI 3-K) by wortmannin did not affect the berberine effect on basal glucose uptake. Berberine did not augment tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate (IRS)-1. Further, berberine had no effect on the activity of the insulin-sensitive downstream kinase, atypical protein kinase C (PKCzeta/lambda). However, interestingly, extracellular signal-regulated kinases (ERKs), which have been known to be responsible for the expression of glucose transporter (GLUT)1, were significantly activated in berberine-treated 3T3-L1 cells. As expected, the level of GLUT1 protein was increased both in normal and insulin-resistant cells in response to berberine. But berberine affected the expression of GLUT4 neither in normal nor in insulin-resistant cells. In addition, berberine treatment increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 cells, which has been reported to be associated with GLUT1-mediated glucose uptake. Together, we concluded that berberine increases glucose transport activity of 3T3-L1 adipocytes by enhancing GLUT1 expression and also stimulates the GLUT1-mediated glucose uptake by activating GLUT1, a result of AMPK stimulation.

  17. Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats.

    PubMed

    Jia, Yuzhen; Xu, Binger; Xu, Jisen

    2017-12-01

    Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear. This study compares the pharmacokinetics of berberine between normal and T2DM model rats. The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method. The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, Cmax, t1/2 and AUC(0-t) of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 μg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 μg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg). In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.

  18. Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

    PubMed Central

    Lee, Chao Yu; Wang, Liang-Fei; Wu, Chun-Hu; Ke, Chia-Hua; Chen, Szu-Fu

    2014-01-01

    Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg−1) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect. PMID:25546475

  19. Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation.

    PubMed

    Teodoro, João Soeiro; Duarte, Filipe Valente; Gomes, Ana Patrícia; Varela, Ana Teresa; Peixoto, Francisco Manuel; Rolo, Anabela Pinto; Palmeira, Carlos Marques

    2013-11-01

    Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the central role of liver and thus hepatic mitochondria in whole-body metabolism, berberine effects on hepatic mitochondrial function in an obesity model are still unknown. Here, we demonstrate that berberine treatment recovers mitochondrial efficiency when altered by a high-fat feeding. Mitochondria isolated from the liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired mitochondrial membrane potential, oxygen consumption and cellular ATP levels. Interestingly, the recovery of mitochondrial function by berberine was associated with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion, berberine potent protective effects against metabolic syndrome may rely on increasing mitochondrial SirT3 activity, normalizing mitochondrial function and preventing a state of energetic deficit caused by impaired OXPHOS.

  20. The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition.

    PubMed

    Lo, Sheng-Nan; Shen, Chien-Chang; Chang, Chia-Yu; Tsai, Keng-Chang; Huang, Chiung-Chiao; Wu, Tian-Shung; Ueng, Yune-Fang

    2015-07-01

    The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as anti-inflammation and lipid-lowering effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows resistance to the inhibition. To reveal the influence of oxidative metabolism on CYP1 inhibition by berberine, berberine oxidation and the metabolite-mediated inhibition were determined. After NADPH-fortified preincubation of berberine with P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant. Demethyleneberberine was identified as the most abundant metabolite of CYP1A1- and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity (V max) and exhibited positive cooperativity, suggesting the assistance of substrate binding when the first substrate was present. In contrast, the demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1-catalyzed berberine oxidation had low K m values, but it had V max values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low K m values of CYP1B1-catalyzed oxidation might include more than the rate constants describing berberine binding. The natural protoberberine/berberine fmetabolites with methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine) and the demethylation (thalifendine and berberrubine) caused weak CYP1 inhibition. These results demonstrated that berberine was not efficiently oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1.

  1. Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

    PubMed Central

    Chu, Ming; Zhang, Ming-bo; Liu, Yan-chen; Kang, Jia-rui; Chu, Zheng-yun; Yin, Kai-lin; Ding, Ling-yu; Ding, Ran; Xiao, Rong-xin; Yin, Yi-nan; Liu, Xiao-yan; Wang, Yue-dan

    2016-01-01

    Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases. PMID:27103062

  2. Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine.

    PubMed

    Shi, Chunyang; Tong, Qing; Fang, Jianguo; Wang, Chenguang; Wu, Jizhou; Wang, Wenqing

    2015-07-10

    Berberine, a pure crystalline quaternary ammonium salt with the basic structure of isoquinoline alkaloid, has multiple pharmacological bioactivities. But the poor bioavailability of berberine limited its wide clinical applications. In the present study, we aimed to develop an amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine (HPC) in order to improve its bioavailability. The physical characterization studies such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectrophotometry (FT-IR) and scanning electron microscopy (SEM) were conducted to characterize the formation of amorphous berberine HPC solid dispersion (BHPC-SD). The everted intestinal sac and single-pass intestinal perfusion study proved that permeability and intestinal absorption of amorphous BHPC-SD was improved compared with that of pure crystalline berberine, and the pharmacokinetic study results demonstrated that the extent of bioavailability was significantly increased as well. However, the dissolution study indicated that the aqueous cumulative dissolution percentages of berberine remained unchanged or even lower by means of preparation into solid dispersion with HPC. Therefore, according to the previous mechanistic studies, the present results supported that it is the enhanced molecularly dissolved concentration (supersaturation) of berberine by transformation from crystalline structure into amorphous solid dispersions that triggers the enhanced permeability, and consequently results in the improved intestinal absorption and bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Increased Oxidative Stress in Cultured 3T3-L1 Cells was Attenuated by Berberine Treatment.

    PubMed

    Dong, Shi-Fen; Yasui, Naomi; Negishb, Hiroko; Kishimoto, Aya; Sun, Jian-Ning; Ikeda, Katsumi

    2015-06-01

    The 3T3-L1 cell line is one of the most well-characterized and reliable models for studying adipocytes. Increased oxidative stress in accumulated fat was found in 3T3-L1 cells. Berberine, an isoquinoline alkaloid, could suppress fat deposition in 3T3-L1 cells; however, whether berberine suppresses increased oxidative stress is not well known. In this study, we observed the effect of berberine on increased oxidative stress in 3T3-L1 cells. 3T3-L1 cells were cultured and treated with berberine (5-20 μM) from day 3 to day 8. We confirmed that berberine markedly inhibited fat accumulation and lipid droplets in 3T3-L1 adipocytes and decreased triglyceride content. Berberine inhibited increased oxidative stress in 3T3-L1 cells by suppressing reactive oxygen species (ROS) production, and increased glutathione peroxidase (GPx) gene expression and GPx activity. Berberine also markedly reduced adipokines secreted by adipocytes, including leptin and resistin.

  4. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders.

    PubMed

    Caliceti, Cristiana; Franco, Placido; Spinozzi, Silvia; Roda, Aldo; Cicero, Arrigo F G

    2016-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.

  5. Role of Berberine on molecular markers involved in migration of esophageal cancer cells.

    PubMed

    Mishan, M A; Ahmadiankia, N; Matin, M M; Heirani-Tabasi, A; Shahriyari, M; Bidkhori, H R; Naderi-Meshkin, H; Bahrami, A R

    2015-12-14

    Berberine is an isoquinoline alkaloid found in several plant species like famous chinese herb, Rhizoma coptidis which has been used locally as a strong gastrointestinal remedy for thousands of years. The inhibitory effects of berberine on tumor progression properties have been reported before. In this study, we investigated the effect of berberine on an esophageal cancer cell line, KYSE-30 with emphasis on its effects on the expression of certain chemokine receptors. The cytotoxic effect of berberine on KYSE-30 cells was analyzed by MTT assay. In vitro cell migration assay was also applied to the treated cells and the expression levels of the selected chemokine receptors (CXCR4 and CCR7) was measured at mRNA level. A retarded growth, associated with increasing concentrations of berberine, was obvious. On the other hand, the migration rate of the cells was decreased when they were treated with different concentrations of berberine and the expression levels of the two chemokine receptors, involved in the migration and metastasis of esophageal cancer cells, were decreased following the same treatments. With these results, we tend to conclude that berberine might be a proper candidate for further investigations, by targeting the chemokine receptors, and possible applications as anti-metastatic agent in cancer studies.

  6. Interaction of herbal compounds with biological targets: a case study with berberine.

    PubMed

    Chen, Xiao-Wu; Di, Yuan Ming; Zhang, Jian; Zhou, Zhi-Wei; Li, Chun Guang; Zhou, Shu-Feng

    2012-01-01

    Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach.

  7. Berberine-loaded Janus nanocarriers for magnetic field-enhanced therapy against hepatocellular carcinoma.

    PubMed

    Wang, Zheng; Wang, Ying-Shuai; Chang, Zhi-Min; Li, Li; Zhang, Yi; Lu, Meng-Meng; Zheng, Xiao; Li, Mingqiang; Shao, Dan; Li, Jing; Chen, Li; Dong, Wen-Fei

    2017-03-01

    Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3 O4 -mSiO2 NPs) consisting of a Fe3 O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH-sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment-responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, and low cytotoxicity. Berberine-loaded Fe3 O4 -mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH-responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3 O4 -mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma. © 2016 John Wiley & Sons A/S.

  8. Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

    NASA Astrophysics Data System (ADS)

    Chu, Ming; Zhang, Ming-Bo; Liu, Yan-Chen; Kang, Jia-Rui; Chu, Zheng-Yun; Yin, Kai-Lin; Ding, Ling-Yu; Ding, Ran; Xiao, Rong-Xin; Yin, Yi-Nan; Liu, Xiao-Yan; Wang, Yue-Dan

    2016-04-01

    Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.

  9. Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

    PubMed Central

    Chen, Xiao-Wu; Di, Yuan Ming; Zhang, Jian; Zhou, Zhi-Wei; Li, Chun Guang; Zhou, Shu-Feng

    2012-01-01

    Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach. PMID:23213296

  10. Berberine Depresses Contraction of Smooth Muscle via Inhibiting Myosin Light-chain Kinase.

    PubMed

    Xu, Zhili; Zhang, Mingbo; Dou, Deqiang; Tao, Xiaojun; Kang, Tingguo

    2017-01-01

    Berberine is a natural isoquinoline alkaloid possessing various pharmacological effects, particularly apparent in the treatment of diarrhea, but the underlying mechanism remains unclear. Smooth muscle myosin light-chain kinase (MLCK) plays a crucial role in the smooth muscle relaxation-contraction events, and it is well known that berberine can effectively depress the contraction of smooth muscle. Hence, whether berberine could inhibit MLCK and then depress the smooth muscle contractility might be researched. The purpose of this study is to investigate the effects of berberine on MLCK. Based on this, the contractility of gastro-intestine, catalysis activity of MLCK, and molecular docking are going to be evaluated. The experiment of smooth muscle contraction was directly monitored the contractions of the isolated gastrointestine by frequency and amplitude at different concentration of berberine. The effects of berberine on MLCK were measured in the presence of Ca(2+)-calmodulin, using the activities of 20 kDa myosin light chain (MLC20) phosphorylation, and myosin Mg(2+)-ATPase induced by MLCK. The docking study was conducted with expert software in the meantime. The phosphorylation of myosin and the Mg(2+)-ATPase activity is reduced in the presence of berberine. Moreover, berberine could inhibit the contractibility of isolated gastric intestine smooth muscle. Berberine could bind to the ATP binding site of MLCK through hydrophobic effect and hydrogen bonding according to the docking study. The present work gives a deep insight into the molecular mechanism for the treatment of diarrhea with berberine, i.e., berberine could suppress the contractility of smooth muscle through binding to MLCK and depressing the catalysis activity of MLCK. Berberine significantly reduced the amplitude of contraction in isolated duodenum and gastric strips in ratsBerberine inhibited the phosphorylated extents of MLC20 and Mg2+-ATPase activity of phosphorylated myosin induced by

  11. Activation of AMP-Activated Protein Kinase Is Required for Berberine-Induced Reduction of Atherosclerosis in Mice: The Role of Uncoupling Protein 2

    PubMed Central

    Wang, Qilong; Zhang, Miao; Liang, Bin; Shirwany, Najeeb; Zhu, Yi; Zou, Ming-Hui

    2011-01-01

    Aims Berberine, a botanical alkaloid purified from Coptidis rhizoma, is reported to activate the AMP-activated protein kinase (AMPK). Whether AMPK is required for the protective effects of berberine in cardiovascular diseases remains unknown. This study was designed to determine whether AMPK is required for berberine-induced reduction of oxidative stress and atherosclerosis in vivo. Methods ApoE (ApoE-/-) mice and ApoE-/-/AMPK alpha 2-/- mice that were fed Western diets were treated with berberine for 8 weeks. Atherosclerotic aortic lesions, expression of uncoupling protein 2 (UCP2), and markers of oxidative stress were evaluated in isolated aortas. Results In ApoE-/- mice, chronic administration of berberine significantly reduced aortic lesions, markedly reduced oxidative stress and expression of adhesion molecules in aorta, and significantly increased UCP2 levels. In contrast, in ApoE-/-/AMPK alpha 2-/- mice, berberine had little effect on those endpoints. In cultured human umbilical vein endothelial cells (HUVECs), berberine significantly increased UCP2 mRNA and protein expression in an AMPK-dependent manner. Transfection of HUVECs with nuclear respiratory factor 1 (NRF1)-specific siRNA attenuated berberine-induced expression of UCP2, whereas transfection with control siRNA did not. Finally, berberine promoted mitochondrial biogenesis that contributed to up-regulation of UCP2 expression. Conclusion We conclude that berberine reduces oxidative stress and vascular inflammation, and suppresses atherogenesis via a mechanism that includes stimulation of AMPK-dependent UCP2 expression. PMID:21980456

  12. Role of berberine in anti-bacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor

    PubMed Central

    2014-01-01

    Background Berberine is an isoquinoline alkaloid mainly extracted from Rhizoma Coptidis and has been shown to possess a potent inhibitory activity against bacterial. However, the role of berberine in anti-bacterial action has not been extensively studied. Methods The animal model was established to investigate the effects of berberine on bacterial and LPS infection. Docking analysis, Molecular dynamics simulations and Real-time RT-PCR analysis was adopted to investigate the molecular mechanism. Results Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNβ in the RAW264.7 challenged with LPS. Conclusion Berberine can act as a LPS antagonist and block the LPS/TLR4 signaling from the sourse, resulting in the anti-bacterial action. PMID:24602493

  13. Berberine hydrochloride attenuates lipopolysaccharide-induced endometritis in mice by suppressing activation of NF-κB signal pathway.

    PubMed

    Fu, Kaiqiang; Lv, Xiaopei; Li, Weishi; Wang, Yu; Li, Huatao; Tian, Wenru; Cao, Rongfeng

    2015-01-01

    Endometritis is a common disease in animal production and influences breeding all over the world. Berberine is one of the main alkaloids isolated from Rhizoma coptidis. Previous reports showed that berberine has anti-inflammatory potential. However, there have been a limited number of published reports on the anti-inflammatory effect of berberine hydrochloride on LPS-induced endometritis. The purpose of the present study was to investigate the effects of berberine hydrochloride on LPS-induced mouse endometritis. Berberine hydrochloride was administered intraperitoneally at 1h before and 12h after LPS induction. Then, a biopsy was performed, and uterine myeloperoxidase (MPO) and nitric oxide (NO) concentrations were determined. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in the uterus homogenate were measured by ELISA. The extent of IκB-α and P65 phosphorylation was detected by Western blot. The results showed that berberine hydrochloride significantly attenuated neutrophil infiltration, suppressed myeloperoxidase activity and decreased NO, TNF-αand IL-1βproduction. Furthermore, berberine hydrochloride inhibited the phosphorylation of the NF-κB p65 subunit and the degradation of its inhibitor, IκBα. These findings suggest that berberine hydrochloride exerts potent anti-inflammatory effects on LPS-induced mouse endometritis and might be a potential therapeutic agent for endometritis.

  14. Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.

    PubMed

    Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Yang, Qing; Wang, Yajie; Guo, Yan; Zhou, Bingbing; Weng, Xiaogang; Liu, Xuchen; Li, Yujie; Zhu, Xiaoxin; Dong, Yu

    2015-10-01

    Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.

  15. Comparison of the antidiabetic activity of Berberis lyceum root extract and berberine in alloxan-induced diabetic rats.

    PubMed

    Gulfraz, M; Mehmood, S; Ahmad, A; Fatima, N; Praveen, Z; Williamson, E M

    2008-09-01

    Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects. Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3-7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.

  16. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice

    PubMed Central

    Wang, Lihong; Shi, Yan; Cao, Hanwei; Liu, Liping; Washington, M. Kay; Chaturvedi, Rupesh; Israel, Dawn A.; Cao, Hailong; Wang, Bangmao; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

    2012-01-01

    Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSS-upregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. PMID:22173918

  17. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

    PubMed

    Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

    2017-02-01

    Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer(+)CD8(+) cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

  18. Differential inhibition of CYP1-catalyzed regioselective hydroxylation of estradiol by berberine and its oxidative metabolites.

    PubMed

    Chang, Yu-Ping; Huang, Chiung-Chiao; Shen, Chien-Chang; Tsai, Keng-Chang; Ueng, Yune-Fang

    2015-10-01

    Berberine is a pharmacologically active alkaloid present in widely used medicinal plants, such as Coptis chinensis (Huang-Lian). The hormone estradiol is oxidized by cytochrome P450 (CYP) 1B1 to primarily form the genotoxic metabolite 4-hydroxyestradiol, whereas CYP1A1 and CYP1A2 predominantly generate 2-hydroxyestradiol. To illustrate the effect of berberine on the regioselective oxidation of estradiol, effects of berberine and its metabolites on CYP1 activities were studied. Among CYP1s, CYP1B1.1, 1.3 (L432V), and 1.4 (N453S)-catalyzed 4-hydroxylation were preferentially inhibited by berberine. Differing from the competitive inhibition of CYP1B1.1 and 1.3, N453S substitution in CYP1B1 allowed a non-competitive or mixed-type pattern. An N228T in CYP1B1 highly decreased its activity and preference to 4-hydroxylation. A reverse mutation of T223N in CYP1A2 retained its 2-hydroxylation preference, but enhanced its inhibition susceptibility to berberine. Compared with berberine, metabolites demethyleneberberine and thalifendine caused weaker inhibition of CYP1A1 and CYP1B1 activities. Unexpectedly, thalifendine was more potent than berberine in the inhibition of CYP1A2, in which case an enhanced interaction through polar hydrogen-π bond was predicted from the docking analysis. These results demonstrate that berberine preferentially inhibits the estradiol 4-hydroxylation activity of CYP1B1 variants, suggesting that 4-hydroxyestradiol-mediated toxicity might be reduced by berberine, especially in tissues/tumors highly expressing CYP1B1.

  19. Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model.

    PubMed

    Liu, Xuefei; Zhang, Xinghua; Ye, Lin; Yuan, Haitao

    2016-04-01

    Berberine, an alkaloid derivative extracted from numerous plants of the general Berberis and Coptis, has been reported to have immunomodulatory effects against immune-mediated disorders in emerging studies. In this study, the effects of berberine and its underlying molecular mechanisms were investigated from the myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with berberine and specific JAK inhibitor AG490 as a positive control. Our data showed that both berberine and AG490 significantly reduced the impaired cardiac function and the pathophysiological severity, impeded high levels of anti-cardiac myosin antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN-γ were up-regulated in EAM. However, the excessive increase of Th17/Th1 responses was restored by berberine and AG490. We also examined the expression level of phosphorylated proteins of JAK-STAT pathway which has a key role in the Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1,STAT3 and STAT4 increased significantly in EAM, while berberine notably attenuated their excessive expression. This effect of berberine was equivalent to that of AG490 blockade. Our current study demonstrated that berberine could ameliorate EAM and the underling mechanisms may be due to the fact that berberine differentially modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1 cell differentiation.

  20. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance.

    PubMed

    Ye, Lifang; Liang, Shu; Guo, Chao; Yu, Xizhong; Zhao, Juan; Zhang, Hao; Shang, Wenbin

    2016-12-01

    Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. Berberine significantly decreased F4/80(+)/CD11c(+)/CD206(-) cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Berberine acts as a putative epigenetic modulator by affecting the histone code.

    PubMed

    Wang, Zhixiang; Liu, Yuan; Xue, Yong; Hu, Haiyan; Ye, Jieyu; Li, Xiaodong; Lu, Zhigang; Meng, Fanyi; Liang, Shuang

    2016-10-01

    Berberine, an isoquinoline plant alkaloid, exhibits a wide range of biochemical and pharmacological effects. However, the precise mechanism of these bioactivities remains poorly understood. In this study, we found significant similarity between berberine and two epigenetic modulators (CG-1521 and TSA). Reverse-docking using berberine as a ligand identified lysine-N-methyltransferase as a putative target of berberine. These findings suggested the potential role of berberine in epigenetic modulation. The results of PCR array analysis of epigenetic chromatin modification enzymes supported our hypothesis. Furthermore, the analysis showed that enzymes involved in histone acetylation and methylation were predominantly affected by treatment with berberine. Up-regulation of histone acetyltransferase CREBBP and EP300, histone deacetylase SIRT3, histone demethylase KDM6A as well as histone methyltransferase SETD7, and down-regulation of histone acetyltransferase HDAC8, histone methyltransferase WHSC1I, WHSC1II and SMYD3, in addition to 38 genes from histone clusters 1-3 were observed in berberine-treated cells using real-time PCR. In parallel, western blotting analyses revealed that the expression of H3K4me3, H3K27me3 and H3K36me3 proteins decreased with berberine treatment. These results were further confirmed in acute myelocytic leukemia (AML) cell lines HL-60/ADR and KG1-α. Taken together, this study suggests that berberine might modulate the expression of epigenetic regulators important for many downstream pathways, resulting in the variation of its bioactivities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Berberine attenuates autophagy in adipocytes by targeting BECN1.

    PubMed

    Deng, Yujie; Xu, Jun; Zhang, Xiaoyan; Yang, Jian; Zhang, Di; Huang, Jian; Lv, Pengfei; Shen, Weili; Yang, Ying

    2014-10-01

    The lysosomal degradation pathway, autophagy, is essential for the maintenance of cellular homeostasis. Recently, autophagy has been demonstrated to be required in the process of adipocyte conversion. However, its role in mature adipocytes under physiological and pathological conditions remains unclear. Here, we report a major function of BECN1 in the regulation of basal autophagy in mature adipocytes. We also show that berberine, a natural plant alkaloid, inhibits basal autophagy in adipocytes and adipose tissue of mice fed a high-fat diet via downregulation of BECN1 expression. We further demonstrate that berberine has a pronounced effect on the stability of Becn 1 mRNA through the Mir30 family. These findings explore the potential of BECN1 as a key molecule and a drug target for regulating autophagy in mature adipocytes.

  3. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    PubMed Central

    Lu, Jin-Jian; Bao, Jiao-Lin; Chen, Xiu-Ping; Huang, Min; Wang, Yi-Tao

    2012-01-01

    Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made. PMID:22988474

  4. Berberine inhibits mouse insulin gene promoter through activation of AMP activated protein kinase and may exert beneficial effect on pancreatic β-cell.

    PubMed

    Shen, Ning; Huan, Yi; Shen, Zhu-fang

    2012-11-05

    Berberine is one of the main alkaloids of Rhizoma coptidis, proven to have anti-diabetic potentials through activation of AMP activated protein kinase (AMPK) in liver and muscle. However, the role of berberine on the insulin gene is unknown. Therefore, the effect of berberine on insulin gene transcription was investigated in the present study. Reporter gene assays were used in the mouse β-cell line NIT-1 to test the effect of berberine on the promoter of mouse insulin gene Ins2. The mRNA and protein levels of insulin were also detected. Diet induced glucose intolerant mice were used to explore the effect of berberine on blood glucose homeostasis and insulin resistance in vivo. The insulin content in islet was semi-quantified by an image analysis software in the immunohistochemistry sections. The results revealed that berberine caused a reversible concentration-dependent inhibition of insulin gene transcription in NIT-1 cells which showed a significant difference from the long term used AMPK activator metformin. Such inhibition on insulin promoter resulted in the reduction of mRNA and protein of insulin. Furthermore, the inhibition of insulin promoter was totally abolished by AMPK inhibitor Compound C. Berberine significantly improved insulin resistance and glucose intolerance of mice. Likewise, insulin content in islets of berberine treated mice was also decreased. Thus, the insulin gene represents a novel target of AMPK that may contribute to the action of berberine in type 2 diabetes mellitus.

  5. Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

    PubMed Central

    Zhang, Junfang; Cao, Hailong; Zhang, Bing; Cao, Hanwei; Xu, Xiuqin; Ruan, Hang; Yi, Tingting; Tan, Li; Qu, Rui; Song, Gang; Wang, Bangmao; Hu, Tianhui

    2013-01-01

    As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer. PMID:24015932

  6. Berberine induces apoptosis and DNA damage in MG‑63 human osteosarcoma cells.

    PubMed

    Zhu, Yu; Ma, Nan; Li, Hui-Xiang; Tian, Lin; Ba, Yu-Feng; Hao, Bin

    2014-10-01

    Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, has been found to exhibit marked anticancer effects on a panel of established cancer cells. Among the human osteosarcoma lines treated, MG‑63 cells were found to be the most sensitive. The present study investigated the potential genotoxic effect of berberine on MG‑63 human osteosarcoma cells. The effect of berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow cytometry and a DNA ladder assay. γH2AX focus formation was used to detect DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis in MG-63 cells in a concentration- and time-dependent manner, as determined by DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control. In conclusion, these observations indicated that berberine induced apoptosis and DNA damage in MG‑63 cells.

  7. Metformin and Berberine Prevent Olanzapine-Induced Weight Gain in Rats

    PubMed Central

    Hu, Yueshan; Young, Alan J.; Ehli, Erik A.; Nowotny, Dustin; Davies, Paige S.; Droke, Elizabeth A.; Soundy, Timothy J.; Davies, Gareth E.

    2014-01-01

    Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure. PMID:24667776

  8. Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

    PubMed

    Wojtyczka, Robert D; Dziedzic, Arkadiusz; Kępa, Małgorzata; Kubina, Robert; Kabała-Dzik, Agata; Mularz, Tomasz; Idzik, Danuta

    2014-05-22

    Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  9. Inhibitory effect of berberine on human skin squamous cell carcinoma A431 cells.

    PubMed

    Li, D X; Zhang, J; Zhang, Y; Zhao, P W; Yang, L M

    2015-09-08

    Berberine (BBR) is a natural alkaloid with significant anti-tumor activity against many types of cancer cells. In this study, we investigated the molecular mechanisms employed by BBR to repress the proliferation and growth of skin squamous cell carcinoma A431 cells. Berberine was reported to inhibit the proliferation of A431 cells in a dose- and time-dependent manner and was observed to induce a series of biochemical events, including the loss of mitochondrial membrane potential, release of cytochrome-c to cytosol, induction of proteins of the Bcl-2 family and caspases, and the cleavage of poly(ADP)-ribose polymerase. This suggested its ability to induce apoptosis. The results of a wound healing test revealed that berberine inhibited the migration of A431 cells. Ezrin was transfected into A431 cells by RNA interference. The level of expression of Ezrin in the transfected A431 cells was observed to decrease with berberine treatment, which suggested that berberine might inhibit the invasion of A431 cells through Ezrin. The results of this study demonstrated that berberine could potentially inhibit proliferation, induce apoptosis, and inhibit the invasion of A431 cells.

  10. Recent Advances in Nucleic Acid Binding Aspects of Berberine Analogs and Implications for Drug Design.

    PubMed

    Bhowmik, Debipreeta; Kumar, Gopinatha Suresh

    2016-01-01

    Berberine is one of the most widely known alkaloids belonging to the protoberberine group exhibiting myriad therapeutic properties. The anticancer potency of berberine appears to derive from its multiple actions including strong interaction with nucleic acids exhibiting adenine-thymine base pair specificity, inhibition of the enzymes topoisomerases and telomerases, and stabilizing the quadruplex structures. It was realized that the development of berberine as a potential anticancer agent necessitates enhancing its nucleic acid binding efficacy through appropriate structural modifications. More recently a number of such approaches have been attempted in various laboratories with great success. Several derivatives have been synthesized mostly with substitutions at the 8, 9 and 13 positions of the isoquinoline chromophore, and studied for enhanced nucleic acid binding activity. In this article, we present an up to date review of the details of the interaction of berberine and several of its important synthetic 8, 9 and 13 substituted derivatives with various nucleic acid structures reported recently. These studies provide interesting knowledge on the mode, mechanism, sequence and structural specificity of the binding of berberine derivatives and correlate structural and energetic aspects of the interaction providing better understanding of the structure- activity relations for designing and development of berberine based therapeutic agents with higher efficacy and therapeutic potential.

  11. Metformin and berberine prevent olanzapine-induced weight gain in rats.

    PubMed

    Hu, Yueshan; Young, Alan J; Ehli, Erik A; Nowotny, Dustin; Davies, Paige S; Droke, Elizabeth A; Soundy, Timothy J; Davies, Gareth E

    2014-01-01

    Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.

  12. Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice.

    PubMed

    Zhao, Xiaoyan; Zhang, Jie; Tong, Nannan; Chen, Youran; Luo, Yonghuang

    2012-01-01

    Doxorubicin, a very potent and often used anti-cancer drug, is largely limited due to the dose-related toxic effects. The present study investigated whether berberine, a natural product alkaloid, can reduce the liver injury induced by doxorubicin. Mice of either gender were randomly divided into four groups: the control group, doxorubicin group, berberine group, and berberine+doxorubicin group. In the tests, body weight, general condition and mortality of the mice were observed, and serum alanine aminotransferase and aspartate transaminase levels were determined to evaluate liver function. Furthermore, the liver was excised for determination of the weight changes, as well as histopathological analysis in the tissues. Mortality rate and significant decline in body weight, and increased plasma alanine aminotransferase and aspartate transaminase activities were observed in doxorubicin-treated mice. These changes were significantly prevented by pretreatment with berberine. Histopathological studies showed that doxorubicin caused structural injuries, such as vascular congestion, inflammatory cell infiltration, hepatocellular degeneration and necrosis, fibrosis in the liver. These histopathological changes were largely attenuated by berberine pretreatment. These findings indicate that berberine has the hepatoprotective effect on doxorubicin-induced liver injury in mice.

  13. Berberine induces apoptosis and DNA damage in MG-63 human osteosarcoma cells

    PubMed Central

    ZHU, YU; MA, NAN; LI, HUI-XIANG; TIAN, LIN; BA, YU-FENG; HAO, BIN

    2014-01-01

    Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, has been found to exhibit marked anticancer effects on a panel of established cancer cells. Among the human osteosarcoma lines treated, MG-63 cells were found to be the most sensitive. The present study investigated the potential genotoxic effect of berberine on MG-63 human osteosarcoma cells. The effect of berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow cytometry and a DNA ladder assay. γH2AX focus formation was used to detect DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis in MG-63 cells in a concentration- and time-dependent manner, as determined by DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control. In conclusion, these observations indicated that berberine induced apoptosis and DNA damage in MG-63 cells. PMID:25050485

  14. Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model.

    PubMed

    Li, Huiying; Miyahara, Tatsuro; Tezuka, Yasuhiro; Tran, Quan Le; Seto, Hikaru; Kadota, Shigetoshi

    2003-01-01

    The effects of berberine in senescence accelerated mice P6 (SAMP6) were investigated to learn whether the alkaloid affects bone mineral density (BMD). Oral administration of berberine (10 mg/kg/d) to male and female mice for 22 weeks resulted in an increase in BMD in both sexes. A decreased concentration of deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no effect on body or tibia weight or on the concentration of procollagen type I carboxyterminal extension peptide (PICP) in serum.

  15. Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: Selectivity, kinetic characterization, and molecular modeling

    SciTech Connect

    Lo, Sheng-Nan; Chang, Yu-Ping; Tsai, Keng-Chang; Chang, Chia-Yu; Wu, Tian-Shung; Ueng, Yune-Fang

    2013-11-01

    Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2.1 activity was barely affected. Kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1, whereas palmatine and jatrorrhizine caused either competitive or mixed type of inhibition. Among protoberberines, berberine caused the most potent and selective inhibitory effect on CYP1B1.1 with the least K{sub i} value of 44 ± 16 nM. Berberine also potently inhibited CYP1B1.1 activities toward 7-ethoxycoumarin and 7-methoxyresorufin, whereas the inhibition of benzo(a)pyrene hydroxylation activity was less pronounced. Berberine inhibited the polymorphic variants, CYP1B1.3 (V432L) and CYP1B1.4 (N453S), with IC{sub 50} values comparable to that for CYP1B1.1 inhibition. Berberine-mediated inhibition was abolished by a mutation of Asn228 to Thr in CYP1B1.1, whereas the inhibition was enhanced by a reversal mutation of Thr223 to Asn in CYP1A2.1. This result in conjugation with the molecular modeling revealed the crucial role of hydrogen-bonding interaction of Asn228 on CYP1B1.1 with the methoxy moiety of berberine. These findings demonstrate that berberine causes a selective CYP1B1-inhibition, in which Asn228 appears to be crucial. The inhibitory effects of berberine on CYP1B1 activities toward structurally diverse substrates can be different. - Highlights: • Berberine preferentially inhibited CYP1B1 activity. • Berberine caused similar inhibitory effects on CYP1B1.1, CYP1B1.3 and CYP1B1.4. • Asn228 in CYP

  16. Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations.

    PubMed

    Tang, Jun; Feng, Yibin; Tsao, Saiwah; Wang, Ning; Curtain, Robert; Wang, Youwei

    2009-10-29

    Coptidis rhizoma (huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of huanglian in treating diseases by removing damp-heat and purging fire and counteracting toxicity. To trace the long history of the traditional use of huanglian from folk medicines, especially from Chinese medicine, to recent pharmacological studies of huanglian and berberine, with an emphasis on their antineoplastic effects and the promise as novel antineoplastic agents. A total of seven databases were extensively searched for literature research. The terms and keywords for searching included huanglian, berberine, Coptis, Coptidis rhizoma, anticancer, anti-invasion, antimatastasis and mechanism. The papers including ours with studies on anticancer and mechanism, pharmacology and toxicology of huanglian and/or berberine were focused. In view of traditional use, the anticancer effects of huanglian can be ascribed to its CM trait by removing damp-heat, fire and toxicity. From modern biomedical studies, anticancer effects have been demonstrated in both huanglian and berberine. The underlying molecular mechanisms involve cell-cycle arrest, apoptosis induction and anti-inflammation. Berberine is an essential anticancer compound in huanglian. In some studies, the use of huanglian was shown to be more effective and beneficial than the use of berberine alone. The presence of other protoberberine-type alkaloids in huanglian might give synergistic effects for the anticancer effects. Berberine also demonstrates effects of antiangiogenesis, anti-invasion and anti-metastasis in some cancer cell lines, however, more investigations are required to unravel the underlying mechanisms involved. The modern evidences of treating cancer with huanglian and berberine have a strong linkage with traditional concept and rules of using huanglian in CM practice

  17. Berberine suppresses Id-1 expression and inhibits the growth and development of lung metastases in hepatocellular carcinoma.

    PubMed

    Tsang, Chi Man; Cheung, Kenneth Chat Pan; Cheung, Yuk Chun; Man, Kwan; Lui, Vivian Wai-Yan; Tsao, Sai Wah; Feng, Yibin

    2015-03-01

    Hepatocellular carcinoma (HCC) is an invasive cancer with a high rate of recurrence and metastasis. Agents with anti-proliferative as well as anti-metastatic activity will be ideal for effective treatment. Here, we demonstrated that berberine, an isoquinoline alkaloid, harbored potent anti-metastatic and anti-proliferative activities in vivo. Using an orthotopic model of HCC (MHCC-97L), which spontaneously develops lung metastases (one of the most common sites of HCC metastasis), we found that berberine treatment (10mg/kg/2days) significantly reduced lung metastasis from the liver tumors by ~85% (quantitated by bioluminescence emitted from lung metastases). Histological examination also confirmed the reduced incidence and number of lung metastases in berberine-treated mice. Furthermore, berberine effectively suppressed extra-tumor invasion of the primary HCC implant into the surrounding normal liver tissue, illustrating its potent anti-metastatic action in vivo. Consistent with previous reports in other cancer, berberine's anti-tumor activity was accompanied by suppression of cellular proliferation, invasiveness and HIF-1α/VEGF signaling. Strikingly, further mechanistic investigation revealed that berberine exerted profound inhibitory effect on the expression of Id-1, which is a key regulator for HCC development and metastasis. Berberine could suppress the transcription level of Id-1 through inhibiting its promotor activity. Specific downregulation of Id-1 by knocking down its RNA transcripts in HCC cells inhibited cellular growth, invasion and VEGF secretion, demonstrating the functional relevance of Id-1 downregulation induced by berberine. Lastly, berberine's anti-proliferative and anti-invasive activities could be partially rescued by Id-1 overexpression in HCC models, revealing a novel anti-cancer/anti-invasive mechanism of berberine via Id-1 suppression.

  18. Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells

    PubMed Central

    Wang, Lihong; Cao, Hailong; Lu, Ning; Liu, Liping; Wang, Bangmao; Hu, Tianhui; Israel, Dawn A.; Peek, Richard M.; Polk, D. Brent; Yan, Fang

    2013-01-01

    Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter. The aim of this study was to investigate the effects and mechanisms of berberine on regulation of EGFR activity and proliferation in colonic tumor cell lines and in vivo. We reported that berberine significantly inhibited basal level and EGF-stimulated EGFR activation and proliferation in the immorto Min mouse colonic epithelial (IMCE) cells carrying the APCmin mutation and human colonic carcinoma cell line, HT-29 cells. Berberine acted to inhibit proliferation through inducing G1/S and G2/M cell cycle arrest, which correlated with regulation of the checkpoint protein expression. In this study, we also showed that berberine stimulated ubiquitin ligase Cbl activation and Cbl's interaction with EGFR, and EGFR ubiquitinylation and down-regulation in these two cell lines in the presence or absence of EGF treatment. Knock-down Cbl expression blocked the effects of berberine on down-regulation of EGFR and inhibition of proliferation. Furthermore, berberine suppressed tumor growth in the HT-29 cell xenograft model. Cell proliferation and EGFR expression level was decreased by berberine treatment in this xenograft model and in colon epithelial cells of APCmin/+ mice. Taken together, these data indicate that berberine enhances Cbl activity, resulting in down-regulation of EGFR expression and inhibition of proliferation in colon tumor cells. PMID:23457600

  19. Involvement of mitochondrial and B-RAF/ERK signaling pathways in berberine-induced apoptosis in human melanoma cells.

    PubMed

    Burgeiro, Ana; Gajate, Consuelo; Dakir, El Habib; Villa-Pulgarín, Janny A; Oliveira, Paulo J; Mollinedo, Faustino

    2011-07-01

    The natural isoquinoline alkaloid berberine exhibits a wide spectrum of biological activities including antitumor activity, but its mechanism of action remains to be fully elucidated. Here, we report that berberine induced apoptosis in human melanoma cells, through a process that involved mitochondria and caspase activation. Berberine-induced activation of a number of caspases, including caspases 3, 4, 7, 8, and 9. Pan-caspase inhibitor, z-VAD-fmk, and caspase-8 and caspase-9 inhibitors prevented apoptosis. Berberine also led to the generation of the p20 cleavage fragment of BAP31, involved in directing proapoptotic signals between the endoplasmic reticulum and the mitochondria. Treatment of SK-MEL-2 melanoma cells with berberine induced disruption of the mitochondrial transmembrane potential, release of cytochrome c and apoptosis-inducing factor from the mitochondria to the cytosol, generation of reactive oxygen species (ROS), and a decreased ATP/ADP ratio. Overexpression of bcl-xL by gene transfer prevented berberine-induced cell death, mitochondrial transmembrane potential loss, and cytochrome c and apoptosis-inducing factor release, but not ROS generation. N-acetyl-L-cysteine inhibited the production of ROS, but did not abrogate the berberine-induced apoptosis. Inhibition of extracellular signal-regulated kinase (ERK) phosphorylation, by using the mitogen-activated protein kinase/ERK kinase inhibitor PD98059, and reduction of B-RAF levels by silencing RNA induced cell death of SK-MEL-2 cells, and diminished the berberine concentration required to promote apoptosis. These data show that berberine-induced apoptosis in melanoma cells involves mitochondria and caspase activation, but ROS generation was not essential. Our results indicate that inhibition of B-RAF/ERK survival signaling facilitates the cell death response triggered by berberine.

  20. Uptake of and Resistance to the Antibiotic Berberine by Individual Dormant, Germinating and Outgrowing Bacillus Spores as Monitored by Laser Tweezers Raman Spectroscopy.

    PubMed

    Wang, Shiwei; Yu, Jing; Suvira, Milomir; Setlow, Peter; Li, Yong-qing

    2015-01-01

    Berberine, an alkaloid originally extracted from the plant Coptis chinensis and other herb plants, has been used as a pharmacological substance for many years. The therapeutic effect of berberine has been attributed to its interaction with nucleic acids and blocking cell division. However, levels of berberine entering individual microbial cells minimal for growth inhibition and its effects on bacterial spores have not been determined. In this work the kinetics and levels of berberine accumulation by individual dormant and germinated spores were measured by laser tweezers Raman spectroscopy and differential interference and fluorescence microscopy, and effects of berberine on spore germination and outgrowth and spore and growing cell viability were determined. The major conclusions from this work are that: (1) colony formation from B. subtilis spores was blocked ~ 99% by 25 μg/mL berberine plus 20 μg/mL INF55 (a multidrug resistance pump inhibitor); (2) 200 μg/mL berberine had no effect on B. subtilis spore germination with L-valine, but spore outgrowth was completely blocked; (3) berberine levels accumulated in single spores germinating with ≥ 25 μg/mL berberine were > 10 mg/mL; (4) fluorescence microscopy showed that germinated spores accumulated high-levels of berberine primarily in the spore core, while dormant spores accumulated very low berberine levels primarily in spore coats; and (5) during germination, uptake of berberine began at the time of commitment (T1) and reached a maximum after the completion of CaDPA release (Trelease) and spore cortex lysis (Tlysis).

  1. Uptake of and Resistance to the Antibiotic Berberine by Individual Dormant, Germinating and Outgrowing Bacillus Spores as Monitored by Laser Tweezers Raman Spectroscopy

    PubMed Central

    Wang, Shiwei; Yu, Jing; Suvira, Milomir; Setlow, Peter; Li, Yong-qing

    2015-01-01

    Berberine, an alkaloid originally extracted from the plant Coptis chinensis and other herb plants, has been used as a pharmacological substance for many years. The therapeutic effect of berberine has been attributed to its interaction with nucleic acids and blocking cell division. However, levels of berberine entering individual microbial cells minimal for growth inhibition and its effects on bacterial spores have not been determined. In this work the kinetics and levels of berberine accumulation by individual dormant and germinated spores were measured by laser tweezers Raman spectroscopy and differential interference and fluorescence microscopy, and effects of berberine on spore germination and outgrowth and spore and growing cell viability were determined. The major conclusions from this work are that: (1) colony formation from B. subtilis spores was blocked ~ 99% by 25 μg/mL berberine plus 20 μg/mL INF55 (a multidrug resistance pump inhibitor); (2) 200 μg/mL berberine had no effect on B. subtilis spore germination with L-valine, but spore outgrowth was completely blocked; (3) berberine levels accumulated in single spores germinating with ≥ 25 μg/mL berberine were > 10 mg/mL; (4) fluorescence microscopy showed that germinated spores accumulated high-levels of berberine primarily in the spore core, while dormant spores accumulated very low berberine levels primarily in spore coats; and (5) during germination, uptake of berberine began at the time of commitment (T1) and reached a maximum after the completion of CaDPA release (Trelease) and spore cortex lysis (Tlysis). PMID:26636757

  2. Berberine-induced apoptosis via decreasing the survivin protein in K562 cell line.

    PubMed

    Pazhang, Yaghub; Ahmadian, Shahin; Mahmoudian, Massoud; Shafiezadeh, Mahshid

    2011-12-01

    Berberine is an isoquinoline alkaloid with multiple pharmacological activities, including anti-inflammatory and anti-diarrhea effect, the induction of apoptosis and anti-cancer effect. It has been reported that berberine exerts its anti-inflammatory effect via suppressing nuclear factor-kappa B (NF-κB) expression. Survivin and inducible nitric oxide synthase (iNOS) proteins may contribute to the causal relationship between anti-inflammatory and anti-apoptotic function. To investigate the mechanism of berberine-induced apoptotic activities, the human erythro-myeloblastoid leukemia cell line (K562 cell line) was treated with different concentrations of berberine (25-100 μM). The most significant cellular growth arrest and apoptotic effects were observed in the cells treated with 75 μM of berberine for 72 h. The results indicate that survivin and iNOS protein levels were decreased in berberine-treated cells. However, decrease in the iNOS activity did not affect the cell growth and apoptosis. Moreover, the addition of NO donor, sodium nitroprusside, to culture medium decreased the cell growth in the present cell line, but it seemed that its concentration was too low to induce apoptosis. So despite its production by iNOS in untreated cells, NO does not play a significant role in carcinogenesis in this cell line. These results indicate that the apoptotic activity of berberine may be mediated through the reduction of survivin in K562 cells, but iNOS level and its activity does not play a significant role in berberine-induced apoptosis.

