Ma, Yuxin; Tian, Sumin; Sun, Lingzhi; Yao, Shizhang; Liang, Zihao; Li, Shanshan; Liu, Jing; Zang, Linquan; Li, Guoying
Acori graminei Rhizoma (AGR), the dry rhizoma of Acorus gramineus Soland (Araceae), has been used as an Asian traditional herbal medicine against senile dementia, stroke, and cardiovascular disease. Previous studies have revealed neuroprotective effects of AGR on neuronal damage and learning impairment, while mostly focused on the effect of volatile oil fraction of AGR. This study aimed to investigate the neuroprotective effects of different extract fractions from AGR against Alzheimer disease-like symptoms induced by Amyloid Beta (Aß) 1-42 intra-hippocampal injection. On day 7 after intra-hippocampal injection of saline or Aβ1-42, spatial memory was assessed by the first Morris water maze, followed by 3-week intra-gastric administration of saline or water extract, volatile oil fraction, or defatted decoction fraction of AGR respectively. Mice were subsequently subjected to the second Morris water maze task. Levels of Aβ1-42 and expressions of doublecortin and nestin in the hippocampus were examined using immunohistochemistry. Our results suggested that treatment with these different extract fractions from AGR could ameliorate cognitive impairment and down-regulate expressions of doublecortin and nestin in the hippocampus of Aβ1-42 injected mice, in which water extract and volatile oil fractions were more effective in spatial memory than defatted decoction fraction.
Dai, Jian; Ha, Chengyong; Shen, Minmin
Supercritical CO2 extraction (SCE) technology was used to extract a volatile oil, rich in beta-asarone, from Acori graminei rhizoma (AGR). The effect of different extraction and fractionation parameters on oil yield and selectivity towards beta-asarone was investigated by SCE using commercial AGR samples. The optimal conditions (P(e)/T(e) = 10 MPa/45 degrees C; P(f1)/T(f1) = 8 MPa/-10 degrees C; P(f2)/T(f2 )= 2 MPa/10 degrees C) gave a good oil yield and selectivity for beta-asarone. The extracts were also analyzed by GC-MS and compared with the volatile oil obtained by hydrodistillation, in which 39 main constituents including beta-asarone were found. Different cultivated AGR samples obtained from three areas of China were evaluated in terms of their volatile oil compositions obtained by extraction of commercial AGR samples under optimal conditions; the extract of the Guangdong (GD) sample showed a high beta-asarone content.
Zhang, Wuxia; Song, Dan; Xu, Dan; Wang, Tingting; Chen, Lu; Duan, Jinyou
Rhizoma Acori Tatarinowii is widely used in traditional Chinese medicine. In this study, three novel polysaccharides designated RATPW, RATPS1 and RATPS2 were isolated from Rhizoma Acori Tatarinowii by DEAE-52 cellulose chromatography. Their structures were characterized using physicochemical and spectral methods. Chemical analysis indicated that RATPW (6.5×10(3)Da) mainly composed of glucose and fructose. RATPS1 (1.5×10(5)Da) contained galactose and arabinose, while RATPS2 (5.3×10(4)Da) contained ∼49.5% galacturonic acid along with rhamnose, fructose, galactose, and arabinose. In vitro, RATPS2 showed the most significant scavenging activity on DPPH and hydroxyl radical. Three polysaccharides could protect the PC12 cells from H2O2-induced damage. Immunological tests indicated that both RATPW and RATPS2 significantly stimulated NO production and phagocytic activity in RAW264.7, and promoted splenocyte proliferation. These data suggested that polysaccharides RATPW and RATPS2 had the potential as novel natural sources of antioxidative and immunopotentiating agents.
Kai-Xin-San, a Chinese Herbal Decoction Containing Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria, Stimulates the Expression and Secretion of Neurotrophic Factors in Cultured Astrocytes
Zhu, Kevin Yue; Xu, Sherry Li; Choi, Roy Chi-Yan; Yan, Artemis Lu; Dong, Tina Ting-Xia; Tsim, Karl Wah-Keung
Kai-xin-san (KXS), a Chinese herbal decoction prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria. In China, KXS has been used to treat stress-related psychiatric diseases with the symptoms of depression and forgetfulness. Although animal study has supported the antidepression function of KXS, the mechanism in cellular level is still unknown. Here, a chemically standardized water extract of KXS was applied onto cultured astrocytes in exploring the action mechanisms of KXS treatment, which significantly stimulated the expression and secretion of neurotrophic factors, including NGF, BDNF, and GDNF, in a dose-dependent manner: the stimulation was both in mRNA and protein levels. In addition, the water extracts of four individual herbs did not significantly stimulate the expression of neurotrophic factors, which could explain the optimized effect of KXS in a herbal decoction. The KXS-induced expression of neurotrophic factors did not depend on signaling mediated by estrogen receptor or protein kinase. The results suggested that the antidepressant-like action of KXS might be mediated by an increase of expression of neurotrophic factors in astrocytes, which fully supported the clinical usage of this decoction. PMID:24222781
Lam, Kelly Y. C.; Chen, Jianping; Lam, Candy T. W.; Wu, Qiyun; Yao, Ping; Dong, Tina T. X.; Lin, Huangquan; Tsim, Karl W. K.