  3. Synergistic approach for treatment of chicken coccidiosis using berberine--A plant natural product.

    PubMed

    Malik, Tauseef Ahmad; Kamili, Azra N; Chishti, M Z; Tanveer, Syed; Ahad, Shazia; Johri, R K

    2016-04-01

    Despite the advent of anticoccidial drugs and vaccines, coccidiosis continues to result in substantial economic losses to the poultry industry. Berberine, a natural alkaloid is well known in studies involving synergistic approaches, thereby reducing the dosage of principal drugs. Therefore, a study was designed to see whether a synergistic anticoccidial effect could be obtained between amprolium and berberine, in vivo using broiler chicken. Anticoccidial activity was measured in comparison to the reference drug amprolium on the basis of oocyst output reduction, mean weight gain and feed conversion ratio. Oocyst output was measured using Mc-Masters counting technique. Different combinations of berberine and amprolium were tested and out of which 1:1 ratio was the most effective for controlling these parasites. Oral gavaging of 100(50 + 50) mg/kg body weight of 1:1 ratio of amprolium and berberine caused the equivalent reduction in number of oocysts (38.85 ± 9.61) one day prior to that of standard drug amprolium (49.95 ± 16.65) as well as pure berberine (44.4 ± 9.61) used in the study. Weight gain of birds was also highest in the synergistic group (1547.43 ± 12.86) among all the infected groups. Besides feed conversion ratio in the synergistic group was also better (1.387 ± 0.026). The results of this study proved the effectiveness of both amprolium and berberine and revealed synergism between amprolium and berberine against coccidian oocysts, confirmed by significant reduction in the number of coccidian oocysts shed in the feces, leading to better weight gain and improved feed conversion ratio. The study deep-rooted the synergistic potential of berberine, a natural bioactive compound for controlling a protozoan parasite and the results of this study corroborate with its use for treatment of severe diarrhoea, amoebiasis and intestinal infections.

  4. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome

    PubMed Central

    Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862

  5. Modulations of cytochrome P450 expression in diabetic mice by berberine.

    PubMed

    Chatuphonprasert, Waranya; Nemoto, Nobuo; Sakuma, Tsutomu; Jarukamjorn, Kanokwan

    2012-03-05

    Berberine, an isoquinoline alkaloid isolated from medicinal plants such as Berberis aristata, Coptis chinesis, Coptis japonica, Coscinium fenestatun, and Hydrastis Canadensis, is widely used in Asian countries for the treatment of diabetes, hypertension, and hypercholesterolemia. Interaction between berberine and the cytochrome P450 enzymes (CYPs) has been extensively reported, but there are only a few reports of this interaction in the diabetic state. In this study, the effect of berberine on the mRNA of the CYPs in primary mouse hepatocytes and in streptozotocin (STZ)-induced diabetic mice was investigated. In primary mouse hepatocytes, berberine suppressed the induction of Cyp1a1, Cyp1a2, Cyp2e1, Cyp3a11, Cyp4a10, and Cyp4a14 mRNA expression by their prototypical inducers in a concentration-dependent fashion. However, berberine treatment alone increased the expression of Cyp2b9 and Cyp2b10 mRNA. In vivo, berberine showed the same hypoglycemic activity as metformin, an established hypoglycemic drug. The hepatic mRNA levels of Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11, Cyp4a10, and Cyp4a14 were increased in STZ-induced diabetic mice. Interestingly, berberine itself suppressed the expression of Cyp2e1, an adverse hepatic event-associated enzyme, while the expression of Cyp3a11, Cyp4a10, and Cyp4a14 were restored to normal levels by berberine. In conclusion, berberine has the potential to modify the expression of CYPs by either suppression or enhancement of CYPs' levels. Consumption of berberine as an anti-hyperglycemic compound by diabetic patients might provide an extra benefit due to its potential to restore the expression of Cyp2e1, Cyp3a, and Cyp4a to normal levels. However, an herb-drug interaction might be of concern since any berberine-containing product would definitely cause pronounced interactions based on CYP3A4 inhibition.

  6. Digital Gene Expression Analysis of Microsporum canis Exposed to Berberine Chloride

    PubMed Central

    Xiao, Chen-Wen; Ji, Quan-An; Wei, Qiang; Liu, Yan; Pan, Li-Jun; Bao, Guo-Lian

    2015-01-01

    Berberine, a natural isoquinoline alkaloid of many medicinal herbs, has an active function against a variety of microbial infections including Microsporum canis (M. canis). However, the underlying mechanisms are poorly understood. To study the effect of berberine chloride on M. canis infection, a Digital Gene Expression (DGE) tag profiling was constructed and a transcriptome analysis of the M. canis cellular responses upon berberine treatment was performed. Illimina/Hisseq sequencing technique was used to generate the data of gene expression profile, and the following enrichment analysis of Gene Ontology (GO) and Pathway function were conducted based on the data of transcriptome. The results of DGE showed that there were 8476945, 14256722, 7708575, 5669955, 6565513 and 9303468 tags respectively, which was obtained from M. canis incubated with berberine or control DMSO. 8,783 genes were totally mapped, and 1,890 genes have shown significant changes between the two groups. 1,030 genes were up-regulated and 860 genes were down-regulated (P<0.05) in berberine treated group compared to the control group. Besides, twenty-three GO terms were identified by Gene Ontology functional enrichment analysis, such as calcium-transporting ATPase activity, 2-oxoglutarate metabolic process, valine catabolic process, peroxisome and unfolded protein binding. Pathway significant enrichment analysis indicated 6 signaling pathways that are significant, including steroid biosynthesis, steroid hormone biosynthesis, Parkinson’s disease, 2,4-Dichlorobenzoate degradation, and tropane, piperidine and Isoquinoline alkaloid biosynthesis. Among these, eleven selected genes were further verified by qRT-PCR. Our findings provide a comprehensive view on the gene expression profile of M. canis upon berberine treatment, and shed light on its complicated effects on M. canis. PMID:25874937

  7. Vinca Alkaloids

    PubMed Central

    Moudi, Maryam; Go, Rusea; Yien, Christina Yong Seok; Nazre, Mohd.

    2013-01-01

    Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine (VCR) and vindesine (VDS). VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard. PMID:24404355

  8. Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages

    PubMed Central

    Bae, Young-An

    2016-01-01

    Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction. PMID:27382358

  9. Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice.

    PubMed

    Cui, Guoliang; Qin, Xia; Zhang, Yuebo; Gong, Zhenwei; Ge, Baoxue; Zang, Ying Qin

    2009-10-09

    Berberine, an alkaloid derivative from Berberis vulgaris L., has been used extensively in traditional Chinese medicine to treat diarrhea and diabetes, but the underlying mechanisms for treating diabetes are not fully understood. Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation. Because type 1 diabetes is caused by T cell-mediated destruction of beta cells and severe islet inflammation, we hypothesized that berberine could ameliorate type 1 diabetes through its immune regulation properties. Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion. Berberine suppressed Th17 and Th1 differentiation by reducing the expression of lineage markers. We found that berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation. Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation, and it controlled the stability of STAT4 through the ubiquitin-proteasome pathway. Our findings indicate that berberine targets MAPK to suppress Th17 and Th1 differentiation in type 1 diabetic NOD mice. This study revealed a novel role of ERK in Th17 differentiation through down-regulation of STAT3 phosphorylation and RORgamma t expression.

  10. Berberine ameliorates cartilage degeneration in interleukin-1β-stimulated rat chondrocytes and in a rat model of osteoarthritis via Akt signalling

    PubMed Central

    Zhao, Honghai; Zhang, Tongen; Xia, Chun; Shi, Lei; Wang, Shaojie; Zheng, Xinpeng; Hu, Tianhui; Zhang, Bing

    2014-01-01

    Berberine, a plant alkaloid used in Chinese medicine, has broad cell-protective functions in a variety of cell lines. Chondrocyte apoptosis contributes to the pathogenesis of cartilage degeneration in osteoarthritis (OA). However, little is known about the effect and underlying mechanism of berberine on OA chondrocytes. Here, we assessed the effects of berberine on cartilage degeneration in interleukin-1β (IL-1β)-stimulated rat chondrocytes and in a rat model of OA. The results of an MTT assay and western blotting analysis showed that berberine attenuated the inhibitory effect of IL-1β on the cell viability and proliferating cell nuclear antigen expression in rat chondrocytes. Furthermore, berberine activated Akt, which triggered p70S6K/S6 pathway and up-regulated the levels of aggrecan and Col II expression in IL-1β-stimulated rat chondrocytes. In addition, berberine increased the level of proteoglycans in cartilage matrix and the thickness of articular cartilage, with the elevated levels of Col II, p-Akt and p-S6 expression in a rat OA model, as demonstrated by histopathological and immunohistochemistry techniques. The data thus strongly suggest that berberine may ameliorate cartilage degeneration from OA by promoting cell survival and matrix production of chondrocytes, which was partly attributed to the activation of Akt in IL-1β-stimulated articular chondrocytes and in a rat OA model. The resultant chondroprotective effects indicate that berberine merits consideration as a therapeutic agent in OA. PMID:24286347

  11. Berberine inhibits the metastatic ability of prostate cancer cells by suppressing epithelial-to-mesenchymal transition (EMT)-associated genes with predictive and prognostic relevance.

    PubMed

    Liu, Chia-Hung; Tang, Wan-Chun; Sia, Peik; Huang, Chi-Chen; Yang, Pei-Ming; Wu, Ming-Heng; Lai, I-Lu; Lee, Kuen-Haur

    2015-01-01

    Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progression. As such, targeting the EMT represents an important therapeutic strategy for preventing or treating prostate cancer metastasis. Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanism by which berberine represses the metastatic potential of prostate cancer. The effects of berberine on cell migration and invasion were determined by transwell migration assay and Matrigel invasion assay. Expressions of EMT-related genes were determined by an EMT PCR Array and a quantitative RT-PCR. The prognostic relevance of berberine's modulation of EMT-related genes in prostate cancer was evaluated using Kaplan-Meier survival analysis. Berberine exerted inhibitory effects on the migratory and invasive abilities of highly metastatic prostate cancer cells. These inhibitory effects of berberine resulted in significant repression of a panel of mesenchymal genes that regulate the developmental EMT. Among EMT-related genes downregulated by berberine, high BMP7, NODAL and Snail gene expressions of metastatic prostate cancer tissues were associated with shorter survival of prostate cancer patients and provide potential therapeutic interventions. We concluded that berberine should be developed as a pharmacological agent for use in combination with other anticancer drug for treating metastatic prostate cancer.

  12. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Ghareeb, Doaa A.; Hafez, Hani S.; Bajorath, Jürgen; Ahmed, Hany E. A.; Sarhan, Eman; Elwakeel, Eiman; El-Demellawy, Maha A.

    2015-01-01

    Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (AβPP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (Aβ 40) and increased beta-amyloid42 (Aβ 42) in the hippocampal region. Daily administration of berberine (50 mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity. PMID:26576191

  13. Berberine: a potential phytochemical with multispectrum therapeutic activities.

    PubMed

    Vuddanda, Parameswara Rao; Chakraborty, Subhashis; Singh, Sanjay

    2010-10-01

    The use of traditional medicines of natural origin is being encouraged for the treatment of chronic disorders, as synthetic drugs in such cases may cause unpredictable adverse effects. Berberine, a traditional plant alkaloid, is used in Ayurvedic and Chinese medicine for its antimicrobial and antiprotozoal properties. Interestingly, current clinical research on berberine has revealed its various pharmacological properties and multi-spectrum therapeutic applications. An extensive search in three electronic databases (Unbound Medline, PubMed and ScienceDirect) and internet search engines (Scirus and Google Scholar) were used to identify the clinical studies on berberine, without any time constraints. This review elaborates the recent studies which reveal that with time, the drug has evolved with superior therapeutic activities. In addition, this review will also attract the attention of formulation scientists towards the issues and challenges associated in its drug delivery and the probable approaches that may be explored to help patients reap the maximum benefit of this potentially useful drug. A relatively large number of studies discussed here have revealed the possible areas where this phytochemical constituent can exhibit its therapeutic activities in the treatment of chronic ailments or diseases including diabetes, cancer, depression, hypertension and hypercholesterolemia. The potential of the drug remains to be harvested by designing a suitable formulation that could overcome its inherent low bioavailability.

  14. Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels

    PubMed Central

    Alzamora, Rodrigo; O’Mahony, Fiona; Ko, Wing-Hung; Yip, Tiffany Wai-Nga; Carter, Derek; Irnaten, Mustapha; Harvey, Brian Joseph

    2011-01-01

    Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl− secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl− secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC50 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K+ current by 88%, suggesting inhibition of KCNQ1 K+ channels. Berberine did not affect either apical Cl− conductance or basolateral Na+–K+-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl− secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl− secretion through inhibition of basolateral KCNQ1 channels responsible for K+ recycling via a PKCα-dependent pathway. PMID:21747769

  15. Differential modes of photosensitisation in cancer cells by berberine and coralyne.

    PubMed

    Bhattacharyya, Rahul; Saha, Bhaskar; Tyagi, Mrityunjaya; Bandyopadhyay, Sandip K; Patro, Birija Sankar; Chattopadhyay, Subrata

    2017-09-05

    In this study, we demonstrated that the cytotoxicity of the protoberberine alkaloids such as coralyne, berberine and jatrorrhizine to several human cancer cell lines can be improved significantly in combination with UVA exposure. However, the phototoxic property of coralyne was much higher than that of the other two alkaloids. The combination of coralyne and UVA (designated as CUVA) induced oxygen-independent cytotoxicity in the human lung cancer A549 cells by producing more lethal DNA double-strand breaks, and the effect was mediated via the replication machinery. In comparison, the berberine-induced phototoxicity to the A549 cells was mediated by reactive oxygen species generation, mitochondrial membrane permeabilisation and caspase-9/caspase-3 activation.

  16. Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis

    PubMed Central

    Jin, Hao; Jin, Xin; Cao, Boran; Wang, Wenbo

    2017-01-01

    Osteosarcoma is one of the most devastating cancers with associated poor prognosis. Chronic bone inflammation frequently predisposes to tumorigenesis and progression of osteosarcoma. In the tumor inflammatory microenvironment, caspase-1 and its processed cytokines such as interleukin 1β (IL-1β) play an important role in the occurrence and development of cancer. Berberine is an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, which has been found to exhibit significant anticancer effects on a wide spectrum of carcinomas including osteosarcoma. However, the mechanisms underlying the anticancer effects of berberine in osteosarcoma remain poorly understood and their elucidation is critical for developing improved therapies. In the present study, we investigated the potential mechanism underlying the anticancer effect of berberine in osteosarcoma. We found that the expression of caspase-1 and its downstream target IL-1β were higher in osteosarcoma cells compared with normal cells both in vitro and in vivo. Furthermore, administration of berberine is capable of reducing the expression of caspase-1 and IL-1β in osteosarcoma cells and inhibiting the growth of tumor cells. Based on the above, for the first time, we propose the hyposis that berberine could gengerate an anti-osteosarcoma property through downregulating caspase-1/IL-1β inflammatory signaling axis. PMID:28000894

  17. Berberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms.

    PubMed

    Ni, Wei-Jian; Ding, Hai-Hua; Tang, Li-Qin

    2015-08-05

    Diabetic nephropathy is a progressive kidney disorder and is pathologically characterized by thickened glomerular and tubular basement membranes, accumulation of the extracellular matrix and increased mesangial hypertrophy. Growing evidence has suggested that diabetic nephropathy is induced by multiple factors, such as dyslipidemia, hyperglycemia, hemodynamic abnormalities and oxidative stress, based on genetic susceptibility. Berberine (BBR; [C20H18NO4](+)), an isoquinoline alkaloid, is the major active constituent of Rhizoma coptidis and Cortex phellodendri. Recent studies have demonstrated that berberine has various pharmacological activities, including lowering blood glucose, regulating blood lipids and reducing inflammation in addition to its antioxidant activity. These findings suggest that berberine has potential applications as a therapeutic drug for diabetic nephropathy, and has significant research value. However, the possible mechanisms have not been fully established. The purpose of this paper is to investigate the renoprotective mechanisms of berberine in diabetic nephropathy and highlight the importance of berberine as a potential therapeutic reagent for diabetic nephropathy treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Berberine protects C57BL/6J mice against ethanol withdrawal-induced hyperexcitability.

    PubMed

    Bhutada, Pravinkumar; Mundhada, Yogita; Bansod, Kuldeep; Hiware, Rahul; Rathod, Sumit; Dixit, Pankaj; Mundhada, Dharmendra

    2011-02-01

    Berberine ([C20H18NO4](+) ), one of the major constituents of the Chinese herb Rhizoma coptidis, is an isoquinoline alkaloid. Plethora of recent reports has indicated its ability to modulate several neurotransmitter systems, especially those implicated in ethanol dependence. Thus, the influence of berberine treatment on the development and expression of ethanol dependence was tested by using the ethanol withdrawal-induced hyperexcitability paradigm. Mice were provided with a nutritionally balanced control liquid diet as the sole nutrient source on day 0; from day 1-4 (ethanol, 3% v/v), from day 5-7 (ethanol, 6% v/v) and from day 8-10 (ethanol, 10% v/v) was incorporated into the liquid diet. On day 11, the ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced hyperexcitability signs were recorded. The results revealed that acute administration of berberine (10 and 20 mg/kg, i.p.) dose-dependently attenuated ethanol withdrawal-induced hyperexcitability signs, and these results were comparable to diazepam (1.25 and 2.5 mg/kg, i.p.). Further, chronic administration of berberine (10 and 20 mg/kg, i.p.) to the ethanol diet fed mice markedly attenuated the ethanol withdrawal-induced hyperexcitability signs. In conclusion, the results and evidence suggest that berberine exhibited an inhibitory influence against ethanol withdrawal-induced hyperexcitability signs, which could be mediated through its neuromodulatory action.

  19. Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis.

    PubMed

    Jin, Hao; Jin, Xin; Cao, Boran; Wang, Wenbo

    2017-02-01

    Osteosarcoma is one of the most devastating cancers with associated poor prognosis. Chronic bone inflammation frequently predisposes to tumorigenesis and progression of osteosarcoma. In the tumor inflammatory microenvironment, caspase-1 and its processed cytokines such as interleukin 1β (IL-1β) play an important role in the occurrence and development of cancer. Berberine is an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, which has been found to exhibit significant anticancer effects on a wide spectrum of carcinomas including osteosarcoma. However, the mechanisms underlying the anticancer effects of berberine in osteosarcoma remain poorly understood and their elucidation is critical for developing improved therapies. In the present study, we investigated the potential mechanism underlying the anticancer effect of berberine in osteosarcoma. We found that the expression of caspase-1 and its downstream target IL-1β were higher in osteosarcoma cells compared with normal cells both in vitro and in vivo. Furthermore, administration of berberine is capable of reducing the expression of caspase-1 and IL-1β in osteosarcoma cells and inhibiting the growth of tumor cells. Based on the above, for the first time, we propose the hyposis that berberine could gengerate an anti-osteosarcoma property through downregulating caspase-1/IL-1β inflammatory signaling axis.

  20. Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy.

    PubMed

    Wang, Huiqiang; Li, Ke; Ma, Linlin; Wu, Shuo; Hu, Jin; Yan, Haiyan; Jiang, Jiandong; Li, Yuhuan

    2017-01-11

    The MEK-ERK signaling pathway and autophagy play an important role for enterovirus71(EV71) replication. Inhibition of MEK-ERK signaling pathway and autophagy is shown to impair EV71 replication. Berberine (BBR), an isoquinoline alkaloid isolated from Berberis vulgaris L., has been reported to have ability to regulate this signaling pathway and autophagy. Herein, we want to determine whether berberine can inhibit EV71 infection by downregulating the MEK/ERK signaling pathway and autophagy. The antiviral effect of berberine was determined by cytopathic effect (CPE) assay, western blotting assay and qRT-PCR assay. The mechanism of BBR anti-virus was determined by western blotting assay and immunofluorescence assay. We showed that berberine does-dependently reduced EV71 RNA and protein synthesis, which was, at least in part, the result of inhibition of activation of MEK/ERK signaling pathway. Furthermore, we found that berberine suppressed the EV71-induced autophagy by activating AKT protein and inhibiting the phosphorylation of JNK and PI3KIII. BBR inhibited EV71 replication by downregulating autophagy and MEK/ERK signaling pathway. These findings suggest that BBR may be a potential agent or supplement against EV71 infection.

  1. Chemopreventive effects of berberine on intestinal tumor development in Apcmin/+ mice

    PubMed Central

    2013-01-01

    Background Berberine, an isoquinoline alkaloid, has shown inhibitory effects on growth of several tumor cell lines in vitro. The aim of this study was to investigate chemopreventive effects of berberine on intestinal tumor development in Apcmin/+ mice. Methods Four-week old Apcmin/+ mice were treated with 0.05% or 0.1% berberine in drinking water for twelve weeks. The number and the size of tumors were measured to evaluate intestinal tumor development. Tissue sections were prepared for PCNA and Ki-67 immunostaining to detect cell proliferation, and TUNEL assay and cleaved caspase-3 immunostaining for apoptosis. Western blot analysis and immunostaining were performed to detect the activation of Wnt and epidermal growth factor receptor (EGFR) signaling pathways and COX-2 expression in the intestinal tumor cells. The prostaglandin E2 level in the small intestine was detected using ELISA. Results Compared with untreated Apcmin/+ mice, the total numbers of tumors in the small intestine and the colon were reduced by 39.6% and 62.5% in 0.05% and 0.1% berberine-treated mice, respectively. The numbers of tumors in proximal, middle, and distal segments of the small intestine in 0.1% berberine-treated mice were significantly reduced by 53.7%, 55.3%, and 76.5% respectively. Berberine treatment also decreased the numbers of all sizes of tumors (>2 mm, 1–2 mm, and <1 mm) in the small intestine. Berberine suppressed tumor cell proliferation and increased apoptosis. Furthermore, berberine decreased the activation levels of Wnt and EGFR signaling pathways, and down-regulated COX-2 expression in intestinal tumor cells and prostaglandin E2 production in the small intestine. Conclusions Berberine inhibits intestinal tumor development, which is correlated with its activity to suppress tumor cell proliferation and increase apoptosis in Apcmin/+ mice. Down-regulation of Wnt and EGFR signaling pathways and COX-2 expression by berberine may be involved in its anti-tumorigenic effects

  2. Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.

    PubMed

    Barreto, M Carmo; Pinto, Ruy E; Arrabaça, João D; Pavão, M Leonor

    2003-12-15

    The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity.

  3. Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer.

    PubMed

    Jabbarzadeh Kaboli, Parham; Rahmat, Asmah; Ismail, Patimah; Ling, King-Hwa

    2014-10-05

    Breast cancer is the most common cancer among women worldwide and novel therapeutic agents are needed to treat this disease. The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors. This review will discuss recent studies and consider the application of new prospective approaches based on microRNAs and other crucial regulators for use in future studies to define the action of berberine in cancer. The effects of berberine on cancer cell survival and proliferation are also outlined.

  4. Involvement of CjMDR1, a plant multidrug-resistance-type ATP-binding cassette protein, in alkaloid transport in Coptis japonica

    PubMed Central

    Shitan, Nobukazu; Bazin, Ingrid; Dan, Kazuyuki; Obata, Kazuaki; Kigawa, Koji; Ueda, Kazumitsu; Sato, Fumihiko; Forestier, Cyrille; Yazaki, Kazufumi

    2003-01-01

    Alkaloids comprise one of the largest groups of plant secondary metabolites. Berberine, a benzylisoquinoline alkaloid, is preferentially accumulated in the rhizome of Coptis japonica, a ranunculaceous plant, whereas gene expression for berberine biosynthetic enzymes has been observed specifically in root tissues, which suggests that berberine synthesized in the root is transported to the rhizome, where there is high accumulation. We recently isolated a cDNA encoding a multidrug-resistance protein (MDR)-type ATP-binding cassette (ABC) transporter (Cjmdr1) from berberine-producing cultured C. japonica cells, which is highly expressed in the rhizome. Functional analysis of Cjmdr1 by using a Xenopus oocyte expression system showed that CjMDR1 transported berberine in an inward direction, resulting in a higher accumulation of berberine in Cjmdr1-injected oocytes than in the control. Typical inhibitors of ABC proteins, such as vanadate, nifedipine, and glibenclamide, as well as ATP depletion, clearly inhibited this CjMDR1-dependent berberine uptake, suggesting that CjMDR1 functioned as an ABC transporter. Conventional membrane separation methods showed that CjMDR1 was localized in the plasma membrane of C. japonica cells. In situ hybridization indicated that Cjmdr1 mRNA was expressed preferentially in xylem tissues of the rhizome. These findings strongly suggest that CjMDR1 is involved in the translocation of berberine from the root to the rhizome. PMID:12524452

  5. Extractions of isoquinoline alkaloids with butanol and octanol.

    PubMed

    Gregorová, Jana; Babica, Jan; Marek, Radek; Paulová, Hana; Táborská, Eva; Dostál, Jirí

    2010-09-01

    Six different isoquinoline alkaloids (sanguinarine, chelerythrine, berberine, coptisine, allocryptopine, and protopine) were extracted by butanol and octanol from aqueous solution, pH 4.5. The samples were analyzed by HPLC. Butanol extraction was non-selective, alkaloids passed into organic phase in 83-98%. Octanol extraction provided more selective yields: sanguinarine 99%, chelerythrine 94%, berberine 18%, coptisine 16%, allocryptopine 7.5%, protopine 7%. Further, we tested octanol treatment of extract from Dicranostigma lactucoides. The octanol extraction yields were also selective: sanguinarine 98%, chelerythrine 92%, chelirubine 92.5%, protopine 6% and allocryptopine 3.5%. 6-Butoxy-5,6-dihydrosanguinarine and 6-butoxy-5,6-dihydrochelerythrine were prepared and their NMR and MS data are reported and discussed.

  6. Photoreduction and ketone-sensitized reduction of alkaloids.

    PubMed

    Görner, Helmut; Miskolczy, Zsombor; Megyesi, Mónika; Biczók, László

    2011-01-01

    The photoprocesses of berberine, palmatine, coralyne, sanguinarine, flavopereirine and ellipticine were studied in several solvents. The quantum yields Φ(Δ) of singlet molecular oxygen formation of berberine, palmatine and sanguinarine are moderate in dichloromethane (0.2-0.6) and much smaller in acetonitrile or trifluoroethanol. For the other alkaloids examined, Φ(Δ) is rather independent of solvent polarity. The direct and ketone-sensitized photolysis, using steady-state irradiation at 313 nm or 248/308 nm laser pulses, was studied by absorption and fluorescence spectroscopy. Thereby, radicals were observed yielding eventually dihydro derivatives as major products, which are thermally back-converted on admission of oxygen. The quantum yield of conversion of alkaloids to dihydroalkaloids is enhanced in the presence of triethylamine. The reaction in the presence of ketones and electron or H-atom donors has a quantum yield of close to unity.

  7. Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigen 1-dependent mechanism.

    PubMed

    Wang, Chao; Wang, Huan; Zhang, Yaqian; Guo, Wei; Long, Cong; Wang, Jingchao; Liu, Limei; Sun, Xiaoping

    2017-04-01

    Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx cavity, and is closely associated with Epstein-Barr virus (EBV) infection. In addition to NPC, EBV causes various human malignancies, such as gastric cancer, hematological tumors and lymphoepithelioma-like carcinomas. Epstein-Barr nuclear antigen 1 (EBNA1) encoded by EBV is indispensable for replication, partition, transcription and maintenance of viral genomes. Berberine, a naturally occurring isoquinoline alkaloid, shows anti-inflammatory, anticholinergic, antioxidative, and anticancer activities. In the present study, the antitumor effect of berberine was studied. Cell Counting Kit-8 (CCK-8) assays were performed to demonstrate whether the proliferation of EBV-positive NPC cells was inhibited by berberine. Flow cytometric results revealed that berberine induced cell cycle arrest and apoptosis. Quantitative-PCR and western blotting results indicated that berberine decreased the expression of EBNA1 at both the mRNA and protein levels in the EBV-positive NPC cells. The function of EBNA1 promoter Qp which is to drive EBNA1 transcription in type Ⅱ latent infection was strongly suppressed by berberine. Overexpression of EBNA1 attenuated this inhibitory effect. Berberine also suppressed the activity of signal transducer and activator of transcription 3 which is a new therapeutic target in a series of malignancies, including NPC. Viral titer experiments demonstrated that berberine decreased the production of virions in HONE1 and HK1-EBV cells. In a mouse xenograft model of NPC induced by HONE1 cells, berberine significantly inhibited tumor formation. Altogether, these results indicate that berberine decreases the expression of EBNA1 and exhibits an antitumor effect against NPC both in vitro and in vivo.

  8. Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

    PubMed

    He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli

    2016-05-01

    This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

  9. BIAdb: A curated database of benzylisoquinoline alkaloids

    PubMed Central

    2010-01-01

    Background Benzylisoquinoline is the structural backbone of many alkaloids with a wide variety of structures including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine. Many benzylisoquinoline alkaloids have been reported to show therapeutic properties and to act as novel medicines. Thus it is important to collect and compile benzylisoquinoline alkaloids in order to explore their usage in medicine. Description We extract information about benzylisoquinoline alkaloids from various sources like PubChem, KEGG, KNApSAcK and manual curation from literature. This information was processed and compiled in order to create a comprehensive database of benzylisoquinoline alkaloids, called BIAdb. The current version of BIAdb contains information about 846 unique benzylisoquinoline alkaloids, with multiple entries in term of source, function leads to total number of 2504 records. One of the major features of this database is that it provides data about 627 different plant species as a source of benzylisoquinoline and 114 different types of function performed by these compounds. A large number of online tools have been integrated, which facilitate user in exploring full potential of BIAdb. In order to provide additional information, we give external links to other resources/databases. One of the important features of this database is that it is tightly integrated with Drugpedia, which allows managing data in fixed/flexible format. Conclusions A database of benzylisoquinoline compounds has been created, which provides comprehensive information about benzylisoquinoline alkaloids. This database will be very useful for those who are working in the field of drug discovery based on natural products. This database will also serve researchers working in the field of synthetic biology, as developing medicinally important alkaloids using synthetic process are one of important challenges. This database is available from http

  10. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats.

    PubMed

    Zhou, Ji Yin; Zhou, Shi Wen; Zhang, Ke Bin; Tang, Jian Lin; Guang, Li Xia; Ying, Yi; Xu, Ying; Zhang, Le; Li, Dan Dan

    2008-06-01

    Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARalpha/delta expression and reduced PPARgamma expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARalpha/delta/gamma protein expression in liver.

  11. Effects of Berberine on Cell Cycle, DNA, Reactive Oxygen Species, and Apoptosis in L929 Murine Fibroblast Cells

    PubMed Central

    Gu, Manman; Xu, Jing; Han, Chunyang; Kang, Youxi; Liu, Tengfei; He, Yanfei; Huang, Yanfei; Liu, Cuiyan

    2015-01-01

    Berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines (TCM), exhibits a strong antimicrobial activity in the treatment of diarrhea. However, it causes human as well as animal toxicity from heavy dosage. The present study was conducted to investigate the cytotoxicity of berberine and its possible trigger mechanisms resulting in cell cycle arrest, DNA damage, ROS (reactive oxygen species) level, mitochondrial membrane potential change, and cell apoptosis in L929 murine fibroblast (L929) cells. The cells were cultured in vitro and treated with different concentrations of berberine for 24 h. The results showed that cell viability was significantly decreased in a subjected dose-dependent state; berberine concentrations were higher than 0.05 mg/mL. Berberine at a concentration above 0.1 mg/mL altered the morphology of L929 cells. Cells at G2/M phase were clear that the level of ROS and cell apoptosis rates increased in 0.1 mg/mL group. Each DNA damage indicator score (DIS) increased in groups where concentration of berberine was above 0.025 mg/mL. The mitochondrial membrane potential counteractive balance mechanics were significantly altered when concentrations of berberine were above 0.005 mg/mL. In all, the present study suggested that berberine at high dosage exhibited cytotoxicity on L929 which was related to resultant: cell cycle arrest; DNA damage; accumulation of intracellular ROS; reduction of mitochondrial membrane potential; and cell apoptosis. PMID:26508985

  12. Berberine down-regulates the Th1/Th2 cytokine gene expression ratio in mouse primary splenocytes in the absence or presence of lipopolysaccharide in a preventive manner.

    PubMed

    Lin, Wei-Chi; Lin, Jin-Yuarn

    2011-12-01

    Berberine is a natural isoquinoline alkaloid. This study investigated the effects of berberine on cytokine gene expression in mouse primary splenocytes in the absence or presence of lipopolysaccharide (LPS) using 4 different experimental models in vitro. The relative expression of the following cytokine genes was determined using a real-time quantitative polymerase chain reaction assay: pro-inflammatory tumor necrosis factor (TNF)-α, anti-inflammatory interleukin (IL)-10, T-helper type 1 (Th1) (IL-2), and Th2 (IL-4) cytokines. The results showed that berberine down-regulated ratios of the relative Th1 (IL-2)/Th2 (IL-4) cytokines expression fold in mouse primary splenocytes in the absence or presence of LPS in a preventive manner. This study suggests that berberine may possess anti-inflammatory potential by shifting the Th1/Th2 balance toward Th2 polarization.

  13. Characterization of the Promoter Region of Biosynthetic Enzyme Genes Involved in Berberine Biosynthesis in Coptis japonica

    PubMed Central

    Yamada, Yasuyuki; Yoshimoto, Tadashi; Yoshida, Sayumi T.; Sato, Fumihiko

    2016-01-01

    The presence of alkaloids is rather specific to certain plant species. However, berberine, an isoquinoline alkaloid, is relatively broadly distributed in the plant kingdom. Thus, berberine biosynthesis has been intensively investigated, especially using Coptis japonica cell cultures. Almost all biosynthetic enzyme genes have already been characterized at the molecular level. Particularly, two transcription factors (TFs), a plant-specific WRKY-type TF, CjWRKY1, and a basic helix-loop-helix TF, CjbHLH1, were shown to comprehensively regulate berberine biosynthesis in C. japonica cells. In this study, we characterized the promoter region of some biosynthetic enzyme genes and associated cis-acting elements involved in the transcriptional regulation via two TFs. The promoter regions of three berberine biosynthetic enzyme genes (CYP80B2, 4′OMT and CYP719A1) were isolated, and their promoter activities were dissected by a transient assay involving the sequentially truncated promoter::luciferase (LUC) reporter constructs. Furthermore, transactivation activities of CjWRKY1 were determined using the truncated promoter::LUC reporter constructs or constructs with mutated cis-elements. These results suggest the involvement of a putative W-box in the regulation of biosynthetic enzyme genes. Direct binding of CjWRKY1 to the W-box DNA sequence was also confirmed by an electrophoresis mobility shift assay and by a chromatin immunoprecipitation assay. In addition, CjbHLH1 also activated transcription from truncated 4′OMT and CYP719A1 promoters independently of CjWRKY1, suggesting the involvement of a putative E-box. Unexpected transcriptional activation of biosynthetic enzyme genes via a non-W-box sequence and by CjWRKY1 as well as the possible involvement of a GCC-box in berberine biosynthesis in C. japonica are discussed. PMID:27642289

  14. Relaxant action mechanism of berberine identified as the active principle of Argemone ochroleuca Sweet in guinea-pig tracheal smooth muscle.

    PubMed

    Sánchez-Mendoza, María Elena; Castillo-Henkel, Carlos; Navarrete, Andrés

    2008-02-01

    In this study we investigated the relaxant effect of the aerial parts of Argemone ochroleuca (Papaveraceae), which is used in Mexican traditional medicine for the treatment of various respiratory diseases such as cough, bronchitis and asthma. The alkaloid berberine was identified as one of the active relaxant principles (EC50 = 118.50 +/-3.91 microM) in the dichloromethane extract of A. ochroleuca (EC50 = 78.03 +/- 2.15 microg mL(-1) with 95.12 +/- 3.56% of relaxation). Berberine concentration-dependently relaxed the carbachol-induced precontractions but not histamine- or KCl-induced precontraction. The relaxant effect of berberine was unaffected by the presence of propranolol (3 microM), glibenclamide (10 microM) or ODQ (10microM). However, 2', 5'-dideoxyadenosine (10 microM) blocked the log concentration-response curves of berberine. On the other hand, berberine produced a leftward shift of the log concentration-response curves of isoproterenol, forskolin and nitroprusside. Additionally, berberine produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner with a pA2 of 3.87 +/- 0.045. The above results suggest that the relaxant effect of berberine on tracheal muscle is due to its antagonistic effect on muscarinic acetylcholine receptors.

  15. Diterpenoid alkaloids.

    PubMed

    Wang, Feng-Peng; Chen, Qiao-Hong; Liu, Xiao-Yu

    2010-04-01

    The lasting attention that researchers have devoted to diterpenoid alkaloids is due to their various bioactivities and toxicities, structural complexity, and intriguing chemistry. From 1998 to the end of 2008, more than 300 new diterpenoid alkaloids were isolated from Nature. This review focuses on their structural relationships, and investigations into their chemical reactions, synthesis, and biological activities. A table that lists the names, plant sources, and structural types is given along with 363 references.

  16. On the mechanism of antidepressant-like action of berberine chloride.

    PubMed

    Kulkarni, Shrinivas K; Dhir, Ashish

    2008-07-28

    Berberine, an alkaloid isolated from Berberis aristata Linn. has been used in the Indian system of medicines as a stomachic, bitter tonic, antiamoebic and also in the treatment of oriental sores. Evidences have demonstrated that berberine possesses central nervous system activities, particularly the ability to inhibit monoamine oxidase-A, an enzyme involved in the degradation of norepinephrine and serotonin (5-HT). With this background, the present study was carried out to elucidate the antidepressant-like effect of berberine chloride in different behavioural paradigms of despair. Berberine (5, 10, 20 mg/kg, i.p.) inhibited the immobility period in mice in both forced swim and tail-suspension test, however, the effect was not dose-dependent. Berberine (5 and 10 mg/kg, i.p.) also reversed the reserpine-induced behavioral despair. Berberine (5 mg/kg, i.p.) enhanced the anti-immobility effect of subeffective doses of various typical but not atypical antidepressant drugs in forced swim test. Berberine (5 mg/kg, i.p.) following its acute administration in mice resulted in increased levels of norepinephrine (31%), serotonin (47%) and dopamine (31%) in the whole brain. Chronic administration of berberine (5 mg/kg, i.p.) for 15 days significantly increased the levels of norepinephrine (29%), serotonin (19%) as well as dopamine (52%) but at higher dose (10 mg/kg, i.p.), there was no change in the norepinephrine (12%) levels but a significant increase in the serotonin (53%) and dopamine (31%) levels was found. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced swim test was prevented by pretreatment with l-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). On the contrary, pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, i.p.) or methylene blue (10 mg/kg, i.p.) potentiated the effect of berberine (2 mg/kg, i.p.) in the forced swim test. Pretreatment of mice with (+)-pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma1 receptor agonist

  17. Myocardial Salvaging Effects of Berberine in Experimental Diabetes Co-Existing with Myocardial Infarction

    PubMed Central

    Borde, Manjusha K.; Mohanty, Ipseeta Ray; Maheshwari, Ujwala; Deshmukh, Y.A.

    2016-01-01

    Introduction Berberine, an isoquinoline alkaloid isolated from the Berberis aristata, has been shown to display a wide array of pharmacological activities (hypoglycaemic and hypolipidemic). Aim The present study was designed to investigate whether these pharmacological properties translate into the cardioprotective effects of Berberine in the setting of diabetes mellitus. Materials and Methods Necessary approval from the Institutional Animal Ethics Committee was taken for the study. Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was induced by administering Isoproterenol (ISP): 85mg/kg, sc to rats on 35th & 36th day. After the confirmation of diabetes on 7th day (>200mg/dl), Berberine (100 mg/kg) was administered orally to experimental rats from day 8 and continued for 30 days thereafter. Various anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB), metabolic (lipid profile), safety {liver function (SGPT, kidney function (Creatinine)} and histopathological indices of injury were evaluated in Healthy Control, Diabetic Control and Berberine treated groups. Results Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, SGPT, creatinine levels (p<0.001) in the diabetic control group rats as compared to healthy control. Berberine treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to diabetic control group. In addition, Berberine favourably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL). Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Berberine in setting of diabetes. In addition, Berberine

  18. Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice.

    PubMed

    Zhang, Zhijie; Li, Xiuhua; Li, Fayin; An, Lijun

    2016-09-01

    Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after surgery, especially for the elderly. Accumulating evidence has demonstrated that neuroinflammation plays a key role in the pathogenesis of POCD. Thus, we hypothesized that berberine, an isoquinoline alkaloid with anti-inflammatory effects, could improve surgery-induced cognitive impairment. Twenty-month-old male C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. For the interventional studies, mice received berberine (10mg/kg) or vehicle intraperitoneally. For the in vitro study, we examined the effects of berberine on lipopolysaccharide (LPS)-induced inflammatory mediators by cultured BV2 cells. Behavioral tests, expressions of IBA1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were performed at the indicated time points. In the present study, we showed that surgery impaired the contextual fear memory, as evidenced by the significantly decreased freezing time to the context. This behavioral change coincided with marked increases in IBA1, TNF-α, IL-1β, and IL-6 in the prefrontal cortex and hippocampus only at 24h but not 7 d after surgery. In BV2 cells, LPS induced significantly increased TNF-α and IL-1β expressions. Notably, berberine treatment rescued surgery-induced cognitive impairment and inhibited the release of IBA1, IL-1β, and IL-6 in the hippocampus. In line with the in vivo study, berberine treatment suppressed LPS-stimulated production of TNF-α and IL-1β in BV2 cells. In conclusion, our study suggests that berberine could alleviate POCD by suppressing neuroinflammation in aged mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells.

    PubMed

    Naveen, C R; Gaikwad, Sagar; Agrawal-Rajput, Reena

    2016-06-15

    Berberine, a plant alkaloid, has been used since many years for treatment of gastrointestinal disorders. It also shows promising medicinal use against metabolic disorders, neurodegenerative disorders and cancer; however its efficacy in neuroblastoma (NB) is poorly explored. EMT is important in cancer stemness and metastasis resulting in failure to differentiate; thus targeting EMT and related pathways can have clinical benefits. Potential of berberine was investigated for (i) neuronal differentiation and cancer stemness inhibition, (ii) underlying molecular mechanisms regulating cancer-stemness and (iii) EMT reversal. Using neuro2a (N2a) neuroblastoma cells (NB); we investigated effect of berberine on neuronal differentiation, cancer-stemness, EMT and underlying signalling by immunofluorescence, RT-PCR, Western blot. High glucose-induced TGF-β mediated EMT model was used to test EMT reversal potential by Western blot and RT-PCR. STRING analysis was done to determine and validate functional protein-interaction networks. We demonstrate berberine induces neuronal differentiation accompanying increased neuronal differentiation markers like MAP2, β-III tubulin and NCAM; generated neurons were viable. Berberine attenuated cancer stemness markers CD133, β-catenin, n-myc, sox2, notch2 and nestin. Berberine potentiated G0/G1 cell cycle arrest by inhibiting proliferation, cyclin dependent kinases and cyclins resulting in apoptosis through increased bax/bcl-2 ratio. Restoration of tumor suppressor proteins, p27 and p53, indicate promising anti-cancer property. The induction of NCAM and reduction in its polysialylation indicates anti-migratory potential which is supported by down regulation of MMP-2/9. It increased epithelial marker laminin and smad and increased Hsp70 levels also suggest its protective role. Molecular insights revealed that berberine regulates EMT via downregulation of PI3/Akt and Ras-Raf-ERK signalling and subsequent upregulation of p38-MAPK. TGF

  20. Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

    PubMed Central

    Hawkins, Kristy M; Smolke, Christina D

    2010-01-01

    The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches. PMID:18690217

  1. [Effects of alkaloids from Coptidis Rhizoma on mouse peritoneal macrophages in vitro].

    PubMed

    Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang

    2015-12-01

    This work was mainly studied the effects of the four alkaloids from Coptidis Rhizoma on the mouse peritoneal macrophages in vitro and preliminarily discussed the regulating mechanisms. The effect of alkaloids from Coptidis Rhizoma on the vitality of macrophages was measured by the MTT assay. The effect of alkaloids on the phagocytosis of macrophages was determined by neutral red trial and respiratory burst activity was tested by NBT. The expressions of respiratory-burst-associated genes influenced by alkaloids were detected by qRT-PCR. The conformation change of membrane protein in macrophages by the impact of alkaloids was studied by fluorospectro-photometer. Results showed that the four alkaloids from Coptidis Rhizoma could increase the phagocytosis of macrophages in different level and berberine had the best effect. Berberine, coptisine and palmatine had up-regulation effects on respiratory burst activity of mouse peritoneal macrophages stimulated by PMA and regulatory activity on the mRNA expression of PKC, p40phox or p47phox, whereas the epiberberine had no significant influence on respiratory burst. Moreover, alkaloids from Coptidis Rhizoma could change the conformation of membrane protein and the berberine showed the strongest activity. The results suggested that the four alkaloids from Coptidis Rhizoma might activate macrophages through changing the conformation of membrane protein of macrophages and then enhanced the phagocytosis and respiratory burst activity of macrophages. Furthermore, the regulatory mechanism of alkaloids on the respiratory burst activity of macrophages may be also related to the expression level of PKC, p40phox and p47phox.

  2. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    NASA Astrophysics Data System (ADS)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  3. Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats.

    PubMed

    Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Khaksari, Mehdi; Norouzi, Pirasteh; Ahooie, Malihea; Mahboobi, Fatemeh

    2014-04-01

    Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. Berberine, a natural isoquinoline alkaloid, is reported to exhibit beneficial effect in various neurodegenerative and neuropsychiatric disorders. Moreover, astrocytes are proving critical for normal CNS function, and alterations in their activity and impaired oxidative stress could contribute to diabetes-related cognitive dysfunction. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP) as an astrocytic marker. Therefore, we examined the effects of berberine on glial reactivity of hippocampus in streptozotocin (STZ)-induced diabetic rats, using GFAP immunohistochemistry. Lipid peroxidation, superoxide dismutase (SOD) activity, and nitrite levels were assessed as the parameters of oxidative stress. Eight weeks after diabetes induction, we observed increased numbers of GFAP(+) astrocytes immunostaining associated with increased lipid peroxidation, decreased superoxide dismutase activity, and elevated nitrite levels in the hippocampus of STZ-diabetic rats. In contrast, chronic treatment with berberine (50 and 100 mg/kg p.o. once daily) lowered hyperglycemia, reduced oxidative stress, and prevented the upregulation of GFAP in the brain of diabetic rats. In conclusion, the present study demonstrated that the treatment with berberine resulted in an obvious reduction of oxidative stress and GFAP-immunoreactive astrocytes in the hippocampus of STZ-induced diabetic rats.

  4. Downregulation of cellular c-Jun N-terminal protein kinase and NF-κB activation by berberine may result in inhibition of herpes simplex virus replication.

    PubMed

    Song, Siwei; Qiu, Min; Chu, Ying; Chen, Deyan; Wang, Xiaohui; Su, Airong; Wu, Zhiwei

    2014-09-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-κB pathways.

  5. Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

    PubMed Central

    Song, Siwei; Qiu, Min; Chu, Ying; Chen, Deyan; Wang, Xiaohui; Su, Airong

    2014-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-κB pathways. PMID:24913175

  6. [Advances of the mechanism study on berberine in the control of blood glucose and lipid as well as metabolism disorders].

    PubMed

    Shen, Ning; Li, Cai-Na; Huan, Yi; Shen, Zhu-Fang

    2010-06-01

    Berberine, an isoquinoline alkaloid isolated from some Chinese medicinal herbs such as Coptidis rhizoma, has been used for the treatment of diarrhea and other gastrointestinal infections as an antibacterial drug in Chinese medicine. In recent years, it was reported to have beneficial effects on the metabolism disorders states of diabetes. The mechanisms involve many aspects of the diabetes, including regulating the blood cholesterol and triglyceride, lowering blood glucose, ameliorating the insulin resistant state and influencing the function of the pancreatic beta cell.

  7. Potential benefits of berberine in the management of perimenopausal syndrome.

    PubMed

    Caliceti, Cristiana; Rizzo, Paola; Cicero, Arrigo Francesco Giuseppe

    2015-01-01

    Cardiovascular diseases are one of the leading causes of morbidity and mortality in women after menopause and 56% of all causes of death in Western European countries. Nowadays, with increasing life span, women spend approximately one-third of their life-time in postmenopausal state; therefore, the development of new strategies to improve the prevention and treatment of menopause-associated pathologies is important topic in clinical practice. The studies to assess the safety of hormone replacement therapy in women with estrogen deficiency have not been conclusive due to the relative contraindications; therefore, hormone replacement therapy is prescribed only in selected cases and for a limited time. For this reason, today women are encouraged to use naturally available compounds to prevent or to attenuate menopausal symptoms and correlated pathologies, with fewer side effects. Among these compounds, berberine, an isoquinoline alkaloid derived from plants of the generis Berberis, has been recognized as being capable of decreasing oxidative stress, LDL, triglycerides, and insulin resistance and of improving the mood. This review describes the cellular and clinical effects associated with the use of berberine, which suggest that this molecule could be an effective natural supplement to ensure a smooth peri- and postmenopausal transition.

  8. Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group.

    PubMed

    Li, Cailan; Xie, Jianhui; Chen, Xiaoying; Mo, Zhizhun; Wu, Wen; Liang, Yeer; Su, Zuqing; Li, Qian; Li, Yucui; Su, Ziren; Yang, Xiaobo

    2016-03-01

    Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time-dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis-blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease.

  9. Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

    SciTech Connect

    Bonon, Anna; Mangolini, Alessandra; Pinton, Paolo; Senno, Laura del; Aguiari, Gianluca

    2013-11-22

    Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new

  10. [Effect of berberine in treating type 2 diabetes mellitus and complications and its relevant mechanisms].

    PubMed

    Zhang, Qing; Li, Yan; Chen, Lei

    2015-05-01

    Berberine (BBR) is a type of alkaloids isolated from Coptidis Rhizoma and Phellodendri Chinensis Cortex and has been used to treat bacterial gastroenteritis, diarrhea and other digestive diseases for more than 1 000 years. According to recent studies, berberine has been found to have multiple pharmacological activities, including lowering blood glucose and lipid, anti-inflammation, antioxidation, relieving type 2 diabetic nephropathy (DN), diabetic cardiovascular disease, diabetic peripheral neuropathy ( DPN) and other complications. In this article, the authors summarized the literature reports about the effects of BBR in lowering blood glucose and preventing and treating the above type 2 diabetes and its complications, in order to provide reference to further studies and promotion of BBR's application.

  11. Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San.

    PubMed

    Chin, Lengsu William; Cheng, Yu-Wen; Lin, Shih-Shen; Lai, Ya-Yun; Lin, Long-Yau; Chou, Ming-Yung; Chou, Ming-Chih; Yang, Chi-Chiang

    2010-12-01

    Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has the most potent antimicrobial activity. By high-pressure liquid chromatography, the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26 mg/mL. To explore the potential use of Ching-Wei-San against herpes simplex virus (HSV) infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells were assayed. The selectivity index of berberine was about 1.2-1.5 times higher than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral activities correspond to the content of berberine in the aqueous solution. Berberine may interfere with the viral replication cycle after virus penetration and no later than the viral DNA synthesis step, and its activities were not affected by the preparation processes. Berberine, the natural plants that contain this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti-HSV effects.

  12. Potential of berberine to enhance antimicrobial activity of commonly used antibiotics for dairy cow mastitis caused by multiple drug-resistant Staphylococcus epidermidis infection.

    PubMed

    Zhou, X; Yang, C; Li, Y; Liu, X; Wang, Y

    2015-08-19

    Berberine is a plant alkaloid with antimicrobial activity against a variety of microorganisms. In this study, the antimicrobial properties of berberine against multi-drug resistant field isolates of Staphylococcus epidermidis were investigated using berberine alone or in combination with a commonly used antibiotics in veterinary clinics, including penicillin, lincomycin, and amoxicillin. The results indicated that the minimum inhibitory concentrations of berberine, penicillin, lincomycin, and amoxicillin against field S. epidermidis isolates were 2-512, 0.8-213, 0.4-1024, and 0.4-256 mg/mL, respectively. Furthermore, the synergistic effects of antimicrobial activity against these multi-drug resistant isolates were observed when the berberine was combined with penicillin, lincomycin, or amoxicillin; no antagonistic effect of the combination was detected in any of the clinical isolates. These observations were further confirmed using a time-killing assay, in which a combination of 2 agents yielded a greater than 2.03-2.44 log10 decrease in colony-forming unit/mL compared with each agent alone. These findings suggest that berberine is a promising compound for preventing and treating multi-drug resistant S. epidermidis infected mastitis in dairy cows either alone or in combination with other commonly used antibiotics, such as penicillin, lincomycin, and amoxicillin.

  13. Quantitative evaluation of berberine subcellular distribution and cellular accumulation in non-small cell lung cancer cells by UPLC-MS/MS.

    PubMed

    Yuan, Zhong-Wen; Leung, Elaine Lai-Han; Fan, Xing-Xing; Zhou, Hua; Ma, Wen-Zhe; Liu, Liang; Xie, Ying

    2015-11-01

    Berberine, an isoquinoline alkaloid, has been demonstrated to be a safe anti-cancer agent with multiple effects on mitochondria. Intracellular concentration and distribution around the targeting sites are determinants of efficacy, but subcellular distribution of berberine has not been fully elucidated yet, which relies on the sensitive and robustness assay. In this study, a sensitive and robust UPLC-MS/MS method has been developed and validated with optimized extraction solvents and detection conditions. Key factors such as the purity and integrity of isolated organelle fractions, and the effects of isolation procedures on the subcellular concentration of berberine were systemically evaluated. With the developed assay, we found that the intracellular accumulations of berberine in two gefitinib resistant NSCLC cell lines H1650 and H1975 were 2-3 folds higher than that of normal epithelial cells BEAS-2B. Moreover, significantly different subcellular distribution profiles in NSCLC cancer cells from that of BEAS-2B cells with a striking increase in content in most organelles may contribute to its selective cytotoxicity to cancer cells. Furthermore, a predominant accumulation of berberine was observed for the first time in microsomal fraction for all three cell lines. Therefore, this method could be used for quantitative evaluation of subcellular distribution and cellular accumulation of berberine and for further evaluation of the concentration-effects relationship.

  14. Berberine Induced Apoptosis of Human Osteosarcoma Cells by Inhibiting Phosphoinositide 3 Kinase/Protein Kinase B (PI3K/Akt) Signal Pathway Activation.

    PubMed

    Chen, Zhi-Ze

    2016-05-01

    Osteosarcoma is a malignant tumor with high mortality but effective therapy has not yet been developed. Berberine, an isoquinoline alkaloid component in several Chinese herbs including Huanglian, has been shown to induce growth inhibition and the apoptosis of certain cancer cells. The aim of this study was to determine the role of berberine on human osteosarcoma cell lines U2OS and its potential mechanism. The proliferation effect of U20S was exanimed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and the percentage of apoptotic cells were determined by flow cytometric analysis. The expression of PI3K, p-Akt, Bax, Bcl-2, cleavage-PARP and Caspase3 were detected by Western blott. Berberine treatment caused dose-dependent inhibiting proliferation and inducing apoptosis of U20S cell. Mechanistically, berberine inhibits PI3K/AKT activation that, in turn, results in up-regulating the expression of Bax, and PARP and down-regulating the expression of Bcl-2 and caspase3. In all, berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation. Berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation.

  15. Berberine Induced Apoptosis of Human Osteosarcoma Cells by Inhibiting Phosphoinositide 3 Kinase/Protein Kinase B (PI3K/Akt) Signal Pathway Activation

    PubMed Central

    2016-01-01

    Background: Osteosarcoma is a malignant tumor with high mortality but effective therapy has not yet been developed. Berberine, an isoquinoline alkaloid component in several Chinese herbs including Huanglian, has been shown to induce growth inhibition and the apoptosis of certain cancer cells. The aim of this study was to determine the role of berberine on human osteosarcoma cell lines U2OS and its potential mechanism. Methods: The proliferation effect of U20S was exanimed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and the percentage of apoptotic cells were determined by flow cytometric analysis. The expression of PI3K, p-Akt, Bax, Bcl-2, cleavage-PARP and Caspase3 were detected by Western blott. Results: Berberine treatment caused dose-dependent inhibiting proliferation and inducing apoptosis of U20S cell. Mechanistically, berberine inhibits PI3K/AKT activation that, in turn, results in up-regulating the expression of Bax, and PARP and down-regulating the expression of Bcl-2 and caspase3. In all, berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation. Conclusion: Berberine can suppress the proliferation and induce the apoptosis of U2OS cell through inhibiting the PI3K/Akt signaling pathway activation. PMID:27398330

  16. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells

    PubMed Central

    2011-01-01

    Background- Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1) plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. Results- We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. Conclusion- These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer through inhibition of AP-1 and

  17. Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation.

    PubMed

    Hu, Y; Davies, G E

    2009-09-01

    It is known that a number of transcription factors are key regulators in the complex process of adipocyte differentiation including peroxisome proliferator activated receptor gamma (PPARgamma) and the CCAAT enhancer binding protein alpha (C/EBPalpha). Studies have demonstrated that in pre-adipocyte 3T3-L1 cells constitutive expression of the DNA binding proteins GATA-2 and GATA-3 results in protein/protein interactions with C/EBPalpha resulting in down regulation of PPARgamma and subsequent suppressed adipocyte differentiation with cells trapped at the pre-adipocyte stage. Thus it appears that GATA-2 and GATA-3 are of critical importance in regulating adipocyte differentiation through molecular interactions with PPARgamma and C/EBPalpha. Recent reports suggest that berberine, an isoquinoline derivative alkaloid isolated from many medicinal herbs prevents differentiation of 3T3-L1 cells via a down regulation of PPARgamma and C/EBPalpha expression. The aim of this study was to determine the effect of berberine on GATA-2 and 3 gene and protein expression levels during differentiation of 3T3-L1 cells. MTT (Methylthiazolyldiphenyl-tetrazolium bromide) was used to detect the cytotoxic effects of berberine on the viability of 3T3-L1 cells during proliferation and differentiation. Differentiation of 3T3-L1 cells was monitored by Oil Red O staining and RT-PCR of PPARgamma and C/EBPalpha and the expression of GATA-2 and 3 was determined by RT-PCR and Western Blot. Results show that following treatment with 8microM berberine the mRNA and protein expression levels of GATA-2 and 3 were elevated and accompanied by inhibited adipocyte differentiation. These results may lead to the use of berberine to target the induction of specific genes such as GATA-2 and GATA-3 which affect adipocyte differentiation.

  18. The effect of varying alkaloid concentrations on the feeding behavior of gypsy moth larvae, Lymantria dispar (L.) (Lepidoptera: Lymantriidae)

    PubMed Central

    Shields, Vonnie D.C.; Smith, Kristen P.; Arnold, Nicole S.; Gordon, Ineta M.; Shaw, Taharah E.; Waranch, Danielle

    2010-01-01

    Nine alkaloids (acridine, aristolochic acid, atropine, berberine, caffeine, nicotine, scopolamine, sparteine, and strychnine) were evaluated as feeding deterrents for gypsy moth larvae (Lymantria dispar (L.); Lepidoptera: Lymantriidae). Our aim was to determine and compare the taste threshold concentrations, as well as the ED50 values, of the nine alkaloids to determine their potency as feeding deterrents. The alkaloids were applied to disks cut from red oak leaves (Quercus rubra) (L.), a plant species highly favored by larvae of this polyphagous insect species. We used two-choice feeding bioassays to test a broad range of biologically relevant alkaloid concentrations spanning five logarithmetic steps. We observed increasing feeding deterrent responses for all the alkaloids tested and found that the alkaloids tested exhibited different deterrency threshold concentrations ranging from 0.1 mM to 10 mM. In conclusion, it appears that this generalist insect species bears a relatively high sensitivity to these alkaloids, which confirms behavioral observations that it avoids foliage containing alkaloids. Berberine and aristolochic acid were found to have the lowest ED50 values and were the most potent antifeedants. PMID:21278814

  19. Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.

    PubMed

    Ming, Ming; Sinnett-Smith, James; Wang, Jia; Soares, Heloisa P; Young, Steven H; Eibl, Guido; Rozengurt, Enrique

    2014-01-01

    Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC) cells (PANC-1, MiaPaCa-2) with the isoquinoline alkaloid berberine (0.3-6 µM) inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70%) the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice. Mechanistic studies revealed that berberine decreased mitochondrial membrane potential and intracellular ATP levels and induced potent AMPK activation, as shown by phosphorylation of AMPK α subunit at Thr-172 and acetyl-CoA carboxylase (ACC) at Ser79. Furthermore, berberine dose-dependently inhibited mTORC1 (phosphorylation of S6K at Thr389 and S6 at Ser240/244) and ERK activation in PDAC cells stimulated by insulin and neurotensin or fetal bovine serum. Knockdown of α1 and α2 catalytic subunit expression of AMPK reversed the inhibitory effect produced by treatment with low concentrations of berberine on mTORC1, ERK and DNA synthesis in PDAC cells. However, at higher concentrations, berberine inhibited mitogenic signaling (mTORC1 and ERK) and DNA synthesis through an AMPK-independent mechanism. Similar results were obtained with metformin used at doses that induced either modest or pronounced reductions in intracellular ATP levels, which were virtually identical to the decreases in ATP levels obtained in response to berberine. We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways.

  20. Alkaloids in Marine Algae

    PubMed Central

    Güven, Kasım Cemal; Percot, Aline; Sezik, Ekrem

    2010-01-01

    This paper presents the alkaloids found in green, brown and red marine algae. Algal chemistry has interested many researchers in order to develop new drugs, as algae include compounds with functional groups which are characteristic from this particular source. Among these compounds, alkaloids present special interest because of their pharmacological activities. Alkaloid chemistry has been widely studied in terrestrial plants, but the number of studies in algae is insignificant. In this review, a detailed account of macro algae alkaloids with their structure and pharmacological activities is presented. The alkaloids found in marine algae may be divided into three groups: 1. Phenylethylamine alkaloids, 2. Indole and halogenated indole alkaloids, 3. Other alkaloids. PMID:20390105

  1. Polymorphic Nucleic Acid Binding of Bioactive Isoquinoline Alkaloids and Their Role in Cancer

    PubMed Central

    Maiti, Motilal; Kumar, Gopinatha Suresh

    2010-01-01

    Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form) and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity. PMID:20814427

  2. Measurement of antiphotooxidative properties of isoquinoline alkaloids using transient thermal lens spectroscopy

    NASA Astrophysics Data System (ADS)

    Hung, J.; Castillo, J.; Laboren, I.; Rodríguez, M.; Hassegawa, M.

    2005-11-01

    The antiphotooxidative properties of boldine and chloride berberine were studied by time-resolved thermal lensing technique. These compounds belong to isoquinoline alkaloids possessing interesting biological activity (e.g. antibacterial, antimalarial, antitumor). Antiphotooxidative properties of the alkaloids were studied by mechanism of energy transference between powerful oxidizing agents such as singlet oxygen. Singlet oxygen was produced by energy transfer from chlorophyll-sensitized photooxidation of oil by exposure of high light intensities like laser. The lifetimes of singlet oxygen in dimethylsulfoxide, methanol and water were determined to confirm the assignment of the singlet molecular oxygen O II (1Δ g) in the experiments. In order to understand the effect of the alkaloids on active oxygen species, we carried out in detail an analysis of the thermal lensing signal. It was shown that the alkaloids can act as quenchers of singlet oxygen. To demonstrate the ability of the alkaloids to act efficient singlet oxygen acceptors, we have measured the fluorescence spectra of the studied alkaloids in the presence and in the absence of singlet oxygen. The antiphotooxidative activity of boldine and chloride berberine can be explained by the ability to quench singlet oxygen.

  3. Effect of berberine on nitric oxide production during oxygen-glucose deprivation/reperfusion in OLN-93 oligodendrocytes.

    PubMed

    Nadjafi, Shabnam; Ebrahimi, Soltan-Ahmad; Rahbar-Roshandel, Nahid

    2014-11-01

    In this study, the effect of berberine, an isoquinoline alkaloid isolated from Coptidis rhizoma, on Nitric Oxide (NO) production, as a possible involved factor, during excitotoxic injury in oligodendroglial cells were evaluated. The overactivation of ionotropic glutamate receptors which is known as the excitotoxicity, is an important phenomenon because of the contribution in acute injury to the central nervous system, chronic neurodegenerative disorders, oligodendrocyte loss and demyelinating diseases as Multiple Sclerosis (MS). Intracellular Ca2+ overload, have a key role during excitotoxic injury and such increase in cytoplasmic Ca2+ triggers a series of events such as production of NO that end to cell death. Previous report showed the protective effects of berberine on ischemic-induced excitotoxic insult in oligodendrocytes. Hereby, we intended to know if the NO production could be associated with oxygen-glucose deprivation/reperfusion-induced excitotoxic damage in oligodendrocyte; moreover, the alteration of NO production could be considered as an involved mechanism for protective effect of berberine in such condition. Therefore, the effect of berberine (2 μM) on NO production during oxygen-glucose deprivation/24 h reperfusion in oligodendrocytes were examined. The OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. Thirty minutes-oxygen-glucose deprivation/24 h reperfusion was used to induce excitotoxicity. NO production was evaluated by Griess method. Our results demonstrated that berberine (2 μM) significantly decreased NO production during 30 min oxygen-glucose deprivation/reperfusion. It seems that blockade of NO production by berberine may also participate in oligodendroglial cell protection against oxygen-glucose deprivation/reperfusion-induced insult.

  4. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats.

    PubMed

    Zhou, Jiyin; Zhou, Shiwen; Tang, Jianlin; Zhang, Kebin; Guang, Lixia; Huang, Yongping; Xu, Ying; Ying, Yi; Zhang, Le; Li, Dandan

    2009-03-15

    Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Berberine is one of the main alkaloids of Rhizoma coptidis which has been used to treat diabetes for more than 1400 years in China. The present study was designed to evaluate the protective effects of berberine against beta cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats with hyperlipidemia were induced by intraperitoneally injection 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Rats were divided into 7 groups at the end of week 16: untreated control, untreated diabetic, 75, 150, 300 mg/kg berberine-treated diabetic, 100 mg/kg fenofibrate-treated, and 4 mg/kg rosiglitazone-treated. After 16 weeks treatment, serum insulin level, insulin expression in pancreas, and malonaldehyde content, superoxide dismutase activity in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining and transmission electron microscope. Pancreas to body weight ratio, insulin level, insulin sensitivity index, malonaldehyde content and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with 150, 300 mg/kg berberine. Mitochondrial vacuolization and swelling, dilatation of the endoplasmic reticulum were observed in beta cells of diabetic rats. The pancreatic islet area atrophied and secretory granules of beta cells decreased in diabetic rats. Slight pathological changes existed in beta cells of 150, 300 mg/kg berberine-treated diabetic pancreas. These findings suggest that berberine has protective effect for diabetes through increasing insulin expression, beta cell regeneration, antioxidant enzyme activity and decreasing lipid peroxidation.

  5. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway

    PubMed Central

    Wang, Jiwei; Qi, Qichao; Feng, Zichao; Zhang, Xin; Huang, Bin; Chen, Anjing; Prestegarden, Lars; Li, Xingang; Wang, Jian

    2016-01-01

    There is an urgent need for new therapeutic strategies for patients with glioblastoma multiforme (GBM). Previous studies have shown that berberine (BBR), a natural plant alkaloid, has potent anti-tumor activity. However, the mechanisms leading to cancer cell death have not been clearly elucidated. In this study, we show that BBR has profound effects on the metabolic state of GBM cells, leading to high autophagy flux and impaired glycolytic capacity. Functionally, these alterations reduce the invasive properties, proliferative potential and induce apoptotic cell death. The molecular alterations preceding these changes are characterized by inhibition of the AMPK/mTOR/ULK1 pathway. Finally, we demonstrate that BBR significantly reduces tumor growth in vivo, demonstrating the potential clinical benefits for autophagy modulating plant alkaloids in cancer therapy. PMID:27557493

  6. Alkaloids from Delphinium pentagynum.

    PubMed

    Díaz, Jesús G; Ruiz, Juan García; Herz, Werner

    2004-07-01

    Aerial parts of a collection of Delphinium pentagynum Lam. from Niebla, Southern Spain, furnished one diterpene alkaloid, 2-dehydrodeacetylheterophylloidine, two norditerpene alkaloids, 14-demethyl-14-isobutyrylanhweidelphinine and 14-demethyl-14-acetylanhweidelphinine, the known alkaloids 14-deacetylnudicauline, methyllycaconitine, 14-deacetyl-14-isobutyrylnudicauline, 14-acetylbrowniine, browniine, delcosine, lycoctonine, 18-methoxygadesine, neoline, karakoline and the aporphine alkaloid magnoflorine. Structures of the alkaloids were established by MS, 1D and 2-D NMR techniques.

  7. Isolation and identification of urinary metabolites of berberine in rats and humans.

    PubMed

    Qiu, Feng; Zhu, Zhiyong; Kang, Ning; Piao, Shujuan; Qin, Gengyao; Yao, Xinsheng

    2008-11-01

    The urinary metabolites of berberine, an isoquinoline alkaloid isolated from several Chinese herbal medicines, were investigated in rats and humans. Using macroporous adsorption resin chromatography, open octadecyl silane column chromatography and preparative high-performance liquid chromatography, we isolated seven metabolites (HM1-HM7) from human urine and five metabolites (RM1-RM5) from rat urine after oral administration. Their structures were elucidated by enzymatic deconjugation and analyses of mass spectrometry, (1)H NMR, and nuclear Overhauser effect spectroscopy spectra. Besides the three known metabolites demethyleneberberine-2-O-sulfate (HM1 and RM3), jatrorrhizine-3-O-sulfate (HM5), and thalifendine (RM5), six new metabolites were identified, namely, jatrorrhizine-3-O-beta-D-glucuronide (HM2), thalifendine-10-O-beta-D-glucuronide (HM3), berberrubine-9-O-beta-D-glucuronide (HM4 and RM2), 3,10-demethylpalmatine-10-O-sulfate (HM6 and RM4), columbamin-2-O-beta-D-glucuronide (HM7), and demethyleneberberine-2,3-di-O-beta-D-glucuronide (RM1). These findings suggest that berberine undergoes similar biotransformation in rats and humans. Possible metabolic pathways of berberine in rats and humans are proposed.

  8. 13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells.

    PubMed

    Chow, Yit-Lai; Sogame, Mami; Sato, Fumihiko

    2016-12-05

    Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity. 13-Methylberberine down-regulated the expression of the main adipocyte differentiation transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα), as well as their target genes. PPARγ, C/EBPα, and sterol regulatory element binding protein 1 (SREBP-1) protein levels were reduced, and this lipid-reducing effect was attenuated by an AMP-activated protein kinase (AMPK) inhibitor, indicating that the effect of this compound requires the AMPK signaling pathway. Decreased Akt phosphorylation suggested reduced de novo lipid synthesis. C-13 methyl substitution of berberine increased its accumulation in treated cells, suggesting that 13-methylberberine has improved absorption and higher accumulation compared to berberine. Our findings suggest that 13-methylberberine has potential as an anti-obesity drug.

  9. 13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells

    PubMed Central

    Chow, Yit-Lai; Sogame, Mami; Sato, Fumihiko

    2016-01-01

    Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity. 13-Methylberberine down-regulated the expression of the main adipocyte differentiation transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα), as well as their target genes. PPARγ, C/EBPα, and sterol regulatory element binding protein 1 (SREBP-1) protein levels were reduced, and this lipid-reducing effect was attenuated by an AMP-activated protein kinase (AMPK) inhibitor, indicating that the effect of this compound requires the AMPK signaling pathway. Decreased Akt phosphorylation suggested reduced de novo lipid synthesis. C-13 methyl substitution of berberine increased its accumulation in treated cells, suggesting that 13-methylberberine has improved absorption and higher accumulation compared to berberine. Our findings suggest that 13-methylberberine has potential as an anti-obesity drug. PMID:27917887

  10. [Hypoglycemic activity of berberin and extract obtained from the bark of Phellodendron lavalei, introduced in sub tropic areas of Georgia].

    PubMed

    2010-01-01

    The goal of this study was to evaluate hypoglycemic activity of Berberin and extract obtained from the bark of Phellodendron Lavalei, which is introduced in sub tropic areas of Georgia-Kobuleti. The study was carried out to reveal comparative hypoglycemic activity and acute toxicity of alkaloid Berberin and bark extract of Phellodendron Lavalei. Effects of Berberin hydrochloride and bark extract on blood glucose level was studied on mice. Measurement of blood glucose level was carried out on fasting animals using glucose meter "GlucoLab"--auto-coding. The study showed that Berberin hydrochloride dose 150 mg/kg, extract (obtained from the bark of Phellodendron Lavalei) dose 400 mg/kg and glybenclamid dose 0.25 mg/kg practically decreased blood glucose level of mice in a same pattern. Received data allows us to suggest that Phellodendron Lavalei, introduced in sub tropic areas of Georgia contains active hypoglycemic components. In conclusion the possible use of Phellodendron Lavalei as a plant raw material for obtaining hypoglycemic substances needs to be decided after further study of efficacy, mechanism of action of extracts and active components of Phellodendron Lavalei on experimental models of diabetes mellitus.

  11. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies.

    PubMed

    Chang, Wenguang; Chen, Li; Hatch, Grant M

    2015-10-01

    The incidence of type 2 diabetes is increasing rapidly worldwide, and the development of novel anti-diabetic drugs is emerging. However, most anti-diabetic drugs cannot be used in patients with hepatic dysfunction, renal disease, and heart disease, which makes pharmacological therapy of type 2 diabetes complicated. Despite continued introduction of novel agents, the search for an ideal drug that is useful as both a hypoglycemic agent and to reduce diabetes-related complications remains elusive. Berberine is an isoquinoline alkaloid extract that has shown promise as a hypoglycemic agent in the management of diabetes in animal and human studies. Mechanistic studies have revealed beneficial effects of berberine on diabetes-related complications. Although there have been few clinical reports of the anti-diabetic effects of berberine, little documentation of adverse effects in humans positions it as a potential candidate drug to treat type 2 diabetes. In the present review, the anti-diabetic mechanism of berberine, its effect on diabetes-related complications, and its recent use in human clinical studies is highlighted. In addition, we summarize the different treatments for type 2 diabetes in adults and children.

  12. Cultivation of Thalictrum rugosum cell suspension in an improved airlift bioreactor: stimulatory effect of carbon dioxide and ethylene on alkaloid production.

    PubMed

    Kim, D I; Pedersen, H; Chin, C K

    1991-08-05

    Airlift bioreactor operations have been studied for the growth-associated production of secondary metabolites from plant cell suspension cultures. The model system used in this work was Thalictrum rugosum producing berberine, an isoquinoline alkaloid. The airlift system was well suited for growth of Thalictrum cell suspension cultures unless the cell density was high. At high cell density, the airlift system with a draught tube was not adequate due to large aggregates clogging the recirculation paths. This was overcome by use of a cell scraper in the reactor. For berberine production, gas-stripping also played a significant role and it was discovered that CO(2) and ethylene were important for product formation. By supplying a mixture of CO(2) and ethylene into the airlift system, the specific berberine content was increased twofold. It is evident that continuous gas sparging was harmful for the production of berberine without supplementation with other gases.

  13. Effect of Catnip Charcoal on the In Vivo Pharmacokinetics of the Main Alkaloids of Rhizoma Coptidis

    PubMed Central

    He, Yanfei; Chen, Siyu; Yu, Hai; Zhu, Long; Liu, Yayun; Han, Chunyang; Liu, Cuiyan

    2016-01-01

    This study aims to explore the effect of catnip Nepeta cataria (CNC) charcoal on the pharmacokinetics of the main alkaloids of Rhizoma Coptidis in vivo. Twenty-four rabbits were randomly divided into four groups and given oral administration of an aqueous extract of Rhizoma Coptidis (RCAE), RCAE plus CNC, RCAE plus activated carbon (AC), or distilled water, respectively. Plasma samples were collected after administration. The concentrations of berberine, coptisine, palmatine, and epiberberine in plasma were measured by high-performance liquid chromatography (HPLC). The pharmacokinetics data were calculated using pharmacokinetic DAS 2.0 software. The results showed that the area under the concentration-time curve (AUC) of berberine increased, while the AUC of coptisine, palmatine, and epiberberine decreased in the rabbits that received RCAE plus CNC. Meanwhile, the AUC of berberine, coptisine, palmatine, and epiberberine decreased in the group given RCAE plus AC. The difference of main pharmacokinetics parameters among the four groups was significant (P < 0.05). This study showed that CNC improved the bioavailability of berberine in comparison to AC and prolonged its release in comparison to RCAE alone. However, it decreased the bioavailability of coptisine, palmatine, and epiberberine. In comparison, AC uniformly declined the bioavailability of berberine, coptisine, palmatine, and epiberberine. PMID:27313645

  14. Effect of Catnip Charcoal on the In Vivo Pharmacokinetics of the Main Alkaloids of Rhizoma Coptidis.

    PubMed

    He, Yanfei; Chen, Siyu; Yu, Hai; Zhu, Long; Liu, Yayun; Han, Chunyang; Liu, Cuiyan

    2016-01-01

    This study aims to explore the effect of catnip Nepeta cataria (CNC) charcoal on the pharmacokinetics of the main alkaloids of Rhizoma Coptidis in vivo. Twenty-four rabbits were randomly divided into four groups and given oral administration of an aqueous extract of Rhizoma Coptidis (RCAE), RCAE plus CNC, RCAE plus activated carbon (AC), or distilled water, respectively. Plasma samples were collected after administration. The concentrations of berberine, coptisine, palmatine, and epiberberine in plasma were measured by high-performance liquid chromatography (HPLC). The pharmacokinetics data were calculated using pharmacokinetic DAS 2.0 software. The results showed that the area under the concentration-time curve (AUC) of berberine increased, while the AUC of coptisine, palmatine, and epiberberine decreased in the rabbits that received RCAE plus CNC. Meanwhile, the AUC of berberine, coptisine, palmatine, and epiberberine decreased in the group given RCAE plus AC. The difference of main pharmacokinetics parameters among the four groups was significant (P < 0.05). This study showed that CNC improved the bioavailability of berberine in comparison to AC and prolonged its release in comparison to RCAE alone. However, it decreased the bioavailability of coptisine, palmatine, and epiberberine. In comparison, AC uniformly declined the bioavailability of berberine, coptisine, palmatine, and epiberberine.

  15. Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages.

    PubMed

    Shin, Ji-Sun; Choi, Hye-Eun; Seo, SeungHwan; Choi, Jung-Hye; Baek, Nam-In; Lee, Kyung-Tae

    2016-07-01

    Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects; however, the underlying mechanisms responsible for its actions are poorly understood. In the present study, we investigated the inhibitory effects of berberine and the molecular mechanisms involved in lipopolysaccharide (LPS)-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice. In both macrophage cell types, berberine inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression, but it had no effect on iNOS mRNA transcription. Suppression of LPS-induced iNOS protein expression by berberine occurred via a human antigen R (HuR)-mediated reduction of iNOS mRNA stability. Molecular data revealed that the suppression on the LPS-induced HuR binding to iNOS mRNA by berberine was accompanied by a reduction in nucleocytoplasmic HuR shuttling. Pretreatment with berberine reduced LPS-induced iNOS protein expression and the cytoplasmic translocation of HuR in liver tissues and increased the survival rate of mice with LPS-induced endotoxemia. These results show that the suppression of iNOS protein expression by berberine under LPS-induced inflammatory conditions is associated with a reduction in iNOS mRNA stability resulting from inhibition of the cytoplasmic translocation of HuR. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. A sensitive and specific liquid chromatography mass spectrometry method for simultaneous determination of berberine, palmatine, coptisine, epiberberine and jatrorrhizine from Coptidis Rhizoma in rat plasma

    NASA Astrophysics Data System (ADS)

    Yu, Sen; Pang, Xiaoyan; Deng, Yuanxiong; Liu, Li; Liang, Yan; Liu, Xiaodong; Xie, Lin; Wang, Guangji; Wang, Xinting

    2007-11-01

    A sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method has been developed and validated for the identification and quantification of five protoberberine alkaloids, which are berberine, palmatine, coptisine, epiberberine and jatrorrhizine, in rat plasma using tetrahydroberberine as an internal standard. Following solid-phase extraction, the analytes were separated by linear gradient elution on a Shim-pack ODS (4.6 [mu]m, 150 mm × 2.0 mm i.d.) column and analyzed in selected ion monitoring (SIM) mode with a positive electrospray ionization (ESI) interface using the respective [M]+ and [M + H]+ ions, [M]+ = 336 for berberine; 320 for coptisine; 336 for epiberberine; 338 for jatrorrhizine; 352 for palmatine and [M + H]+ = 340 for the internal standard. The method was validated over the concentration range of 0.31-20 ng mL-1 for all the five protoberberine alkaloids. Within-batch and between-batch precisions (R.S.D.%) were all within 15% and accuracy (%Er) ranged from -5 to 5%. The lower limits of quantification were 0.31 ng mL-1 for all analytes. The extraction recoveries were on average 80.8% for berberine, 67E0% for coptisine, 66.2% for epiberberine, 71.8% for jatrorrhizine and 73E2% for palmatine. The validated method was used to study the pharmacokinetic profile of the five protoberberine alkaloids in rat plasma after oral administration of Coptidis Rhizoma extract.

  17. Berberine stimulates glucose transport through a mechanism distinct from insulin.

    PubMed

    Zhou, Libin; Yang, Ying; Wang, Xiao; Liu, Shangquan; Shang, Wenbin; Yuan, Guoyue; Li, Fengying; Tang, Jinfeng; Chen, Mingdao; Chen, Jialun

    2007-03-01

    Berberine exerts a hypoglycemic effect, but the mechanism remains unknown. In the present study, the effect of berberine on glucose uptake was characterized in 3T3-L1 adipocytes. It was revealed that berberine stimulated glucose uptake in 3T3-L1 adipocytes in a dose- and time-dependent manner with the maximal effect at 12 hours. Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components. Unlike insulin, the effect of berberine on glucose uptake was insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and SB203580, an inhibitor of p38 mitogen-activated protein kinase. Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin-induced phosphorylation of Akt. Meanwhile, the expression and cellular localization of glucose transporter 4 (GLUT4) were not altered by berberine. Berberine did not increase GLUT1 gene expression. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation. These findings suggest that berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine.

  18. Spectroscopic investigation of the interaction between G-quadruplex of KRAS promoter sequence and three isoquinoline alkaloids

    NASA Astrophysics Data System (ADS)

    Wen, Li-Na; Xie, Meng-Xia

    2017-01-01

    KRAS promoter can form G-quadruplex structure and regulate gene transcription. The drugs which can bind with G-quadruplex of KRAS promoter may be potential remedy for treatment of cancers associated with KRAS mutation. The interaction mechanism between the G-quadruplex of KRAS promoter and three isoquinoline alkaloids (jatrorrhizine, berberine and sanguinarine) has been investigated by UV-visible, fluorescence and circular dichroism spectroscopic methods. The results showed that the three alkaloids can form complexes with G-quadruplex KRAS promoter with the molecular ratio of 1:1, and the binding constants were (0.90 ± 0.16) × 106 L mol- 1, (0.93 ± 0.21) × 106 L mol- 1 and (1.16 ± 0.45) × 106 L mol- 1 for jatrorrhizine, berberine and sanguinarine. The absorption spectra, KI quenching and fluorescence anisotropy and polarization studies suggested jatrorrhizine and berberine interacted with G-quadruplex by not only end-stacking binding mode but also grooves or loops binding mode, while sanguinarine by end-stacking binding mode. Sanguinarine was more beneficial to maintain the stability and parallel conformation of KRAS promoter G-quadruplex. MTT assay was performed to evaluate antiproliferation effects of the three isoquinoline alkaloids on SW620 cells, and the antiproliferation effects of the three alkaloids were sanguinarine > berberine > jatrorrhizine. All the three alkaloids can bind with KRAS promoter G-quadruplex, and sanguinarine had the better binding property and antiproliferation effects on SW620 cells. The results obtained are meaningful to explore potential reagents targeting the parallel G-quadruplex structure of KRAS promoter for gene theraphy of colorectal carcinomas.

  19. [Alkaloids of Pausinystalia macroceras].

    PubMed

    Leboef, M; Cavé, A; Mangeney, P; Bouquet, A

    1981-04-01

    A study of the alkaloidal content of trunk-barks of Pausinystalia macroceras (K. Schum.) Pierre, Rubiaceae, resulted in the isolation of six alkaloids, five of which are indole alkaloids that belong to the yohimbane and heteroyohimbane groups; among them, yohimbine was found in major amount. Moreover, the levorotatory isomer of calycanthine, a quinoline dimeric tryptophane derived base, has been isolated for the first time. The phytochemical significance of calycanthine and related alkaloids is discussed.

  20. Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa

    PubMed Central

    Morita, Yuji; Nakashima, Ken-ichi; Nishino, Kunihiko; Kotani, Kenta; Tomida, Junko; Inoue, Makoto; Kawamura, Yoshiaki

    2016-01-01

    The emergence and spread of multidrug-resistant P. aeruginosa infections is of great concern, as very few agents are effective against strains of this species. Methanolic extracts from the Coptidis Rhizoma (the rhizomes of Coptis japonica var. major Satake) or Phellodendri Cortex (the bark of Phellodendron chinense Schneider) markedly reduced resistance to anti-pseudomonal aminoglycosides (e.g., amikacin) in multidrug-resistant P. aeruginosa strains. Berberine, the most abundant benzylisoquinoline alkaloid in the two extracts, reduced aminoglycoside resistance of P. aeruginosa via a mechanism that required the MexXY multidrug efflux system; berberine also reduced aminoglycoside MICs in Achromobacter xylosoxidans and Burkholderia cepacia, two species that harbor intrinsic multidrug efflux systems very similar to the MexXY. Furthermore this compound inhibited MexXY-dependent antibiotic resistance of other classes including cephalosporins (cefepime), macrolides (erythromycin), and lincosamides (lincomycin) demonstrated using a pseudomonad lacking the four other major Mex pumps. Although phenylalanine-arginine beta-naphthylamide (PAβN), a well-known efflux inhibitor, antagonized aminoglycoside in a MexXY-dependent manner, a lower concentration of berberine was sufficient to reduce amikacin resistance of P. aeruginosa in the presence of PAβN. Moreover, berberine enhanced the synergistic effects of amikacin and piperacillin (and vice versa) in multidrug-resistant P. aeruginosa strains. Thus, berberine appears to be a novel type inhibitor of the MexXY-dependent aminoglycoside efflux in P. aeruginosa. As aminoglycosides are molecules of choice to treat severe infections the clinical impact is potentially important. PMID:27547203

  1. Simultaneous quantification of three alkaloids of Coptidis Rhizoma in rat urine by high-performance liquid chromatography: application to pharmacokinetic study.

    PubMed

    Tan, Bo; Ma, Yueming; Shi, Rong; Wang, Tianming

    2007-12-01

    A high-performance liquid chromatographic method with ultraviolet detection was established and validated for quantification of three alkaloids (coptisine, palmatine and berberine) in rat urine. Following a single-step liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column with water-formic acid-triethylamine-methanol as the mobile phase at a flow rate of 1 ml/min. The linear ranges of the calibration curves were 1.6-160 ng/ml for all three alkaloids. The lower limit of quantification was 1.6 ng/ml for all three alkaloids. The within-batch accuracy was 90.4-108.3% for coptisine, 88.6-107.8% for berberine and 88.4-110.1% for palmatine. The between-batch accuracy was 99.3-100.3% for coptisine, 94.3-100.6% for berberine and 93.7-100.0% for palmatine. The within-batch and between-batch precisions were alkaloids of Coptidis Rhizoma in urine simultaneously and thus to investigate the pharmacokinetics of the alkaloids from Xiexin Decoction in rats.

  2. Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.

    PubMed

    Chang, Wenguang; Zhang, Ming; Meng, Zhaojie; Yu, Yang; Yao, Fan; Hatch, Grant M; Chen, Li

    2015-12-15

    Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy.

  3. Berberine alters epigenetic modifications, disrupts microtubule network, and modulates HPV-18 E6-E7 oncoproteins by targeting p53 in cervical cancer cell HeLa: a mechanistic study including molecular docking.

    PubMed

    Saha, Santu Kumar; Khuda-Bukhsh, Anisur Rahman

    2014-12-05

    Increased evidence of chemo-resistance, toxicity and carcinogenicity necessitates search for alternative approaches for determining next generation cancer therapeutics and targets. We therefore tested the efficacy of plant alkaloid berberine on human papilloma virus (HPV) -18 positive cervical cancer cell HeLa systematically-involving certain cellular, viral and epigenetic factors. We observed disruptions of microtubule network and changes in membrane topology due to berberine influx through confocal and atomic force microscopies (AFM). We examined nuclear uptake, internucleosomal DNA damages, mitochondrial membrane potential (MMP) alterations and cell migration assays to validate possible mode of cell death events. Analytical data on interactions of berberine with pBR322 through fourier transform infrared (FTIR) and gel migration assay strengthen berberine׳s biologically significant DNA binding abilities. We measured cellular uptake, DNA ploidy and DNA strand-breaks through fluorescence activated cell sorting (FACS). To elucidate epigenetic modifications, in support of DNA binding associated processes, if any, we conducted methylation-specific restriction enzyme (RE) assay, methylation specific-PCR (MSP) and expression studies of histone proteins. We also analyzed differential interactions and localization of cellular tumor suppressor p53 and viral oncoproteins HPV-18 E6-E7 through siRNA approach. We further made in-silico approaches to determine possible binding sites of berberine on histone proteins. Overall results indicated cellular uptake of berberine through cell membrane depolarization causing disruption of microtubule networks and its biological DNA binding abilities that probably contributed to epigenetic modifications. Results of modulation in p53 and viral oncoproteins HPV-18 E6-E7 by berberine further proved its potential as a promising chemotherapeutic agent in cervical cancer.

  4. Berberine

    MedlinePlus

    ... claw, fenugreek, garlic, guar gum, horse chestnut seed, Panax ginseng, psyllium, Siberian ginseng, and others.Herbs and ... herbs include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, and others.Herbs and supplements with sedative ...

  5. Exploiting plant alkaloids.

    PubMed

    Schläger, Sabrina; Dräger, Birgit

    2016-02-01

    Alkaloid-containing plants have been used for medicine since ancient times. Modern pharmaceuticals still rely on alkaloid extraction from plants, some of which grow slowly, are difficult to cultivate and produce low alkaloid yields. Microbial cells as alternative alkaloid production systems are emerging. Before industrial application of genetically engineered bacteria and yeasts, several steps have to be taken. Original alkaloid-forming enzymes have to be elucidated from plants. Their activity in the heterologous host cells, however, may be low. The exchange of individual plant enzymes for alternative catalysts with better performance and optimal fermentation parameters appear promising. The overall aim is enhancement and stabilization of alkaloid yields from microbes in order to replace the tedious extraction of low alkaloid concentrations from intact plants.