Acori Tatarinowii Rhizoma (ATR), the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, α-asarone and β-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, α-asarone or β-asarone, stimulated the expression of neurofilaments, a bio-marker for neurite outgrowth, in a concentration-dependent manner. The co-treatment of ATR volatile oil, α-asarone or β-asarone, with low concentration of nerve growth factor (NGF) potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB). In the potentiation of NGF-induced signaling in cultured PC12 cells, α-asarone and β-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved. PMID:27685847
Cai, Ru; Su, Huidan; Li, Yunlong
The alkaloids in the processed Rhizoma Corydalis and the crude Rhizoma Corydalis were qualitatively and semiquantitatively analyzed using gas chromatography-mass spectrometry (GC/MS) method. The processing herb drug procedure was carried out according to the standard method of Chinese Pharmacopoeia. The samples were extracted using Soxhlet extractor with different solvents: methanol and acetone. The extraction effect on different solvents was investigated. The results showed that 11 kinds of alkaloids were identified from the crude Rhizoma Corydalis and only two were from the processed Rhizoma Corydalis. A total of 13 kinds of alkaloids were all based on two backbones. The alkaloids in the processed sample were less than those in the crude Rhizoma Corydalis significantly, while almost the corydaline has been changed in conformation after the sample had undergone processing, which provided support for the conclusion of reducing toxicity when the herbal medicine having been undergone a traditional drugs treatment process. PMID:25210643
Rhizoma perennial peanut (RPP) (Arachis glabrata Benth.) is a vegetatively propagated tropical legume that combines high forage nutritive value and long-term persistence under a wide range of grazing and harvested hay systems. The objectives of this study were to measure the genetic relatedness amo...
Wu, L; Wang, X; Mao, S; Cheng, L
Using the qualitative standard of Rhizoma Arisaematis stipulated in Pharmacopoeia and combining with the toxic reaction in experimental mice, the optimum amount of KAl(SO4)2.12H2O for eliminating the toxic reaction of Rhizoma Arisaematis was selected. Based on the comparison of experiments, two new technologies for processing Rhizoma Arisaematis have been established. Pilot production shows that these technologies are feasible for mass production.
Lin, Wen-Shuo; Chen, Rong; Li, Yong-Zeng; Feng, Shang-Yuan; Huang, Zu-Fang; Xie, Bing-Xian
A novel and compact near-infrared (NIR) Raman system was developed using 785 nm diode laser, volume-phase technology holographic system, and NIR intensified charge-coupled device (CCD). The Raman spectra and first derivative spectra of rhizoma dioscoreae were obtained. The Raman spectra of rhizoma dioscoreae showed three strong characteristic peaks at 477, 863 and 936 cm(-1), respectively. The major ingredients are protein, amino acid, starch, polysaccharides and so on, matching the known basic biochemical composition of rhizoma dioscoreae. In the first derivative spectra of rhizoma dioscoreae, the distinguishing characteristic peaks appeared at 467, 484, 870 and 943 cm(-1). Contrasted with rhizoma dioscoreae Raman spectra in the ranges of 600 to 800 cm(-1) and 1 000 to 1 400 cm(-1), the changes in rhizoma dioscoreae Raman first derivative spectra are represented more clearly than the rhizoma dioscoreae Raman spectra. So the rhizoma dioscoreae Raman first derivative spectra can be an accurate supplementary analysis method to the rhizoma dioscoreae Raman spectra.
Zhou, Xia; Wan, Jun; Chu, Liang; Liu, Wengang; Jing, Yafeng; Wu, Chunjie
Background: Pinelliae Rhizoma is a commonly used Chinese herb which will change brown during the natural drying process. However, sulfur fumed Pinelliae Rhizoma will get a better appearance than naturally dried one. Sulfur fumed Pinelliae Rhizoma is potentially toxical due to sulfur dioxide and sulfites formed during the fuming procedures. The odor components in sulfur fumed Pinelliae Rhizoma is complex. At present, there is no analytical method available to determine sulfur fumed Pinelliae Rhizoma simply and rapidly. To ensure medication safety, it is highly desirable to have an effective and simple method to identify sulfur fumed Pinelliae Rhizoma. Materials and Methods: This paper presents a novel approach using an electronic nose based on metal oxide sensors to identify whether Pinelliae Rhizoma was fumed with sulfur, and to predict the fuming degree of Pinelliae Rhizoma. Multivariate statistical methods such as principal components analysis (PCA), discriminant factorial analysis (DFA) and partial least squares (PLS) were used for data analyzing and identification. The use of the electronic nose to discriminate between different fuming degrees Pinelliae Rhizoma and naturally dried Pinelliae Rhizoma was demonstrated. Results: The electronic nose was also successfully applied to identify unknown samples including sulfur fumed samples and naturally dried samples, high recognition value was obtained. Quantitative analysis of fuming degree of Pinelliae Rhizoma was also demonstrated. The method developed is simple and fast, which provides a new quality control method of Chinese herbs from the aspect of odor. Conclusion: It has shown that this electronic nose based metal oxide sensor is sensitive to sulfur and sulfides. We suggest that it can serve as a supportive method to detect residual sulfur and sulfides. PMID:24914293
Rhizoma peanut (Arachis glabrata Benth.) is a warm-season perennial forage legume, adapted to southern USA. It has similar dry matter (DM) and nutritive value to alfalfa (Medicago sativa L.). Recent studies indicated that rhizoma peanut can be grown further north (zone '8b) than previously suggest...