  6. Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp.

    PubMed Central

    da Silva, Anderson Ramos; de Andrade Neto, João Batista; da Silva, Cecília Rocha; Campos, Rosana de Sousa; Costa Silva, Rose Anny; Freitas, Daniel Domingues; do Nascimento, Francisca Bruna Stefany Aires; de Andrade, Larissa Nara Dantas; Sampaio, Letícia Serpa; Grangeiro, Thalles Barbosa; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; de Moraes, Manoel Odorico

    2016-01-01

    The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such as Berberis aquifolium, Berberis vulgaris, Berberis aristata, and Hydrastis canadensis, and of Phellodendron amurense. Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistant Candida and Cryptococcus neoformans strains, as well as against the biofilm form of Candida spp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistant Candida and Cryptococcus neoformans strains showed berberine MICs equal to 8 μg/ml and 16 μg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (P < 0.001). PMID:27021328

  7. Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp.

    PubMed

    da Silva, Anderson Ramos; de Andrade Neto, João Batista; da Silva, Cecília Rocha; Campos, Rosana de Sousa; Costa Silva, Rose Anny; Freitas, Daniel Domingues; do Nascimento, Francisca Bruna Stefany Aires; de Andrade, Larissa Nara Dantas; Sampaio, Letícia Serpa; Grangeiro, Thalles Barbosa; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; de Moraes, Manoel Odorico; Nobre Júnior, Hélio Vitoriano

    2016-06-01

    The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such as Berberis aquifolium, Berberis vulgaris, Berberis aristata, and Hydrastis canadensis, and of Phellodendron amurense Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistant Candida and Cryptococcus neoformans strains, as well as against the biofilm form of Candida spp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistant Candida and Cryptococcus neoformans strains showed berberine MICs equal to 8 μg/ml and 16 μg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (P < 0.001). Copyright © 2016 da

  8. Two-stage fractionation of polar alkaloids from Rhizoma coptidis by countercurrent chromatography considering the strategy of reactive extraction.

    PubMed

    Li, Yang; Cai, Fanfan; Zhang, Min; Zhang, Hongyang; Wang, Yuerong; Hu, Ping

    2015-01-23

    Separation of polar alkaloids by countercurrent chromatography (CCC) is challengeable due to their close partition behaviors in solvent system. In this paper, a two-stage method for isolation of epiberberine, jatrorrhizine, palmatine, coptisine, and berberine from Rhizoma coptidis was presented. The first stage separation performed on CCC was based on the principle of reactive extraction. Trifluoroacetic acid was acted as a modulator to selectively react with alkaloids, which changed their partition coefficients in solvent system. Purified epiberberine and other partially separated targets were eluted by ammonium adjusted mobile phase. In the second stage, four alkaloids were purified in pH-zone-refining CCC mode. All the targets collected were over 97% pure determined by HPLC. The method developed demonstrates performing of reactive extraction on standard CCC as an option for separation of polar alkaloids from medicinal plants.

  9. Simultaneous determination of the content of isoquinoline alkaloids in Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids by high-performance liquid chromatography with diode array detection.

    PubMed

    Chen, Yali; Li, Min; Liu, Jianjun; Yan, Qian; Zhong, Mei; Liu, Junxi; Di, Duolong; Liu, Jinxia

    2015-01-01

    A simple and efficient method was developed for the simultaneous determination of eight isoquinoline alkaloids in methanol extracts of Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids of D. leptopodum by high-performance liquid chromatography with diode array detection. The chromatographic conditions were optimized on a SinoChrom ODS-BP column to obtain a good separation of the four types of alkaloid analytes, including two aporphines (isocorydine, corydine), two protopines (protopine and allocryptopine), a morphine (sinoacutine), and three quaternary protoberberine alkaloids (berberrubine, 5-hydroxycoptisine, and berberine). The separation of these alkaloids was significantly affected by the composition of the mobile phase, and particularly by its pH value. Acetonitrile (A) and 0.2% phosphoric acid solution adjusted to pH 6.32 with triethylamine (B) were selected as the mobile phase with a gradient elution. With this method, a new quaternary protoberberine alkaloid was isolated and the two structural isomers (isocorydine and corydine) were baseline separated. The appropriate harvest period for D. leptopodum was also recommended based on our analysis. The method for the effective fraction of the alkaloids of D. leptopodum was optimized under this method with regard to the varying significant pharmacological activities of the alkaloids.

  10. Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats.

    PubMed

    Kalalian-Moghaddam, Hamid; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz

    2013-01-05

    Chronic diabetes mellitus initiates apoptosis and negatively affects synaptic plasticity in the hippocampus with ensuing impairments of learning and memory. Berberine, an isoquinoline alkaloid, exhibits anti-diabetic, antioxidant and nootropic effects. This study was conducted to evaluate the effect of berberine on hippocampal CA1 neuronal apoptosis, synaptic plasticity and learning and memory of streptozotocin (STZ)-diabetic rats. Long-term potentiation (LTP) in perforant path-dentate gyrus synapses was recorded for assessment of synaptic plasticity and field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. PS amplitude and fEPSP significantly decreased in diabetic group versus control, and chronic berberine treatment (100mg/kg/day, p.o.) restored PS amplitude and fEPSP and ameliorated learning and memory impairment and attenuated apoptosis of pyramidal neurons in the CA1 area, as determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling method. In summary, chronic berberine treatment of STZ-diabetic rats significantly ameliorates learning and memory impairment and part of its beneficial effect could be attributed to improvement of synaptic dysfunction and anti-apoptotic property.

  11. Amaryllidaceae and Sceletium alkaloids.

    PubMed

    Jin, Zhong

    2009-03-01

    Alkaloids from the plants of Amaryllidaceae family consists of an unique class of nitrogen-containing compounds showing diverse and significant biological activities, including anticancer and acetylcholinesterase (AChE) inhibitory activities. This review summarizes the research into the isolation, structure elucidation, biological activity, and chemical aspects of the Amaryllidaceae alkaloids over the last two years. In addition, structurally closely related Sceletium alkaloids are also discussed.

  12. [Berberine inhibits cardiac fibrosis of diabetic rats].

    PubMed

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  13. Enhancing effects of chitosan and chitosan hydrochloride on intestinal absorption of berberine in rats.

    PubMed

    Chen, Wei; Fan, Dongjiao; Meng, Lingkuo; Miao, Yuqiang; Yang, Shenshen; Weng, Yan; He, Haibing; Tang, Xing

    2012-01-01

    Berberine chloride (BBR) is a plant alkaloid that has been used for centuries for treatment of inflammation, dysentery, and liver diseases. It is poorly absorbed from the gastrointestinal (GI) tract and its various clinical uses are limited because of its poor bioavailability. The object of the present study was to investigate the absorption enhancing effect of chitosan on BBR. Mixtures of BBR and chitosan were prepared and the absorption enhancement was investigated in rats. The results showed a dose-dependent absorption enhancement produced by chitosan. Formulations containing 0.5%, 1.5%, and 3.0% chitosan resulted in improvement of AUC(0-36 h) values by 1.9, 2.2, 2.5 times. The absorption enhancing ability of chitosan may be due to its ability to improve the BBR paracellular pathway in the intestinal tract. Chitosan hydrochloride, a salt of chitosan, was also investigated in this study. However, the addition of 2.0% and 3.3% chitosan hydrochloride to BBR solution did not produce any increase in either C(max) or AUC(0-36 h) of BBR. Subsequent solubility studies suggested that the reduced berberine chloride solubility in chitosan hydrochloride may limit the enhancement ability. This study showed that the optimum formulation producing the highest BBR absorption is the BBR solution containing 3.0% chitosan.

  14. Integrative analysis of differential miRNA and functional study of miR-21 by seed-targeting inhibition in multiple myeloma cells in response to berberine

    PubMed Central

    2014-01-01

    Background Berberine is a natural alkaloid derived from a traditional Chinese herbal medicine. It is known to modulate microRNA (miRNA) levels, although the mechanism for this action is unknown. Here, we previously demonstrate that the expression of 87 miRNAs is differentially affected by berberine in multiple myeloma cells. Among 49 miRNAs that are down-regulated, nine act as oncomirs, including miR-21. Integrative analysis showed that 28 of the down-regulated miRNAs participate in tumor protein p53 (TP53) signaling and other cancer pathways. miR-21 is involved in all these pathways, and is one of the most important oncomirs to be affected by berberine in multiple myeloma cells. Results We confirmed that berberine down-regulated miRNA-21 expression and significantly up-regulated the expression of programmed cell death 4 (PDCD4), a predicted miR-21 target. Luciferase reporter assays confirmed that PDCD4 was directly regulated by miR-21. Bioinformatic analysis revealed that the miR-21 promoter can be targeted by signal transducer and activator of transcription 3 (STAT3). Down-regulation of interleukin 6 (IL6) by berberine might lead to inhibition of miR-21 transcription through STAT3 down-regulation in multiple myeloma. Furthermore, both berberine and seed-targeting anti-miR-21 oligonucleotide induced apoptosis, G2-phase cell cycle arrest and colony inhibition in multiple myeloma cell lines. Depletion of PDCD4 by short interfering RNA could rescue berberine-induced cytotoxicity in multiple myeloma cells. Conclusions Our results suggest that berberine suppresses multiple myeloma cell growth, at least in part, by down-regulating miR-21 levels possibly through IL6/STAT3. This led to increased PDCD4 expression, which is likely to result in suppression of the p53 signaling pathway. These findings may also provide new mechanistic insight into the anti-cancer effects of certain compounds in traditional Chinese herbal medicines. PMID:25000828

  15. Effects of berberine and red yeast on proinflammatory cytokines IL-6 and TNF-α in peripheral blood mononuclear cells (PBMCs) of human subjects

    PubMed Central

    Spatuzza, Carmen; Postiglione, Loredana; Covelli, Bianca; Ricciardone, Margherita; Benvenuti, Claudio; Mondola, Paolo; Belfiore, Anna

    2014-01-01

    Background and Aims: Obesity is a condition associated with chronic or acute inflammatory response characterized by an increase of proinflammatory cytokine levels. Peripheral blood mononuclear cells (PBMCs) migrate in adipose tissue inducing synthesis and secretion of adipocytokines as IL-6 and TNF-α. The aim of this study was to investigate the effect of berberine (a natural alkaloid) and red yeast (a natural antioxidant) on IL-6 and TNF-α cytokines release and gene expression, in circulating lipopolisaccarides (LPS) stimulated PBMCs. Methods and Results: PBMCs isolated from whole blood of healthy donors were stimulated with LPS to induce cytokines production; simultaneously cells were treated with increasing doses of berberine and red yeast. The substances were administered alone or in association. IL-6 and TNF-α protein levels in the culture medium and their mRNA levels were assessed by ELISA and real time PCR, respectively. Berberine and red yeast treatment prevented the LPS induction of IL-6 release in the culture medium of PBMCs. In addition, berberine plus red yeast treatment showed a synergic inhibitory effect on IL-6 release at low concentration. Berberine and red yeast showed an inhibitory effect also on LPS induction of TNF-α release exerting a synergic effect mainly at high concentrations. On the contrary, berberine and red yeast did not significantly affect IL-6 and TNF-α mRNA levels induced by LPS. In this case, only concomitant treatment of PBMCs with high doses of berberine and red yeast inhibits LPS induced IL-6 or TNF-α mRNA levels. Conclusions: The results of our study show that both berberine and red yeast were able to carry out anti-inflammatory action through an inhibition of proinflammatory IL-6 and TNF-α protein release. Moreover, when given in combination these substances were able to inhibit IL-6 and TNF-α gene expression in PBMCs activated by LPS. Therefore, these substances could represent a useful pharmacological treatment to

  16. In vitro biological assessment of berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects

    PubMed Central

    2013-01-01

    Background Berberis vulgaris is a well known plant with traditional herbal medical history. The aims of this study was to bioscreen and compare the in vitro biological activity (antioxidant, cholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine active compound. Methods The effect of B. vulgaris extract and berberine chloride on cellular thiobarbituric acid reactive species (TBARS) formation, diphenyle–α-picrylhydrazyl (DPPH) oxidation, cellular nitric oxide (NO) radical scavenging capability, superoxide dismutase (SOD), glutathione peroxidase (GPx), acetylcholinesterase (AChE) and α-gulcosidase activities were spectrophotometrically determined. On the other hand, the effect of extract and berberine as anticancer was estimated on three different cell lines which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay which compared with control normal cells (PBMC). Results Our results showed that barberry crude extract contains 0.6 mg berberine/mg crude extract. Barberry extract showed potent antioxidative capacity through decreasing TBARS, NO and the oxidation of DPPH that associated with GPx and SOD hyperactivation. Inhibitory effect of berberis crude extract on α-glucosidase was more potent than that of berberine chloride, while both had the same AChE inhibitory effect. Besides, different concentrations of both berberine chloride and barberry ethanolic extract showed to have no growth inhibitory effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon cancer cell lines (MCF7, HepG2 and CACO-2, respectively) at different incubation times starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose dependant manner. Conclusion This work demonstrates the potential of the barberry crude extract and its active alkaloid, berberine, on suppressing lipid peroxidation

  17. FoxO proteins' nuclear retention and BH3-only protein Bim induction evoke mitochondrial dysfunction-mediated apoptosis in berberine-treated HepG2 cells.

    PubMed

    Shukla, Shatrunajay; Rizvi, Fatima; Raisuddin, Sheikh; Kakkar, Poonam

    2014-11-01

    Mammalian forkhead-box family members belonging to the 'O' category (FoxO) manipulate a plethora of genes modulating a wide array of cellular functions including cell cycle regulation, apoptosis, DNA damage repair, and energy metabolism. FoxO overexpression and nuclear accumulation have been reported to show correlation with hindered tumor growth in vitro and size in vivo, while FoxO's downregulation via phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway has been linked with tumor promotion. In this study, we have explored for the first time intervention of berberine, a plant-derived isoquinoline alkaloid, with FoxO family proteins in hepatoma cells. We observed that berberine significantly upregulated the mRNA expression of both FoxO1 and FoxO3a. Their phosphorylation-mediated cytoplasmic sequestration followed by degradation was prevented by berberine-induced downmodulation of the PI3K/Akt/mTOR pathway which promoted FoxO nuclear retention. PTEN, a tumor suppressor gene and negative regulator of the PI3K/Akt axis, was upregulated while phosphorylation of its Ser380 residue (possible mechanism of PTEN degradation) was significantly decreased in treated HepG2 cells. Exposure to berberine induced a significant increase in transcriptional activity of FoxO, as shown by GFP reporter assay. FoxO transcription factors effectively heightened BH3-only protein Bim expression, which in turn, being a direct activator of proapoptotic protein Bax, altered Bax/Bcl-2 ratio, culminating into mitochondrial dysfunction, caspases activation, and DNA fragmentation. The pivotal role of Bim in berberine-mediated cytotoxicity was further corroborated by knockdown experiments where Bim-silencing partially restored HepG2 cell viability during berberine exposure. In addition, a correlation between oxidative overload and FoxO's nuclear accumulation via JNK activation was evident as berberine treatment led to a pronounced increase in JNK phosphorylation together with enhanced

  18. Poor permeability and absorption affect the activity of four alkaloids from Coptis.

    PubMed

    Cui, Han-Ming; Zhang, Qiu-Yan; Wang, Jia-Long; Chen, Jian-Long; Zhang, Yu-Ling; Tong, Xiao-Lin

    2015-11-01

    Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra‑performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil‑water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P‑glycoprotein (P‑gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l‑1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0‑1.2x10‑6 cm·s‑1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical‑to‑basolateral (AP‑BL) surface and the basolateral‑to‑apical (BL‑AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BL‑AP surface was significantly faster (P<0.01), compared with that on the AP‑BL surface and, following the addition of verpamil (a P‑gp inhibitor), the Papp (AP‑BL) of the four alkaloids increased, whereas the Papp (BL‑AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER

  19. Two Faces of Alkaloids

    NASA Astrophysics Data System (ADS)

    Dostál, Jirí

    2000-08-01

    Alkaloids can occur in two forms, denoted as ammonium salts and free bases. These forms differ substantially in their properties and in some cases in their structures. The article discusses and compares the salts and free bases of six well-known alkaloids: nicotine, morphine, cocaine, sanguinarine, allocryptopine, and magnoflorine. Relevance for the biological and medical uses of these compounds is emphasized.

  20. Amaryllidaceae and Sceletium alkaloids.

    PubMed

    Jin, Zhong

    2016-10-26

    Covering: July 2012 to June 2015. Previous review: Nat. Prod. Rep., 2013, 30, 849-868The latest progress on the isolation, identification, biological activity and synthetic studies of the structurally diverse alkaloids from plants of family Amaryllidaceae has been summarized in this review. In addition, the structurally related alkaloids isolated from Sceletium species were discussed as well.

  1. Alkaloids from Menispermum dauricum.

    PubMed

    Yu, Bing-Wu; Chen, Jian-Yong; Wang, Yan-Ping; Cheng, Kin-Fin; Li, Xiao-Yu; Qin, Guo-Wei

    2002-10-01

    The alkaloids, dechloroacutumidine and 1-epidechloroacutumine, together with three known alkaloids, acutumidine, acutumine, and dechloroacutumine, were isolated from the rhizomes of Menispermum dauricum and their structures established by spectral and chemical methods. The cytotoxicity of each compound against the growth of human cell lines was studied, and acutumine selectively inhibited T-cell growth.

  2. Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system

    PubMed Central

    Zou, Kun; Li, Zhao; Zhang, Yong; Zhang, Hao-yue; Li, Bo; Zhu, Wei-liang; Shi, Ji-ye; Jia, Qi; Li, Yi-ming

    2017-01-01

    It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation. In this review, we summarize the advances in studing berberine and its derivatives as anti-inflammatory and anti-tumor agents in the digestive system; we also discuss their structure-activity relationship. These data should be useful for the development of this natural product as novel anticancer drugs with anti-inflammation activity. PMID:27917872

  3. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes.

    PubMed

    Bhutada, Pravinkumar; Mundhada, Yogita; Bansod, Kuldeep; Tawari, Santosh; Patil, Shaktipal; Dixit, Pankaj; Umathe, Sudhir; Mundhada, Dharmendra

    2011-06-20

    Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats.

  4. Metabolites of protoberberine alkaloids in human urine following oral administration of Coptidis Rhizoma decoction.

    PubMed

    Yang, Yihui; Kang, Ning; Xia, Hongjun; Li, Jun; Chen, Lixia; Qiu, Feng

    2010-11-01

    Coptidis Rhizoma has been used as a traditional Chinese herbal medicine to treat typhoid, pharyngolaryngitis, diabetes mellitus, gastroenteritis and secretory diarrhea for more than a thousand years in China. However, there is little information on the IN VIVO chemical constituents of Coptidis Rhizoma following oral administration. In this paper, the alkaloid constituents in urine were studied in humans following oral administration of Coptidis Rhizoma decoction. Using macroporous adsorption resin chromatography, open ODS column chromatography, and preparative high-performance liquid chromatography, twelve protoberberine alkaloid constituents were isolated. Their structures were elucidated by chemical evidence, enzymatic deconjugation and analyses of mass, (1)H-NMR and NOESY spectra. The identified alkaloid constituents include berberine ( P1), groenlandicine 3-O- β-D-glucuronide (M1), dehydrocheilanthifoline 2-O-β-D-glucuronide (M2), thalifendine 10-O-β-D-glucuronide (M3), jatrorrhizine 3-O-β-D-glucuronide (M4), columbamine 2-O-β-D-glucuronide (M5), berberrubine 9-O-β-D-glucuronide (M6), jatrorrhizine 3-O-sulfate (M7), demethyleneberberine 2-O-sulfate (M8), dehydrocorydalmine 10-O-sulfate (M9), 3,10-demethylpalmatine 10-O-sulfate (M10) and 2,3,10-trihydroxyberberine 2-O-sulfate ( M11). No other parent protoberberine alkaloids from Coptidis Rhizoma except for a trace of berberine were found in the urine. These findings suggested that the protoberberine alkaloids, which were absorbed in vivo following oral administration of Coptidis Rhizoma decoction, were mainly conjugated with glucuronic acid or sulfuric acid to form phase II metabolites directly or after biotransformation to phase I metabolites, and finally excreted in urine.

  5. Berberine Suppresses Adipocyte Differentiation via Decreasing CREB Transcriptional Activity.

    PubMed

    Zhang, Juan; Tang, Hongju; Deng, Ruyuan; Wang, Ning; Zhang, Yuqing; Wang, Yao; Liu, Yun; Li, Fengying; Wang, Xiao; Zhou, Libin

    2015-01-01

    Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been demonstrated to lower blood glucose, blood lipid, and body weight in patients with type 2 diabetes mellitus. The anti-obesity effect of berberine has been attributed to its anti-adipogenic activity. However, the underlying molecular mechanism remains largely unknown. In the present study, we found that berberine significantly suppressed the expressions of CCAAT/enhancer-binding protein (C/EBP)α, peroxisome proliferators-activated receptor γ2 (PPARγ2), and other adipogenic genes in the process of adipogenesis. Berberine decreased cAMP-response element-binding protein (CREB) phosphorylation and C/EBPβ expression at the early stage of 3T3-L1 preadipocyte differentiation. In addition, CREB phosphorylation and C/EBPβ expression induced by 3-isobutyl-1-methylxanthine (IBMX) and forskolin were also attenuated by berberine. The binding activities of cAMP responsive element (CRE) stimulated by IBMX and forskolin were inhibited by berberine. The binding of phosphorylated CREB to the promoter of C/EBPβ was abrogated by berberine after the induction of preadipocyte differentiation. These results suggest that berberine blocks adipogenesis mainly via suppressing CREB activity, which leads to a decrease in C/EBPβ-triggered transcriptional cascades.

  6. Berberine chloride improved synaptic plasticity in STZ induced diabetic rats.

    PubMed

    Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz

    2013-09-01

    Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P < 0.01) and this effect prevented by chronic berberine treatment (50,100 mg/kg). However, there were no differences between responses of the control berberine 100 mg/kg treated and diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect.

  7. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent.

  8. Berberine Suppresses Adipocyte Differentiation via Decreasing CREB Transcriptional Activity

    PubMed Central

    Deng, Ruyuan; Wang, Ning; Zhang, Yuqing; Wang, Yao; Liu, Yun; Li, Fengying; Wang, Xiao; Zhou, Libin

    2015-01-01

    Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been demonstrated to lower blood glucose, blood lipid, and body weight in patients with type 2 diabetes mellitus. The anti-obesity effect of berberine has been attributed to its anti-adipogenic activity. However, the underlying molecular mechanism remains largely unknown. In the present study, we found that berberine significantly suppressed the expressions of CCAAT/enhancer-binding protein (C/EBP)α, peroxisome proliferators-activated receptor γ2 (PPARγ2), and other adipogenic genes in the process of adipogenesis. Berberine decreased cAMP-response element-binding protein (CREB) phosphorylation and C/EBPβ expression at the early stage of 3T3-L1 preadipocyte differentiation. In addition, CREB phosphorylation and C/EBPβ expression induced by 3-isobutyl-1-methylxanthine (IBMX) and forskolin were also attenuated by berberine. The binding activities of cAMP responsive element (CRE) stimulated by IBMX and forskolin were inhibited by berberine. The binding of phosphorylated CREB to the promoter of C/EBPβ was abrogated by berberine after the induction of preadipocyte differentiation. These results suggest that berberine blocks adipogenesis mainly via suppressing CREB activity, which leads to a decrease in C/EBPβ-triggered transcriptional cascades. PMID:25928058

  9. Alkaloids from Narcissus serotinus.

    PubMed

    Pigni, Natalia B; Ríos-Ruiz, Segundo; Martínez-Francés, Vanessa; Nair, Jerald J; Viladomat, Francesc; Codina, Carles; Bastida, Jaume

    2012-09-28

    Narcissus serotinus belongs to the Amaryllidaceae family, a group well known for an exclusive variety of alkaloids with interesting biological activities. This study was aimed at identifying the alkaloid constituents of N. serotinus collected in the Spanish region of Valencia, using a combination of chromatographic, spectroscopic, and spectrometric methods, including GC-MS and 2D NMR techniques. GC-MS analysis allowed for the direct identification of five known compounds. In addition, the isolation and structure elucidation of six new Amaryllidaceae alkaloids are described.

  10. Alkaloids of Ocotea brachybotra.

    PubMed

    Vecchietti, V; Casagrande, C; Ferrari, G

    1977-11-01

    Aporphine, proaporphine and morphinane alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea brachybotra (Meiss.) Mez. The known alkaloids were identified through their physico-chemical properties as: (I) (+/-)-glaziovine, (II) dicentrine, (III) ocopodine, (IV) cassynthicine, (V) predicentrine, (VI) leucoxine, (IX) sinacutine and (X) pallidine. The structure of (VI) leucoxine was confirmed by a detailed analysis of the N.M.R. spectra recorded in various conditions. New morphinane alkaloids, (XI) ocobotrine and (XII) 14-espisinomenine, having the unusual B/C-trans configuration were also isolated. Their structures were determined using spectroscopic methods and chemical correlations.

  11. Quantitative analysis of berberine in urine samples by chemical ionization mass fragmentography.

    PubMed

    Miyazaki, H; Shirai, E; Ishibashi, M; Niizima, K

    1978-05-11

    A highly specific and sensitive method has been developed for the quantitative determination of berberine in human urine. In order to carry out the microdetermination of berberine by chemical ionization mass fragmentography, berberine was reduced with sodium borohydride in methanol to tetrahydroberberine and subjected to gas chromatography-mass spectrometry. Berberine concentrations as low as 1 ng/ml urine can be measured by this method, with [2H3]berberine chloride as an internal standard.

  12. Berberine acutely activates the glucose transport activity of GLUT1.

    PubMed

    Cok, Alexandra; Plaisier, Christina; Salie, Matthew J; Oram, Daniel S; Chenge, Jude; Louters, Larry L

    2011-07-01

    Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the acute affects of berberine on the transport activity of the insulin-insensitive glucose transporter, GLUT1. Therefore, we examined the acute effects of berberine on glucose uptake in L929 fibroblast cells, a cell line that express only GLUT1. Berberine- activated glucose uptake reaching maximum stimulation of five-fold at >40 μM. Significant activation (P < 0.05) was measured within 5 min reaching a maximum by 30 min. The berberine effect was not additive to the maximal stimulation by other known stimulants, azide, methylene blue or glucose deprivation, suggesting shared steps between berberine and these stimulants. Berberine significantly reduced the K(m) of glucose uptake from 6.7 ± 1.9 mM to 0.55 ± 0.08 mM, but had no effect on the V(max) of uptake. Compound C, an inhibitor of AMP kinase, did not affect berberine-stimulated glucose uptake, but inhibitors of downstream kinases partially blocked berberine stimulation. SB203580 (inhibitor of p38 MAP kinase) did not affect submaximal berberine activation, but did lower maximal berberine stimulation by 26%, while PD98059 (inhibitor of ERK kinase) completely blocked submaximal berberine activation and decreased the maximal stimulation by 55%. It appears from this study that a portion of the hypoglycemic effects of berberine can be attributed to its acute activation of the transport activity of GLUT1.

  13. The antibacterial mechanism of berberine against Actinobacillus pleuropneumoniae.

    PubMed

    Kang, Shuai; Li, Zhengwen; Yin, Zhongqiong; Jia, Renyong; Song, Xu; Li, Li; Chen, Zhenzhen; Peng, Lianci; Qu, Jing; Hu, Zhiqiang; Lai, Xin; Wang, Guangxi; Liang, Xiaoxia; He, Changliang; Yin, Lizi

    2015-01-01

    This study demonstrated berberine to be a potential natural compound against Actinobacillus pleuropneumoniae. Liquid doubling dilution, transmission electron microscopy (TEM), SDS-PAGE and 4',6-diamidino-2-phenylindole (DAPI) staining were employed to elucidate the antibacterial activity and mechanism of berberine. The minimal inhibitory concentration of berberine was 0.3125 mg/mL, and time-kill curves showed concentration and time dependence. The TEM micrographs displayed damaged cell wall, concentrated cytoplasm, cytoplasmic content leakage and cell death. SDS-PAGE and DAPI assays revealed that berberine can restrain DNA and protein syntheses. Berberine inhibited the synthesis of proteins associated with the growth and cleavage of bacteria and then blocked the division and development of bacteria. The compound ultimately induced cytoplasm pyknosis and bacterial death.

  14. Protein ligand interactions. Part 5: Isoquinoline alkaloids as inhibitors of acetylcholinesterase from Electrophorus electricus.

    PubMed

    Whiteley, C G; Daya, S

    1995-01-01

    Kinetic analysis has shown that papaverine, berberine and isoquinoline alkaloids acts as reversible competitive inhibitors of acetylcholinesterase with respect to the substrate, acetylthiocholine chloride. The inhibitor constants (Ki) vary from 3.5 microM to 88 microM. With time they act as irreversible covalent inhibitors with papaverine producing 85% inactivation after 40 min. Pseudo first-order kinetics are observed with the rate constant being proportional to the concentration of the ligand and the order of reaction being equal to one. Spectrophotometry was used to study the binding of the ligands with acetylcholinesterase and Scatchard analysis used to calculate the respective dissociation constants and the number of binding sites.

  15. Occurrence of halogenated alkaloids.

    PubMed

    Gribble, Gordon W

    2012-01-01

    Once considered to be isolation artifacts or chemical "mistakes" of nature, the number of naturally occurring organohalogen compounds has grown from a dozen in 1954 to >5000 today. Of these, at least 25% are halogenated alkaloids. This is not surprising since nitrogen-containing pyrroles, indoles, carbolines, tryptamines, tyrosines, and tyramines are excellent platforms for biohalogenation, particularly in the marine environment where both chloride and bromide are plentiful for biooxidation and subsequent incorporation into these electron-rich substrates. This review presents the occurrence of all halogenated alkaloids, with the exception of marine bromotyrosines where coverage begins where it left off in volume 61 of The Alkaloids. Whereas the biological activity of these extraordinary compounds is briefly cited for some examples, a future volume of The Alkaloids will present full coverage of this topic and will also include selected syntheses of halogenated alkaloids. Natural organohalogens of all types, especially marine and terrestrial halogenated alkaloids, comprise a rapidly expanding class of natural products, in many cases expressing powerful biological activity. This enormous proliferation has several origins: (1) a revitalization of natural product research in a search for new drugs, (2) improved compound characterization methods (multidimensional NMR, high-resolution mass spectrometry), (3) specific enzyme-based and other biological assays, (4) sophisticated collection methods (SCUBA and remote submersibles for deep ocean marine collections), (5) new separation and purification techniques (HPLC and countercurrent separation), (6) a greater appreciation of traditional folk medicine and ethobotany, and (7) marine bacteria and fungi as novel sources of natural products. Halogenated alkaloids are truly omnipresent in the environment. Indeed, one compound, Q1 (234), is ubiquitous in the marine food web and is found in the Inuit from their diet of whale

  16. Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach.

    PubMed

    Orvos, Péter; Virág, László; Tálosi, László; Hajdú, Zsuzsanna; Csupor, Dezső; Jedlinszki, Nikoletta; Szél, Tamás; Varró, András; Hohmann, Judit

    2015-01-01

    Chelidonium majus or greater celandine is spread throughout the world, and it is a very common and frequent component of modern phytotherapy. Although C. majus contains alkaloids with remarkable physiological effect, moreover, safety pharmacology properties of this plant are not widely clarified, medications prepared from this plant are often used internally. In our study the inhibitory effects of C. majus herb extracts and alkaloids on hERG potassium current as well as on cardiac action potential were investigated. Our data show that hydroalcoholic extracts of greater celandine and its alkaloids, especially berberine, chelidonine and sanguinarine have a significant hERG potassium channel blocking effect. These extracts and alkaloids also prolong the cardiac action potential in dog ventricular muscle. Therefore these compounds may consequently delay cardiac repolarization, which may result in the prolongation of the QT interval and increase the risk of potentially fatal ventricular arrhythmias. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Marine Indole Alkaloids

    PubMed Central

    Netz, Natalie; Opatz, Till

    2015-01-01

    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

  18. Alkaloids from Esenbeckia pilocarpoides.

    PubMed

    Bevalot, F; Fournet, A; Moretti, C; Vaquette, J

    1984-12-01

    A preliminary screening showed the occurrence of alkaloids only in root bark and roots of ESENBECKIA PILOCARPOIDES H. B. K., (Rutaceae). Six alkaloids have been isolated and identified from root bark: one acridone, 1-hydroxy-3-methoxy- N-methyl-acridone; four furoquinolines, maculine, flindersiamine, kokusaginine, kokusagine; the sixth, isomaculine, a furo-4-quinolone, known as a synthetic product, has been isolated for the first time from a natural source.

  19. Enhancement of alkaloid production in opium and California poppy by transactivation using heterologous regulatory factors.

    PubMed

    Apuya, Nestor R; Park, Joon-Hyun; Zhang, Liping; Ahyow, Maurice; Davidow, Patricia; Van Fleet, Jennifer; Rarang, Joel C; Hippley, Matthew; Johnson, Thomas W; Yoo, Hye-Dong; Trieu, Anthony; Krueger, Shannon; Wu, Chuan-yin; Lu, Yu-ping; Flavell, Richard B; Bobzin, Steven C

    2008-02-01

    Genes encoding regulatory factors isolated from Arabidopsis, soybean and corn have been screened to identify those that modulate the expression of genes encoding for enzymes involved in the biosynthesis of morphinan alkaloids in opium poppy (Papaver somniferum) and benzophenanthridine alkaloids in California poppy (Eschscholzia californica). In opium poppy, the over-expression of selected regulatory factors increased the levels of PsCOR (codeinone reductase), Ps4'OMT (S-adenosyl-l-methionine:3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase) and Ps6OMT [(R,S)-norcoclaurine 6-O-methyltransferase] transcripts by 10- to more than 100-fold. These transcriptional activations translated into an enhancement of alkaloid production in opium poppy of up to at least 10-fold. In California poppy, the transactivation effect of regulatory factor WRKY1 resulted in an increase of up to 60-fold in the level of EcCYP80B1 [(S)-N-methylcoclaurine 3'-hydroxylase] and EcBBE (berberine bridge enzyme) transcripts. As a result, the accumulations of selected alkaloid intermediates were enhanced up to 30-fold. The transactivation effects of other regulatory factors led to the accumulation of the same intermediates. These regulatory factors also led to the production of new alkaloids in California poppy callus culture.

  20. Hydroxyl radical scavenging activities of isoquinoline alkaloids isolated from Coptis chinensis.

    PubMed

    Jang, Moon Hee; Kim, Hyun Young; Kang, Ki Sung; Yokozawa, Takako; Park, Jeong Hill

    2009-03-01

    The hydroxyl radical (*OH) scavenging and ferrous ion chelating activities of four isoquinoline alkaloids isolated from Coptis chinensis Franch were studied for the identification of their structural characteristics to scavenge *OH. The *OH was generated via Fe(II)-catalazed Fenton reaction in this study and the reliable measurement of *OH scavenging activities of isoquinoline alkaloids were achieved using electron spin resonance (ESR) spectrometry method. At the 1 mM concentration, berberrubine (85%) showed the strongest *OH scavenging activity and the next were in the decreasing order of coptisine (79%), berberine (23%), and palmatine (22%). The ferrous ion chelating effects of the alkaloids showed similar pattern with their *OH scavenging effects. These results suggest that *OH scavenging effects of the alkaloids were closely related to their ferrous ion chelating activities. In addition, metal chelating functional groups such as hydroxy group at C-9 and methylenedioxy group at C-9 and C-10 were thought to contribute to the *OH scavenging activities of the isoquinoline alkaloids.

  1. Sarpagine and related alkaloids

    PubMed Central

    Namjoshi, Ojas A.; Cook, James M.

    2016-01-01

    The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the Apocynaceae family. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids as well as the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles has been presented, which involves application of the asymmetric Pictet–Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since the year 2000. PMID:26827883

  2. Separation and detection of isoquinoline alkaloids using MEEKC coupled with field-amplified sample injection induced by ACN.

    PubMed

    Yu, Li-Shuang; Xu, Xue-Qin; Huang, Lu; Lin, Jin-Ming; Chen, Guo-Nan

    2009-02-01

    New methods based on MEEKC coupling with field-amplified sample injection (FASI) induced by ACN were proposed for five isoquinoline alkaloids (berberine, palmatine, jatrorrhizine, sinomenine and homoharringtonine) in no salt and high salt sample solution (HS). For the separation of five isoquinoline alkaloids, a running buffer composed of 18 mM sodium cholate, 2.4% v/v butan-1-ol, 0.6% v/v ethyl acetate, 10% v/v (or 30% v/v) methanol and 87.0% v/v (or 67% v/v) 5 mM Na2B4O7~10 mM NaH2PO4 buffer (pH 7.5) was developed. In order to improve the sensitivity, FASI induced by ACN was applied to increase the detection sensitivity. The detection limit was found to be as low as 0.0002 microg/mL in no salt sample solution and 0.062 microg/mL in HS. The method has been applied for the analysis of human urine spiked with analytes, and the assay results were proved to be satisfactory, and also the determination of berberine in urine sample after oral administration berberine.

  3. Beneficial Effects of Berberine on Oxidized LDL-Induced Cytotoxicity to Human Retinal Müller Cells

    PubMed Central

    Fu, Dongxu; Yu, Jeremy Y.; Connell, Anna R.; Yang, Shihe; Hookham, Michelle B.; McLeese, Rebecca; Lyons, Timothy J.

    2016-01-01

    Purpose Limited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal Müller cells. We now explore pathogenic effects of modified LDL on Müller cells, and the efficacy of berberine in mitigating this cytotoxicity. Methods Confluent human Müller cells were exposed to in vitro–modified ‘highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/without pretreatment with berberine (5 μM, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C (5 μM, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-α), and glial cell activation (glial fibrillary acidic protein). Results Native-LDL had no effect on cultured human Müller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P < 0.05), and its effects were mitigated by AMPK inhibition (P < 0.05). Conclusions Berberine inhibits modified LDL-induced Müller cell injury by activating

  4. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae

    PubMed Central

    Peng, Lianci; Kang, Shuai; Yin, Zhongqiong; Jia, Renyong; Song, Xu; Li, Li; Li, Zhengwen; Zou, Yuanfeng; Liang, Xiaoxia; Li, Lixia; He, Changliang; Ye, Gang; Yin, Lizi; Shi, Fei; Lv, Cheng; Jing, Bo

    2015-01-01

    The antibacterial activity and mechanism of berberine against Streptococcus agalactiae were investigated in this study by analyzing the growth, morphology and protein of the S. agalactiae cells treated with berberine. The antibacterial susceptibility test result indicated minimum inhibition concentration (MIC) of berberine against Streptococcus agalactiae was 78 μg/mL and the time-kill curves showed the correlation of concentration-time. After the bacteria was exposed to 78 μg/mL berberine, the fragmentary cell membrane and cells unequal division were observed by the transmission electron microscopy (TEM), indicating the bacterial cells were severely damaged. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) study demonstrated that berberine could damage bacterial cells through destroying cellular proteins. Meanwhile, Fluorescence microscope revealed that berberine could affect the synthesis of DNA. In conclusion, these results strongly suggested that berberine may damage the structure of bacterial cell membrane and inhibit synthesis of protein and DNA, which cause Streptococcus agalactiae bacteria to die eventually. PMID:26191220

  5. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma.

    PubMed

    Ko, Byoung-Seob; Choi, Soo Bong; Park, Seong Kyu; Jang, Jin Sun; Kim, Yeong Eun; Park, Sunmin

    2005-08-01

    Our preliminary study demonstrated that 70% ethanol Cortidis Rhizoma extracts (CR) had a hypoglycemic action in diabetic animal models. We determined whether CR fractions acted as anti-diabetic agent, and a subsequent investigation of the action mechanism of the major compound, berberine ([C(20)H(18)NO(4)](+)), was carried out in vitro. The 20, 40 and 60% methanol fractions from the XAD-4 column contained the most insulin sensitizing activities in 3T3-L1 adipocytes. The common major peak in these fractions was berberine. Treatment with 50 microM berberine plus differentiation inducers significantly reduced triglyceride accumulation by decreased differentiation of 3T3-L1 fibroblasts to adipocytes and triglyceride synthesis. Significant insulin sensitizing activity was observed in 3T3-L1 adipocytes which were given 50 microM berberine plus 0.2 nM insulin to reach a glucose uptake level increased by 10 nM of insulin alone. This was associated with increased glucose transporter-4 translocation into the plasma membrane via enhancing insulin signaling pathways and the insulin receptor substrate-1-phosphoinositide 3 Kinase-Akt. Berberine also increased glucose-stimulated insulin secretion and proliferation in Min6 cells via an enhanced insulin/insulin-like growth factor-1 signaling cascade. Data suggested that berberine can act as an effective insulin sensitizing and insulinotropic agent. Therefore, berberine can be used as anti-diabetic agent for obese diabetic patients.

  6. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae.

    PubMed

    Peng, Lianci; Kang, Shuai; Yin, Zhongqiong; Jia, Renyong; Song, Xu; Li, Li; Li, Zhengwen; Zou, Yuanfeng; Liang, Xiaoxia; Li, Lixia; He, Changliang; Ye, Gang; Yin, Lizi; Shi, Fei; Lv, Cheng; Jing, Bo

    2015-01-01

    The antibacterial activity and mechanism of berberine against Streptococcus agalactiae were investigated in this study by analyzing the growth, morphology and protein of the S. agalactiae cells treated with berberine. The antibacterial susceptibility test result indicated minimum inhibition concentration (MIC) of berberine against Streptococcus agalactiae was 78 μg/mL and the time-kill curves showed the correlation of concentration-time. After the bacteria was exposed to 78 μg/mL berberine, the fragmentary cell membrane and cells unequal division were observed by the transmission electron microscopy (TEM), indicating the bacterial cells were severely damaged. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) study demonstrated that berberine could damage bacterial cells through destroying cellular proteins. Meanwhile, Fluorescence microscope revealed that berberine could affect the synthesis of DNA. In conclusion, these results strongly suggested that berberine may damage the structure of bacterial cell membrane and inhibit synthesis of protein and DNA, which cause Streptococcus agalactiae bacteria to die eventually.

  7. Berberine hydrochloride: anticancer activity and nanoparticulate delivery system.

    PubMed

    Tan, Wen; Li, Yingbo; Chen, Meiwan; Wang, Yitao

    2011-01-01

    Berberine hydrochloride is a conventional component in Chinese medicine, and is characterized by a diversity of pharmacological effects. However, due to its hydrophobic properties, along with poor stability and bioavailability, the application of berberine hydrochloride was hampered for a long time. In recent years, the pharmaceutical preparation of berberine hydrochloride has improved to achieve good prospects for clinical application, especially for novel nanoparticulate delivery systems. Moreover, anticancer activity and novel mechanisms have been explored, the chance of regulating glucose and lipid metabolism in cancer cells showing more potential than ever. Therefore, it is expected that appropriate pharmaceutical procedures could be applied to the enormous potential for anticancer efficacy, to give some new insights into anticancer drug preparation in Chinese medicine. We accessed conventional databases, such as PubMed, Scope, and Web of Science, using "berberine hydrochloride", "anti-cancer mechanism", and "nanoparticulate delivery system" as search words, then summarized the progress in research, illustrating the need to explore reprogramming of cancer cell metabolism using nanoparticulate drug delivery systems. With increasing research on regulation of cancer cell metabolism by berberine hydrochloride and troubleshooting of issues concerning nanoparticulate delivery preparation, berberine hydrochloride is likely to become a natural component of the nanoparticulate delivery systems used for cancer therapy. Meanwhile, the known mechanisms of berberine hydrochloride, such as decreased multidrug resistance and enhanced sensitivity of chemotherapeutic drugs, along with improvement in patient quality of life, could also provide new insights into cancer cell metabolism and nanoparticulate delivery preparation.

  8. [ILs-HPLC simultanesous determination of five alkaloids in phellodenddri chinensis cortex].

    PubMed

    Jiang, Xin-Yi; Zhang, Hui-Fen; Wang, Sheng-Nan; Chen, Xiao-Hui

    2014-10-01

    A RP-HPLC method was established for simultaneous determination of phellodendrine hydrochloride (PH1), magnoflorine hydrochloride (MH), jatrorrhizine hydrochloride (JH), palmatine hydrochloride (PH2) and berberine hydrochloride (BH) in Phellodendri Chinensis Cortex by using ionic liquids as mobile phase additives. The separation was performed on a Kromasil C18 (4.6 mm x 250 mm, 5 μm) coupled with ultraviolet (UV) detection. The effect of extraction solvent, detection wavelength, length of alkyl chain on different imidazolium ionic liquids and concentration of ionic liquids on the separation and determination of alkaloids were investigated. Ionic liquid, [BMIm] BF4, can obviously improve the resolution and peak shape. This ILs-HPLC method is simple, rapid, and reliable, which can be used for determination of alkaloids in Phellodenddri Chinensis Cortex.

  9. Pharmacokinetics Studies of 12 Alkaloids in Rat Plasma after Oral Administration of Zuojin and Fan-Zuojin Formulas.

    PubMed

    Qian, Ping; Zhang, You-Bo; Yang, Yan-Fang; Xu, Wei; Yang, Xiu-Wei

    2017-01-30

    Zuojin formula (ZJ) is a traditional Chinese medicine (TCM) prescription consisted of Coptidis Rhizoma (CR) and Euodiae Fructus (EF), and has been used to treat gastrointestinal (GI) disease for more than 700 years. Fan-Zuojin formula (FZJ) is a related TCM prescription also consisted of CR and EF with the opposite proportion. In recent years, ZJ was getting more attention for its antitumor potential, but the indeterminate pharmacokinetic (PK) behavior restricted its clinical applications, and the PK differences between ZJ and FZJ were also largely unknown. Consequently it is necessary to carry out a full-scale PK study to demonstrate the physiological disposition of ZJ, as well as the comparative PK study between ZJ and FZJ to illustrate the compatibility dose effects. Therefore a liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method was established and validated for the determinations of coptisine, epiberberine, palmatine, berberine, 8-oxocoptisine, 8-oxoepiberberine, noroxyhydrastinine, corydaldine, dehydroevodiamine, evodiamine, wuchuyuamide-I, and evocarpine in rat plasma. PK characteristics of 12 alkaloids after oral administration of ZJ and FZJ were compared, and the result was analyzed and discussed with the help of an in silico study. Then an integrated PK study was carried out with the AUC-based weighting method and the total drug concentration method. The established method has been successfully applied to reveal the PK profiles of the 12 alkaloids in rat plasma after oral administration of ZJ and FZJ. The results showed that: (1) double peaks were observed in the plasma concentration-time (C-T) curves of the alkaloids after ZJ administration; but the C-T curves approximately matched the two-compartment model after FZJ administration; (2) There were wide variations in the absorption levels of these alkaloids; and even for a certain alkaloid, the dose modified systemic exposure levels and elimination rate also varied significantly after

  10. Cytotoxicity of Hymenocallis expansa alkaloids.

    PubMed

    Antoun, M D; Mendoza, N T; Ríos, Y R; Proctor, G R; Wickramaratne, D B; Pezzuto, J M; Kinghorn, A D

    1993-08-01

    From the bulbs and leaves of Hymenocallis expansa (Amaryllidaceae), three alkaloid constituents were identified: (+)-tazettine, (+)-hippeastrine, and (-)-haemanthidine. These alkaloids demonstrated significant cytotoxicity when tested against a panel of human and murine tumor cell lines.

  11. Combinations of alkaloids affecting different molecular targets with the saponin digitonin can synergistically enhance trypanocidal activity against Trypanosoma brucei brucei.

    PubMed

    Krstin, Sonja; Peixoto, Herbenya Silva; Wink, Michael

    2015-11-01

    The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments.

  12. Combinations of Alkaloids Affecting Different Molecular Targets with the Saponin Digitonin Can Synergistically Enhance Trypanocidal Activity against Trypanosoma brucei brucei

    PubMed Central

    Peixoto, Herbenya Silva

    2015-01-01

    The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almost all alkaloids against trypanosomes. The strongest effect was measured in a combination of digitonin with vinblastine. The highest dose reduction indexes (DRI) were measured in the two-drug combination of digitonin or piperine with vinblastine, where the dose of vinblastine could be reduced 9.07-fold or 7.05-fold, respectively. The synergistic effects of mutual combinations of alkaloids and of alkaloids with digitonin present a new avenue to treat trypanosomiasis but one which needs to be corroborated in future animal experiments. PMID:26349826

  13. Alkaloids from Hippeastrum papilio.

    PubMed

    de Andrade, Jean Paulo; Berkov, Strahil; Viladomat, Francesc; Codina, Carles; Zuanazzi, José Angelo S; Bastida, Jaume

    2011-08-18

    Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl®) for the treatment of Alzheimer's disease (AD), is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11β-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11β-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine.

  14. The Iboga Alkaloids.

    PubMed

    Lavaud, Catherine; Massiot, Georges

    Iboga alkaloids are a particular class of indolomonoterpenes most often characterized by an isoquinuclidine nucleus. Their first occurrence was detected in the roots of Tabernanthe iboga, a sacred plant to the people of Gabon, which made it cult object. Ibogaine is the main representative of this class of alkaloids and its psychoactive properties are well documented. It has been proposed as a drug cessation treatment and has a wide range of activities in targeting opioids, cocaine, and alcohol. The purpose of this chapter is to provide a background on this molecule and related compounds and to update knowledge on the most recent advances made. Difficulties linked to the status of ibogaine as a drug in several countries have hampered its development, but 18-methoxycoronaridine is currently under evaluation for the same purposes and for the treatment of leishmaniasis. The chapter is divided into six parts: an introduction aiming at defining what is called an iboga alkaloid, and this is followed by current knowledge on their biosynthesis, which unfortunately remains a "black box" as far as the key construction step is concerned. Many of these alkaloids are still being discovered and the third and fourth parts of the chapter discuss the analytical tools in use for this purpose and give lists of new monomeric and dimeric alkaloids belonging to this class. When necessary, the structures are discussed especially with regard to absolute configuration determinations, which remain a point of weakness in their assignments. Part V gives an account of progress made in the synthesis, partial and total, which the authors believe is key to providing solid solutions to the industrial development of the most promising molecules. The last part of the chapter is devoted to the biological properties of iboga alkaloids, with particular emphasis on ibogaine and 18-methoxycoronaridine.

  15. Synthesis and evaluation of antioxidant and cytotoxicity of the N-Mannich base of berberine bearing benzothiazole moieties.

    PubMed

    Mistry, Bhupendra M; Keum, Young-Soo; Pandurangan, Muthuraman; Kim, Doo Hwan; Moon, So Hyun; Kadam, Avinash A; Shinde, Surendra; Shin, Han-Seung; Patel, Rahul V

    2017-07-10

    The N-Mannich base of an isoquinoline alkaloid, berberine, bearing substituted benzothiazole moieties was obtained. Novel synthesized analogues were in vitro screened for antioxidant efficacy toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radicals and in vitro cytotoxicity towards cervical cancer cell lines (HeLa and CaSki), an ovarian cancer cell line (SK-OV-3) and human renal cancer cell line (Caki-2). Cytotoxicity of the compounds toward normal cell lines was examined using the Madin-Darby canine kidney (MDCK) non-cancer cell line. Analogues bearing a methoxy functional group (5e), acid functionality (5c), and a cyano group (5m) showed remarkable radical scavenging potential in DPPH and ABTS bioassays. Potent cytotoxicity exhibited by berberine against the HeLa cell line was attributable to the presence of a 2-aminobenzothaizole moiety (5a) and its 6-chloro congener (5g) on the berberine core, and the 6-cyano group (5m) on the benzothiazole ring revealed strong sensitivity for the CaSki cell line, whereas subjected scaffolds demonstrated diminished activity against the SK-OV-3 cell line. In addition, the compound with a 2-aminobenzothaizole moiety (5a), compound with methoxy functional group (5e) and compound with cyano group appeared with the most significant cytotoxicity effect in Caki-2 cell line. Their structures have been elucidated by FT-IR, 1H NMR, 13C NMR, and elemental analyses (CHN) essential research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Novel molecularly imprinted magnetic nanoparticles for the selective extraction of protoberberine alkaloids in herbs and rat plasma.

    PubMed

    Meng, Jiawei; Zhang, Wenpeng; Bao, Tao; Chen, Zilin

    2015-06-01

    In this work, a novel magnetic nanomaterial functionalized with a molecularly imprinted polymer was prepared for the extraction of protoberberine alkaloids. Molecularly imprinted polymers were made on the surface of Fe3 O4 nanoparticles by using berberine as template, acetonitrile/water as porogen, acrylamide as functional monomer and ethylene glycol dimethacrylate as cross-linker. The optimized molar ratio of template/functional monomer was 1:7. The polymeric magnetic nanoparticles were characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The stability and adsorption capacity of the molecularly imprinted polymers were investigated. The molecularly imprinted polymers were used as a selective sorbent for the magnetic molecularly imprinted solid-phase extraction and determination of jatrorrhizine, palmatine, and berberine. Extraction parameters were studied including loading pH, sample volume, stirring speed, and extraction time. Finally, a magnetic molecularly imprinted solid-phase extraction coupled to high-performance liquid chromatography method was developed. Under the optimized conditions, the method showed good linear range of 0.1-150 ng/mL for berberine and 0.1-100 ng/mL for jatrorrhizine and palmatine. The limit of detection was 0.01 ng/mL for berberine and 0.02 ng/mL for jatrorrhizine and palmatine. The proposed method has been applied to determine protoberberine alkaloids in Cortex phellodendri and rat plasma samples. The recoveries ranged from 87.33-102.43%, with relative standard deviation less than 4.54% in Cortex phellodendri and from 102.22-111.15% with relative standard deviation less than 4.59% in plasma.

  17. Analysis of Ergot Alkaloids

    PubMed Central

    Crews, Colin

    2015-01-01

    The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes. PMID:26046699

  18. Analysis of Ergot Alkaloids.

    PubMed

    Crews, Colin

    2015-06-03

    The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes.

  19. [Progress of berberine for treatment of type 2 diabetes].

    PubMed

    Deng, Xiao-Wei; Xie, Ning

    2014-04-01

    Berberine is the major component of Coptidis Rhizoma and it has been used as anti-infection, anti-inflammation drug for gastrointestinal diseases. In recent years, evidence showed that it could regulate glucose and lipid metabolism. Moreover, its activity had been tested by clinical trials and animal researches. The mechanisms of berberine in diabetes include: improving the function of beta-cell; prompting insulin secretion and islets regeneration, lowing lipid level, regulating glucose and lipid metabolic by influence transcriptional factors expression such as PPARgamma, C/EBPalpha, SREBP-1c, LXR, having the activities of anti-oxidation and inhibiting reductase to repress oxidative stress state and regulate metabolic signal pathway. Although numbers of data supported that berberine could improving insulin resistance by clinical trials and animal studies, the large scale, multicenter clinical trials are needed to evaluate the effects of berberine for diabetes and its complications in the time of evidence-based medicine.

  20. Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus fumigatus

    PubMed Central

    Baccile, Joshua A.; Spraker, Joseph E.; Le, Henry H.; Brandenburger, Eileen; Gomez, Christian; Bok, Jin Woo; Macheleidt, Juliane; Brakhage, Axel A.; Hoffmeister, Dirk; Keller, Nancy P.; Schroeder, Frank C.

    2016-01-01

    Natural product discovery efforts have focused primarily on microbial biosynthetic gene clusters (BGCs) containing large multi-modular PKSs and NRPSs; however, sequencing of fungal genomes has revealed a vast number of BGCs containing smaller NRPS-like genes of unknown biosynthetic function. Using comparative metabolomics, we show that a BGC in the human pathogen Aspergillus fumigatus named fsq, which contains an NRPS-like gene lacking a condensation domain, produces several novel isoquinoline alkaloids, the fumisoquins. These compounds derive from carbon-carbon bond formation between two amino acid-derived moieties followed by a sequence that is directly analogous to isoquinoline alkaloid biosynthesis in plants. Fumisoquin biosynthesis requires the N-methyltransferase FsqC and the FAD-dependent oxidase FsqB, which represent functional analogs of coclaurine N-methyltransferase and berberine bridge enzyme in plants. Our results show that BGCs containing incomplete NRPS modules may reveal new biosynthetic paradigms and suggest that plant-like isoquinoline biosynthesis occurs in diverse fungi. PMID:27065235

  1. Combination of upflow anaerobic sludge blanket (UASB) and membrane bioreactor (MBR) for berberine reduction from wastewater and the effects of berberine on bacterial community dynamics.

    PubMed

    Qiu, Guanglei; Song, Yonghui; Zeng, Ping; Duan, Liang; Xiao, Shuhu

    2013-02-15

    Berberine is a broad-spectrum antibiotic extensively used in personal medication. The production of berberine results in the generation of wastewater containing concentrated residual berberine. However, few related studies up to date focus on berberine removal from wastewaters. In this study, a lab-scale upflow anaerobic sludge blanket (UASB)-membrane bioreactor (MBR) process was developed for berberine removal from synthetic wastewater. The performance of the UASB-MBR system on berberine, COD and NH(4)(+)--N removal was investigated at different berberine loadings. And the effects of berberine on bacterial communities were evaluated using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Results showed that, as the increase of berberine loadings, UASB performance was affected remarkably, whereas, efficient and stable performance of MBR ensured the overall removal rates of berberine, COD and NH(4)(+)--N consistently reached up to 99%, 98% and 98%, respectively. Significant shifts of bacterial community structures were detected in both UASB and MBR, especially in the initial operations. Along with the increase of berberine loadings, high antibiotic resisting species and some functional species, i.e. Acinetobacter sp., Clostridium sp., Propionibacterium sp., and Sphingomonas sp. in UASB, as well as Sphingomonas sp., Methylocystis sp., Hydrogenophaga sp. and Flavobacterium sp. in MBR were enriched in succession. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Efficacy of berberine in patients with type 2 diabetes mellitus.

    PubMed

    Yin, Jun; Xing, Huili; Ye, Jianping

    2008-05-01

    Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients. In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5%+/-0.5% to 7.5%+/-0.4%, P<.01), fasting blood glucose (from 10.6+/-0.9 mmol/L to 6.9+/-0.5 mmol/L, P<.01), postprandial blood glucose (from 19.8+/-1.7 to 11.1+/-0.9 mmol/L, P<.01), and plasma triglycerides (from 1.13+/-0.13 to 0.89+/-0.03 mmol/L, P<.05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering fasting blood glucose and postprandial blood glucose from 1 week to the end of the trial. Hemoglobin A1c decreased from 8.1%+/-0.2% to 7.3%+/-0.3% (P<.001). Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1% and 44.7% (P<.001), respectively. Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well. During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.

  3. Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.

    PubMed

    Yu, Chao; Tan, Shanjun; Zhou, Chunyu; Zhu, Cuilin; Kang, Xin; Liu, Shuai; Zhao, Shuang; Fan, Shulin; Yu, Zhen; Peng, Ai; Wang, Zhen

    2016-11-01

    Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

  4. Simple Indolizidine and Quinolizidine Alkaloids.

    PubMed

    Michael, Joseph P

    2016-01-01

    This review of simple indolizidine and quinolizidine alkaloids (i.e., those in which the parent bicyclic systems are in general not embedded in polycyclic arrays) is an update of the previous coverage in Volume 55 of this series (2001). The present survey covers the literature from mid-1999 to the end of 2013; and in addition to aspects of the isolation, characterization, and biological activity of the alkaloids, much emphasis is placed on their total synthesis. A brief introduction to the topic is followed by an overview of relevant alkaloids from fungal and microbial sources, among them slaframine, cyclizidine, Steptomyces metabolites, and the pantocins. The important iminosugar alkaloids lentiginosine, steviamine, swainsonine, castanospermine, and related hydroxyindolizidines are dealt with in the subsequent section. The fourth and fifth sections cover metabolites from terrestrial plants. Pertinent plant alkaloids bearing alkyl, functionalized alkyl or alkenyl substituents include dendroprimine, anibamine, simple alkaloids belonging to the genera Prosopis, Elaeocarpus, Lycopodium, and Poranthera, and bicyclic alkaloids of the lupin family. Plant alkaloids bearing aryl or heteroaryl substituents include ipalbidine and analogs, secophenanthroindolizidine and secophenanthroquinolizidine alkaloids (among them septicine, julandine, and analogs), ficuseptine, lasubines, and other simple quinolizidines of the Lythraceae, the simple furyl-substituted Nuphar alkaloids, and a mixed quinolizidine-quinazoline alkaloid. The penultimate section of the review deals with the sizable group of simple indolizidine and quinolizidine alkaloids isolated from, or detected in, ants, mites, and terrestrial amphibians, and includes an overview of the "dietary hypothesis" for the origin of the amphibian metabolites. The final section surveys relevant alkaloids from marine sources, and includes clathryimines and analogs, stellettamides, the clavepictines and pictamine, and bis

  5. LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets.

    PubMed

    Cheng, Minlu; Liu, Ruijuan; Wu, Yao; Gu, Pan; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2016-01-25

    An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4 mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients>0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063 ng/mL to 2.034 ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ± 15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72 h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose.

  6. Determination of mycotoxins, alkaloids, phytochemicals, antioxidants and cytotoxicity in Asiatic ginseng (Ashwagandha, Dong quai, Panax ginseng).

    PubMed

    Filipiak-Szok, Anna; Kurzawa, M; Szłyk, E; Twarużek, M; Błajet-Kosicka, A; Grajewski, J

    2017-01-01

    Mycotoxins and selected hazardous alkaloids in the medicinal plants (Panax ginseng, Angelica sinensis, and Withania somnifera) and dietary supplements were determined. Purine alkaloids were found in majority of samples; however, isoquinoline alkaloids were less abundant than indole. The predominant alkaloids appear to be caffeine (purine group), harman (indole group) and berberine (isoquinoline). Examined medicinal plants and dietary supplements were contaminated by mycotoxins (especially ochratoxin A 1.72-5.83 µg kg(-1)), and many species of mold (e.g. Cladosporium, Eurotium, Aspergillus, Rhizopus, Penicillium). MTT cytotoxicity tests revealed that plant and supplements extracts exhibited medium or high cytotoxicity (only Dong quai-low). Moreover, antioxidant activity, total phenolics content and selected phytochemicals were analyzed by spectrophotometric and chromatographic methods. Quercetin and rutin were predominant flavonols (1.94-9.51 and 2.20-7.28 mg 100 g(-1), respectively). Analysis of phenolic acids revealed-gallic acid, as the most abundant, except Panax ginseng, where ferulic acid was prevailing. The results were analyzed by chemometric methods (cluster analysis, ANOVA).

  7. A Tale of Three Cell Types: Alkaloid Biosynthesis Is Localized to Sieve Elements in Opium Poppy

    PubMed Central

    Bird, David A.; Franceschi, Vincent R.; Facchini, Peter J.

    2003-01-01

    Opium poppy produces a diverse array of pharmaceutical alkaloids, including the narcotic analgesics morphine and codeine. The benzylisoquinoline alkaloids of opium poppy accumulate in the cytoplasm, or latex, of specialized laticifers that accompany vascular tissues throughout the plant. However, immunofluorescence labeling using affinity-purified antibodies showed that three key enzymes, (S)-N-methylcoclaurine 3′-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and codeinone reductase (COR), involved in the biosynthesis of morphine and the related antimicrobial alkaloid sanguinarine, are restricted to the parietal region of sieve elements adjacent or proximal to laticifers. The localization of laticifers was demonstrated using antibodies specific to the major latex protein (MLP), which is characteristic of the cell type. In situ hybridization showed that CYP80B1, BBE, and COR gene transcripts were found in the companion cell paired with each sieve element, whereas MLP transcripts were restricted to laticifers. The biosynthesis and accumulation of alkaloids in opium poppy involves cell types not implicated previously in plant secondary metabolism and dramatically extends the function of sieve elements beyond the transport of solutes and information macromolecules in plants. PMID:14508000

  8. The Securinega alkaloids.

    PubMed

    Chirkin, Eqor; Atkatlian, William; Porée, François-Hugues

    2015-01-01

    Securinega alkaloids represent a family of plant secondary metabolites known for 50 years. Securinine (1), the most abundant and studied alkaloid of this series was isolated by Russian researchers in 1956. In the following years, French and Japanese scientists reported other Securinega compounds and extensive work was done to elucidate their intriguing structures. The homogeneity of this family relies mainly on its tetracyclic chemical backbone, which features a butenolide moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C). Interestingly, after a period of latency of 20 years, the Securinega topic reemerged as a prolific source of new natural structures and to date more than 50 compounds have been identified and characterized. The oligomeric subgroup gathering dimeric, trimeric, and tetrameric units is of particular interest. The unprecedented structure of the Securinega alkaloids was the subject of extensive synthetic efforts culminating in several efficient and elegant total syntheses. The botanical distribution of these alkaloids seems limited to the Securinega, Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a limited number of plant species have been considered for their alkaloid contents, and additional phytochemical as well as genetic studies are needed. Concerning the biosynthesis, experiments carried out with radiolabelled aminoacids allowed to identify lysine and tyrosine as the precursors of the piperidine ring A and the CD rings of securinine (1), respectively. Besides, plausible biosynthetic pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive and additional studies seem necessary to understand their mode of production. The scope of biological of activities of the Securinega alkaloids was mainly centered on the CNS

  9. Vacuole-Localized Berberine Bridge Enzyme-Like Proteins Are Required for a Late Step of Nicotine Biosynthesis in Tobacco1[C][W

    PubMed Central

    Kajikawa, Masataka; Shoji, Tsubasa; Kato, Akira; Hashimoto, Takashi

    2011-01-01

    Tobacco (Nicotiana tabacum) plants synthesize nicotine and related pyridine-type alkaloids, such as anatabine, in their roots and accumulate them in their aerial parts as chemical defenses against herbivores. Herbivory-induced jasmonate signaling activates structural genes for nicotine biosynthesis and transport by way of the NICOTINE (NIC) regulatory loci. The biosynthesis of tobacco alkaloids involves the condensation of an unidentified nicotinic acid-derived metabolite with the N-methylpyrrolinium cation or with itself, but the exact enzymatic reactions and enzymes involved remain unclear. Here, we report that jasmonate-inducible tobacco genes encoding flavin-containing oxidases of the berberine bridge enzyme family (BBLs) are expressed in the roots and regulated by the NIC loci. When expression of the BBL genes was suppressed in tobacco hairy roots or in tobacco plants, nicotine production was highly reduced, with a gradual accumulation of a novel nicotine metabolite, dihydromethanicotine. In the jasmonate-elicited cultured tobacco cells, suppression of BBL expression efficiently inhibited the formation of anatabine and other pyridine alkaloids. Subcellular fractionation and localization of green fluorescent protein-tagged BBLs showed that BBLs are localized in the vacuoles. These results indicate that BBLs are involved in a late oxidation step subsequent to the pyridine ring condensation reaction in the biosynthesis of tobacco alkaloids. PMID:21343426

  10. Alkaloids in Bulgarian Pancratium maritimum L.

    PubMed

    Berkov, Strahil; Evstatieva, Luba; Popov, Simeon

    2004-01-01

    A GC/MS analysis of alkaloids from leaves, bulbs and roots of Pancratium maritimum was performed. From the identified 16 alkaloids, 5 alkaloids were reported for the first time for this plant. Several compounds with pharmacological activity were found. Haemanthamine was main alkaloid in the leaves and bulbs whereas galanthane was found to be main alkaloid in roots.

  11. Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies.

    PubMed

    Yu, Yunli; Liu, Li; Wang, Xinting; Liu, Xiang; Liu, Xiaodong; Xie, Lin; Wang, Guangji

    2010-04-01

    Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells. Our previous studies showed that berberine increased GLP-1 secretion in streptozotocin-induced diabetic rats. The aim of this study was to investigate whether berberine affected GLP-1 release in normal rats and in NCI-H716 cells. Proglucagon and prohormone convertase 3 genes regulating GLP-1 biosynthesis were analyzed by RT-PCR. Effects of pharmacological inhibitors on berberine-mediated GLP-1 release were studied. In vivo, 5-week treatment of berberine enhanced GLP-1 secretion induced by glucose load and promoted proglucagon mRNA expression as well as L cell proliferation in intestine. In vitro, berberine concentration-dependently stimulated GLP-1 release in NCI-H716 cells. Berberine also promoted both prohormone convertase 3 and proglucagon mRNA expression. Chelerythrine (inhibitor of PKC) concentration-dependently suppressed berberine-mediated GLP-1 secretion. Compound C (inhibitor of AMPK) also inhibited berberine-mediated GLP-1 secretion. But only low concentrations of H89 (inhibitor of PKA) showed inhibitory effects on berberine-mediated GLP-1 release. The present results demonstrated that berberine showed its modulation on GLP-1 via promoting GLP-1 secretion and GLP-1 biosynthesis. Some signal pathways including PKC-dependent pathway were involved in this process. Elucidation of mechanisms controlling berberine-mediated GLP-1 secretion may facilitate the understanding of berberine's antidiabetic effects.

  12. Thin-Layer Chromatography/Desorption Electrospray Ionization Mass Spectrometry: Investigation of Goldenseal Alkaloids

    SciTech Connect

    Van Berkel, Gary J; Tomkins, Bruce A; Kertesz, Vilmos

    2007-01-01

    Desorption electrospray ionization mass spectrometry was investigated as a means to qualitatively identify and to quantify analytes directly from developed normal-phase thin layer chromatography plates. The atmospheric sampling capillary of a commercial ion trap mass spectrometer was extended to permit sampling and ionization of analytes in bands separated on intact TLC plates (up to 10 cm x 10 cm). A surface positioning software package and the appropriate hardware enabled computer-controlled surface scanning along the length of development lanes or at fixed RF value across the plates versus the stationary desorption electrospray emitter. Goldenseal (Hydrastis canadensis) and related alkaloids and commercial dietary supplements were used as standards and samples. Alkaloid standards and samples were spotted and separated on aluminum- or glass-backed plates using established literature methods. The mass spectral signal levels as a function of desorption spray solvent were investigated with acetonitrile proving superior to methanol. The detection levels (ca. 5 ng each or 14 -28 pmol) in mass spectral full scan mode were determined statistically from the calibration curves (2.5 - 100 pmol) for the standards berberine, palmatine and hydrastinine spotted as a mixture and separated on the plates. Qualitative screening of the major alkaloids present in six different over-the-counter "goldenseal" dietary supplements was accomplished by obtaining full scan mass spectra during surface scans along the development lane in the direction of increasing RF value. In one sample, alkaloids were detected that strongly suggested the presence of at least one additional herb undeclared on the product label. These same data indicated the misidentification of one of the alkaloids in the TLC literature. Quantities of the alkaloids present in two of the samples determined using the mass spectral data were in reasonable agreement with the label values indicating the quantitative ability of

  13. [Evaluation of crude drugs by means of colorimeter (I). Study on correlation between color and alkaloids content of coptidis rhizoma].

    PubMed

    Yoshimitsu, Michiyo; Qu, Xian-You; Luo, Wei-Zao; Qin, Song-Yun

    2014-05-01

    To examine the correlation between alkaloids content and L*, a* and b* color indices of Rhizoma Coptidis for quality control. A colorimeter was used for the measurement of reflected light from sieved powder samples using the CIE 1976 L* a* b* color system. The content of six alkaloids were determined by HPLC. The correlation between alkaloids content and color indices of Rhizoma Coptidis was analyzed. When the particle size of Rhizoma Coptidis was less than 355 microm and the colorimeter parameters were set as measurement diameter of 3 mm, observation degree of 10, and light source of F2 and F7, the measured color was significantly correlated with total alkaloids content (r = 0.793, P < 0.05). As light source of F11, the measured color was significantly correlated with berberine content (r = 0.867, P < 0.01). The correlation between the color of powdered Coptidis Rhizoma and its alkaloids contents was found in this study. Measurment of the color of Coptidis Rhizoma can be used to assess its quality.

  14. Antibacterial Activity of Alkaloid Fractions from Berberis microphylla G. Forst and Study of Synergism with Ampicillin and Cephalothin.

    PubMed

    Manosalva, Loreto; Mutis, Ana; Urzúa, Alejandro; Fajardo, Victor; Quiroz, Andrés

    2016-01-11

    Berberis microphylla is a native plant that grows in Patagonia and is commonly used by aboriginal ethnic groups in traditional medicine as an antiseptic for different diseases. The present study evaluated the antibacterial and synergistic activity of alkaloid extracts of B. microphylla leaves, stems and roots used either individually or in combination with antibiotics against Gram-positive and Gram-negative bacteria. The in vitro antibacterial activities of leaf, stem and root alkaloid extracts had significant activity only against Gram-positive bacteria. Disc diffusion tests demonstrated that the root extract showed similar activity against B. cereus and S. epidermidis compared to commercial antibiotics, namely ampicillin and cephalothin, and pure berberine, the principal component of the alkaloid extracts, was found to be active only against S. aureus and S. epidermidis with similar activity to that of the root extract. The minimum inhibitory concentrations (MICs) of the alkaloid extracts ranged from 333 to 83 μg/mL, whereas minimum bactericidal concentrations (MBCs) varied from 717 to 167 μg/mL. In addition, synergistic or indifferent effects between the alkaloid extracts and antibiotics against bacterial strains were confirmed.

  15. Berberine hydrochloride: anticancer activity and nanoparticulate delivery system

    PubMed Central

    Tan, Wen; Li, Yingbo; Chen, Meiwan; Wang, Yitao

    2011-01-01

    Background Berberine hydrochloride is a conventional component in Chinese medicine, and is characterized by a diversity of pharmacological effects. However, due to its hydrophobic properties, along with poor stability and bioavailability, the application of berberine hydrochloride was hampered for a long time. In recent years, the pharmaceutical preparation of berberine hydrochloride has improved to achieve good prospects for clinical application, especially for novel nanoparticulate delivery systems. Moreover, anticancer activity and novel mechanisms have been explored, the chance of regulating glucose and lipid metabolism in cancer cells showing more potential than ever. Therefore, it is expected that appropriate pharmaceutical procedures could be applied to the enormous potential for anticancer efficacy, to give some new insights into anticancer drug preparation in Chinese medicine. Methods and results We accessed conventional databases, such as PubMed, Scope, and Web of Science, using “berberine hydrochloride”, “anti-cancer mechanism”, and “nanoparticulate delivery system” as search words, then summarized the progress in research, illustrating the need to explore reprogramming of cancer cell metabolism using nanoparticulate drug delivery systems. Conclusion With increasing research on regulation of cancer cell metabolism by berberine hydrochloride and troubleshooting of issues concerning nanoparticulate delivery preparation, berberine hydrochloride is likely to become a natural component of the nanoparticulate delivery systems used for cancer therapy. Meanwhile, the known mechanisms of berberine hydrochloride, such as decreased multidrug resistance and enhanced sensitivity of chemotherapeutic drugs, along with improvement in patient quality of life, could also provide new insights into cancer cell metabolism and nanoparticulate delivery preparation. PMID:21931477

  16. Indole alkaloids from Geissospermum reticulatum.

    PubMed

    Reina, M; Ruiz-Mesia, W; López-Rodríguez, M; Ruiz-Mesia, L; González-Coloma, A; Martínez-Díaz, R

    2012-05-25

    Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.

  17. Protein tyrosine phosphatase 1B inhibitory activity of alkaloids from Rhizoma Coptidis and their molecular docking studies.

    PubMed

    Choi, Jae Sue; Ali, Md Yousof; Jung, Hyun Ah; Oh, Sang Ho; Choi, Ran Joo; Kim, Eon Ji

    2015-08-02

    Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugar-lowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine. In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO(-)-mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation. The Coptis alkaloids 1-4 exhibited remarkable inhibitory activities against PTP1B with the IC50 values of 16.43, 24.19, 28.14, and 51.04 μM, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO(-)-mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using the Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=-6.7 to -7.8 kcal/mol; Fred 2.0=-59.4 to -68.2 kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme. Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO(-)-mediated protein tyrosine nitration, and thus hold

  18. Highly sensitive method for simultaneous determination of nine alkaloids of Shuanghua Baihe tablets in human plasma by LC-MS/MS and its application.

    PubMed

    Wu, Yao; Liu, Ruijuan; Gu, Pan; Cheng, Minlu; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2015-12-15

    Shuanghua Baihe tablets (SBT) is a traditional Chinese medicinal formula which has been used to treat recurrent aphthous stomatitis for many years. To study the pharmacokinetic profiles of berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline in human after administration of SBT, a sensitive liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous quantification of these nine alkaloids in human plasma. After protein precipitation, the nine alkaloids in human plasma sample was separated on a Hanbon C18 (150mm×2.1mm, 5μm) column with gradient elution using methanol and 0.5% formic acid water solution, and detected by a triple quadrupole mass spectrometer with an electrospray ionization source. It is a challenge to design different calibration ranges for different analytes in a bioanalytical method for simultaneous determination of multi-analytes in bio-samples. To ensure that each alkaloid in the plasma was determined accurately by the simultaneous quantitation method, the upper limits of quantification for the nine alkaloids were designed at 100, 300, 800, 1800 and 5000pg/mL, respectively, according to the maximum plasma concentration value of each alkaloid obtained from the pilot pharmacokinetic study. The lower limit of quantification was 15pg/mL for berberine, epiberberine, coptisine, magnoflorine, berberrubine, corynoline and acetylcorynoline, while for palmatine and jatrorrhizine it was 1.5pg/mL. This method was successfully applied to investigate the pharmacokinetic profiles of the nine alkaloids in healthy Chinese volunteers after a single oral administration of SBT.

  19. Quinolizidine alkaloids from Lupinus lanatus

    NASA Astrophysics Data System (ADS)

    Neto, Alexandre T.; Oliveira, Carolina Q.; Ilha, Vinicius; Pedroso, Marcelo; Burrow, Robert A.; Dalcol, Ionara I.; Morel, Ademir F.

    2011-10-01

    In this study, one new quinolizidine alkaloid, lanatine A ( 1), together with three other known alkaloids, 13-α- trans-cinnamoyloxylupanine ( 2), 13-α-hydroxylupanine ( 3), and (-)-multiflorine ( 4) were isolated from the aerial parts of Lupinus lanatus (Fabaceae). The structures of alkaloids 1- 4 were elucidated by spectroscopic data analysis. The stereochemistry of 1 was determined by single crystal X-ray analysis. Bayesian statistical analysis of the Bijvoet differences suggests the absolute stereochemistry of 1. In addition, the antimicrobial potential of alkaloids 1- 4 is also reported.

  20. Quinoline alkaloids from Acronychia laurifolia.

    PubMed

    Cui, B; Chai, H; Dong, Y; Horgen, F D; Hansen, B; Madulid, D A; Soejarto, D D; Farnsworth, N R; Cordell, G A; Pezzuto, J M; Kinghorn, A D

    1999-09-01

    Bioassay-directed fractionation of a root extract of Acronychia laurifolia (Rutaceae) using the KB-V1+ human tumor cell line led to the isolation of six quinoline alkaloids. One of these alkaloids is novel, namely, 2,3-methylenedioxy-4,7-dimethoxyquinoline and the other five were identified as the known compounds, evolitrine, gamma-fagarine, skimmianine, kokusaginine and maculosidine. Two known bis-tetrahydrofuran lignans, sesamolin and yangambin, were also identified. The structure of the new alkaloid was determined by spectroscopic methods. All of the isolates were evaluated against a panel of human cancer cell lines; four of the alkaloids showed weak cytotoxic activity.

  1. Berberine interfered with breast cancer cells metabolism, balancing energy homeostasis.

    PubMed

    Tan, Wen; Li, Ning; Tan, Rui; Zhong, Zhangfeng; Suo, Zhanwei; Yang, Xian; Wang, Yitao; Hu, Xiaodong

    2015-01-01

    Berberine exerted anti-cancer effect in various cancer cell lines, and was also implied in the treatment of metabolic related diseases. Given the metabolic modulation, we hypothesized that berberine possessed anti-cancer effect under the assistance of metabolic interference. Working as a modulator, metabolic enzyme inhibitor or complex network regulator in energy metabolism, berberine was highlighted in current cancer research. A reasonable cross talk between Chinese medicine and energy homeostasis provided a solid foundation for berberine interference on cancer cells reprogramming metabolism. Our result showed that berberine regulated the reprogramming metabolism through three aspects simultaneously, including mitochondrial oxidative phosphorylation, glycolysis and macromolecular synthesis. This interference with reprogramming metabolism was a continuous, simultaneous and sustainable approach in a moderate mode. And it could be regarded as a gentle and virtuous cycle from a multi-level perspective, indicating an integrated approach in cancer therapy. Meanwhile, we thought that Chinese medicine could link cancer and metabolic related diseases from a dynamic perspective through integrated network pharmacology. This cross talk would be a realistic and significant strategy for anti-cancer drug discovery and needs further investigation in future.

  2. Interaction of berberine with human platelet. alpha. sub 2 adrenoceptors

    SciTech Connect

    Hui, Ka Kit; Yu, Jun Liang; Chan, Wai Fong A.; Tse, E. )

    1991-01-01

    Berberine was found to inhibit competitively the specific binding of ({sup 3}H)-yohimbine. The displacement curve was parallel to those of clonidine, epinephrine, norepinephrine, with the rank order of potency (IC{sub 50}) being clonidine {gt} epinephrine {gt} norepinephrine (14.5 {mu}M) = berberine. Increasing concentrations of berberine from 0.1 {mu}M to 10 {mu}M inhibited ({sup 3}H)-yohimbine binding, shifting the saturation binding curve to the right without decreasing the maximum binding capacity. In platelet cyclic AMP accumulation experiments, berberine at concentrations of 0.1 {mu}M to 0.1 mM inhibited the cAMP accumulation induced by 10 {mu}M prostaglandin E{sub 1} in a dose dependent manner, acting as an {alpha}{sub 2} adrenoceptor agonist. In the presence of L-epinephrine, berberine blocked the inhibitory effect of L-epinephrine behaving as an {alpha}{sub 2} adrenoceptor antagonist.

  3. A new bisbenzylisoquinoline alkaloid isolated from Thalictrum foliolosum, as a potent inhibitor of DNA topoisomerase IB of Leishmania donovani.

    PubMed

    Kumar, Ashish; Chowdhury, Somenath Roy; Sarkar, Tapas; Chakrabarti, Tulika; Majumder, Hemanta K; Jha, Tarun; Mukhopadhyay, Sibabrata

    2016-03-01

    Chemical investigation of the stem of Thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). The structures of the new compounds were established by detailed 2D NMR spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. Inhibitory activities of these four compounds against DNA topoisomerase IB of Leishmania donovani were evaluated. Compound 2 exhibited almost complete inhibition of the enzyme activity at 50 μM concentration and it was found to be effective in killing both wild type as well as SAG resistant promastigotes of the parasite.

  4. The involvement of multidrug and toxin extrusion protein 1 in the distribution and excretion of berberine.

    PubMed

    Xiao, Ling; Xue, Yaru; Zhang, Cuifeng; Wang, Le; Lin, Yunfei; Pan, Guoyu

    2017-03-16

    1. Berberine (BBR), an isoquinoline alkaloid, has demonstrated multiple clinical pharmacological actions. As a substrate of multiple transporters in the liver, BBR is rarely excreted into the bile but can be found in the urine. The purpose of the present study was to investigate the role of multidrug and toxin extrusion protein 1 (MATE1) in the transport of BBR in the liver and kidney. 2. Using human MATE1 (hMATE1)-transfected HEK293 cells, BBR was shown to be a substrate of hMATE1 (Km = 4.28 ± 2.18 μM). In primary rat hepatocytes, pH-dependent uptake and efflux studies suggested that the transport of BBR was driven by the exchange of H(+) and involved Mate1. In rats, we found that pyrimethamine (PYR), an inhibitor of Mate1, increased hepatic and renal distribution of BBR and decreased systematic excretion of BBR. 3. These findings indicated that BBR is a substrate of MATE1 and that hepatic and renal Mate1 promote excretion of BBR into bile and urine, respectively. In conclusion, Mate1 plays a key role in the distribution and excretion of BBR, and we speculate that drug-drug interactions (DDIs) caused by MATE1 may occur between BBR and other co-administered drugs.

  5. Berberine nanosuspension enhances hypoglycemic efficacy on streptozotocin induced diabetic C57BL/6 mice.

    PubMed

    Wang, Zhiping; Wu, Junbiao; Zhou, Qun; Wang, Yifei; Chen, Tongsheng

    2015-01-01

    Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.

  6. Anti-adipogenic activity of berberine is not mediated by the WNT/β-catenin pathway.

    PubMed

    Bae, Sungmin; Yoon, Yoosik

    2013-06-01

    Adipogenesis is a differentiation process from preadipocytes to adipocytes, accompanied by the inductions of adipogenic transcription factors and lipid metabolizing enzymes. Among cellular pathways regulating adipogenesis, the WNT/β-catenin pathway is well-known as a suppressor of adipogenesis. Berberine (BBR) is an isoquinoline alkaloid component of the medicinal plants including Coptis chinensis and Coptis japonica with diverse biological activities. This study was conducted to elucidate whether the anti-adipogenic effect of BBR is mediated by the WNT/β-catenin pathway. The results of the present study confirmed that BBR efficiently inhibited adipogenesis of 3T3-L1 cells. However, the anti-adipogenic effects of BBR were not accompanied by the modulations of the WNT/β-catenin pathway members including WNT10B, LRP6, DVL2, GSK3β and β-catenin. When β-catenin was knocked down by its siRNA transfection, the anti-adipogenic effects of BBR including the expression of adipogenic transcription factors and lipid metabolizing enzymes as well as the intracellular fat accumulation were not affected at all. The results of this study showed that the anti-adipogenic effect of BBR is not mediated by the WNT/β-catenin pathway.

  7. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats.

    PubMed

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

  8. Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

    PubMed Central

    Gong, Jing; Hu, Meilin; Huang, Zhaoyi; Fang, Ke; Wang, Dingkun; Chen, Qingjie; Li, Jingbin; Yang, Desen; Zou, Xin; Xu, Lijun; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2017-01-01

    Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages. PMID:28217099

  9. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses.

    PubMed

    Varghese, Finny S; Kaukinen, Pasi; Gläsker, Sabine; Bespalov, Maxim; Hanski, Leena; Wennerberg, Krister; Kümmerer, Beate M; Ahola, Tero

    2016-02-01

    Chikungunya virus (CHIKV) is an arthritogenic arbovirus of the Alphavirus genus, which has infected millions of people after its re-emergence in the last decade. In this study, a BHK cell line containing a stable CHIKV replicon with a luciferase reporter was used in a high-throughput platform to screen approximately 3000 compounds. Following initial validation, 25 compounds were chosen as primary hits for secondary validation with wild type and reporter CHIKV infection, which identified three promising compounds. Abamectin (EC50 = 1.5 μM) and ivermectin (EC50 = 0.6 μM) are fermentation products generated by a soil dwelling actinomycete, Streptomyces avermitilis, whereas berberine (EC50 = 1.8 μM) is a plant-derived isoquinoline alkaloid. They inhibited CHIKV replication in a dose-dependent manner and had broad antiviral activity against other alphaviruses--Semliki Forest virus and Sindbis virus. Abamectin and ivermectin were also active against yellow fever virus, a flavivirus. These compounds caused reduced synthesis of CHIKV genomic and antigenomic viral RNA as well as downregulation of viral protein expression. Time of addition experiments also suggested that they act on the replication phase of the viral infectious cycle.

  10. Comparative Pharmacokinetic Profiles of Three Protoberberine-type Alkaloids from Raw and Bile-processed Rhizoma coptidis in Heat Syndrome Rats

    PubMed Central

    Zi-min, Yuan; Yue, Chen; Hui, Gao; Jia, Lv; Gui-rong, Chen; Wang, Jing

    2017-01-01

    Background: The Bile-processed Rhizoma coptidis (BRC), which has a colder drug property than Rhizoma coptidis (RC), is widely used for the treatment of heat syndrome. We compared the pharmacokinetics of the protoberberine-type alkaloids in BRC and RC in rats with heat syndrome to elucidate the bile-processing mechanism. Material and Methods: We established a rapid and sensitive method for simultaneously determining three alkaloids: berberine, palmatine, and jatrorrhizine, in rat plasma based on ultra-performance liquid chromatography/tandem mass spectrometry. The separation was carried out on a Waters ACQUITY BEA C18 column. The mobile phase consisted of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid and 10 mmol/L ammonium acetate) and carbamazepine was used as an internal standard. The detection was carried out in a multiple reaction monitoring mode (MRM) using electrospray ionization in the positive ion mode. Results: Pharmacokinetic profiles indicated that the Cmax of berberine and palmatine increased two times and the Tmax of the three alkaloids decreased three times after bile processing. AUC0→∞ and AUC0→t of the alkaloids were similar between RC and BRC. Conclusion: The results suggest that bile processing could increase the absorption rate of alkaloids. This study broadens our understanding of Chinese herbal medicine processing. SUMMARY Contents of berberine, palmatine and jatrorrhizine, in heat syndrome rats’ plasma between the raw and bile-processed Rhizoma coptidis (RC) were determined by UPLC-MS/MS.The whole pharmacokinetic profiles of three alkaloids in the bile-processed Rhizoma coptidis (BRC) were similar to those of RC.The shorter Tmax and increased 2-fold Cmax were obtained after RC bile-processing.Bile-processing could promote the absorption rate of alkaloids in a certain degree. Abbreviation Used: RC: Rhizoma coptidis, BRC: Bile-processed Rhizoma coptidis, HPLC: high-performance liquid chromatography

  11. Nuclear magnetic resonance spectral analysis and molecular properties of berberine

    NASA Astrophysics Data System (ADS)

    Huang, Ming-Ju; Lee, Ken S.; Hurley, Sharon J.

    An extensive theoretical study of berberine has been performed at the ab initio HF/6-31G**, HF/6-311G**, and B3LYP/6-311G** levels with and without solvent effects. The optimized structures are compared with X-ray data. We found that the optimized structures with solvent effects are in slightly better agreement with X-ray data than those without solvent effects. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of berberine were calculated by using the gauge-independent atomic orbital (GIAO) (with and without solvent effects), CSGT, and IGAIM methods. The calculated chemical shifts were compared with the two-dimensional NMR experimental data. Overall, the calculated chemical shifts show very good agreement with the experimental results. The harmonic vibrational frequencies for berberine were calculated at the B3LYP/6-311G** level.

  12. Ergot and Its Alkaloids

    PubMed Central

    Schiff, Paul L.