Cheng, Yang; Mai, Jing-Yin; Hou, Tian-Lu; Ping, Jian; Chen, Jian-Jie
Atractylodis Rhizoma is a traditional medicinal herb, which has antibacterial, antiviral, anti-inflammatory and anti-allergic, anticancer, gastroprotective and neuroprotective activities. It is widely used for treating fever, cold, phlegm, edema and arthralgia syndrome in South-East Asian nations. In this study, 6 chemical compositions of Atractylodis Rhizoma were characterized by spectral analysis and their antiviral activities were evaluated in vitro and in vivo. Among them, atractylon showed most significant antiviral activities. Atractylon treatment at doses of 10–40 mg/kg for 5 days attenuated influenza A virus (IAV)-induced pulmonary injury and decreased the serum levels of interleukin (IL)-6, tumor necrosis factor-α and IL-1β, but increased interferon-β (IFN-β) levels. Atractylon treatment upregulated the expression of Toll-like receptor 7 (TLR7), MyD88, tumor necrosis factor receptor-associated factor 6 and IFN-β mRNA but downregulated nuclear factor-κB p65 protein expression in the lung tissues of IAV-infected mice. These results demonstrated that atractylon significantly alleviated IAV-induced lung injury via regulating the TLR7 signaling pathway, and may warrant further evaluation as a possible agent for IAV treatment. PMID:27600871
Zheng, Fang; Jiang, Ze-bo; Zhang, Xian; Hu, Jin-ping; Li, Si-ming; Zhao, Jin; Zeng, Xing
To study the effect of the combined administration of different doses of Glycyrrhizae Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma on the proliferation of DFMO-treated intestinal epithelial cells (IEC-6) and p53, p21 mRNA and protein expressions, in order to define the molecular basis for the effect of the combined administration of different doses of Glycyrrhizae Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma on the cell proliferation. The effect of the drugs on the cell division rate and cell cycle of IEC-6 cells was detected by FCM. Quantitative Real-time PCR (qRT-PCR) was used to analyze the effect of the drugs on mRNA of p2l and p53 related to IEC-6 proliferation. Western blot was used to analyze the effect of the drugs on p2l and p53 protein expressions of IEC-6 cells. Atractylodis Macrocephalae Rhizoma could increase p53, p21 mRNA and proteins expression in DFMO-treated IEC-6 cells. The combined administration of different ratios of Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma could significantly down-regulate Atractylodis Macrocephalae Rhizoma's effect on p53, p21 mRNA and proteins expression in DFMO-treated IEC-6 cells and promote the proliferation of IEC-6 cells. The combined administration of Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma could down-regulate Atractylodis Macrocephalae Rhizoma's effect on DFMO-treated intestinal epithelial cells (IEC-6).
Luo, Fen; Lu, Dan; Chi, Yumei; Wu, Hao; Yu, Hongli
The fingerprint chromatograms of Arisaematis Rhizoma were established by HPLC. The analysis was performed on a Lichrospher C18 (4.6 mm x 200 mm, 5 microm) column with acetonitrile-water (containing 0.1% acetic acid) as mobile phase at a flow rate of 1.0 mL x min(-1). The detection wavelength was set at 270 nm, and the column temperature was 30 degrees C. The similarities of the fingerprint chromatograms were calculated over 0.9 between 11 batches of Arisaematis Rhizoma samples by analyzing 14 common peaks with adenosine as reference substance. However, their fingerprint chromatograms were significantly different from those of Pinellia pedatisecta and P. ternate. Adenine, hypoxanthine, xanthine, uridine, guanosine, adenosine, schaftoside, and isoschaftoside were identified by comparing the retention times and their ultraviolet spectra. The method is repeatable, exclusive and can be used for identification and evaluation of Arisaematis Rhizoma.
Yan, Xiao-jing; Yang, Ye; Bi, Lei; Chen, Shan-shan; Zhu, Jing-jing; Chen, Wei-ping
This study aims to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 using the orthogonal design method, and to investigate its effects of the component formula on cell proliferation, apoptosis and cytoskeleton in lung cancer A549 cells. The orthogonal design method was introduced to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time cell analysis were adapted to analyze the effect of component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells viability at different time and dose. Cell apoptosis was measured by Annexin V- FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was detected by high content screening (HCS). The optimizing component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell viability in both dose- and time-dependent manner compared with control group (P < 0.01). Moreover, the increase of cell apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry when cells treated with the component formula, which indicating that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in a time-dependent manner compared with control group (P < 0.01). Furthermore, compared with control group, a significant decrease in A549 cell skeleton area was found in the component formula-exposed cells in the dose-dependent manner (P < 0.01). In summary, the component formula
Sun, Lei; Jin, Yong; Liu, Xiao-Qing; Qiao, Shan-Yi; Gao, Song; Che, Yan-Zhong
The chromatographic fingerprint was established by eluting with the mobile phase consisted of acetonitrile and 0.2% formic acid water on an Agilent TC-C18 (2) column (4.6 mm x 250 mm, 5 microm). Six chromatographic peaks were identified by HPLC-MS/MS method. Ten batches of Glycyrrhizea Radix et Rhizoma Praeparata Cum Melle were determined, and the similarity was arranged from 0.72 to 0.99. Good precision, stability and repeatability were obtained, and this study provides a reference for the quality control of Glycyrrhizea Radix et Rhizoma Praeparata Cum Melle.
Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Duangjai, Acharaporn; Saokaew, Surasak; Mehmood Khan, Tahir; Lee, Learn-Han; Goh, Bey-Hing
Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs. PMID:27774066
Xu, Min; Yang, Shi-Long; Zhang, Chao; Wan, Jun; Wu, Na; Li, Xin-Yi; Huang, Qin-Wan; Zhou, Xia; Wu, Chin-Jie
Different processed products of Coptidis Rhizoma have its unique odor, which is an important assessment index for pro- cessed products identification of Coptidis Rhizoma. Objectify odor as an entry point in this study, an electronic nose technology was used, and a suitable method for Coptidis Rhizoma measurement was built firstly. Then different processed products of Coptidis Rhizoma were detected by the method built. Finally, different processed products were identified by combining with chemometrics based on the objective odor information obtained. Electronic nose detection indicated that a significant difference in odor between different processed products was performed. Coptidis Rhizoma processed or not can be distinguished based on statistical quality control (SQC) and soft independent modeling of class analogy (SIMCA). Principle component analysis (PCA) model showed that Coptidis Rhizoma and its various processed products discriminated obviously. In addition, in order to identify the processed products of Coptidis Rhizoma, a correct recognition rate of 100% was acquired by discriminant factor analysis (DFA) , and the initial identification rate and cross-validation recognition rate of linear discriminant analysis (LDA) is 100%, 94.4% respectively. In conclusion, differentiationin odor of different processed Coptidis Rhizoma was performed by the electronic nose technology used, and different products Coptidis Rhizoma were dis- criminated by combining with chemometrics. This research can be a reference for objective identification in odor of traditional Chinese medicine, and is good for the inheritance and development of traditional experience in odor identification.
Li, Shi-ping; Sha, Long; Zhao, Yi-wu; Xu, Zhi-liang; Huang, Wen-zhe; Wang, Zhen-zhong; Xiao, Wei
This paper summarized the recent 30 years research progress of the chemical constituents from Notopterygii Rhizoma et Radix. The chemical constituents from Notopterygii Rhizoma et Radix mainly consist of coumarins, polyene-polyacetylenes, sesquiterpenes, phenolic acids, while steroids and flavonoids were less reported. All constituents were confirmed and corrected through SciFinder. We also checked the Chinese name and English name and listed the CAS number of each compound. It can provide some guidelines for the research, development and utilization of Notopterygii Rhizoma et Radix in the future. Whether there is columbianin in the Notopterygii Rhizoma et Radix need to be further researched.
Zhou, Yang; Xie, Meng; Song, Yan; Wang, Wenping; Zhao, Haoran; Tian, Yuxin; Wang, Yan; Bai, Shaojuan; Zhao, Yichen; Chen, Xiaoyi; She, Gaimei
Curcumae Rhizoma, known as Ezhu (Chinese: 莪术), and Curcumae Radix, known as Yujin (Chinese: 郁金), are different plant parts coming from three same species according to China Pharmacopoeia. Actually, they are used in different ways in TCM clinical treatment. Curcumae Rhizoma is mainly used as antitumor drug, while Curcumae Radix has been used as antidepressant and cholagogue. Curcumae Rhizoma and Curcumae Radix are confused in variety and source, even in clinical trials by some nonprofessional workers. So it is important for us to make them clear. This review is aimed at summarizing the ethnopharmacology, phytochemical, and pharmacological differences between Curcumae Radix and Curcumae Rhizoma by SciFinder, CNKI, and so on, to use them exactly and clearly. Further studies on Curcumae Rhizoma and Curcumae Radix can lead to the development of new drugs and therapeutics for various diseases on the basis of the TCM theory. PMID:27057197
Zhou, Yang; Xie, Meng; Song, Yan; Wang, Wenping; Zhao, Haoran; Tian, Yuxin; Wang, Yan; Bai, Shaojuan; Zhao, Yichen; Chen, Xiaoyi; She, Gaimei
Curcumae Rhizoma, known as Ezhu (Chinese: ), and Curcumae Radix, known as Yujin (Chinese: ), are different plant parts coming from three same species according to China Pharmacopoeia. Actually, they are used in different ways in TCM clinical treatment. Curcumae Rhizoma is mainly used as antitumor drug, while Curcumae Radix has been used as antidepressant and cholagogue. Curcumae Rhizoma and Curcumae Radix are confused in variety and source, even in clinical trials by some nonprofessional workers. So it is important for us to make them clear. This review is aimed at summarizing the ethnopharmacology, phytochemical, and pharmacological differences between Curcumae Radix and Curcumae Rhizoma by SciFinder, CNKI, and so on, to use them exactly and clearly. Further studies on Curcumae Rhizoma and Curcumae Radix can lead to the development of new drugs and therapeutics for various diseases on the basis of the TCM theory.