    2006-01-01

    This manuscript reviews the history and pharmacognosy of ergot, and describes the isolation/preparation, chemistry, pharmacodynamics, and pharmacotherapeutics of the major ergot alkaloids and their derivatives. A brief discussion of the hallucinogenic properties of lysergic acid diethylamide is also featured. An abbreviated form of the material found in this paper is presented in a 4-hour didactic format to third-professional year PharmD students as part of their study of vascular migraine headaches, Parkinson's disease, and naturally occurring hallucinogens/hallucinogen derivatives in the modular course offering Neurology/Psychiatry. PMID:17149427

  13. Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome.

    PubMed

    Kim, Jang Hoon; Ryu, Young Bae; Lee, Woo Song; Kim, Young Ho

    2014-11-01

    Clostridium perfringens is a Gram-positive spore-forming bacterium that causes food poisoning. The neuraminidase (NA) protein of C. perfringens plays a pivotal role in bacterial proliferation and is considered a novel antibacterial drug target. Based on screens for novel NA inhibitors, a 95% EtOH extract of Corydalis turtschaninovii rhizome showed NA inhibitory activity (68% at 30 μg/ml), which resulted in the isolation of 10 isoquinoline alkaloids; namely, palmatine (1), berberine (2), coptisine (3), pseudodehydrocorydaline (4), jatrorrhizine (5), dehydrocorybulbine (6), pseudocoptisine (7), glaucine (8), corydaline (9) and tetrahydrocoptisine (10). Interestingly, seven quaternary isoquinoline alkaloids 1-7 (IC50 = 12.8 ± 1.5 to 65.2 ± 4.5 μM) showed stronger NA inhibitory activity than the tertiary alkaloids 8-10. In addition, highly active compounds 1 and 2 showed reversible non-competitive behavior based on a kinetic study. Molecular docking simulations using the Autodock 4.2 software increased our understanding of receptor-ligand binding of these compounds. In addition, we demonstrated that compounds 1 and 2 suppressed bacterial growth.

  14. Evidence for the monophyletic evolution of benzylisoquinoline alkaloid biosynthesis in angiosperms.

    PubMed

    Liscombe, David K; MacLeod, Benjamin P; Loukanina, Natalia; Nandi, Owi I; Facchini, Peter J

    2005-10-01

    Benzylisoquinoline alkaloids (BIAs) consist of more than 2500 diverse structures largely restricted to the order Ranunculales and the eumagnoliids. However, BIAs also occur in the Rutaceae, Lauraceae, Cornaceae and Nelumbonaceae, and sporadically throughout the order Piperales. Several of these alkaloids function in the defense of plants against herbivores and pathogens--thus the capacity for BIA biosynthesis is expected to play an important role in the reproductive fitness of certain plants. Biochemical and molecular phylogenetic approaches were used to investigate the evolution of BIA biosynthesis in basal angiosperms. The occurrence of (S)-norcoclaurine synthase (NCS; EC 4.2.1.78) activity in 90 diverse plant species was compared to the distribution of BIAs superimposed onto a molecular phylogeny. These results support the monophyletic origin of BIA biosynthesis prior to the emergence of the eudicots. Phylogenetic analysis of NCS, berberine bridge enzyme and several O-methyltransferases suggest a latent molecular fingerprint for BIA biosynthesis in angiosperms not known to accumulate such alkaloids. The limited occurrence of BIAs outside the Ranunculales and eumagnoliids suggests the requirement for a highly specialized, yet evolutionarily unstable cellular platform to accommodate or reactivate the pathway in divergent taxa. The molecular cloning and functional characterization of NCS from opium poppy (Papaver somniferum L.) is also reported. Pathogenesis--related (PR)10 and Bet v 1 major allergen proteins share homology with NCS, but recombinant polypeptides were devoid of NCS activity.

  15. Evidence for the monophyletic evolution of benzylisoquinoline alkaloid biosynthesis in angiosperms.

    PubMed

    Liscombe, David K; Macleod, Benjamin P; Loukanina, Natalia; Nandi, Owi I; Facchini, Peter J

    2005-06-01

    Benzylisoquinoline alkaloids (BIAs) consist of more than 2500 diverse structures largely restricted to the order Ranunculales and the eumagnoliids. However, BIAs also occur in the Rutaceae, Lauraceae, Cornaceae and Nelumbonaceae, and sporadically throughout the order Piperales. Several of these alkaloids function in the defense of plants against herbivores and pathogens - thus, the capacity for BIA biosynthesis is expected to play an important role in the reproductive fitness of certain plants. Biochemical and molecular phylogenetic approaches were used to investigate the evolution of BIA biosynthesis in basal angiosperms. The occurrence of (S)-norcoclaurine synthase (NCS; EC 4.2.1.78) activity in 90 diverse plant species was compared to the distribution of BIAs superimposed onto a molecular phylogeny. These results support the monophyletic origin of BIA biosynthesis prior to the emergence of the eudicots. Phylogenetic analyses of NCS, berberine bridge enzyme and several O-methyltransferases suggest a latent molecular fingerprint for BIA biosynthesis in angiosperms not known to accumulate such alkaloids. The limited occurrence of BIAs outside the Ranunculales and eumagnoliids suggests the requirement for a highly specialized, yet evolutionarily unstable cellular platform to accommodate or reactivate the pathway in divergent taxa. The molecular cloning and functional characterization of NCS from opium poppy (Papaver somniferum L.) is also reported. Pathogenesis-related (PR)10 and Bet v 1 major allergen proteins share homology with NCS, but recombinant polypeptides were devoid of NCS activity.

  16. CYP2D plays a major role in berberine metabolism in liver of mice and humans.

    PubMed

    Guo, Ying; Li, Feng; Ma, Xiaochao; Cheng, Xingguo; Zhou, Honghao; Klaassen, Curtis D

    2011-11-01

    Berberine is a widely used plant extract for gastrointestinal infections, and is reported to have potential benefits in treatment for diabetes and hypercholesterolemia. It has been suggested that interactions between berberine-containing products and cytochromes P450 (CYPs) exist, but little is known about which CYPs mediate the metabolism of berberine in vivo. In this study, berberine metabolites in urine and feces of mice were analyzed, and the role that CYPs play in producing these metabolites were characterized in liver microsomes from mice (MLM) and humans (HLM), as well as recombinant human CYPs. Eleven berberine metabolites were identified in mice, including 5 unconjugated metabolites, mainly in feces, and 6 glucuronide and sulfate conjugates, predominantly in urine. Three novel berberine metabolites were observed. Three unconjugated metabolites of berberine were produced by MLM, HLM, and recombinant human CYPs. CYP2D6 was the primary recombinant human CYP producing these metabolites, followed by CYP1A2, 3A4, 2E1 and CYP2C19. The metabolism of berberine in MLM and HLM was decreased the most by a CYP2D inhibitor, and moderately by inhibitors of CYP1A and 3A. CYP2D plays a major role in berberine biotransformation, therefore, CYP2D6 pharmacogenetics and potential drug-drug interactions should be considered when berberine is used.

  17. Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin.

    PubMed

    Kwon, Mihwa; Choi, Young A; Choi, Min-Koo; Song, Im-Sook

    2015-01-01

    Berberine, the main active component of the herbal medicine Rhizoma Coptidis, has been reported to have hypoglycemic and insulin-sensitizing effects and, therefore, could be combined with metformin therapy. Thus, we assessed the potential drug-drug interactions between berberine and metformin. We investigated the in vitro inhibitory potency of berberine on metformin uptake in HEK293 cells overexpressing organic cation transporter (OCT) 1 and 2. To investigate whether this inhibitory effect of berberine on OCT1 and OCT2 could change the pharmacokinetics of metformin in vivo, we measured the effect of berberine co-administration on the pharmacokinetics of metformin at a single intravenous dose of 2 mg/kg metformin and 10 mg/kg berberine. In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 μM, respectively. Co-administration of berberine increased the initial plasma concentration and AUC of metformin and decreased systemic clearance and volume of distribution of metformin in rats, suggesting that berberine inhibited disposition of metformin, which is governed by OCT1 and OCT2. Berberine inhibited the transport activity of OCT1 and OCT2 and showed significant potential drug-drug interactions with metformin in in vivo rats.

  18. Transcription factors in alkaloid biosynthesis.

    PubMed

    Yamada, Yasuyuki; Sato, Fumihiko

    2013-01-01

    Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.

  19. In Vitro Screening for Antihepatic Steatosis Active Components within Coptidis Rhizoma Alkaloids Extract Using Liver Cell Extraction with HPLC Analysis and a Free Fatty Acid-Induced Hepatic Steatosis HepG2 Cell Assay.

    PubMed

    Fan, Hui; Chen, Yuan-Yuan; Bei, Wei-Jian; Wang, Lai-You; Chen, Bao-Tian; Guo, Jiao

    2013-01-01

    A high-throughput method was developed and applied to screen for the active antihepatic steatosis components within Coptidis Rhizoma Alkaloids Extract (CAE). This method was a combination of two previously described assays: HepG2 cell extraction with HPLC analysis and a free fatty acid-induced (FFA) hepatic steatosis HepG2 cell assay. Two alkaloids within CAE, berberine and coptisine, were identified by HepG2 cell extraction with HPLC analysis as high affinity components for HepG2. These alkaloids were also determined to be active and potent compounds capable of lowering triglyceride (TG) accumulation in the FFA-induced hepatic steatosis HepG2 cell assay. This remarkable inhibition of TG accumulation (P < 0.01) by berberine and coptisine occurred at concentrations of 0.2  μ g/mL and 5.0 μ g/mL, respectively. At these concentrations, the effect seen was similar to that of a CAE at 100.0  μ g/mL. Another five alkaloids within CAE, palmatine, epiberberine, jateorhizine, columbamine, and magnoline, were found to have a lower affinity for cellular components from HepG2 cells and a lower inhibition of TG accumulation. The finding of two potent and active compounds within CAE indicates that the screening method we developed is a feasible, rapid, and useful tool for studying traditional Chinese medicines (TCMs) in treating hepatic steatosis.

  20. Effect of sample handling on alkaloid and mineral content of aqueous extracts of greater celandine (Chelidonium majus L.).

    PubMed

    Then, M; Szentmihályi, K; Sárközi, A; Illés, V; Forgács, E

    2000-08-11

    The authors examined the extraction of alkaloids from the greater celandine (Chelidonium majus L.) by different methods (traditional pressing and tea making, microwave and supercritical fluid extraction). The extractants were water and propylene glycol. For comparison of the extraction methods, the yield was evaluated according to total alkaloid content measured by spectroscopy. The highest alkaloid yield was obtained by microwave extraction and by making tea. Distribution of the components was studied by thin-layer chromatography and densitometry. The concentration and the ratio of alkaloid components in extracts are significantly different depending on the extraction method. The solution obtained by supercritical fluid extraction contains coptisine and chelidonine, while berberine could be obtained by microwave extraction only. Extracts with high coptisine content were obtained by supercritical fluid extraction, followed by pressing and microwave extraction. Mineral element content of the drug and extracts was also determined by inductively coupled plasma atomic emission spectrometry. Element content (Na, Ca, Fe) was found to be highest in microwave extracts.

  1. Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice.

    PubMed

    Ma, Hang; Hu, Yinran; Zou, Zongyao; Feng, Min; Ye, Xiaoli; Li, Xuegang

    2016-06-01

    Preclinical Research Rhizoma Coptidis (RC), the root of Coptis chinensis Franch, a species in the genus Coptis (family Ranunculaceae), has been commonly prescribed for the treatment of diabetes in Chinese traditional herbal medicine applications. The present study is focused on the assessment of the antihyperglycemia and antidiabetic hyperlipidemia effect of five protoberberine alkaloids, berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI), and jatrorrhizine (JAT), separated from R. Coptidis in hepatocellular carcinoma HepG2 cells and diabetic KK-Ay mice. Protoberberine alkaloids are effective in modulating hyperglycemia and hyperlipidemia. After adding BBR and COP to culture medium, glucose consumption of HepG2 cells was increased. In KK-Ay mice assays, suppressed fasting blood glucose level and ameliorated glucose tolerance were observed after BBR/COP administration. After treated with berberine and coptisine, in the same dose of 5 µg/mL, the glucose consumption of HepG2 cells were promoted and, respectively, reached 96.1% and 17.6%. Body weight, food consumption, water intake, and urinary output of KK-Ay mice were reduced after treated with EPI. Serum total cholesterol and triglyceride of mice were decreased after treated with palmatine and jatrorrhizine. Serum high-density lipoprotein cholesterol of mice was increased after palmatine, jatrorrhizine, and berberine administrated. Moreover, hepatomegaly was attenuated in JTR-treated mice. Suggested that these protoberberine alkaloids from R. Coptidis have potential curative effect for diabetes. Drug Dev Res 77 : 163-170, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Estimation of berberine in ayurvedic formulations containing Berberis aristata.

    PubMed

    Rout, Kedar Kumar; Pradhan, Subhalaxmi; Mishra, Sagar Kumar

    2008-01-01

    A sensitive, simple, rapid, and efficient high-performance thin-layer chromatographic (HPTLC) method has been developed and validated for the analysis of berberine in marketed Ayurvedic formulations containing Berberis aristata DC for regulatory purposes. Chromatography of methanolic extracts of these formulations was performed on silica gel 60 F254 aluminum-backed TLC plates of 0.2 mm layer thickness. The plate was developed up to 66 mm with the ternary-mobile phase butanol-acetic acid-water (8 + 1 + 1, v/v/v) at 33 +/- 5 degrees C with 5 min of tank saturation. The marker, berberine, was quantified at its maximum absorbance of 350 nm. The limit of detection and limit of quantitation values were found to be 5 and 10 ng/spot. The linear regression analysis data for the calibration plot showed a good linear relationship with correlation coefficient = 0.9994 in the concentration range of 10 to 50 ng/spot for berberine with respect to peak area. The instrumental precision was found to be 0.49% coefficient of variation (CV), and repeatability of the method was 0.73% CV. Recovery values from 98.27 to 99.11% indicate excellent accuracy of the method. The developed HPTLC method is very accurate, precise, and cost-effective, and it has been successfully applied to the assay of marketed formulations containing B. aristata for determination of berberine.

  3. Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma.

    PubMed

    Pierpaoli, Elisa; Damiani, Elisa; Orlando, Fiorenza; Lucarini, Guendalina; Bartozzi, Beatrice; Lombardi, Paolo; Salvatore, Carmela; Geroni, Cristina; Donati, Abele; Provinciali, Mauro

    2015-10-01

    Berberine (BBR) is a natural isoquinoline alkaloid with proven antiangiogenic and anticancer activities. We recently demonstrated that BBR and its synthetic derivative 13-(4-chlorophenylethyl)berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells. In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase of senescence associated β-galactosidase and p16 expression, and reduced expression of heparanase were observed in tumors from NAX014-treated mice than in tumors from control animals. Finally, NAX014 treatment decreased the level of perforine and granzyme mRNA in mammary tumors. Berberine did not show any statistically significant modulation in comparison with control mice. The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene. The antitumor efficacy of NAX014 is mainly related to its effect on tumor vascular network and on induction of tumor cell senescence.

  4. Determination of berberine in pharmaceutical preparations using acidic hydrogen peroxide-nitrite chemiluminescence system.

    PubMed

    Liang, Yao-Dong; Yu, Chun-Xia

    2013-03-01

    A stronger chemiluminescence (CL) was observed when hydrogen peroxide was mixed with nitrite and berberine in sulfuric acid solution. The stronger CL originated from peroxidation of berberine by peroxynitrous acid that was synthesized online by the mixing of acidic hydrogen peroxide solution with nitrite solution in a flow system. The emitting species was excited state oxyberberine, a peroxidized product of berberine. Based on the stronger CL, a flow injection CL method for the determination of berberine was proposed. Under optimum experimental conditions, the stronger CL intensity was linearly related to the concentration of berberine over the range of 2.0 × 10(-7) -2.0 × 10(-5) mol L(-1) . The limit of detection (s/n = 3) was 6.2 × 10(-8) mol L(-1) . The proposed method has been evaluated by analyzing berberine in pharmaceutical preparations.

  5. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.

  6. Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

    PubMed Central

    Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

    2016-01-01

    Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent. PMID:27322681

  7. Effects of berberine on glucose metabolism in vitro.

    PubMed

    Yin, Jun; Hu, Renming; Chen, Mingdao; Tang, Jinfeng; Li, Fengying; Yang, Ying; Chen, Jialun

    2002-11-01

    The action of berberine was compared with metformin and troglitazone (TZD) with regard to the glucose-lowering action in vitro. HepG2 cell line, phenotypically similar to human hepatocytes, was used for glucose consumption (GC) studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. In moderate high glucose concentration (11.1 mmol/L), GC of HepG2 cells was increased by 32% to 60% (P <.001 to P <.0001) with 5 x 10(-6) mol/L to 1 x 10(-4) mol/L berberine, which was comparable to that with 1 x 10(-3) mol/L metformin. The glucose-lowering effect of berberine decreased as the glucose concentration increased. The maximal potency was reached in the presence of 5.5 mmol/L glucose, and it was abolished when the glucose concentration increased to 22.2 mmol/L. The effect was not dependent on insulin concentration, which was similar to that of metformin and was different from that of TZD, whose glucose-lowering effect is insulin dependent. TZD had a better antihyperglycemic potency than metformin when insulin was added (P <.001). In the meantime, a significant toxicity of the drug to HepG2 cells was also observed. The betaTC3 cell line was used for insulin release testing, and no secretogogue effect of berberine was observed. These observations suggest that berberine is able to exert a glucose-lowering effect in hepatocytes, which is insulin independent and similar to that of metformin, but has no effect on insulin secretion.

  8. Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats.

    PubMed

    Dong, Shi-Fen; Hong, Ying; Liu, Ming; Hao, Ying-Zhi; Yu, Hai-Shi; Liu, Yang; Sun, Jian-Ning

    2011-06-25

    The positive effects of berberine (30 mg/kg/day, i.g. for 6 weeks) on cardiac dysfunction were evaluated in the rat model of hyperglycemia and hypercholesterolemia. Hyperglycemia and hypercholesterolemia were induced by feeding high-sucrose/fat diet (HSFD) consisting of 20% sucrose, 10% lard, 2.5% cholesterol, 1% bile salt for 12 weeks and streptozotocin (30 mg/kg, i.p.). The plasma sugar, total cholesterol, and triglyceride levels were significantly increased (422, 194 and 82%, respectively) in the HSFD/streptozotocin-treated rats, when compared with control animals receiving normal diet and vehicle. Berberine treatment reduced the plasma sugar and lipid levels by 24-69% in the rat model of hyperglycemia and hypercholesterolemia. Cardiac functions signed as values of cardiac output, left ventricular systolic pressure, the maximum rate of myocardial contraction (+dp/dtmax), left ventricular end diastolic pressure and the maximum rate of myocardial diastole (-dp/dtmax) were injured by 16-55% in the hyperglycemic/hypercholesterolemic rats. Berberine increased cardiac output, left ventricular systolic pressure and +dp/dtmax by 64, 16 and 79%, but decreased left ventricular end diastolic pressure and -dp/dtmax by 121 and 61% in the rats receiving HSFD/streptozotocin, respectively, when compared with the drug-untreated rats of hyperglycemia and hypercholesterolemia. Berberine caused significant increase in cardiac fatty acid transport protein-1 (159%), fatty acid transport proteins (56%), fatty acid beta-oxidase (52%), as well as glucose transporter-4 and peroxisome proliferator-activated receptor-γ (PPARγ), but decrease in PPARα mRNA and protein expression in hyperglycemic/hypercholesterolemic rats. These results indicated that berberine exerted protective effects on cardiac dysfunction induced by hyperglycemia/hypercholesterolemia through alleviating cardiac lipid accumulation and promoting glucose transport.

  9. Thousand fold concentration of an alkaloid in capillary zone electrophoresis by micelle to solvent stacking.

    PubMed

    Zhu, Hua-dong; Ren, Cui-ling; Hu, Shao-qiang; Zhou, Xi-min; Chen, Hong-li; Chen, Xing-guo

    2011-02-04

    In this paper, the co-solvent of methanol-water was used to facilitate the sodium dodecyl sulfate (SDS) micelles collapse, thereby inducing the on-line sample focusing technique of micelle to solvent stacking (MSS). To demonstrate this stacking method, the mechanism of micelles collapse in co-solvent was discussed. The details of the required conditions were investigated and the optimized conditions were: running buffer, 20mM H(3)BO(3) and 20mM NaH(2)PO(4) solution (pH 4.0); micellar sample matrix, 20mM SDS, 20mM H(3)BO(3) and 20mM NaH(2)PO(4) solution (pH 4.0); co-solvent buffer, 20mM H(3)BO(3) and 20mM NaH(2)PO(4) in methanol/water (90:10, v/v). The validity of the developed method was tested using cationic alkaloid compounds (ephedrine and berberine) as model analytes. Under the optimized conditions, this proposed method afforded limits of detection (LODs) of 0.5 and 1.1ng/mL with 300 and 1036-fold improvements in sensitivity for ephedrine and berberine, respectively, within 15min.

  10. Purine alkaloids in Paullinia.

    PubMed

    Weckerle, Caroline S; Stutz, Michael A; Baumann, Thomas W

    2003-10-01

    Among the few purine alkaloid-containing genera consumed as stimulants, Paullinia is the least investigated with respect to both chemotaxonomy and within-the-plant allocation of caffeine and its allies. Since purine alkaloids (PuA) have been proved to be valuable marker compounds in chemotaxonomy, 34 species of Paullinia and related genera were screened for them, but only one, P. pachycarpa, was positive in addition to the already known P. cupana and P. yoco. The PuA allocation in P. pachycarpa was examined and found to be restricted to theobromine in the stem, leaves and flowers. Moreover, the theobromine concentration in the stem cortex increased significantly towards the base of the plant. Since the stem cortex of P. yoco is traditionally used by the natives of Colombia and Ecuador to prepare a caffeine-rich beverage, we suspected that within the genus Paullinia the PuA are preferentially allocated to the older parts of the stem and not to young shoots like e.g., in the coffee plant (Coffea spp.). Indeed, the axis (greenhouse) of P. cupana (guaraná), known for its caffeine-rich seeds, exhibited a basipetal PuA gradient (0.005-0.145%). Moreover, the analysis of young cortex samples (herbarium) and of one piece of old stem (museum collection) revealed the same for P. yoco, even though we found much less (0.5 vs 2.5%) caffeine in the old cortex as compared to the only two analyses in 1926 of similar material. However, this discrepancy may be explained by the high variability of the PuA pattern we detected among yoco, the diversity of which the Indians take advantage.

  11. Berberine-induced anticancer activities in FaDu head and neck squamous cell carcinoma cells.

    PubMed

    Seo, Yo-Seob; Yim, Min-Ji; Kim, Bok-Hee; Kang, Kyung-Rok; Lee, Sook-Young; Oh, Ji-Su; You, Jae-Seek; Kim, Su-Gwan; Yu, Sang-Joun; Lee, Gyeong-Je; Kim, Do Kyung; Kim, Chun Sung; Kim, Jin-Soo; Kim, Jae-Sung

    2015-12-01

    In the present study, we investigated berberine‑induced apoptosis and the signaling pathways underlying its activity in FaDu head and neck squamous cell carcinoma cells. Berberine did not affect the viability of primary human normal oral keratinocytes. In contrast, the cytotoxicity of berberine was significantly increased in FaDu cells stimulated with berberine for 24 h. Furthermore, berberine increased nuclear condensation and apoptosis rates in FaDu cells than those in untreated control cells. Berberine also induced the upregulation of apoptotic ligands, such as FasL and TNF-related apoptosis-inducing ligand, and triggered the activation of caspase-8, -7 and -3, and poly(ADP ribose) polymerase, characteristic of death receptor-dependent extrinsic apoptosis. Moreover, berberine activated the mitochondria‑dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bax, Bad, Apaf-1, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. In addition, berberine increased the expression of the tumor suppressor p53 in FaDu cells. The pan-caspase inhibitor Z-VAD-fmk suppressed the activation of caspase-3 and prevented cytotoxicity in FaDu cells treated with berberine. Interestingly, berberine suppressed cell migration through downregulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38, components of the mitogen-activated protein kinase pathway that are associated with the expression of MMP and VEGF, was suppressed in FaDu cells treated with berberine for 24 h. Therefore, these data suggested that berberine exerted anticancer effects in FaDu cells through induction of apoptosis and suppression of migration. Berberine may have potential applications as a chemotherapeutic agent for the management of head and neck squamous carcinoma.

  12. Biosynthetic Pathways of Ergot Alkaloids

    PubMed Central

    Gerhards, Nina; Neubauer, Lisa; Tudzynski, Paul; Li, Shu-Ming

    2014-01-01

    Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes. PMID:25513893

  13. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

  14. Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization

    PubMed Central

    Piao, Meiyu; Cao, Hailong; He, NaNa; Yang, Boli; Dong, Wenxiao; Xu, Mengque; Yan, Fang; Zhou, Bing

    2016-01-01

    Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks. Primary macrophages were isolated; after berberine treatment, the change in signaling cascade was determined. The total number and size of polyps were reduced remarkably in berberine group, compared with control group. A significant decrease in protein levels of F4/80, mannose receptor (MR), and COX-2 in stroma of intestinal polyps and an increase in the level of iNOS were observed after berberine treatment. The mRNA level of MR and Arg-1 in berberine group was significantly lower than those in IL-10 or IL-4 group, while no significant difference in mRNA levels of iNOS and CXCL10 was observed. The migration and invasiveness assays in vitro showed that berberine could reduce the capability of migration and invasiveness. These findings suggest that berberine attenuates intestinal tumorigenesis by inhibiting the migration and invasion of colorectal tumor cells via regulation of macrophage polarization. PMID:27493671

  15. Effects of cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers.

    PubMed

    Huang, Zhaoyi; Lu, Fu'er; Dong, Hui; Xu, Lijun; Chen, Guang; Zou, Xin; Lei, Hongwei

    2011-06-01

    The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers, and the compatibility mechanism of Jiao-Tai-Wan (JTW) composed of Rhizoma Coptidis granules and Cinnamon granules were investigated. The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatography (HPLC) after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules (JTW). The plasma concentration-time curves of berberine were plotted. The data were analyzed with Drug and Statistics (DAS) 2.0 pharmacokinetic program (Chinese Pharmacology Society) to obtain the main pharmacokinetic parameters. The results showed that the plasma concentration-time curve of berberine was described by a two-compartment model. The C(max), T(max), t(1/2) and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 μg/L, 2.0 h, 3.882 h, 119.320 L·h(-1)·kg(-1) respectively, and those of berberine in JTW were 396.124 μg/L, 1.5 h, 4.727 h, 57.709 L·h(-1)·kg(-1) respectively. It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration of berberine, promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.

  16. Berberine Attenuates Axonal Transport Impairment and Axonopathy Induced by Calyculin A in N2a Cells

    PubMed Central

    Abid, Morad Dirhem Naji; Yan, Huanhuan; Huang, Hao; Wan, Limin; Feng, Zuohua; Chen, Juan

    2014-01-01

    Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD. PMID:24713870

  17. Organic anion-transporting polypeptides contribute to the hepatic uptake of berberine.

    PubMed

    Chen, Chen; Wu, Zhi-Tao; Ma, Lei-Lei; Ni, Xuan; Lin, Yun-Fei; Wang, Le; Chen, Ke-Ping; Huang, Cheng-gang; Pan, Guoyu

    2015-01-01

    1. The purpose of this study was to investigate the mechanism of hepatic uptake of berberine. Berberine accumulation in hepatocytes was found to be highly dependent on active uptake, which could not be explained by liver organic cation transporter (OCT) alone. 2. Our studies indicated that berberine uptake was significantly suppressed by rifampicin, cyclosporine A and glycyrrhizic acid, which act as specific inhibitors of different Oatp isoforms (Oatp1a1, Oatp1a4 and Oatp1b2) in rat hepatocytes. The combination of OCT and OATP inhibitors further reduced berberine accumulation in both rat and human hepatocytes. The uptake of berberine could be increased in human HEK293-OATP1B3 but not in OATP1B1-transfected HEK 293 cells. 3. Rifampicin could reduce the berberine liver extraction ratio (ER) and double its concentration in the effluent in isolated rat livers. Further in vivo study indicated that berberine plasma exposure could be significantly increased by co-administration of the OATP inhibitor rifampicin or the substrate rosuvastatin. 4. In conclusion, this study demonstrated that both OCT and OATP contribute to the accumulation of berberine in the liver. OATPs may have important roles in berberine liver disposition and potential clinically relevant drug--drug interactions.

  18. Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells.

    PubMed

    Wang, Ning; Wang, Xuanbin; Tan, Hor-Yue; Li, Sha; Tsang, Chi Man; Tsao, Sai-Wah; Feng, Yibin

    2016-11-15

    The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCF(β-TrCP)) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine's potential as an anti-tumor agent for clinical cancer therapy.

  19. Berberine sensitizes nasopharyngeal carcinoma cells to radiation through inhibition of Sp1 and EMT.

    PubMed

    Wang, Jun; Kang, Min; Wen, Qin; Qin, Yu-Tao; Wei, Zhu-Xin; Xiao, Jing-Jian; Wang, Ren-Sheng

    2017-04-01

    Nasopharyngeal carcinoma (NPC) is a tumor of epithelial origin with radiotherapy as its standard treatment. However, radioresistance remains a critical issue in the treatment of NPC. This study aimed to investigate the effect of berberine on the proliferation, cell cycle regulation, apoptosis, radioresistance of NPC cells and whether specificity protein 1 (Sp1) is a functional target of berberine. Our results showed that treatment with berberine reduced the proliferation and viability of CNE-2 cells in a dose- and time‑dependent manner. Berberine induced cell cycle arrest in the G0/G1 phase and apoptosis. In CNE-2 cells exposed to gamma‑ray irradiation, berberine reduced cell viability at various concentrations (25, 50, 75 and 100 µmol/l). Berberine significantly decreased mRNA and protein expression of Sp1 in the CNE-2 cells. Mithramycin A, a selective Sp1 inhibitor, enhanced the radiosensitivity and the rate of apoptosis in the CNE-2 cells. Berberine inhibited transforming growth factor-β (TGF-β)-induced tumor invasion and suppressed epithelial-to-mesenchymal transition (EMT) process, as evidenced by increased E-cadherin and decreased vimentin proteins. Sp1 may be required for the TGF-β1-induced invasion and EMT by berberine. In conclusion, berberine demonstrated the ability to suppress proliferation, induce cell cycle arrest and apoptosis, and enhance radiosensitivity of the CNE-2 NPC cells. Sp1 may be a target of berberine which is decreased during the radiosensitization of berberine.

  20. Berberine and Coptidis Rhizoma as potential anticancer agents: Recent updates and future perspectives.

    PubMed

    Wang, Ning; Tan, Hor-Yue; Li, Lei; Yuen, Man-Fung; Feng, Yibin

    2015-12-24

    The antineoplastic property of Coptidis Rhizoma and berberine was correlated with its traditional use of clearing internal fire, removing damp-heat and counteracting toxic pathogens. The anti-tumor effect of Coptidis Rhizoma and berberine was extensively studied since our last comprehensive review in 2009. This study aims to summarize the recent updates and give rise to perspectives of Coptidis Rhizoma and berberine as potential novel antineoplastic agents. Quality studies in recent 5 years were retrieved from PubMed, Medline and CNKI with keywords including Coptis, Coptidis Rhizoma, huanglian, berberine, tumor and cancer. Studies were focused on the pharmacological actions of Coptidis Rhizoma and berberine in cancer progression. It was shown that Coptidis Rhizoma extract and berberine may repress tumor progression by regressing abnormal cell proliferation, arresting cell cycle and inducing cell death. Studies also highlighted the actions of Coptidis Rhizoma extract and berberine in inhibiting tumor cell invasion and angiogenesis, which in turn abolish cancer metastasis. Some studies have also been conducted to reveal the potential effect of Coptidis Rhizoma extract and berberine in regulating tumor stromal microenvironment, as well as in preventing carcinogenesis. Most of the results have been demonstrated with in vivo models, but results of high-quality clinical trials are not yet available. Unspecified cancer type and staging, fluctuated dose information and variants of targets across studies of berberine/ Coptidis Rhizoma impede their clinical use for cancer treatment. Recent advances highlighted by this review may shed light on future direction of studies featuring Coptidis Rhizoma and berberine as novel antineoplastic agents, which should be repeatedly proven in future animal and clinical studies. Although more evidences on its specificity and clinical efficacy are necessary to support its clinical use, Coptidis Rhizoma and berberine are highly expected to be

  1. Simultaneous determination of eight alkaloids and oleandrin in herbal cosmetics by dispersive solid-phase extraction coupled with ultra high performance liquid chromatography and tandem mass spectrometry.

    PubMed

    Xun, Zhiqing; Liu, Donghong; Huang, Rongrong; He, Shuang; Hu, Du; Guo, Xindong; Xian, Yanping

    2017-03-20

    We utilized ultra high performance liquid chromatography with tandem mass spectrometry and dispersive solid-phase extraction to develop a new method for the detection of nine analytes (scopolamine, cephaeline, strychnine, hyoscyamine, brucine, hydrastine, ajmalicine, colchicine and oleandrin) in herbal cosmetics. Acetonitrile/water and 2-propylaminoethylamine were used to disperse and purify during the dispersive solid-phase extraction step. The analytes were separated by a Waters UPLC HSS T3 column and detected through electrospray ionization source in the positive mode with multi-reaction monitoring conditions. Under the optimal conditions, the calibration curves were linear in the range of 0.2-100.0 μg L(-1) with the correlation coefficients higher than 0.995. The method limit of quantitation (S/N = 10) were 5.0 μg kg(-1) for oleandrin and 1.0 μg kg(-1) for the other eight alkaloids. The mean recoveries at three spiked concentration levels of 1.0-10.0 μg kg(-1) were in the range of 86.9-116.5% with the intra-day relative standard deviations (n = 6) ranging from 2.4 to 8.8%, and inter-day relative standard deviations ranging from 2.7 to 5.7%. This method is accurate, simple and rapid, and has been applied to the quality supervision of herbal cosmetics in Guangzhou. This article is protected by copyright. All rights reserved.

  2. Inhibitory Effects of Coptidis rhizoma and Berberine on Cocaine-induced Sensitization

    PubMed Central

    Lee, Bombi; Yang, Chae Ha; Hahm, Dae-Hyun; Choe, Eun Sang; Lee, Hye-Jung; Pyun, Kwang-Ho; Shim, Insop

    2009-01-01

    Substantial evidence suggests that the behavioral and reinforcing effects of cocaine can be mediated by the central dopaminergic systems. Repeated injections of cocaine produce an increase in locomotor activity and the expression of tyrosine hydroxylase (TH) in the main dopaminergic areas. Protoberberine alkaloids affect neuronal functions. Coptidis rhizoma (CR) and its main compound, berberine (BER) reduced the dopamine content in the central nervous system. In order to investigate the effects of CR or BER on the repeated cocaine-induced neuronal and behavioral alterations, we examined the influence of CR or BER on the repeated cocaine-induced locomotor activity and the expression of TH in the brain by using immunohistochemistry. Male SD rats were given repeated injections of saline or cocaine hydrochloride (15 mg/kg, i.p. for 10 consecutive days) followed by one challenge injection on the 4th day after the last daily injection. Cocaine challenge (15 mg/kg, i.p) produced a larger increase in locomotor activity and expression of TH in the central dopaminergic areas. Pretreatment with CR (50, 100, 200 and 400 mg/kg, p.o.) and BER (200 mg/kg, p.o.) 30 min before the daily injections of cocaine significantly inhibited the cocaine-induced locomotor activity as well as TH expression in the central dopaminergic areas. Our data demonstrate that the inhibitory effects of CR and BER on the repeated cocaine-induced locomotor activity were closely associated with the reduction of dopamine biosynthesis and post-synaptic neuronal activity. These results suggest that CR and BER may be effective for inhibiting the behavioral effects of cocaine by possibly modulating the central dopaminergic system. PMID:18955248

  3. Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats.

    PubMed

    Chen, Xueyan; Zhang, Yu; Zhu, Zhongning; Liu, Huanlong; Guo, Huicai; Xiong, Chen; Xie, Kerang; Zhang, Xiaofei; Su, Suwen

    2016-05-01

    Doxorubicin (DOX), a potent broad‑spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non‑target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX‑induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX‑induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX‑induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX‑induced hepatorenal toxicity in clinical practice.

  4. Antiproliferative effect of berberine on canine mammary gland cancer cell culture.

    PubMed

    Sefidabi, Reyhaneh; Mortazavi, Pejman; Hosseini, Saeed

    2017-01-01

    Canine mammary gland tumors are the most frequent cause of cancer in female dogs. Numerous studies using cancer cell lines and clinical trials have indicated that various natural products and antioxidants reduce or possibly prevent the development of cancer. Berberine (BBR), the most important alkaloid in the Berberidaceae, which exerts a wide range of pharmacological and biochemical effects, has drawn much attention due to its particularly high antitumor activity in vitro and in animal studies. The aim of the present study was to investigate the antiproliferative effect of BBR against a canine mammary gland carcinoma cell line (CF41.Mg) in vitro. CF41.Mg cells were cultured in RPMI-1640 medium containing 10% heat inactived fetal bovine serum (FBS) and 100 mg/ml peniciline-streptomycin. Subsequently the cells were treated with different concentrations of BBR chloride (10, 25, 50, 100 and 200 µM) at a density of 12,000 cells/well in 96-well plates. Following treatment, the MTT assay was used to detect cell viability after 24-, 48- and 72-h incubations at 37°C with 5% CO2. The results indicated that BBR inhibited proliferation of canine mammary gland carcinoma cells, as treatment with 100 µM BBR for 24 h resulted in a significant decrease in cell viability (P<0.005). As the present study demonstrated that BBR (10-200 µM) induced cancer cell death, it is proposed that BBR may serve as a candidate agent against canine mammary tumor cells via its antiproliferative activity.

  5. The cathedulin alkaloids.

    PubMed

    Crombie, L

    1980-01-01

    Studies on fresh and dried leaf and shoot material of Catha edulis (khat) collected in Ethiopia, Kenya and the Yemen Arab Republic have led to the isolation, separation and characterization of new celastraceous alkaloids, the cathedulins, with molecular weights in the 600-1,200 range. All the cathedulins whose structures have been investigated prove to be polyesters or lactones of a sesquiterpene polyol core and fall into three groups: (a) low molecular weight esters of pentahydroxydihydroagarofuran; (b) cathedulins of medium molecular weight characterized by the possession of a euonyminol core and an evonimic acid dilactone bridge; and (c) high molecular weight, more complex esters of euonyminol. Chemical evidence and spectral data were used in assigning structures to the cathedulins studied as well as in placing the various esterifying acids on the different hydroxyl positions of the sesquiterpene core. In addition to cathedulins, neutral products isolated from khat include beta-sitosterol and its glycoside, friedeline, and hydroxylated delta 4-exo-relatives of the latter. Moreover, the pigmented root-bark contains triterpenoid quinones including celastrol, pristimerin, iguesterin and tingenone (tingenin A and B).

  6. Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine.

    PubMed

    Dziedzic, Arkadiusz; Kubina, Robert; Bułdak, Rafał J; Skonieczna, Magda; Cholewa, Krzysztof

    2016-03-17

    The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles

  7. Spectrofluorometric determination of DNA and RNA with berberine

    NASA Astrophysics Data System (ADS)

    Gong, Guo-Quan; Zong, Zhi-Xin; Song, Yu-Min

    1999-08-01

    On binding to nucleic acids, the dye berberine increases its fluorescence quantum efficiency by a factor of 25-30. Based on this, an easy, rapid and accurate method for the determination of nucleic acids was developed. Berberine is very like ethidium bromide (EB), but it is non-poisonous. Determination can be made at any pH between 4 and 10, where the native structure of DNA and RNA is not disrupted. The maximum emission is near 520 nm for excitation at 355 or 450 nm. This method has good sensitivity (0.01 μg ml -1 of ctDNA), high selectivity and a wide linear range (0.05-14.0 μg ml -1 of ctDNA).

  8. Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-α and PPAR-γ.

    PubMed

    Choi, Jae Sue; Kim, Ji-Hye; Ali, Md Yousof; Min, Byung-Sun; Kim, Gun-Do; Jung, Hyun Ah

    2014-10-01

    Obesity is a complex, multifactorial, and chronic disease that increases the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. Developing novel anti-obesity drugs from natural products is a promising solution to the global health problem of obesity. While screening anti-obesity potentials of natural products, the methanol extract of the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine, palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the methanol extract of Coptidis Rhizoma. We determined the chemical structure of these alkaloids through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these alkaloids for their ability to inhibit adipogenesis over a range of concentrations (12.5-50 μM). All five Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability in a concentration dependent manner. In addition, the five alkaloids significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein-α (C/EBP-α). In the present study, we found that the isolated alkaloids inhibited adipogenesis in a dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their abilities to downregulate the protein levels of the adipocyte marker proteins PPAR-γ and C/EBP-α. Thus, these results suggest that Coptidis Rhizoma extract and its isolated alkaloids may be of therapeutic interest with respect to the treatment of obesity.

  9. The Chemistry of the Akuammiline Alkaloids.

    PubMed

    Adams, Gregory L; Smith, Amos B

    2016-01-01

    An update on the literature covering the akuammiline family of alkaloids is presented. This chapter begins with a summary of new akuammiline alkaloids reported since 2000 and is followed by an overview of new reported bioactivities of akuammiline alkaloids since 2000. The remainder of the chapter comprises a comprehensive review of the synthetic chemistry that has been reported in the last 50 years concerning akuammiline alkaloids and their structural motifs.

  10. Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.

    PubMed

    Xu, X; Malavé, A

    2001-05-01

    The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitrite+nitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.

  11. Berberine ameliorates nonbacterial prostatitis via multi-target metabolic network regulation.

    PubMed

    Sun, Hui; Wang, Huiyu; Zhang, Aihua; Yan, Guangli; Zhang, Yue; An, Na; Wang, Xijun

    2015-03-01

    Metabolomics has been increasingly applied to discovering biomarkers and identifying perturbed pathways. Berberine has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties, but its mechanisms for treating nonbacterial prostatitis (NBP) remain unclear completely. We developed the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the metabolite changes in urine samples in order to discover novel potential biomarkers to clarify mechanisms of berberine in treating a rat model of capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic profiling were restored to their base-line values after berberine treatment according to the principal component analysis (PCA) score plots. Fourteen different potential biomarkers and five acutely perturbed metabolic pathways contributing to the treatment of NBP were discovered and identified. Specifically, the berberine-treated rats are located closer to the normal group, indicating that the NBP-induced disturbances to the metabolic profile were partially reversed by berberine treatment. After treatment with berberine, the relative contents of 12 potential biomarkers were effectively regulated, which suggested that the therapeutic effects of berberine on NBP may involve regulating disturbances to the metabolism. Our results show that the protective effect of berberine occurs in part through a reversal of the NBP-caused disturbances.

  12. Berberine Suppresses Cyclin D1 Expression through Proteasomal Degradation in Human Hepatoma Cells

    PubMed Central

    Wang, Ning; Wang, Xuanbin; Tan, Hor-Yue; Li, Sha; Tsang, Chi Man; Tsao, Sai-Wah; Feng, Yibin

    2016-01-01

    The aim of this study is to explore the underlying mechanism on berberine-induced Cyclin D1 degradation in human hepatic carcinoma. We observed that berberine could suppress both in vitro and in vivo expression of Cyclin D1 in hepatoma cells. Berberine exhibits dose- and time-dependent inhibition on Cyclin D1 expression in human hepatoma cell HepG2. Berberine increases the phosphorylation of Cyclin D1 at Thr286 site and potentiates Cyclin D1 nuclear export to cytoplasm for proteasomal degradation. In addition, berberine recruits the Skp, Cullin, F-box containing complex-β-Transducin Repeat Containing Protein (SCFβ-TrCP) complex to facilitate Cyclin D1 ubiquitin-proteasome dependent proteolysis. Knockdown of β-TrCP blocks Cyclin D1 turnover induced by berberine; blocking the protein degradation induced by berberine in HepG2 cells increases tumor cell resistance to berberine. Our results shed light on berberine′s potential as an anti-tumor agent for clinical cancer therapy. PMID:27854312

  13. Berberine Ameliorates Nonbacterial Prostatitis via Multi-Target Metabolic Network Regulation

    PubMed Central

    Sun, Hui; Wang, Huiyu; Zhang, Aihua; Yan, Guangli; Zhang, Yue; An, Na

    2015-01-01

    Abstract Metabolomics has been increasingly applied to discovering biomarkers and identifying perturbed pathways. Berberine has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties, but its mechanisms for treating nonbacterial prostatitis (NBP) remain unclear completely. We developed the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the metabolite changes in urine samples in order to discover novel potential biomarkers to clarify mechanisms of berberine in treating a rat model of capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic profiling were restored to their base-line values after berberine treatment according to the principal component analysis (PCA) score plots. Fourteen different potential biomarkers and five acutely perturbed metabolic pathways contributing to the treatment of NBP were discovered and identified. Specifically, the berberine-treated rats are located closer to the normal group, indicating that the NBP-induced disturbances to the metabolic profile were partially reversed by berberine treatment. After treatment with berberine, the relative contents of 12 potential biomarkers were effectively regulated, which suggested that the therapeutic effects of berberine on NBP may involve regulating disturbances to the metabolism. Our results show that the protective effect of berberine occurs in part through a reversal of the NBP-caused disturbances. PMID:25588034

  14. The influence of clay surface modification with berberine on the sorption of anthocyanins

    NASA Astrophysics Data System (ADS)

    Chulkov, A. N.; Deineka, V. I.; Tikhova, A. A.; Vesentzev, A. I.; Deineka, L. A.