JEONG, SU-HYEON; LEE, JI-EUN; KIM, BO-BAE; KO, YOUNGKYUNG; PARK, JUN-BEOM
Cimicifugae Rhizoma is a traditional herbal medicine used to treat various diseases in Korea, China and Japan. Cimicifugae Rhizoma is primarily derived from Cimicifuga heracleifolia Komarov or Cimicifuga foetida Linnaeus. Cimicifugae Rhizoma has been used as an anti-inflammatory, analgesic and antipyretic remedy. The present study was performed to evaluate the extracts of Cimicifugae Rhizoma on the morphology and viability of human stem cells derived from gingiva. Stem cells derived from gingiva were grown in the presence of Cimicifugae Rhizoma at final concentrations that ranged from 0.001 to 1,000 µg/ml. The morphology of the cells was viewed under an inverted microscope and the analysis of cell proliferation was performed using a Cell Counting kit-8 (CCK-8) assay on days 1, 3, 5 and 7. Under an optical microscope, the control cells exhibited a spindle-shaped, fibroblast-like morphology. The shapes of the cells in the groups treated with 0.001, 0.01, 0.1, 1 and 10 µg/ml Cimicifugae Rhizoma were similar to the shapes in the control group. Significant alterations in morphology were noted in the 100 and 1,000 µg/ml groups when compared with the control group. The cells in the 100 and 1,000 µg/ml groups were rounder, and fewer cells were present. The cultures that were grown in the presence of Cimicifugae Rhizoma at a concentration of 0.001 µg/ml on day 1 had an increased CCK-8 value. The cultures grown in the presence of Cimicifugae Rhizoma at a concentration of 10 µg/ml on day 7 had a reduced CCK-8 value. Within the limits of this study, Cimicifugae Rhizoma influenced the viability of stem cells derived from the gingiva, and its direct application onto oral tissues may have adverse effects at high concentrations. The concentration and application time of Cimicifugae Rhizoma should be meticulously controlled to obtain optimal results. PMID:26622366
He, Kai; Kou, Shuming; Zou, Zongyao; Hu, Yinran; Feng, Min; Han, Bing; Li, Xuegang; Ye, Xiaoli
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.
Chen, Juncheng; Tian, Shan; Shu, Xiaoying; Du, Hongtao; Li, Na; Wang, Junru
A response surface and Box-Behnken design approach was applied to augment polysaccharide extraction from the residue of Rhizoma gastrodiae. Statistical analysis revealed that the linear and quadratic terms for three variables during extraction exhibited obvious effects on extraction yield. The optimum conditions were determined to be a liquid-to-solid ratio of 54 mL/g, an extraction temperature of 74 °C, an extraction time of 66 min, and three extractions. These conditions resulted in a maximum Rhizoma gastrodiae polysaccharide (RGP) extraction yield of 6.11% ± 0.13%. Two homogeneous polysaccharides (RGP-1a and RGP-1b) were obtained using DEAE cellulose-52 and Sephadex G-100 columns. The preliminary characterization of RGP-1a and RGP-1b was performed using HPLC-RID, HPGPC, and FTIR. Tests of the immunological activity in vitro showed that the two polysaccharides could significantly stimulate macrophages to release NO and enhance phagocytosis in a dose-dependent manner. In particular, RGP-1b (200 μg/mL) and LPS (2 μg/mL) had almost the same influence on the NO production and phagocytic activity of RAW 264.7 macrophages (p > 0.05). All the data obtained indicate that RGP-1a and RGP-1b have the potential to be developed as a health food. PMID:27347944
Liu, Xin; Huang, He; Yang, Yan-fang; Wu, He-zhen
To study ecology suitability rank dividing of the total alkaloid content of Coptis Rhizoma for selecting artificial planting base and high-quality industrial raw material in Chongqing province. Based on the investigation of PCB and DEM data of Chongqing province, the relationship between the total alkaloid content in Coptis Rhizoma and topographical conditions was analyzed by statistical analysis. The geographic information systems (GIS)-based assessment and landscape ecological principles were applied to assess eco logy suitability areas of Coptis Rhizoma in Chongqing. slope, aspect and altitude are main topographical factors that affect the content of the total alkaloid content in Coptis Rhizoma The total alkaloid content in Coptis Rhizoma is higher in the lower altitude, shady slope and bigger slope areas. The total alkaloid content is higher in the south areas of Chongqing province and lower in the northeast. Terrain conditions of the southern region of Chongqing are most suitable for The accumulated of total alkaloid Coptis Rhizoma content.
Staples, C R; Emanuele, S M; Prine, G M
Florigraze rhizoma peanut (Arachis glabrata Benth.) is a very persistent, high quality legume that is well adapted to subtropical and tropical environments. This legume was ensiled and compared with corn silage (Zea mays) as a feedstuff for lactating dairy cows. Twelve Holstein cows, including 4 ruminally fistulated cows (mean, 70 days in milk), were used in an experiment with a 4 x 4 Latin square design replicated three times. Diets were formulated to contain 50% concentrate on a dry matter (DM) basis. Dietary treatments were rhizoma peanut silage and corn silage fed at DM ratios of 0:50, 20:30, 35:15, and 50:0. The dry matter intake, digestibilities of DM and crude protein, and production of milk and fat-corrected milk decreased quadratically as the percentage of legume in the diet increased. Nearly all of the decrease occurred when rhizoma peanut silage was the sole forage in the diet. The organic matter digestibility of the two forage types was similar; however, digestion of crude protein in rhizoma peanut silage was only 45% (calculated using simultaneous equations). Ruminal pH increased, and ammonia and total volatile fatty acid concentrations decreased, as the percentage of rhizoma peanut silage in the diet increased. In situ digestion rate constants for DM of rhizoma peanut silage were twice that of corn silage, but extent of DM digestion was greater for corn silage. Passage rates of concentrates and forage were unaffected by dietary treatments. Rhizoma peanut silage can replace 70% of corn silage in diets containing 50% concentrate without affecting dairy cow performance.