    2012-03-01

    The influence of preliminary sorption of berberine on the sorption of anthocyanins by bentonite clay was studied. The cation exchange sorption mechanism was found to be replaced by hydrophobic sorption of these compounds after clay modification with berberine. The enthalpy of sorption along the initial isotherm part changed from endothermic to exothermic.

  15. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis.

    PubMed

    Dong, Hui; Wang, Nan; Zhao, Li; Lu, Fuer

    2012-01-01

    Objectives. To assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus (T2DM). Methods. Randomized trials of berberine compared with lifestyle modification, placebo, and/or oral hypoglycaemics intervention on treating T2DM were included. Study population characteristics and outcome results were extracted independently by two reviewers. Meta-analyses were performed for data available. Results. Fourteen randomized trials, involving 1068 participants, were included in this study. Methodological quality was generally low. Compared with lifestyle modification with or without placebo, the cointervention of berberine and lifestyle modification showed significantly hypoglycaemic and antidyslipidemic response. Compared with oral hypoglycaemics including metformin, glipizide, or rosiglitazone, berberine did not demonstrate a significantly better glycaemic control but showed a mild antidyslipidemic effect. Compared with oral hypoglycaemic drugs, cointerventions with berberine and the same oral hypoglycaemics showed a better glycaemic control. No serious adverse effects from berberine were reported. Conclusions. Berberine appeared to be efficacious for treating hyperglycaemia and dyslipidemia in T2DM. However, the evidence of berberine for treating T2DM should be carefully interpreted due to the low methodological quality, small sample size, limited number of trials, and unidentified risks of bias.

  16. Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.

    PubMed

    Wu, Xiao-Ke; Wang, Yong-Yan; Liu, Jian-Ping; Liang, Rui-Ning; Xue, Hui-Ying; Ma, Hong-Xia; Shao, Xiao-Guang; Ng, Ernest H Y

    2016-09-01

    To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). A multicenter randomized double-blinded placebo-controlled trial. Reproductive and developmental network sites. Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups. Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant. Cumulative live births. The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group. Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole. ChiCTR-TRC-09000376 (http://apps.who.int/trialsearch/). Copyright © 2016. Published by Elsevier Inc.

  17. Mitochondria and NMDA Receptor-Dependent Toxicity of Berberine Sensitizes Neurons to Glutamate and Rotenone Injury

    PubMed Central

    Kysenius, Kai; Brunello, Cecilia A.; Huttunen, Henri J.

    2014-01-01

    The global incidence of metabolic and age-related diseases, including type 2 diabetes and Alzheimer's disease, is on the rise. In addition to traditional pharmacotherapy, drug candidates from complementary and alternative medicine are actively being pursued for further drug development. Berberine, a nutraceutical traditionally used as an antibiotic, has recently been proposed to act as a multi-target protective agent against type 2 diabetes, dyslipidemias, ischemic brain injury and neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. However, the safety profile of berberine remains controversial, as isolated reports suggest risks with acute toxicity, bradycardia and exacerbation of neurodegeneration. We report that low micromolar berberine causes rapid mitochondria-dependent toxicity in primary neurons characterized by mitochondrial swelling, increased oxidative stress, decreased mitochondrial membrane potential and depletion of ATP content. Berberine does not induce caspase-3 activation and the resulting neurotoxicity remains unaffected by pan-caspase inhibitor treatment. Interestingly, inhibition of NMDA receptors by memantine and MK-801 completely blocked berberine-induced neurotoxicity. Additionally, subtoxic nanomolar concentrations of berberine were sufficient to sensitize neurons to glutamate excitotoxicity and rotenone injury. Our study highlights the need for further safety assessment of berberine, especially due to its tendency to accumulate in the CNS and the risk of potential neurotoxicity as a consequence of increasing bioavailability of berberine. PMID:25192195

  18. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  19. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  20. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  1. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  2. 27 CFR 21.99 - Brucine alkaloid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Brucine alkaloid. 21.99... Brucine alkaloid. (a) Identification test. Add a few drops of concentrated nitric acid to about 10 mg of brucine alkaloid. A vivid red color is produced. Dilute the red solution with a few drops of water and...

  3. Time-Dependent Inhibition of CYP2C19 by Isoquinoline Alkaloids: In Vitro and In Silico Analysis.

    PubMed

    Salminen, Kaisa A; Rahnasto-Rilla, Minna; Väänänen, Raija; Imming, Peter; Meyer, Achim; Horling, Aline; Poso, Antti; Laitinen, Tuomo; Raunio, Hannu; Lahtela-Kakkonen, Maija

    2015-12-01

    The cytochrome P450 2C19 (CYP2C19) enzyme plays an important role in the metabolism of many commonly used drugs. Relatively little is known about CYP2C19 inhibitors, including compounds of natural origin, which could inhibit CYP2C19, potentially causing clinically relevant metabolism-based drug interactions. We evaluated a series (N = 49) of structurally related plant isoquinoline alkaloids for their abilities to interact with CYP2C19 enzyme using in vitro and in silico methods. We examined several common active alkaloids found in herbal products such as apomorphine, berberine, noscapine, and papaverine, as well as the previously identified mechanism-based inactivators bulbocapnine, canadine, and protopine. The IC50 values of the alkaloids ranged from 0.11 to 210 µM, and 42 of the alkaloids were confirmed to be time-dependent inhibitors of CYP2C19. Molecular docking and three-dimensional quantitative structure-activity relationship analysis revealed key interactions of the potent inhibitors with the enzyme active site. We constructed a comparative molecular field analysis model that was able to predict the inhibitory potency of a series of independent test molecules. This study revealed that many of these isoquinoline alkaloids do have the potential to cause clinically relevant drug interactions. These results highlight the need for studying more profoundly the potential interactions between drugs and herbal products. When further refined, in silico methods can be useful in the high-throughput prediction of P450 inhibitory potential of pharmaceutical compounds.

  4. Synergetic cholesterol-lowering effects of main alkaloids from Rhizoma Coptidis in HepG2 cells and hypercholesterolemia hamsters.

    PubMed

    Kou, Shuming; Han, Bing; Wang, Yue; Huang, Tao; He, Kai; Han, Yulong; Zhou, Xia; Ye, Xiaoli; Li, Xuegang

    2016-04-15

    Hyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids. The cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured. As compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation. Our results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Selectivity of major isoquinoline alkaloids from Chelidonium majus towards telomeric G-quadruplex: A study using a transition-FRET (t-FRET) assay.

    PubMed

    Noureini, Sakineh Kazemi; Esmaeili, Hosein; Abachi, Farzane; Khiali, Soraia; Islam, Barira; Kuta, Martyna; Saboury, Ali A; Hoffmann, Marcin; Sponer, Jiri; Parkinson, Gary; Haider, Shozeb

    2017-08-01

    Natural bioproducts are invaluable resources in drug discovery. Isoquinoline alkaloids of Chelidonium majus constitute a structurally diverse family of natural products that are of great interest, one of them being their selectivity for human telomeric G-quadruplex structure and telomerase inhibition. The study focuses on the mechanism of telomerase inhibition by stabilization of telomeric G-quadruplex structures by berberine, chelerythrine, chelidonine, sanguinarine and papaverine. Telomerase activity and mRNA levels of hTERT were estimated using quantitative telomere repeat amplification protocol (q-TRAP) and qPCR, in MCF-7 cells treated with different groups of alkaloids. The selectivity of the main isoquinoline alkaloids of Chelidonium majus towards telomeric G-quadruplex forming sequences were explored using a sensitive modified thermal FRET-melting measurement in the presence of the complementary oligonucleotide CT22. We assessed and monitored G-quadruplex topologies using circular dichroism (CD) methods, and compared spectra to previously well-characterized motifs, either alone or in the presence of the alkaloids. Molecular modeling was performed to rationalize ligand binding to the G-quadruplex structure. The results highlight strong inhibitory effects of chelerythrine, sanguinarine and berberine on telomerase activity, most likely through substrate sequestration. These isoquinoline alkaloids interacted strongly with telomeric sequence G-quadruplex. In comparison, chelidonine and papaverine had no significant interaction with the telomeric quadruplex, while they strongly inhibited telomerase at transcription level of hTERT. Altogether, all of the studied alkaloids showed various levels and mechanisms of telomerase inhibition. We report on a comparative study of anti-telomerase activity of the isoquinoline alkaloids of Chelidonium majus. Chelerythrine was most effective in inhibiting telomerase activity by substrate sequesteration through G

  6. Berberine sensitizes ovarian cancer cells to cisplatin through miR-21/PDCD4 axis.

    PubMed

    Liu, Shiguo; Fang, Yue; Shen, Huiling; Xu, Wenlin; Li, Hao

    2013-09-01

    Recent studies have shown that microRNA-21 (miR-21) contributes to tumor resistance to chemotherapy. Interestingly, we have found that berberine could inhibit miR-21 expression in several cancer cell lines. In this study, we investigated whether berberine could modulate the sensitivity of ovarian cancer cells to cisplatin and explored the mechanism. The cisplatin-resistant SKOV3 cells that were incubated with berberine combined with cisplatin had a significantly lower survival than the cisplatin alone group and enhanced cisplatin-induced apoptosis. Berberine could inhibit miR-21 expression and function in ovarian cancer, as shown by an enhancement of its target PDCD4, an important tumor suppressor in ovarian cancer. The results suggested that berberine could modulate the sensitivity of cisplatin via regulating miR-21/PDCD4 axis in the ovarian cancer cells.

  7. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice.

    PubMed

    Hu, Yueshan; Davies, Gareth E

    2010-07-01

    Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARgamma expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

  8. Isolation and identification of berberine and berberrubine metabolites by berberine-utilizing bacterium Rhodococcus sp. strain BD7100.

    PubMed

    Ishikawa, Kazuki; Takeda, Hisashi; Wakana, Daigo; Sato, Fumihiko; Hosoe, Tomoo

    2016-05-01

    Based on the finding of a novel berberine (BBR)-utilizing bacterium, Rhodococcus sp. strain BD7100, we investigated the degradation of BBR and its analog berberrubine (BRU). Resting cells of BD7100 demethylenated BBR and BRU, yielding benzeneacetic acid analogs. Isolation of benzeneacetic acid analogs suggested that BD7100 degraded the isoquinoline ring of the protoberberine skeleton. This work represents the first report of cleavage of protoberberine skeleton by a microorganism.

  9. Piperidine alkaloids from Alocasia macrorrhiza.

    PubMed

    Huang, Wenjie; Yi, Xiaomin; Feng, Jianying; Wang, Yihai; He, Xiangjiu

    2017-11-01

    Six previously undescribed piperidine alkaloids were isolated from the rhizomes of Alocasia macrorrhiza (L.) Schott. Their structures were elucidated based on 1D and 2D NMR, IR, HR-ESI-MS spectroscopic analysis and the application of a modified Mosher method. All isolated alkaloids were evaluated for cytotoxicity against five human cancer cell lines (CNE-1, Detroit 562, Fadu, MGC-803, and MCF-7) using the MTT method. Only one compound exhibited cytotoxic effects against Detroit 562, Fadu, and MCF-7 cell lines with IC50 values less than 10 μM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Determination of berberine and the study of fluorescence quenching mechanism between berberine and enzyme-catalyzed product

    NASA Astrophysics Data System (ADS)

    Wang, Huaiyou; Zhang, Miao; Lv, Qingluan; Yue, Ningning; Gong, Bin

    2009-08-01

    A new method for determining berberine has been established based on the principle of fluorescence quenching. The calibration curve was found to be linear between F0/ F and the concentration of berberine with the range of 3.00-20.0 μg mL -1. The detection limit was 0.51 μg mL -1 and the relative standard derivative was 0.18%. Effects of pH, foreign ions and the optimization of variables on the determination of berberine have been examined. The mechanism of the fluorescence quenching has been discussed. The binding constant and the number of binding sites were 1.70 × 10 6 L mol -1 and 1.14, respectively. The data, Δ H = 42.71 kJ mol -1, Δ S = 264.3 J K -1 mol -1 and the mean value Δ G = -39.65 kJ mol -1 were estimated which showed that the reaction was spontaneous and endothermic. The main binding force was hydrophobic force because both Δ H and Δ S were positive.

  11. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways.

    PubMed

    Yu, Yunli; Hao, Gang; Zhang, Quanying; Hua, Wenyan; Wang, Meng; Zhou, Wenjia; Zong, Shunlin; Huang, Ming; Wen, Xiaozhou

    2015-09-15

    Our previous studies revealed that berberine-mediated GLP-1 secretion was a possible mechanism for berberine exerting good effects on hyperglycemia. This study was designed to ascertain whether berberine-induced secretion of GLP-1 was related with activation of bitter taste receptors expressed in gastrointestinal tract. Western blotting results showed that TAS2R38, a subtype of bitter taste receptor, was expressed on human enteroendocrine NCI-H716 cells. GLP-1 secretion induced by berberine from NCI-H716 cells was inhibited by incubation with anti-TAS2R38 antibody. We further performed gene silencing using siRNA to knockdown TAS2R38 from NCI-H716 cells, which showed that siRNA knockdown of the TAS2R38 reduced berberine-mediated GLP-1 secretion. We adopted inhibitors of PLC and TRPM5 known to be involved in bitter taste transduction to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. It was found that PLC inhibitor U73122 inhibited berberine-induced GLP-1 release in NCI-H716 cells, while TRPM5 blocker quinine failed to attenuate berberine-induced secretion of GLP-1. The present results demonstrated that berberine stimulated GLP-1 secretion via activation of gut-expressed bitter taste receptors in a PLC-dependent manner. Because berberine was found to be a ligand of bitter taste receptor, the results of present study may provide an explanation for some bitter taste substance obtain hypoglycemic effect.

  12. Fungal Indole Alkaloid Biosynthesis: Genetic and Biochemical Investigation of Tryptoquialanine Pathway in Penicillium aethiopicum

    PubMed Central

    Gao, Xue; Chooi, Yit-Heng; Ames, Brian D.; Wang, Peng; Walsh, Christopher T.; Tang, Yi

    2011-01-01

    Tremorgenic mycotoxins are a group of indole alkaloids which include the quinazoline-containing tryptoquivaline 2 that are capable of eliciting intermittent or sustained tremors in vertebrate animals. The biosynthesis of this group of bioactive compounds, which are characterized by an acetylated quinazoline ring connected to a 6-5-5 imidazoindolone ring system via a 5-membered spirolactone, has remained uncharacterized. Here, we report the identification of a gene cluster (tqa) from P. aethiopicum that is involved in the biosynthesis of tryptoquialanine 1, which is structurally similar to 2. The pathway has been confirmed to go through an intermediate common to the fumiquinazoline pathway, fumiquinazoline F, which originates from a fungal trimodular nonribosomal peptide synthetase (NRPS). By systematically inactivating every biosynthetic gene in the cluster, followed by isolation and characterization of the intermediates, we were able to establish the biosynthetic sequence of the pathway. An unusual oxidative opening of the pyrazinone ring by an FAD-dependent berberine bridge enzyme-like oxidoreductase has been proposed based on genetic knockout studies. Notably, a 2-aminoisobutyric acid (AIB)-utilizing NRPS module has been identified and reconstituted in vitro, along with two putative enzymes of unknown functions that are involved in the synthesis of the unnatural amino acid by genetic analysis. This work provides new genetic and biochemical insights into the biosynthesis of this group of fungal alkaloids, including the tremorgens related to 2. PMID:21299212

  13. Fungal indole alkaloid biosynthesis: genetic and biochemical investigation of the tryptoquialanine pathway in Penicillium aethiopicum.

    PubMed

    Gao, Xue; Chooi, Yit-Heng; Ames, Brian D; Wang, Peng; Walsh, Christopher T; Tang, Yi

    2011-03-02

    Tremorgenic mycotoxins are a group of indole alkaloids which include the quinazoline-containing tryptoquivaline (2) that are capable of eliciting intermittent or sustained tremors in vertebrate animals. The biosynthesis of this group of bioactive compounds, which are characterized by an acetylated quinazoline ring connected to a 6-5-5 imidazoindolone ring system via a 5-membered spirolactone, has remained uncharacterized. Here, we report the identification of a gene cluster (tqa) from P. aethiopicum that is involved in the biosynthesis of tryptoquialanine (1), which is structurally similar to 2. The pathway has been confirmed to go through an intermediate common to the fumiquinazoline pathway, fumiquinazoline F, which originates from a fungal trimodular nonribosomal peptide synthetase (NRPS). By systematically inactivating every biosynthetic gene in the cluster, followed by isolation and characterization of the intermediates, we were able to establish the biosynthetic sequence of the pathway. An unusual oxidative opening of the pyrazinone ring by an FAD-dependent berberine bridge enzyme-like oxidoreductase has been proposed based on genetic knockout studies. Notably, a 2-aminoisobutyric acid (AIB)-utilizing NRPS module has been identified and reconstituted in vitro, along with two putative enzymes of unknown functions that are involved in the synthesis of the unnatural amino acid by genetic analysis. This work provides new genetic and biochemical insights into the biosynthesis of this group of fungal alkaloids, including the tremorgens related to 2.

  14. Transcript and metabolite profiling in cell cultures of 18 plant species that produce benzylisoquinoline alkaloids.

    PubMed

    Farrow, Scott C; Hagel, Jillian M; Facchini, Peter J

    2012-05-01

    Benzylisoquinoline alkaloids (BIAs) are a large and diverse group of ~2500 specialized metabolites found predominantly in plants of the order Ranunculales. Research focused on BIA metabolism in a restricted number of plant species has identified many enzymes and cognate genes involved in the biosynthesis of compounds such as morphine, sanguinarine and berberine. However, the formation of most BIAs remains uncharacterized at the molecular biochemical level. Herein a compendium of sequence- and metabolite-profiling resources from 18 species of BIA-accumulating cell cultures was established, representing four related plant families. Our integrated approach consisted of the construction of EST libraries each containing approximately 3500 unigenes per species for a total of 58,787 unigenes. The EST libraries were manually triaged using known BIA-biosynthetic genes as queries to identify putative homologs with similar or potentially different functions. Sequence resources were analyzed in the context of the targeted metabolite profiles obtained for each cell culture using electrospray-ionization and collision-induced dissociation mass spectrometry. Fragmentation analysis was used for the identification or structural characterization coupled with the relative quantification of 72 BIAs, which establishes a key resource for future work on alkaloid biosynthesis. The metabolite profile obtained for each species provides a rational basis for the prediction of enzyme function in BIA metabolism. The metabolic frameworks assembled through the integration of transcript and metabolite profiles allow a comparison of BIA metabolism across several plant species and families. Taken together, these data represent an important tool for the discovery of BIA biosynthetic genes.

  15. Alkaloids with antioxidant activities from Aconitum handelianum.

    PubMed

    Yin, Tian-Peng; Cai, Le; Xing, Yun; Yu, Jing; Li, Xue-Jiao; Mei, Rui-Feng; Ding, Zhong-Tao

    2016-06-01

    A new C20-diterpenoid alkaloid handelidine (1) and twenty-seven known alkaloids (2-28) were isolated from the roots of Aconitum handelianum. Their structures were established on the basis of extensive spectroscopic analyses. The study indicated that denudatine-type C20-diterpenoid alkaloids with vicinal-triol system and benzyltetrahydroisoquinoline alkaloids exhibited significant antioxidant activities measured by three antioxidant test systems. The aconitine-type C19-diterpenoid alkaloids could serve as potential secondary antioxidants for their strong binding effects to metal ions.

  16. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte.

    PubMed

    Choi, Bong-Hyuk; Ahn, In-Sook; Kim, Yu-Hee; Park, Ji-Won; Lee, So-Young; Hyun, Chang-Kee; Do, Myoung-Sool

    2006-12-31

    Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.

  17. In vitro and in vivo antitumor efficacy of berberine-nanostructured lipid carriers against H22 tumor

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-ping; Wu, Jun-biao; Chen, Tong-sheng; Zhou, Qun; Wang, Yi-fei

    2015-03-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded nanostructured lipid carriers (Ber-NLC) was prepared by hot melting and then high pressure homogenization technique. Both in vitro and in vivo anti-hepatocarcinoma effects of Ber-NLC relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NLC were 189.3 nm and -19.3 mV, respectively. MTT assay showed that Ber-NLC effectively inhibited the proliferation of H22 cells, and the corresponding IC50 values were 6.3 μg/ml (22.1 μg/ml of bulk Ber). In vivo studies also showed higher antitumor efficacy, and inhibition rates was 68.3 % (41.4 % of bulk Ber) at 100 mg/kg intragastric administration in the H22 solid tumor bearing mice. These results suggest that the delivery of Ber-NLC is a promising approach for treating tumors.

  18. Epiberberine, a natural protoberberine alkaloid, inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism.

    PubMed

    Tan, Lihua; Li, Cailan; Chen, Hanbin; Mo, Zhizhun; Zhou, Jiangtao; Liu, Yuhong; Ma, Zhilin; Xu, Yuyao; Yang, Xiaobo; Xie, Jianhui; Su, Ziren

    2017-02-04

    In our previous study, Rhizoma Coptidis extract was found to exert more potent inhibitory effect than its major component berberine towards urease from Helicobacter pylori (HPU) and jack bean (JBU). In continuation of our work, the present study was designed to further comparatively investigate the urease inhibitory activities of five major protoberberine alkaloids in Rhizoma Coptidis, namely berberine, palmatine, coptisine, epiberberine, jateorhizine to identify the bioactive constituent, and illuminate the potential mechanism of action. Results indicated that the five protoberberine alkaloids acted as concentration-dependent inactivators of urease with IC50 values ranging between 3.0 and 5087μM for HPU and 2.3->10,000μM for JBU, respectively. Notably, epiberberine (EB) was found to be the most potent inhibitor against both ureases with IC50 values of 3.0±0.01μM for HPU and 2.3±0.01μM for JBU, which was more effective than the standard urease inhibitor, acetohydroxamic acid (83±0.01μM for HPU and 22±0.01μM for JBU, respectively). Further kinetic analysis revealed that the type of EB inhibition against HPU was slow-binding and uncompetitive, with Ki of 10.6±0.01μM, while slow-binding and competitive against JBU with Ki of 4.6±0.01μM. Addition of thiol reagents, such as l-cysteine, glutathione and dithiothreitol, significantly abolished the inhibition, while Ni(2+) competitive inhibitors, boric acid and sodium fluoride, synergetically inhibited urease with EB, indicating the obligatory role of the active site sulfhydryl group for the inhibition. In addition, binding of EB with the urease proved to be reversible, as about 65% and 90% enzymatic activity of HPU and JBU, respectively, could be restored by dithiothreitol application. These findings highlighted the potential role of Rhizoma Coptidis protoberberine alkaloids, especially EB, as a lead urease inhibitor in the treatment of diseases associated with ureolytic bacteria. Thus, EB had good potential

  19. Structural and quantitative analysis of Equisetum alkaloids.

    PubMed

    Cramer, Luise; Ernst, Ludger; Lubienski, Marcus; Papke, Uli; Schiebel, Hans-Martin; Jerz, Gerold; Beuerle, Till

    2015-08-01

    Equisetum palustre L. is known for its toxicity for livestock. Several studies in the past addressed the isolation and identification of the responsible alkaloids. So far, palustrine (1) and N(5)-formylpalustrine (2) are known alkaloids of E. palustre. A HPLC-ESI-MS/MS method in combination with simple sample work-up was developed to identify and quantitate Equisetum alkaloids. Besides the two known alkaloids six related alkaloids were detected in different Equisetum samples. The structure of the alkaloid palustridiene (3) was derived by comprehensive 1D and 2D NMR experiments. N(5)-Acetylpalustrine (4) was also thoroughly characterized by NMR for the first time. The structure of N(5)-formylpalustridiene (5) is proposed based on mass spectrometry results. Twenty-two E. palustre samples were screened by a HPLC-ESI-MS/MS method after development of a simple sample work-up and in most cases the set of all eight alkaloids were detected in all parts of the plant. A high variability of the alkaloid content and distribution was found depending on plant organ, plant origin and season ranging from 88 to 597mg/kg dried weight. However, palustrine (1) and the alkaloid palustridiene (3) always represented the main alkaloids. For the first time, a comprehensive identification, quantitation and distribution of Equisetum alkaloids was achieved.

  20. Alkaloids from cyanobacteria with diverse powerful bioactivities.

    PubMed

    Vasas, G; Borbely, G; Nánási, P; Nánási, P P

    2010-09-01

    Alkaloid containing plants represent a heterogeneous group both taxonomically and chemically, a basic nitrogen being the unifying factor for the various classes. As most alkaloids are extremely toxic, organisms containing them do not feature strongly in medicine but they have always been important in the allopathic system. Typical alkaloids are derived from plant sources, they are basic, they contain one or more nitrogen, and they usually have marked physiological actions in humans or other mammalian species. This review will present various alkaloids generated by cyanobacteria, highlighting their complex structures, powerful bioactivities, and pharmacological properties. The main groups of cyanobacterial alkaloids include the neuromuscular transmission blocker anatoxins, the ion channel blocker saxitoxins, the degenerated amino acid β-methylamino-L-alanine, the protein synthesis inhibitor guanidine alkaloid cylindrospermopsins, and cyanobacterial indol alkaloids with antiviral, antifungal, and cytotoxic activity.

  1. Endophyte-associated ergot alkaloids

    USDA-ARS?s Scientific Manuscript database

    Fescue toxicosis is a very costly (greater than $600 million/annually) for the cattle, horse and small ruminant industries. The tall fescue forage responsible for this intoxication is infected with an endophytic fungus (Neotyphodium coenophialum) that produces ergot alkaloids, which are toxic to th...

  2. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    PubMed

    Bao, Jiaolin; Huang, Borong; Zou, Lidi; Chen, Shenghui; Zhang, Chao; Zhang, Yulin; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao; He, Chengwei

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  3. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents

    PubMed Central

    Zou, Lidi; Chen, Shenghui; Zhang, Chao; Zhang, Yulin; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao; He, Chengwei

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer. PMID:26421434

  4. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

    PubMed

    Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

    2016-07-01

    The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

  5. Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer

    PubMed Central

    Wang, Junxiong; Yang, Shuo; Cai, Xiqiang; Dong, Jiaqiang; Chen, Zhangqian; Wang, Rui; Zhang, Song; Cao, Haichao; Lu, Di; Jin, Tong; Nie, Yongzhan; Hao, Jianyu; Fan, Daiming

    2016-01-01

    Cetuximab plus chemotherapy for advanced gastric cancer (GC) shows an active result in phase 2 trials. Unfortunately, Combination of cetuximab does not provide enough benefit to chemotherapy alone in phase 3 trials. Studies have demonstrated that berberine can suppress the activation of EGFR in tumors. In this study, we evaluated whether berberine could enhance the effects of EGFR-TKIs in GC cell lines and xenograft models. Our data suggest that berberine could effectively enhance the activity of erlotinib and cetuximab in vitro and in vivo. Berberine was found to inhibit growth in GC cell lines and to induce apoptosis. These effects were linked to inhibition of EGFR signaling activation, including the phosphorylation of STAT3. The expressions of Bcl-xL and Cyclind1 proteins were decreased, whereas the levels of cleavage of poly-ADP ribose polymerase (PARP) were considerably increased in the cell lines in response to berberine treatment. These results suggest a potential role for berberine in the treatment of GC, particularly in combination with EGFR-TKIs therapy. Berberine may be a competent therapeutic agent in GC where it can enhance the effects of EGFR inhibitors. PMID:27738318

  6. The Anticonvulsant and Antioxidant Effects of Berberine in Kainate-induced Temporal Lobe Epilepsy in Rats

    PubMed Central

    Mojarad, Tourandokht Baluchnejad; Roghani, Mehrdad

    2014-01-01

    Introduction Temporal lobe epilepsy (TLE) is a long lasting neurological disorder in which patients suffer from spontaneous seizures. New treatments with novel mechanisms of action are needed to help those patients whose seizures are resistant to available drugs. In this study, we investigated the possible neuroprotective effect of berberine in an intrahippocampal kainate model of TLE in rat. Methods In the present study, the anticonvulsant and antioxidant effects of intraperitoneal administration of berberine (25, 50 and 100 mg/kg), was evaluated in intrahippocampal kainate (4µg)-induced TLE in rats. Results The results showed that the kainate rats exhibit acute and spontaneous seizures in 24 hours and two weeks after intrahippocampal kainic acid injection. Administration of berberine, significantly decreased the Racine score and rate of incidence of seizure in kainate rats (P<0.05). On the other hand, berberine ameliorated the lipid peroxidation (P<0.001) and nitrite (P<0.001) level, but had no effect on SOD activity. Discussion These data suggest that berberine pretreatment could attenuate spontaneous recurrent seizures. Since, administration of berberine decreased lipid peroxidation in kainate rats, it seems that berberine favorable effect is due to its effectiveness in lessening of oxidative stress in rat. PMID:25337370

  7. Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

    PubMed

    Li, Xiao-Xing; Li, Chuan-Bao; Xiao, Jie; Gao, Hai-Qing; Wang, He-Wen; Zhang, Xin-Yu; Zhang, Cheng; Ji, Xiao-Ping

    2015-01-01

    Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

  8. Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats

    PubMed Central

    Lu, Li; Zhijian, Huang; Lei, Li; Wenchuan, Chen; Zhimin, Zhu

    2015-01-01

    This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed. PMID:26783411

  9. Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats.

    PubMed

    Lu, Li; Zhijian, Huang; Lei, Li; Wenchuan, Chen; Zhimin, Zhu

    2015-01-01

    This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed.

  10. Selective extraction of berberine from Cortex Phellodendri using polydopamine-coated magnetic nanoparticles.

    PubMed

    Shi, Hai-Li; Peng, Shu-Lin; Sun, Jun; Liu, Yi-Ming; Zhu, Yuan-Ting; Qing, Lin-Sen; Liao, Xun

    2014-03-01

    A new extraction agent featuring dopamine self-polymerized on magnetic Fe3 O4 nanoparticles has been successfully synthesized and evaluated for the SPE of berberine from the extract of the traditional Chinese medicinal plant, Cortex Phellodendri. The nanoparticles prepared possessed a core-shell structure and showed super-paramagnetism. It was found that these polydopamine-coated nanoparticles exhibited strong and selective adsorption for berberine. Among the chemical components present in C. Phellodendri, only berberine was adsorbed by the nanoparticles and extracted by a following SPE procedure. Various conditions such as the amount of polydopamine-coated nanoparticles, desorption solvent, desorption time and equilibrium time were optimized for the SPE of berberine. The purity of berberine extracted from C. Phellodendri was determined to be as high as 91.3% compared with that of 9.5% in the extract. The established SPE protocol combined advantages of highly selective enrichment with easy magnetic separation, and proved to be a facile efficient procedure for the isolation of berberine. Further, the prepared polydopamine-coated magnetic nanoparticles could be reused for multiple times, reducing operational cost. The applicability and reliability of the developed SPE method were demonstrated by isolating berberine from three different C. Phellodendri extracts. Recoveries of 85.4-111.2% were obtained with relative standard deviations ranging from 0.27-2.05%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Effects of berberine on acquisition and reinstatement of morphine-induced conditioned place preference in mice

    PubMed Central

    Vahdati Hassani, Faezeh; Hashemzaei, Mahmoud; Akbari, Edris; Imenshahidi, Mohsen; Hosseinzadeh, Hossein

    2016-01-01

    Objective: It has been shown that berberine, a major component of Berberis vulgaris extract, modulates the activity of several neurotransmitter systems including dopamine (Da) and N-methyl-D-aspartate (NMDA) contributing to rewarding and reinforcing effects of morphine. Drug craving and relapsing even after a long time of abstinence therapy are the most important problems of addiction. In the present study, we investigated the alleviating effects of berberine on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in mice. Materials and Methods: In male NMRI mice, the acquisition of CPP was established by 40 mg/kg of morphine sulphate injection and extinguished after the extinction training and reinstated by a 10 mg/kg injection of morphine. The effects of different doses of berberine (5, 10, and 20 mg/kg) on the acquisition and reinstatement induced by morphine were evaluated in a conditioned place preference test. Results: The results showed that intraperitoneal administration of berberine (5, 10, and 20 mg/kg) did not induce conditioned appetitive or aversive effects. Injection of berberine (10 and 20 mg/kg) 2 h before the morphine administration reduced acquisition of morphine-induced CPP. In addition, same doses of berberine significantly prevented the reinstatement of morphine-induced CPP. Conclusion: These results suggest that berberine can reduce the acquisition and reinstatement of morphine-induced conditioned place preference and may be useful in treatment of morphine addiction. PMID:27222833

  12. Berberine reduces Toll-like receptor-mediated macrophage migration by suppression of Src enhancement.

    PubMed

    Cheng, Wei-Erh; Ying Chang, Miao; Wei, Jyun-Yan; Chen, Yen-Jen; Maa, Ming-Chei; Leu, Tzeng-Horng

    2015-06-15

    Berberine is an isoquinoline with anti-inflammatory activity. We previously demonstrated that there was a loop of signal amplification between nuclear factor kappa B and Src for macrophage mobility triggered by the engagement of Toll-like receptors (TLRs). The simultaneous suppression of lipopolysaccharide (LPS)-mediated upregulation of inducible nitric oxide synthase, cyclooxygenase 2, and cell mobility in berberine-treated macrophages suggested Src might be a target of berberine. Indeed, th reduced migration, greatly suppressed Src induction in both protein and RNA transcript by berberine were observed in macrophages exposed to LPS, peptidoglycan, polyinosinic-polycytidylic acid, and CpG-oligodeoxynucleotides. In addition to Src induction, berberine also inhibited LPS-mediated Src activation in Src overexpressing macrophages and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) could partly restore it. Moreover, berberine suppressed Src activity in fibronectin-stimulated macrophages and in v-Src transformed cells. These results implied that by effectively reducing Src expression and activity, berberine inhibited TLR-mediated cell motility in macrophages.

  13. A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

    PubMed

    Chen, Chunqiu; Tao, Chunhua; Liu, Zhongchen; Lu, Meiling; Pan, Qiuhui; Zheng, Lijun; Li, Qing; Song, Zhenshun; Fichna, Jakub

    2015-11-01

    We aimed to evaluate clinical symptoms in diarrhea predominant irritable bowel syndrome (IBS-D) receiving berberine hydrochloride in a randomized double-blind placebo-controlled clinical trial. Overall, 196 patients with IBS-D were recruited for this study; consequently, 132 patients randomized to receive daily 400 mg of berberine hydrochloride, delivered twice daily or placebo for 8 weeks followed by a 4-week washout period. After a 2-week run-in period, diarrhea, abdominal pain, urgent need for defecation frequency and any adverse events were recorded daily. Prior to administration of the medication and after completing the treatment, assessment of IBS symptom scores, depression and anxiety scale scores and the IBS scale for quality of life (QOL) was carried out. The effects of berberine hydrochloride on IBS-D, defined by a reduction of diarrhea frequency (P = 0.032), abdominal pain frequency (P < 0.01) and urgent need for defecation frequency (P < 0.01), were significantly more pronounced in the berberine group than the placebo group in the 8 weeks of treatment. A trend of improvement (P < 0.05) was observed with berberine hydrochloride for IBS symptom score, depression score and anxiety score and the IBSQOL, compared with placebo. At last, berberine hydrochloride was well tolerated. So we concluded that berberine hydrochloride is well tolerated and reduces IBS-D symptoms, which effectively improved patients QOL.

  14. Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways.

    PubMed

    Zhou, Lin; Song, Fangming; Liu, Qian; Yang, Mingli; Zhao, Jinmin; Tan, Renxiang; Xu, Jun; Zhang, Ge; Quinn, Julian M W; Tickner, Jennifer; Xu, Jiake

    2015-11-13

    Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis.

  15. Modulating gut microbiota as an anti-diabetic mechanism of berberine.

    PubMed

    Han, Junling; Lin, Huiling; Huang, Weiping

    2011-07-01

    Berberine, one of the main constituents of a Chinese traditional herb used to treat bacterial diarrhea, has an effect of lowering glucose, which has been recently confirmed by many studies. However, the mechanism of berberine's antidiabetic effect has not yet been well explained. Recent evidence suggests that the gut microbiota composition is associated with obesity and type 2 diabetes, which are closely associated with a low-grade inflammatory state. The protective effect against diabetes of gut microbiota modulation with probiotics or antibiotics has been confirmed in recent observations. Berberine has significant antimicrobial activity against several microbes through inhibiting the assembly function of FtsZ and halting the bacteria cell division. Because berberine acts topically in the gastrointestinal tract and it is poorly absorbed, berberine might modulate gut microbiota without systemic anti-infective activity. Our hypothesis is that gut microbiota modulation may be one mechanism of the antidiabetic effect of berberine. Our hypothesis may provide a novel explanation for berberine's therapeutic effect in patients with diabetes mellitus.

  16. Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways

    PubMed Central

    Zhou, Lin; Song, Fangming; Liu, Qian; Yang, Mingli; Zhao, Jinmin; Tan, Renxiang; Xu, Jun; Zhang, Ge; Quinn, Julian M. W.; Tickner, Jennifer; Xu, Jiake

    2015-01-01

    Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis. PMID:26580592

  17. The Catharanthus alkaloids: pharmacognosy and biotechnology.

    PubMed

    van Der Heijden, Robert; Jacobs, Denise I; Snoeijer, Wim; Hallard, Didier; Verpoorte, Robert

    2004-03-01

    The Catharanthus (or Vinca) alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development. Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine, Catharanthus roseus became one of the best-studied medicinal plants. Consequently it developed as a model system for biotechnological studies on plant secondary metabolism. The aim of this review is to acquaint a broader audience with the recent progress in this research and with its exciting perspectives. The pharmacognostical aspects of the Catharanthus alkaloids cover botanical (including some historical), phytochemical and analytical data. An up-to-date view on the biosynthesis of the alkaloids is given. The pharmacological aspects of these alkaloids and their semi-synthetic derivatives are only discussed briefly. The biotechnological part focuses on alternative production systems for these alkaloids, for example by in vitro culture of C. roseus cells. Subsequently it will be discussed to what extent the alkaloid biosynthetic pathway can be manipulated genetically ("metabolic engineering"), aiming at higher production levels of the alkaloids. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast. Despite the availability of only a limited number of biosynthetic genes, the research on C. roseus has already led to a broad scientific spin-off. It is clear that many interesting results can be expected when more genes become available.

  18. Ergot alkaloid transport across ruminant gastric tissues.

    PubMed

    Hill, N S; Thompson, F N; Stuedemann, J A; Rottinghaus, G W; Ju, H J; Dawe, D L; Hiatt, E E

    2001-02-01

    Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near-physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal

  19. Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

    PubMed

    Li, Guang-hui; Wang, Dong-lin; Hu, Yi-de; Pu, Ping; Li, De-zhi; Wang, Wei-dong; Zhu, Bo; Hao, Ping; Wang, Jun; Xu, Xian-qiong; Wan, Jiu-qing; Zhou, Yi-bing; Chen, Zheng-tang

    2010-09-01

    Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

  20. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    PubMed

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2.

    PubMed

    Yang, Nan; Srivastava, Kamal; Song, Ying; Liu, Changda; Cho, Sool; Chen, Yujuan; Li, Xiu-Min

    2017-04-01

    Food Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2. The consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined. Berberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%. B-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine. Copyright © 2017. Published by Elsevier B.V.

  2. Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

    PubMed

    Hagel, Jillian M; Morris, Jeremy S; Lee, Eun-Jeong; Desgagné-Penix, Isabel; Bross, Crystal D; Chang, Limei; Chen, Xue; Farrow, Scott C; Zhang, Ye; Soh, Jung; Sensen, Christoph W; Facchini, Peter J

    2015-09-18

    Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites sharing a common biosynthetic origin beginning with tyrosine. Many BIAs have potent pharmacological activities, and plants accumulating them boast long histories of use in traditional medicine and cultural practices. The decades-long focus on a select number of plant species as model systems has allowed near or full elucidation of major BIA pathways, including those of morphine, sanguinarine and berberine. However, this focus has created a dearth of knowledge surrounding non-model species, which also are known to accumulate a wide-range of BIAs but whose biosynthesis is thus far entirely unexplored. Further, these non-model species represent a rich source of catalyst diversity valuable to plant biochemists and emerging synthetic biology efforts. In order to access the genetic diversity of non-model plants accumulating BIAs, we selected 20 species representing 4 families within the Ranunculales. RNA extracted from each species was processed for analysis by both 1) Roche GS-FLX Titanium and 2) Illumina GA/HiSeq platforms, generating a total of 40 deep-sequencing transcriptome libraries. De novo assembly, annotation and subsequent full-length coding sequence (CDS) predictions indicated greater success for most species using the Illumina-based platform. Assembled data for each transcriptome were deposited into an established web-based BLAST portal ( www.phytometasyn.ca) to allow public access. Homology-based mining of libraries using BIA-biosynthetic enzymes as queries yielded ~850 gene candidates potentially involved in alkaloid biosynthesis. Expression analysis of these candidates was performed using inter-library FPKM normalization methods. These expression data provide a basis for the rational selection of gene candidates, and suggest possible metabolic bottlenecks within BIA metabolism. Phylogenetic analysis was performed for each of 15 different enzyme/protein groupings

  3. [Effects of berberine on the recovery of rat liver xenobiotic-metabolizing enzymes after partial hepatectomy].

    PubMed

    Zverinsky, I V; Zverinskaya, H G; Sutsko, I P; Telegin, P G; Shlyahtun, A G

    2015-01-01

    We have studied the effect of berberine on the recovery processes of liver xenobiotic-metabolizing function during its compensatory growth after 70% partial hepatectomy. It was found the hepatic ability to metabolize foreign substances are not restored up to day 8. Administration of berberine (10 mg/kg intraperitoneally) for 6 days led to normalization of both cytochrome P450-dependent and flavin-containing monooxygenases. It is suggested that in the biotransformation of berberine involved not only cytochrome P450, but also flavin-containing monooxygenases.

  4. Considerable fluorescence enhancement upon supramolecular complex formation between berberine and p-sulfonated calixarenes

    NASA Astrophysics Data System (ADS)

    Megyesi, Mónika; Biczók, László

    2006-06-01

    Remarkably strong binding of berberine to 4-sulfonatocalix[8]arene was found in aqueous solution, which led to fluorescence quantum yield increase of a factor about 40 at pH 2. The hypsochromic shift of the fluorescence maximum implied that berberine sensed less polar microenvironment when confined to SCX8. The stability of the supramolecular complex significantly diminished when sulfocalixarenes of smaller ring size served as host compounds but the pH affected the association strength to a much lesser extent. All berberine complexes proved to be barely fluorescent at pH 12.2 because of excited state quenching by the hosts via electron transfer.

  5. Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS.

    PubMed

    Chang, Cheng-Fu; Lee, Yi-Chao; Lee, Kuen-Haur; Lin, Hui-Ching; Chen, Chia-Ling; Shen, Che-Kun James; Huang, Chi-Chen

    2016-10-21

    In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS. Berberine, a traditional herbal medicine, is an inhibitor of mTOR signal and an activator for autophagy. Berberine has been implicated in several kinds of diseases, including the neuronal-related pathogenesis, such as Parkinson's, Huntington's and Alzheimer's diseases. However, the therapeutic effect of berberine on FTLD or ALS pathology has never been investigated. Here we studied the molecular mechanism of berberine in cell culture model with TDP-43 proteinopathies, and found that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal and activation of autophagic degradation pathway. And inhibition of autophagy by specific autophagosome inhibitor, 3-MA, reverses the effect of berberine on reducing the accumulation of insoluble TDP-43 and aggregates formation. These results gave us the notion that inhibition of autophagy by 3-MA reverses the effect of berberine on TDP-43 pathogenesis, and activation of mTOR-regulated autophagy plays an important role in berberine-mediated therapeutic effect on TDP-43 proteinopathies. We supported an important notion that the traditional herb berberine is a potential alternative therapy for TDP-43-related neuropathology. Here we demonstrated that berberine is able to reverse the processing of insoluble TDP-43 aggregates formation through deregulation of mTOR/p70S6K signal

  6. Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives.

    PubMed

    Zhang, Shanshan; Wang, Xiaohong; Yin, Weicheng; Liu, Zhenbao; Zhou, Mi; Xiao, Daipeng; Liu, Yanfei; Peng, Dongming

    2016-10-01

    A series of 9-O-(lipophilic group substituted) berberine derivatives were synthesized and evaluated for their cytotoxicity and hypoglycemic activity against HepG2 cells. All the results indicated that most of the synthesized compounds exhibited lower cytotoxicity and a certain degree of hypoglycemic activity. Especially the compounds 5g and 5h displayed dramatically increased hypoglycemic activity compared with berberine, and the cytotoxicity maintained or even lower than berberine, indicating that they are potential candidates for new anti-type 2 diabetes mellitus drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Update on Berberine in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Liu, Yang; Zhang, Li; Song, Haiyan

    2013-01-01

    Berberine (BBR), an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD). The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD. PMID:23843872

  8. Alkaloids from Hippeastrum equestre. Part I. Phamine, a new phenanthridone alkaloid.

    PubMed

    Döpke, W; Pham, L H; Gründemann, E; Bartoszek, M; Flatau, S

    1995-12-01

    From the bulbs of Vietnamese Hippeastrum equestre Herb. (Amaryllidaceae), besides the well known alkaloids lycorine, tazettine, and hippeastrine, a new alkaloid, phamine, has been isolated. Its structure was established by spectroscopic methods.