Shi, Xiao-Lin; Liu, Kang; Wu, Lian-Guo
Osteoporosis, the sixth most common disease in the world, is bringing increasingly serious harm to people's health. Cathepsin K, which plays an important role in bone resorption, is a potential target in the treatment of osteoporosis. Total flavonoids, the active ingredients in Rhizoma Drynariae, have shown obvious, therapeutic effect on osteoporosis. In previous studies, it was presumed that the mechanism for the therapeutic effect was through inhibiting the expression of Cathepsin K. However, there are still no detailed reports on some key issues such as the specific inhibitory results of total flavonoids on Cathepsin K and the pathway of inhibition and so on. Based on previous studies on total flavonoids from Rhizoma Drynariae, the pathway for the effect of, total flavonoids inhibiting Cathepsin K and their interventional value on Cathepsin K were analyzed in this paper, so as to explore the interventional feasibility and value of total flavonoids in Rhizoma Drynariae on Cathepsin K.
Pang, Bing; Yu, Xiao-Tong; Zhou, Qiang; Zhao, Tian-Yu; Wang, Han; Gu, Cheng-Juan; Tong, Xiao-Lin
The rapidly increasing diabetes mellitus (DM) is becoming a major public health issue globally; considerable progress has been made in the field of western hypoglycemic drug and insulin, but some shortages still exist. As one of the most important parts in complementary and alternative therapies, traditional Chinese medicine (TCM) performs a good clinical practice and is showing a bright future in the treatment of DM. TCM therapy has certain advantages of less toxicity and/or side effects, and Chinese herbal medicine which usually contains various active ingredients could provide multiple therapeutic effects. Huang Lian (Rhizoma coptidis, RC) is a herb frequently used in many traditional formulas for properties of “clearing damp-heat, quenching fire, and counteracting poison” in Asia for centuries. In this review, we summarize the application of RC in the treatment of DM from two aspects of contents. Firstly, theoretical principles are explained, including the properties and related records about RC in ancient references and modern pharmacological researches and pharmacokinetics on RC and its active components. Secondly, the clinical application of RC is mainly reviewed, such as applicable stage and syndrome, the reasonable dose range, the preparation formulations, and the toxicity and/or side effects and solutions to its adverse actions. This review provides scientific evidence about the effective components, pharmacological researches, and toxicity of RC, as well as introducing traditional Chinese medical theory and clinical experience, in order to guide clinician to use RC more suitably and reasonably in the clinical practice. PMID:26508987
Jeon, S-Y; Kwon, S-H; Seong, Y-H; Bae, K; Hur, J-M; Lee, Y-Y; Suh, D-Y; Song, K-S
In the course of searching for BACE1 (beta-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of Smilax Rhizoma (the dried rhizomes of Smilax china L.) showed potent inhibitory activity. The active compounds were identified as a trans/cis-resveratrol mixture, oxyresveratrol, veraphenol, and cis-scirpusin A. They were shown to non-competitively inhibit BACE1 with the Ki values of 5.4 x 10(-6), 5.4 x 10(-6), 3.4 x 10(-6), and 5.4 x 10(-6)M and IC(50) values of 1.5 x 10(-5), 7.6 x 10(-6), 4.2 x 10(-6), and 1.0 x 10(-5)M, respectively. The active compounds were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.
Ko, Byoung-Seob; Choi, Soo Bong; Park, Seong Kyu; Jang, Jin Sun; Kim, Yeong Eun; Park, Sunmin
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.
Xu, Xiaofei; Chen, Hongfeng; Ye, Meina
Mercury-containing preparations are widely used in surgery department of traditional Chinese medicine and have made remarkable achievements. But they are toxic to human kidney, nerve, immune, etc. Smilacis Glabrae Rhizoma is sweet, tasteless and neutral in nature and able to enter liver and stomach channels and detoxify mercury poisoning. This article summarizes the mercury poisoning and the detoxification effect of Smilacis Glabrae Rhizoma in ancient records, pharmaceutical studies and clinical application, in order to provide ideas and methods for the safe use of mercury-containing preparations in surgery department of traditional Chinese medicine.
Lee, Ji-Eun; Kim, Bo-Bae; Ko, Youngkyung; Jeong, Su-Hyeon; Park, Jun-Beom
Cimicifugae Rhizoma, a herb with a long history of use in traditional Oriental medicine is reported to have anti-inflammatory, antioxidant, anti-complement and anticancer effects. The aim of the present study was to evaluate the effects of Cimicifugae Rhizoma extracts on the osteogenic and adipogenic differentiation of human stem cells derived from gingiva. Stem cells derived from gingiva were grown in the presence of Cimicifugae Rhizoma at final concentrations of 0.1, 1 and 10 µg/ml. Cell proliferation analyses were performed at day 15. For osteogenic differentiation experiments, the stem cells were cultured in osteogenic media containing β-glycerophosphate, ascorbic acid-2-phosphate and dexamethasone, and osteogenic differentiation was evaluated by analysis of osteocalcin expression at 21 days. For adipogenic differentiation experiments, the stem cells were grown in adipogenic induction medium, and the adipogenic differentiation was evaluated by analysis of adipocyte fatty acid-binding protein at day 14. The cultures grown in the presence of 0.1 µg/ml Cimicifugae Rhizoma showed a significant increase in cellular proliferation at day 15 compared with the control group. The relative osteogenic differentiation in the presence of Cimicifugae Rhizoma for the 0.1, 1 and 10 µg/ml groups was 171.5±13.7, 125.6±28.7 and 150.5±9.0, respectively, when that of the untreated control group on day 21 was considered to be 100%. The relative adipogenic differentiation at day 14 of the 0.1, 1 and 10 µg/ml groups in the presence of Cimicifugae Rhizoma was 97.5±15.0, 102.9±12.8 and 87.0±6.8%, respectively when that of the untreated control group on day 14 was considered to be 100%. Within the limits of this study, Cimicifugae Rhizoma increased the proliferation of stem cells derived from the gingiva, and low concentrations of Cimicifugae Rhizoma may increase the osteogenic differentiation of stem cells. PMID:28352313
Wu, H; Ye, D; Diao, H; Cai, B
Based on the L9(3)1 orthogonal design with the amount of ginger, amount of alum and decocting time as working factors, and using the method of recording comprehensive scores, an experimental study has been made on the optimization of processing technology for Rhizoma Pinelliae by ginger and alum as stipulated in the Pharmacopoeia. The result shows that the best process is to use 15 kg of ginger juice and 8 kg of alum per 100 kg of Pinellia ternata and decoct them together for 2-3 hours till the juice is fully absorbed by Rhizoma Pinelliae.
Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity.
Yamahara, J; Shimoda, H; Matsuda, H; Yoshikawa, M
Potent immunosuppressants, the dimeric sesquiterpene thioalkaloids, 6-hydroxythiobinupharidine (2), 6,6'-dihydroxythiobinupharidine (3), 6-hydroxythionuphlutine B (5) and 6'-hydroxythionuphlutine B (6), were isolated from a natural medicine, Nupharis Rhizoma, the rhizoma of Nuphar pumilum (TIMM.) DC., through bioassay-guided separation together with five quinolizidine alkaloids (8, 9, 10, 11, 12). Dimeric sesquiterpene thioalkaloids (2, 3, 5, 6) were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mice spleen cells at 10(-6) M concentration. At this concentration, 2, 5 and 6 were found to exhibit no cytotoxicity to mice spleen cells, and 3 also showed only a little cytotoxicity. In addition, the inhibitory activity of several Nuphar alkaloids, dimeric sesquiterpene thioalkaloids (1, 4, 7, 8), and monomeric sesquiterpene alkaloids (9, 10, 11, 12) on anti-sheep erythrocyte plaque forming cell formation was examined and some structural requirement of Nuphar alkaloid for immunosuppressive activity was determined.
Zhang, Cui-ying; Zhang, Hong; Dong, Yu; Ren, Wei-guang; Chen, Heng-wen
A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.
Rhizoma peanut (Arachis glabrata Benth) has potential to provide high quality forage during summer months; however establishment of the stand is slow and cold tolerance is limited. During the three growing seasons from 2006 to 2008, a randomized complete block design experiment was conducted at fo...
Zhou, Xia; Peng, Yao-zong; Huang, Tao; Li, Ling; Mou, Shao-xia; Kou, Shu-ming; Li, Xue-gang
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.
Yang, Yihui; Kang, Ning; Xia, Hongjun; Li, Jun; Chen, Lixia; Qiu, Feng
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.
Kong, Wei-Jun; Zhao, Yan-Ling; Xiao, Xiao-He; Jin, Cheng; Li, Zu-Lun
To control the quality of rhizoma Coptidis, a method based on ultra performance liquid chromatography with photodiode array detector (UPLC-PAD) was developed for quantitative analysis of five active alkaloids and chemical fingerprint analysis. In quantitative analysis, the five alkaloids showed good regression (R > 0.9992) within test ranges and the recovery of the method was in the range of 98.4-100.8%. The limit of detections and quantifications for five alkaloids in PAD were less than 0.07 and 0.22 microg/ml, respectively. In order to compare the UPLC fingerprints between rhizoma Coptidis from different origins, the chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), principal component analysis (PCA) were applied to classify the rhizoma Coptidis samples according to their cultivated origins. Consistent results were obtained to show that rhizoma Coptidis samples could be successfully grouped in accordance with the province of origin. Furthermore, five marker constituents were screened out to be the main chemical marker, which could be applied to accurate discrimination and quality control for rhizoma Coptidis by quantitative analysis. This study revealed that UPLC-PAD method was simple, sensitive and reliable for quantitative and chemical fingerprint analysis, moreover, for the quality evaluation and control of rhizoma Coptidis.
Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei
This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.
Shen, Bao-Jia; Qin, Kun-Ming; Zhang, Xing-Hai; Liu, Qi-Di; Cai, Hao; Liu, Xiao; Cai, Bao-Chang
To establish a fingerprint for Cimicifugae Rhizoma from different producing areas. Column kromasil (4.6 mm x 250 mm, 5 microm) was employed with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution. The flow rate was 1.0 mL x min(-1), the detection wavelength was 254 nm. Twenty chromatographic peaks were extracted as the common peaks of fingerprint, and 21 batches of samples were compared and classified with such methods as similarity evaluation, cluster analysis and principle component analysis. The results showed 12 common peaks and three categories of samples. The method was so highly reproducible, simple and reliable that it could provide basis for quality control and evaluation of Cimicifugae Rhizoma from different producing areas.