  9. Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba.

    PubMed

    Ku, Wai-Foong; Tan, Shin-Jowl; Low, Yun-Yee; Komiyama, Kanki; Kam, Toh-Seok

    2011-12-01

    A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.

  10. Progress of pharmacological studies on alkaloids from Apocynaceae.

    PubMed

    Liu, Lu; Cao, Jian-Xin; Yao, Yuan-Cheng; Xu, Sheng-Ping

    2013-01-01

    Alkaloid was a kind of biological active ingredient. There were various types of alkaloids in Apocynaceae. This paper reviewed the progress on alkaloids from Apocynaceae, which contained origin, structure, and pharmacological activity.

  11. The alkaloids of Delphinium cashmirianum.

    PubMed

    Shamma, M; Chinnasamy, P; Miana, G A; Khan, A; Bashir, M; Salazar, M; Patil, P; Beal, J L

    1979-01-01

    Dephinium cashmirianum Royle (Ranunculaceae) has yielded the new base cashmiradelphine (12), together with the known alkaloids anthranoyllycoctonine (9), lycaconitine (15), avadharidine (17), lappaconitine (4), and N-deacetyllappaconitine (7). Pyridinium chlorochromate oxidation of lycoctonine furnished the new aldehyde lycoctonal (11). The arrhythmogenic and heart rate effects of several of these diterpenoidal alkaloids have been measured on the isolated guinea atria. Lappaconitine was arrhythmogenic at 10(-4)M concentrations. But in contrast to the reference drug aconitine, lappaconitine did not increase the heart rate. In anesthetized rabbits injected with lappaconitine, N-deacetyllappaconitine, and lappaconine up to 1 mg/kg, cardiac arrhythmia was quickly observed. Even up to 5 mg/kg, the other substances were non-arrhythmogenic.

  12. New aporphine alkaloids of Ocotea minarum.

    PubMed

    Vecchietti, V; Casagrande, C; Ferrari, G; Severini Ricca, G

    1979-10-01

    Fourteen aporphine alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea minarum Nees (Mez). The known alkaloids were identified through their physico-chemical properties as: leucoxylonine (VII), dicentrine (IV), ocoteine (V), leucoxine (VI), ocopodine (VIII), predicentrine (IX), dicentrinone (XIV) and thalicminine (XV). Six new aporphine alkaloids were also isolated: ocotominarine (I), ocominarine (III), nor-leucoxylonine (XI), iso-oconovine (xii), 4-hydroxydicentrine (XIII) and ocominarone (XVI). Their structures were determined using spectroscopic methods and chemical correlations.

  13. Four new fluorenone alkaloids and one new dihydroazafluoranthene alkaloid from Caulophyllum robustum Maxim.

    PubMed

    Wang, Xiao-Ling; Liu, Bing-Rui; Chen, Chien-Kuang; Wang, Jun-Ru; Lee, Shoei-Sheng

    2011-09-01

    Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 μM.

  14. Guanidine alkaloids from Plumbago zeylanica.

    PubMed

    Cong, Hai-Jian; Zhang, Shu-Wei; Shen, Yu; Zheng, Yong; Huang, Yu-Jie; Wang, Wen-Qiong; Leng, Ying; Xuan, Li-Jiang

    2013-07-26

    Eleven new guanidine alkaloids, plumbagines A-G (2-8) and plumbagosides A-D (9-12), as well as two known analogues (1, 13), were isolated from the aerial parts of Plumbago zeylanica. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR, MS, IR, and CD methods. The absolute configuration of 1 was determined by single-crystal X-ray diffraction of its derivative (1a).

  15. Alkaloids from Boophone haemanthoides (Amaryllidaceae).

    PubMed

    Nair, Jerald J; Rárová, Lucie; Strnad, Miroslav; Bastidad, Jaume; van Staden, Johannes

    2013-12-01

    In this study, the South African Amaryllid Boophone haemanthoides was examined for its phytochemical composition and cytotoxicity. In the process eight alkaloid structures, including the new compound distichaminol, were identified in bulb ethanolic extracts. Of the isolates, lycorine and distichamine exhibited strong activities against human acute lymphoblastic leukemia (CEM), breast adenocarcinoma (MCF7) and cervical adenocarcinoma (HeLa) cells with IC50S ranging from 1.8 to 9.2 microM.

  16. Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana.

    PubMed

    Díaz Chávez, Maria Luisa; Rolf, Megan; Gesell, Andreas; Kutchan, Toni M

    2011-03-01

    Formation of the methylenedioxy bridge is an integral step in the biosynthesis of benzo[c]phenanthridine and protoberberine alkaloids in the Papaveraceae family of plants. This reaction in plants is catalyzed by cytochrome P450-dependent enzymes. Two cDNAs that encode cytochrome P450 enzymes belonging to the CYP719 family were identified upon interrogation of an EST dataset prepared from 2-month-old plantlets of the Mexican prickly poppy Argemone mexicana that accumulated the benzo[c]phenanthridine alkaloid sanguinarine and the protoberberine alkaloid berberine. CYP719A13 and CYP719A14 are 58% identical to each other and 77% and 60% identical, respectively, to stylopine synthase CYP719A2 of benzo[c]phenanthridine biosynthesis in Eschscholzia californica. Functional heterologous expression of CYP719A14 and CYP719A13 in Spodoptera frugiperda Sf9 cells produced recombinant enzymes that catalyzed the formation of the methylenedioxy bridge of (S)-cheilanthifoline from (S)-scoulerine and of (S)-stylopine from (S)-cheilanthifoline, respectively. Twenty-seven potential substrates were tested with each enzyme. Whereas CYP719A14 transformed only (S)-scoulerine to (S)-cheilanthifoline (K(m) 1.9±0.3; k(cat)/K(m) 1.7), CYP719A13 converted (S)-tetrahydrocolumbamine to (S)-canadine (K(m) 2.7±1.3; k(cat)/K(m) 12.8), (S)-cheilanthifoline to (S)-stylopine (K(m) 5.2±3.0; k(cat)/K(m) 2.6) and (S)-scoulerine to (S)-nandinine (K(m) 8.1±1.9; k(cat)/K(m) 0.7). These results indicate that although CYP719A14 participates in only sanguinarine biosynthesis, CYP719A13 can be involved in both sanguinarine and berberine formation in A. mexicana.

  17. The role of phloem sieve elements and laticifers in the biosynthesis and accumulation of alkaloids in opium poppy.

    PubMed

    Samanani, Nailish; Alcantara, Joenel; Bourgault, Richard; Zulak, Katherine G; Facchini, Peter J

    2006-08-01

    The benzylisoquinoline alkaloids of opium poppy, including the narcotic analgesics morphine and codeine, accumulate in the multinucleate cytoplasm of specialized laticifers that accompany vascular tissues throughout the plant. In mature opium poppy plants, immunofluorescence labeling using specific antibodies showed that four alkaloid biosynthetic enzymes, (S)-norcoclaurine 6-O-methyltransferase (6OMT), (S)-coclaurine N-methyltransferase (CNMT), (S)-3'-hydroxy-N-methylcoclaurine-4'-O-methyltransferase (4'OMT) and salutaridinol-7-O-acetyltransferase (SAT) were restricted to sieve elements of the phloem adjacent or proximal to laticifers. The identity of sieve elements was confirmed by (i) the specific immunogold labeling of the characteristic cytoplasm of this cell type, (ii) the co-localization of a sieve element-specific H(+)-ATPase with all biosynthetic enzymes and (iii) the strict association of sieve plates with immunofluorescent cells. The localization of laticifers was demonstrated antibodies specific to major latex protein (MLP), which is characteristic of this cell type. In situ hybridization using antisense RNA probes for 6OMT, CNMT, 4'OMT and SAT showed that the corresponding gene transcripts were found in the companion cell paired with each sieve element. Seven benzylisoquinoline alkaloid biosynthetic enzymes, (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), berberine bridge enzyme, codeinone reductase, 6OMT, CNMT, 4'OMT and SAT were localized by immunofluorescence labeling to the sieve elements in the root and hypocotyl of opium poppy seedlings. The abundance of these enzymes increased rapidly between 1 and 3 days after seed germination. The localization of seven biosynthetic enzymes to the sieve elements provides strong support for the unique, cell type-specific biosynthesis of benzylisoquinoline alkaloids in the opium poppy.

  18. New alkaloids from Pancratium maritimum.

    PubMed

    Ibrahim, Sabrin R M; Mohamed, Gamal A; Shaala, Lamiaa A; Youssef, Diaa T A; El Sayed, Khalid A

    2013-10-01

    As a part of ongoing search efforts for the discovery of anticancer lead entities from natural sources, bulbs and flowers of the amaryllidaceous plant Pancratium maritimum have been investigated. Fractionation of the extracts of the fresh flowers and bulbs of P. maritimum led to the isolation of four new alkaloids, namely pancrimatines A (1) and B (2), norismine (3), and pancrimatine C (4), together with the previously reported N-methyl-8,9-methylenedioxy-6-phenanthridone (5), trispheridine (6), and N-methyl-8,9-methylenedioxyphenanthridine (7). The structures of these alkaloids were established on the basis of extensive 1D and 2D NMR and high-resolution mass spectral analyses as well as comparison with the literature. Compounds 2 and 7 showed antiproliferative and antimigratory activity against the highly metastatic human prostate cancer cell line PC-3 cells without cytotoxicity. The phenanthridine alkaloid class was identified as having potential for use to control prostate cancer proliferation and migration. Georg Thieme Verlag KG Stuttgart · New York.

  19. Six new alkaloids from Melodinus henryi.

    PubMed

    Ma, Ke; Wang, Jun-Song; Luo, Jun; Kong, Ling-Yi

    2015-01-01

    A total of six new alkaloids, melodinhenines A-F (1-6), were isolated from Melodinus henryi. Melodinhenines A and B are new eburnan-vindolinine-type bisindole alkaloids and melodinhenines C-F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan-vindolinine-type bisindole alkaloid using this method.

  20. Morphinane alkaloid dimers from Sinomenium acutum.

    PubMed

    Jin, Hui-Zi; Wang, Xiao-Ling; Wang, Hong-Bing; Wang, Yu-Bo; Lin, Li-Ping; Ding, Jian; Qin, Guo-Wei

    2008-01-01

    Two new morphinane alkaloid dimers, 2,2'-disinomenine (1) and 7',8'-dihydro-1,1'-disinomenine (2), and known 1, 1'-disinomenine (3), were isolated from ethanol extracts of stems of Sinomenium acutum. Their structures were elucidated on the basis of spectroscopic methods. The absolute configuration of alkaloids 1-3 was determined by direct comparison of their CD spectra with the known alkaloid sinomenine. The isolated alkaloids were tested for cytotoxicity against A549, P388, and HeLa cell lines, and 1 and 3 showed weak inhibition against A549 and Hela cells.

  1. Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway.

    PubMed

    Xie, Xi; Li, Wenyuan; Lan, Tian; Liu, Weihua; Peng, Jing; Huang, Kaipeng; Huang, Juan; Shen, Xiaoyan; Liu, Peiqing; Huang, Heqing

    2011-01-01

    Recently, it is implicated that the abnormality of Akt signaling pathway is involved in the diabetic pathology. Previous studies have demonstrated that berberine could decrease blood glucose by elevating liver glycogen synthesis. However, the underlying mechanism is still unclear. In the present study, we investigated the effects of berberine on fasting blood glucose, liver glycogen, Akt, Glycogen synthase kinase-3, glucokinase and insulin receptor substrate (IRS) in alloxan-induced diabetic mice, exploring its possible hypoglycemic mechanism. We found that in alloxan-induced diabetic mice, the high blood glucose was significantly lowered by berberine treatment. Liver glycogen content, the expression and activity of glucokinase and the phosphorylated Akt and IRS were all significantly reduced in diabetic mice whereas berberine blocked these changes. Berberine also depressed the increasing of phosphorylated GSK-3β in diabetic mice. Collectively, Berberine upregulates the activity of Akt possibly via insulin signaling pathway, eventually lowering high blood glucose in alloxan-induced diabetic mice.

  2. Monanchorin, a bicyclic alkaloid from the sponge Monanchora ungiculata.

    PubMed

    Meragelman, Karina M; McKee, Tawnya C; McMahon, James B

    2004-07-01

    Monanchorin, a guanidine alkaloid with an unusual bicyclic skeleton, together with the known pentacyclic alkaloid crambescidin acid have been isolated from the aqueous extract of the sponge Monanchoraungiculata.

  3. The combinational effect of vincristine and berberine on growth inhibition and apoptosis induction in hepatoma cells.

    PubMed

    Wang, Ling; Wei, Dandan; Han, Xiaojuan; Zhang, Wei; Fan, Chengzhong; Zhang, Jie; Mo, Chunfen; Yang, Ming; Li, Junhong; Wang, Zhe; Zhou, Qin; Xiao, Hengyi

    2014-04-01

    The use of vincristine, a known antitumor agent, in hepatoma therapy is limited particularly because of its toxic effect. Meanwhile, berberine has drawn increasing attention to its antineoplastic effect in recent years. In view of the advantages of combinational drug treatment reported in anti-cancer chemotherapy, we evaluated the effects of co-treatment of vincristine and berberine on hepatic carcinoma cell lines in this study. We find that combinational usage of these two drugs can significantly induce cell growth inhibition and apoptosis even under a concentration of vincristine barely showing cytotoxicity in the same cells when used alone. The underlying mechanism about this combinational effect was addressed in this study by monitoring the signals related to mitochondrial function, apoptotic pathway and endoplasmic reticulum stress. Our results suggest a new value of berberine as a potential adjuvant agent in cancer chemotherapy and provide a hopeful approach for developing hepatoma therapy by utilizing the combinational effect of vincristine and berberine.

  4. Berberine attenuates cAMP-induced lipolysis via reducing the inhibition of phosphodiesterase in 3T3-L1 adipocytes.

    PubMed

    Zhou, Libin; Wang, Xiao; Yang, Ying; Wu, Ling; Li, Fengying; Zhang, Rong; Yuan, Guoyue; Wang, Ning; Chen, Mingdao; Ning, Guang

    2011-04-01

    Berberine, a hypoglycemic agent, has been shown to decrease plasma free fatty acids (FFAs) level in insulin-resistant rats. In the present study, we explored the mechanism responsible for the antilipolytic effect of berberine in 3T3-L1 adipocytes. It was shown that berberine attenuated lipolysis induced by catecholamines, cAMP-raising agents, and a hydrolyzable cAMP analog, but not by tumor necrosis factor α and a nonhydrolyzable cAMP analog. Unlike insulin, the inhibitory effect of berberine on lipolysis in response to isoproterenol was not abrogated by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but additive to that of PD98059, an extracellular signal-regulated kinase kinase inhibitor. Prior exposure of adipocytes to berberine decreased the intracellular cAMP production induced by isoproterenol, forskolin, and 3-isobutyl-1-methylxanthine (IBMX), along with hormone-sensitive lipase (HSL) Ser-563 and Ser-660 dephosphorylation, but had no effect on perilipin phosphorylation. Berberine stimulated HSL Ser-565 as well as adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. However, compound C, an AMPK inhibitor, did not reverse the regulatory effect of berberine on HSL Ser-563, Ser-660, and Ser-565 phosphorylation, nor the antilipolytic effect of berberine. Knockdown of AMPK using RNA interference also failed to restore berberine-suppressed lipolysis. cAMP-raising agents increased AMPK activity, which was not additive to that of berberine. Stimulation of adipocytes with berberine increased phosphodiesterase (PDE) 3B and PDE4 activity measured by hydrolysis of (3)[H]cAMP. These results suggest that berberine exerts an antilipolytic effect mainly by reducing the inhibition of PDE, leading to a decrease in cAMP and HSL phosphorylation independent of AMPK pathway.

  5. Metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of oral-administrated berberine

    PubMed Central

    Gu, Shenghua; Cao, Bei; Sun, Runbin; Tang, Yueqing; Paletta, Janice L.; Wu, Xiao-Lei; Liu, Linsheng; Zha, Weibin; Zhao, Chunyan; Li, Yan; Radlon, Jason M.; Hylemon, Phillip B.; Zhou, Huiping; Aa, Jiye; Wang, Guangji

    2014-01-01

    Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability for intragastric-administered berberine was much lower than that of intraperitoneal-administered berberine, it had stronger lipid-lowing effect, indicating gastrointestinal is a potential target for hypolipidemic effect of berberine. Metabolomic study on both serum and gut content showed that oral-administrated berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the oral-administered berberine modulated the gut microbiota, and BBR showed a significant inhibition on the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to down-regulate the expression and function of CYP7A1 in a negative feed-back way. It was suggested that the hypocholesterolemic effect for oral-administrated berberine is involved in its effect on modulating the turnover of bile acids and farnesoid X receptor signal pathway. PMID:25411028

  6. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

    PubMed Central

    2013-01-01

    Background Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. Methods In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Results Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Conclusions Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC. PMID:24380387

  7. Dual-Targeting of AR and Akt Pathways by Berberine in Castration-Resistant Prostate Cancer

    DTIC Science & Technology

    2015-08-01

    Berberine; natural compound; LuCaP86.2; castration resistant prostate cancer; AR splice variants. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...resistant prostate cancer (CRPC) driven by AR splice variants. 2. Keywords Prostate cancer; androgen receptor; berberine; natural compound; LuCaP86.2...5P20GM103518-10, Louisiana Cancer Research Consortium Fund, Oliver Sartor Prostate Cancer Research Fund, National Natural Science Foundation of China

  8. [Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ].

    PubMed

    Wang, Jiesheng; Dai, Guanhai; Li, Weijia

    2016-05-25

    Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg(-1)·d(-1)), low-dose berberine group (30 mg·kg(-1)·d(-1)), moderate-dose berberine group (60 mg·kg(-1)·d(-1)), and high-dose berberine group (120 mg·kg(-1)·d(-1)). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit. Results: No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all P>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all P<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all P<0.05). Conclusions: Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.

  9. Berberine exerts an anti-inflammatory role in ocular Behcet's disease.

    PubMed

    Yang, Yan; Wang, Qin; Xie, Manyun; Liu, Ping; Qi, Xin; Liu, Xiao; Li, Zhuo

    2017-01-01

    Behcet's disease is a multi‑system inflammatory disorder, and ocular Behcet's disease (OBD) is one of the most common causes of uveitis in China. A number of studies have indicated that Th17 cells, a subset of interleukin-17 (IL-17)-producing CD4+ T‑helper cells, serve important roles in the pathogenesis of OBD. Berberine (BBR) is an isoquinoline derivative alkaloid isolated from Chinese herbs, and has been used traditionally for the treatment of gastrointestinal disorders. The aim of the present study was to investigate the effect of BBR on Th17 cell proliferation and cytokine secretion, and the expression and activation of the signal transducer and activator of transcription 3 (STAT3) transcription factor in OBD in vitro. Blood samples were obtained from healthy controls and patients with active ocular Behcet's disease. Peripheral blood mononuclear cells (PBMCs) or CD4+ T cells were cultured for three days with or without BBR and in the presence of anti‑CD3 and anti‑CD28 antibodies. IL‑17 expression in cell sample supernatants was determined by enzyme‑linked immunosorbent assay, and cell viability was measured using the Cell Counting kit‑8 assay. The number of CD4+IL‑17+ cells and the expression level of phosphorylated (p)‑STAT3 in CD4+ T cells was determined using flow cytometry analysis. The expression of IL‑17 was increased in patients with active OBD following the activation of PBMCs and CD4+ T cells with anti‑CD3 and anti‑CD28 antibodies when compared with healthy controls. However, no significant difference in cell viability following exposure to BBR was observed in PBMCs derived from healthy controls or patients with OBD. Following incubation with BBR, the expression of IL‑17 was reduced and the number of CD4+IL‑17+ cells was decreased in patients with active OBD and healthy controls. Furthermore, the expression of p-STAT3 was significantly decreased in the presence of BBR in healthy controls. In conclusion, the results of

  10. Berberine exerts an anti-inflammatory role in ocular Behcet's disease

    PubMed Central

    Yang, Yan; Wang, Qin; Xie, Manyun; Liu, Ping; Qi, Xin; Liu, Xiao; Li, Zhuo

    2016-01-01

    Behcet's disease is a multi-system inflammatory disorder, and ocular Behcet's disease (OBD) is one of the most common causes of uveitis in China. A number of studies have indicated that Th17 cells, a subset of interleukin-17 (IL-17)-producing CD4+ T-helper cells, serve important roles in the pathogenesis of OBD. Berberine (BBR) is an isoquinoline derivative alkaloid isolated from Chinese herbs, and has been used traditionally for the treatment of gastrointestinal disorders. The aim of the present study was to investigate the effect of BBR on Th17 cell proliferation and cytokine secretion, and the expression and activation of the signal transducer and activator of transcription 3 (STAT3) transcription factor in OBD in vitro. Blood samples were obtained from healthy controls and patients with active ocular Behcet's disease. Peripheral blood mononuclear cells (PBMCs) or CD4+ T cells were cultured for three days with or without BBR and in the presence of anti-CD3 and anti-CD28 antibodies. IL-17 expression in cell sample supernatants was determined by enzyme-linked immunosorbent assay, and cell viability was measured using the Cell Counting kit-8 assay. The number of CD4+IL-17+ cells and the expression level of phosphorylated (p)-STAT3 in CD4+ T cells was determined using flow cytometry analysis. The expression of IL-17 was increased in patients with active OBD following the activation of PBMCs and CD4+ T cells with anti-CD3 and anti-CD28 antibodies when compared with healthy controls. However, no significant difference in cell viability following exposure to BBR was observed in PBMCs derived from healthy controls or patients with OBD. Following incubation with BBR, the expression of IL-17 was reduced and the number of CD4+IL-17+ cells was decreased in patients with active OBD and healthy controls. Furthermore, the expression of p-STAT3 was significantly decreased in the presence of BBR in healthy controls. In conclusion, the results of the present study demonstrate

  11. Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells.

    PubMed

    Ren, Kewei; Zhang, Wenzhe; Wu, Gang; Ren, Jianzhuang; Lu, Huibin; Li, Zongming; Han, Xinwei

    2016-12-01

    Galangin is an active pharmacological ingredient from propolis and Alpinia officinarum Hance, and has been reported to have anti-cancer and antioxidative properties. Berberine, a major component of Berberis vulgaris extract, exhibits potent anti-cancer activities through distinct molecular mechanisms. However, the anticancer effect of galangin in combination with berberine is still unknown. In the present study, we demonstrated that the combination of galangin with berberine synergistically resulted in cell growth inhibition, apoptosis and cell cycle arrest at G2/M phase with the increased intracellular reactive oxygen species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS scavenger promoted the apoptosis dramatically induced by co-treatment with galangin and berberine. Treatment with galangin and berberine alone caused the decreased expressions of Wnt3a and β-catenin. Interestingly, combination of galangin with berberine could further suppress Wnt3a and β-catenin expression and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft tumors, the combinational treatment of galangin and berberine significantly inhibited the tumor growth without obvious toxicity. Overall, galangin in combination with berberine presented outstanding synergistic anticancer role in vitro and in vivo, indicating that the beneficial combination of galangin and berberine might provide a promising treatment for patients with oesophageal carcinoma.

  12. [Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans].

    PubMed

    Tian, Shu-Juan; Gao, Yue; Zang, Cheng-Xu; Cai, Zhan; Ni, Ting-jun-hong; Tan, Shan-Lun; Cao, Yong-Bing; Jiang, Yuan-Ying; Zhang, Da-Zhi

    2014-11-01

    Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

  13. Effects of Berberine on Adipose Tissues and Kidney Function in 3T3-L1 Cells and Spontaneously Hypertensive Rats.

    PubMed

    Kishimoto, Aya; Dong, Shi-Fen; Negishi, Hiroko; Yasui, Naomi; Sun, Jian-Ning; Ikeda, Katsumi

    2015-09-01

    We aimed to investigate the effect of berberine on adipose tissues, as well as its effect on renal injury in 3T3-L1 cells and spontaneously hypertensive rats. 3T3-L1 cells were cultured and treated with berberine (5-20 pM) from days 3 to 8. Berberine added to the cultured medium could significantly down-regulate transcription factors, including CCAAT/enhancer binding protein β, CCAAT/enhancer binding protein a, and peroxisome pro liferator-activated receptor y, and suppress peroxisome proliferator-activated receptor target genes, such as adipocyte fatty acid binding protein and fatty acid synthase, and inhibit 3T3-Ll fibroblast differentiation to adipocytes. Male spontaneously hypertensive rats received either 150 mg/day of berberine or saline orally for 8 weeks. Compared with the control, berberine-treated rats exhibited significant reductions in body weight gain (p < 0.05), as well as retroperitoneal and mesenteric adipose tissues (p < 0.05). Berberine-treated rats significantly decreased urinary albumin excretion, a marker of renal injury (p < 0.05). Long-term treatment with berberine decreased the adipose tissues weight and attenuated renal injury in spontaneously hypertensive rats. Based on these results, berberine has an important role in regulating adipose tissues. These results suggest the protective effect of berberine on metabolic syndrome related diseases, such as renal injury.

  14. A simple fluorescence quenching method for berberine determination using water-soluble CdTe quantum dots as probes

    NASA Astrophysics Data System (ADS)

    Cao, Ming; Liu, Meigui; Cao, Chun; Xia, Yunsheng; Bao, Linjun; Jin, Yingqiong; Yang, Song; Zhu, Changqing

    2010-03-01

    A novel method for the determination of berberine has been developed based on quenching of the fluorescence of thioglycolic acid-capped CdTe quantum dots (TGA-CdTe QDs) by berberine in aqueous solutions. Under optimum conditions, the relative fluorescence intensity was linearly proportional to the concentration of berberine between 2.5 × 10 -8 and 8.0 × 10 -6 mol L -1 with a detection limit of 6.0 × 10 -9 mol L -1. The method has been applied to the determination of berberine in real samples, and satisfactory results were obtained. The mechanism of the proposed reaction was also discussed.

  15. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin.

    PubMed

    Wang, Chunmei; Li, Jing; Lv, Xiaoyan; Zhang, Ming; Song, Yanfang; Chen, Li; Liu, Yanjun

    2009-10-12

    Berberine can improve insulin resistance, lower blood glucose, and regulate lipid metabolism disorders which cause endothelial dysfunction, leading to vascular complications of type 2 diabetes mellitus. The aim of the present study was to investigate the effects of berberine on endothelial dysfunction of aortas in type 2 diabetes mellitus rats and its mechanism. Wistar rats were randomly divided into four groups: diabetic rats, control rats, diabetic rats treated with berberine (100 mg/kg), and control rats treated with berberine. The serum fasting blood glucose, insulin, total cholesterol, triglyceride and nitric oxide (NO) levels were tested. Acetylcholine-induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. The expression of endothelial nitric oxide synthase (eNOS) mRNA was measured by RT-PCR, and the protein expressions of eNOS and NADPH oxidase (NOX4) were analyzed by western blot. The results showed that berberine significantly decreased fasting blood glucose, and triglyceride levels in diabetic rats. Berberine also improved endothelium-dependent vasorelaxation impaired in aorta. The expressions of eNOS mRNA and protein were significantly increased, while NOX4 protein expression was decreased in aortas from diabetic rats with berberine treatment. Moreover, serum NO levels were elevated after berberine treatment. In conclusion, berberine restores diabetic endothelial dysfunction through enhanced NO bioavailability by up-regulating eNOS expression and down-regulating expression of NADPH oxidase.

  16. Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells

    PubMed Central

    Wang, Zeng-si; Lu, Fu-er; Xu, Li-jun; Dong, Hui

    2010-01-01

    Aim: Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of insulin resistance and pancreatic β-cell dysfunction. The aim of this study is to investigate whether the insulin-sensitizing action of berberine is related to reducing ER stress. Methods: ER stress in cultured Hep G2 cells was induced with tunicamycin. Cells were pretreated with berberine in combination with or without insulin. The concentration of glucose was measured by glucose oxidase method. The molecular markers of ER stress, including ORP150, PERK, and eIF2α were analyzed by Western blot or real time PCR. The activity of JNK was also evaluated. Moreover, the insulin signaling proteins such as IRS-1 and AKT were determined by Western blot. Results: The production of glucose stimulated with insulin was reduced. The expressions of ORP150 was decreased both in gene and protein levels when cells were pretreated with berberine, while the activation of JNK was blocked. The levels of phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine. The level of IRS-1 ser307 phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. AKT ser473 phosphorylation was also enhanced significantly in the presence of berberine. Conclusion: The antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress and improvement of insulin signal transduction. PMID:20383171

  17. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes.

    PubMed

    Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian

    2015-09-05

    Ischemia/reperfusion (I/R)-induced autophagy increases the severity of cardiomyocyte injury. The aim of this study was to investigate the effects of berberine, a natural extract from Rhizoma coptidis, on the I/R-induced excessive autophagy in in vitro and in vivo models. Autophagy was increased both in H9c2 myocytes during hypoxia/reoxygenation (H/R) injury and in mouse hearts exposed to I/R. And the expression level of p-AMPK and p-mTORC2 (Ser2481) were increased during H/R period. In addition, the increased autophagy level was correlated with reduced cell survival in H9c2 myocytes and increased infarct size in mouse hearts. However, berberine treatment significantly enhanced the H/R-induced cell viability and reduced I/R-induced myocardial infarct size, which was accompanied by improved cardiac function. The beneficial effect of berberine is associated with inhibiting the cellular autophagy level, due to decreasing the expression level of autophagy-related proteins such as SIRT1, BNIP3, and Beclin-1. Furthermore, both the level of p-AMPK and p-mTORC2 (Ser2481) in H9c2 myocytes exposed to H/R were decreased by berberine. In summary, berberine protects myocytes during I/R injury through suppressing autophagy activation. Therefore, berberine may be a promising agent for treating I/R-induced cardiac myocyte injury.

  18. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.

    PubMed

    Zhi, Duo; Feng, Pan-Feng; Sun, Jia-Liang; Guo, Fengfeng; Zhang, Rui; Zhao, Xin; Li, Bao-Xin

    2015-08-30

    As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity.

  19. The effect of Berberine on the secondary structure of human serum albumin

    NASA Astrophysics Data System (ADS)

    Li, Ying; He, WenYing; Tian, Jianniao; Tang, Jianghong; Hu, Zhide; Chen, Xingguo

    2005-05-01

    The presence of several high affinity binding sites on human serum albumin (HSA) makes it a possible target for many drugs. This study is designed to examine the effect of Berberine (an ancient Chinese drug used for antimicrobial, antiplasmodial, antidiarrheal and cardiovascular) on the solution structure of HSA using fluorescence, Fourier transform infrared (FT-IR), circular dichroism (CD) spectroscopic methods. The fluorescence spectroscopic results show that the fluorescence intensity of HSA was significantly decreased in the presence of Berberine. The Scatchard's plots indicated that the binding of Berberine to HSA at 296, 303, 318 K is characterized by one binding site with the binding constant is 4.071(±0.128)×10 4, 3.741(±0.089)×10 4, 3.454(±0.110)×10 4 M -1, respectively. The protein conformation is altered (FT-IR and CD data) with reductions of α-helices from 54 to 47% for free HSA to 45-32% and with increases of turn structure5% for free HSA to 18% in the presence of Berberine. The binding process was exothermic, enthalpy driven and spontaneous, as indicated by the thermodynamic analyses, Berberine bound to HSA was mainly based on hydrophobic interaction and electrostatic interaction cannot be excluded from the binding. Furthermore, the displace experiments indicate that Berberine can bind to the subdomain IIA, that is, high affinity site (site II).

  20. Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics.

    PubMed

    Gu, Yan; Zhang, Yifei; Shi, Xianzhe; Li, Xiaoying; Hong, Jie; Chen, Jing; Gu, Weiqiong; Lu, Xin; Xu, Guowang; Ning, Guang

    2010-05-15

    A comprehensive metabonomic method, in combination with fingerprint analysis and target analysis, was performed to reveal potential mechanisms of berberine action in the treatment of patients with type 2 diabetes and dyslipidemia. Serum samples of 60 patients before and after treatment with either berberine or placebo were collected. Ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) coupled with pattern recognition analysis were used to identify changes in global serum metabolites. Compared with placebo, patients before and after berberine treatment could be separated into distinct clusters as displayed by the orthogonal signal correction filtered partial least-squares discriminant analysis (OSC-PLS-DA) score plot, which indicated changes in circulating metabolites after berberine treatment. Among them, free fatty acids changed markedly. These were further quantified by UPLC combined with single quadrupole mass spectrometry (UPLC SQ MS). There was a highly significant decrease in the concentrations of 13 fatty acids following berberine administration. 10 fatty acids also differed statistically from placebo. These results suggest that berberine might play a pivotal role in the treatment of type 2 diabetes through down-regulating the high level of free fatty acids and that comprehensive metabonomic measurements are potentially very useful for studying the mechanisms of action of traditional Chinese medicines.

  1. New aspects of Saccharomyces cerevisiae as a novel carrier for berberine.

    PubMed

    Salari, Roshanak; Bazzaz, Bibi Sedigheh Fazly; Rajabi, Omid; Khashyarmanesh, Zahra

    2013-12-20

    Berberine was encapsulated in yeast cells of Saccharomyces cerevisiae as novel carriers to be used in different food and drug industries. The microcapsules were characterized by differential scanning calorimetry (DSC), fourier transform infra red spectroscopy (FT-IR) and fluorescence microscopy. The encapsulation factors such as plasmolysis of yeast cells which affects the % encapsulation yield were studied. Fluorescence microscopy showed the yeast cells became fluorescent after encapsulation process. DSC diagram was representing of new peak for microcapsule which was not the same as berberine and the empty yeast cells peaks, separately. FTIR spectrums of microcapsules and yeast cells were almost the same. The plasmolysed and non plasmolysed microcapsules were loaded with berberine up to about 40.2 ± 0.2% w/w. Analytical methods proved that berberine was encapsulated in the yeast cells. Fluorescence microscopy and FTIR results showed the entrance of berberine inside the yeasts. DSC diagram indicated the appearance of new peak which is due to the synthesis of new product. Although plasmolysis caused changes in yeast cell structure and properties, it did not enhance berberine loading in the cells. The results confirmed that Saccharomyces cerevisiae could be an efficient and safe carrier for active materials.

  2. Berberine Radiosensitizes Human Esophageal Cancer Cells by Downregulating Homologous Recombination Repair Protein RAD51

    PubMed Central

    Liu, Zhaojian; Wang, Yu; Zhao, Minnan; Hao, Chunyan; Feng, Shuai; Guo, Haiyang; Xu, Bing; Yang, Qifeng; Gong, Yaoqin; Shao, Changshun

    2011-01-01

    Background Esophageal squamous cell carcinomas (ESCC) have poor prognosis. While combined modality of chemotherapy and radiotherapy increases survival, most patients die within five years. Development of agents that confer cancer cell-specific chemo- and radiosensitivity may improve the therapy of ESCC. We here reported the discovery of berberine as a potent radiosensitizing agent on ESCC cells. Principal Findings Berberine at low concentrations (<15 µM) substantially radiosensitized ESCC cells. X-ray induced DNA double-strand breaks (DSBs) persist longer in ESCC cells pretreated with berberine. Berberine pretreatment led to a significant downregulation of RAD51, a key player in homologous recombination repair, in ESCC cells, but not in non-malignant human cells. Downregulation of RAD51 by RNA interference similarly radiosensitized the cancer cells, and, conversely, introduction of exogenous RAD51 was able to significantly counteract the radiosensitizing effect of berberine, thus establishing RAD51 as a key determinant in radiation sensitivity. We also observed that RAD51 was commonly overexpressed in human ESCC tissues, suggesting that it is necessary to downregulate RAD51 to achieve high radio- or chemotherapeutic efficacy of ESCC in clinic, because overexpression of RAD51 is known to confer radio- and chemoresistance. Conclusions/Significance Berberine can effectively downregulate RAD51 in conferring radiosensitivity on esophageal cancer cells. Its clinical application as an adjuvant in chemotherapy and radiotherapy of esophageal cancers should be explored. PMID:21858113

  3. Berberine Inhibits Human Hepatoma Cell Invasion without Cytotoxicity in Healthy Hepatocytes

    PubMed Central

    Pan, Xuediao; Yang, Zhicheng; Zang, Linquan

    2011-01-01

    Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its high hepatotoxicity. Many plant-derived agents have been accepted to effectively inhibit hepatoma cell invasion. However, the investigation that whether effectual plant-derived agents against invasive hepatoma cells exert unexpected cytotoxicity in healthy hepatocytes has been ignored. This study demonstrated that berberine exhibited significant cytotoxicity in HepG2 cells mainly through upregulation of reactive oxygen species (ROS) production but was ineffective in normal Chang liver cells. Berberine exerted anti-invasive effect on HepG2 cells through suppression of matrix metalloproteinase-9 (MMP-9) expression. Moreover, berberine could significantly inhibit the activity of PI3K-AKT and ERK pathways. Combination treatment of ERK pathway inhibitor PD98059 or AKT pathway inhibitor LY294002 and berberine could result in a synergistic reduction on MMP-9 expression along with an inhibition of cell invasion. Enhancement of ROS production by berberine had no influence on its suppressive effects on the activity of PI3K-AKT and ERK pathways, as well as MMP-9 expression and HepG2 cell invasion. In conclusion, our results suggest that berberine may be a potential alternative against invasive hepatoma cells through PI3K-AKT and ERK pathways-dependent downregulation of MMP-9 expression. This study also provides a previously neglected insight into the investigation of plant-derived agents-based therapy against tumor invasion with the consideration of damage to healthy cells. PMID:21738655

  4. New aspects of Saccharomyces cerevisiae as a novel carrier for berberine

    PubMed Central

    2013-01-01

    Background Berberine was encapsulated in yeast cells of Saccharomyces cerevisiae as novel carriers to be used in different food and drug industries. The microcapsules were characterized by differential scanning calorimetry (DSC), fourier transform infra red spectroscopy (FT-IR) and fluorescence microscopy. The encapsulation factors such as plasmolysis of yeast cells which affects the % encapsulation yield were studied. Results Fluorescence microscopy showed the yeast cells became fluorescent after encapsulation process. DSC diagram was representing of new peak for microcapsule which was not the same as berberine and the empty yeast cells peaks, separately. FTIR spectrums of microcapsules and yeast cells were almost the same. The plasmolysed and non plasmolysed microcapsules were loaded with berberine up to about 40.2 ± 0.2% w/w. Conclusion Analytical methods proved that berberine was encapsulated in the yeast cells. Fluorescence microscopy and FTIR results showed the entrance of berberine inside the yeasts. DSC diagram indicated the appearance of new peak which is due to the synthesis of new product. Although plasmolysis caused changes in yeast cell structure and properties, it did not enhance berberine loading in the cells. The results confirmed that Saccharomyces cerevisiae could be an efficient and safe carrier for active materials. PMID:24359687

  5. Alkaloids of the flowers of Pancratium maritimum.

    PubMed

    Youssef, D T; Frahm, A W

    1998-10-01

    The defatted ethanolic extract of the fresh flowers of Pancratium maritimum L. yielded the four known alkaloids lycorine, maritidine, lycoramine, and galanthamine. The structures of the isolated alkaloids were determined mainly through spectroscopic studies including one- and two-dimensional NMR (COSY, NOESY, DEPT, HETCOR, and HMBC) and CD techniques. Some spectral data are newly reported or revised.

  6. Halogenated Indole Alkaloids from Marine Invertebrates

    PubMed Central

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade e; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  7. Halogenated indole alkaloids from marine invertebrates.

    PubMed

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade E; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-04-28

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided.

  8. Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae)

    PubMed

    Zelenski, S G

    1977-11-01

    A phytochemical investigation of an alcoholic extract of the petioles of Nelumbo lutea resulted in the identification of the alkaloids N-methylasimilobine, anonaine, and roemerine. The alkaloids nuciferine, armepavine, N-nornuciferine, and N-norarmepavine, previously previously reported in the whole plant, were also identified.

  9. A new indole alkaloid from Alstonia scholaris.

    PubMed

    Jain, Luna; Pandey, M B; Singh, Sarita; Singh, A K; Pandey, V B

    2009-01-01

    A new indole alkaloid, N-formylscholarine, together with picrinine, strictamine and nareline has been isolated from the fruit pods of Alstonia scholaris, and their structures were established by various spectral data. This is the first report of these alkaloids in A. scholaris fruit pods.

  10. Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum.

    PubMed

    Yu, B W; Meng, L H; Chen, J Y; Zhou, T X; Cheng, K F; Ding, J; Qin, G W

    2001-07-01

    Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.

  11. Plant alkaloids of the polymethyleneamine series

    NASA Astrophysics Data System (ADS)

    Rogoza, Ludmila N.; Salakhutdinov, Nariman F.; Tolstikov, Genrikh A.

    2005-04-01

    The published data on the structures and biological activities of the plant alkaloids of the biogenic polymethyleneamine series, viz., putrescine (1,4-diaminobutane), spermidine (1,8-diamino-4 -azaoctane), and spermine (1,12-diamino-4,9-diazadodecane), are considered and systematised. The structures and biological activities of some synthetic analogues of these alkaloids are also presented.

  12. Alkaloids from Rauwolfia cubana Stem Bark.

    PubMed

    Martinez, J A; Gomez, C; Santana, T; Velez, H

    1989-06-01

    Six indole alkaloids, tetrahydroalstonine, aricine, 16- EPI-affinine, ajmaline, amerovolfine, and amerovolficine have been isolated from the ethanolic extract of the stem bark of RAUWOLFIA CUBANA A. DC. Amerovolfine ( N(alpha)-demethylaccedine) and amerovolficine (16-demethoxy-carbonylpagicerine) are new alkaloids related to 16- EPI-affinine, and their structures have been determined by spectroscopic analysis.

  13. Glycoalkaloids and calystegine alkaloids in potatoes

    USDA-ARS?s Scientific Manuscript database

    Potatoes contain two classes of alkaloids: the glycoalkaloids and the calystegines. The presence of glycoalkaloids in potatoes and their toxicity has been known for more than a century and much has been written about them. Discovery of the nortropane calystegine alkaloids is more recent, and the k...

  14. In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids.

    PubMed

    Nair, Jerald J; Bastida, Jaume; van Staden, Johannes

    2016-01-01

    The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects.

  15. Indole Alkaloids from Alocasia macrorrhiza.

    PubMed

    Zhu, Ling-Hua; Chen, Cheng; Wang, Hui; Ye, Wen-Cai; Zhou, Guang-Xiong

    2012-01-01

    Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.

  16. In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies.

    PubMed

    Cui, Hanming; Wang, Jialong; Zhang, Qiuyan; Dang, Mengmeng; Liu, Hui; Dong, Yu; Zhang, Lu; Yang, Fang; Wu, Jianhua; Tong, Xiaolin

    2016-04-08

    We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin. The AUC (p < 0.01) and Cmax (p < 0.01) could be significantly decreased in the berberine-induced group in vivo, and the metabolic activity of HepG2 cell ccould be increased by berberine induction in vitro. The metabolism parameters of lovastatin such as CL, Vmax and Km were increased after the induction of berberine. From the pharmacokinetic study of lovastatin induced with berberine, we obtained pharmacokinetic parameters which are compliance with the metabolic parameters of lovastatin in HepG2 cells with berberine induction in vitro. From the in vivo pharmacokinetics study and the HepG2 cell metabolism study in vitro, berberine could be an inducer for the metabolism of lovastatin according to our previous research on berberine induction effects on HepG2 cells, which may be relevant to the fact that berberine possesses induction effects through the CYP 450 3A4 enzyme.

  17. Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.

    PubMed

    Ma, Weina; Zhu, Man; Zhang, Dongdong; Yang, Liu; Yang, Tianfeng; Li, Xin; Zhang, Yanmin

    2017-02-15

    Berberine, a plant-derived compound isolated from Coptis chinensis used in traditional Chinese medicine, has been shown to possess anti-cancer properties. However, no study has shown that berberine could target ephrin-B2, which plays a critical role in cell proliferation and migration. The aim of this study is to investigate the effect of berberine on cancer cell growth and migration, through the regulation of ephrin-B2 and downstream signaling molecules. In this study, a high ephrin-B2-expressing cell membrane chromatography method was developed to investigate 48 crude extracts from traditional Chinese medicine that could act on ephrin-B2. Cell proliferative and wound-healing assays were used to study the effect of berberine on cancer cell growth and migration. The mechanism of berberine was investigated using western blot. Berberine was isolated from C. chinensis extracts and showed activity on the HEK293/ephrin-B2 cell membrane chromatography column. Berberine showed a greater inhibitory effect in high-expressing ephrin-B2 cells (HEK293/ephrin-B2 cells) than in normal HEK293 cells, and decreased the expression of ephrin-B2 and its PDZ binding proteins, which indicates that ephrin-B2 is a target of berberine. Furthermore, berberine downregulates the phosphorylation of VEGFR2 and downstream signaling members (AKT and Erk1/2), which in turn downregulates the expression of MMP2 and MMP9. The above data confirm the inhibitory effects of berberine on ZR-75-30 cell proliferation and cell migration. Overall, our studies demonstrate that berberine inhibits cell growth and migration by targeting ephrin-B2. Copyright © 2016 Elsevier GmbH. All rights reserved.

  18. Berberine enhances the AMPK activation and autophagy and m