Wang, Xinsheng; Wu, Qi-nan; Wu, Yanfang; Wu, Chengying; Yue, Wei; Liang, Qiaoli
A reversed-phase high-performance liquid chromatographic method was developed for the simultaneous quantification of seven phenolic compounds from Rhizoma Sparganii. The samples were separated on a Waters SunFire C18 column with a temperature of 30°C. Gradient elution was applied, using 0.8% acetic acid (solvent A) and methanol (solvent B) with a flow rate of 1.0 mL/min, and detection wavelength was 280 nm. The validation of the method included linearity, precision, repeatability, stability and recovery. The calibration curves showed good linear regression (R(2) > 0.9996) within the test range. The developed method indicated good precision and accuracy, with the overall intra-day and inter-day variation at less than 3%. The range of recoveries for the seven analytes was 95.34-100.06% with relative standard deviation < 3.08 %. The established method was successfully applied for the determination of seven phenolic compounds in 12 batches of Rhizoma Sparganii. The study may be useful in the quality evaluation of Rhizoma Sparganii, and can provide technical support for pharmacological and clinical research of related drugs.
Li, Bing-jie; Shen, Yong; Liao, Ri-tao; Gao, Guan-zhen; Ke, Li-jing; Zhou, Jian-wu; Rao, Ping-fan
The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.
Bian, Qingya; Yang, Hui; Chan, Chi-On; Jin, Dengping; Mok, Daniel Kam-Wah; Chen, Sibao
Curculiginis Rhizoma (Curculigo orchioides GAERTN.) is a well-known Chinese herbal medicine, as well as an important Rasayana drug in India. Current criteria of quality control on this herb are to quantitatively analyze single compound curculigoside, which fail to comprehensively evaluate quality of this herb. In this paper, a simple and reliable HPLC coupled with diode array detector (DAD) method was developed to evaluate the quality of Curculiginis Rhizoma through establishing chromatographic fingerprint and simultaneously quantitating four phenolic compounds, orcinol glucoside, orcinol, 2,6-dimethoxybenzoic acid and curculigoside. The fingerprint displayed eleven common peaks, and the similarity index of different samples was in a range of 0.890-0.977. Validation of the method was acceptable, with 96.03-102.82% accuracy in recovery test and inter and intra-day precisions were less than 2%. This developed method by having a combination of chromatographic fingerprint and quantitation analysis could be applied to the quality control of Curculiginis Rhizoma.
Wang, Hui; Mu, Wei; Shang, Hongcai; Lin, Jia; Lei, Xiang
Rhizoma Coptidis (Huang Lian in Chinese pinyin) is among the most widely used traditional Chinese herbal medicines and has a profound history of more than 2000 years of being used as a therapeutic herb. The antidiabetic effects of Rhizoma Coptidis have been extensively investigated in animal experiments and clinical trials and its efficacy as a promising antihyperglycemic agent has been widely discussed. In the meantime, findings from modern pharmacological studies have contributed the majority of its bioactivities to berberine, the isoquinoline alkaloids component of the herb, and a number of experiments testing the antidiabetic effects of berberine have been initiated. Therefore, we conducted a review of the current evidence profile of the antihyperglycemic effects of Rhizoma Coptidis as well as its main component berberine and the possible mechanism of actions, in order to summarize research evidence in this area and identify future research directions. PMID:24818152
Li, Cailan; Xie, Jianhui; Chen, Xiaoying; Mo, Zhizhun; Wu, Wen; Liang, Yeer; Su, Zuqing; Li, Qian; Li, Yucui; Su, Ziren; Yang, Xiaobo
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.
Pang, Hanqing; Wu, Liang; Tang, Yuping; Zhou, Guisheng; Qu, Cheng; Duan, Jin-ao
Radix Salviae miltiorrhizae et Rhizoma, known as Danshen in China, is one of the most popular traditional Chinese medicines. Recently, there has been increasing scientific attention on Danshen for its remarkable bioactivities, such as promoting blood circulation, removing blood stasis, and clearing away heat. This review summarized the advances in chemical analysis of Danshen and its preparations since 2009. Representative established methods were reviewed, including spectroscopy, thin layer chromatography, gas chromatography, liquid chromatography (LC), liquid chromatography-mass spectrometry (LC-MS), capillary electrophoresis, electrochemistry, and bioanalysis. Especially the analysis of polysaccharides in Danshen was discussed for the first time. Some proposals were also put forward to benefit quality control of Danshen.
Liu, Yingjiao; Liu, Canhuang; Yu, Yafei; Xu, Bei; Gong, Limin; Zeng, Xiaoyan; Xiao, Lan; Cheng, Qilai; Liu, Tasi
Yuzhu (Polygonati Odorati Rhizoma), Kangdingyuzhu (Polygonati Prattii Rhizoma), and zhugenqiyuzhu (Disporopsis Fuscopictae Rhizoma) are of the same family, but of different genera. They have all often used in Chinese Materia Medica (CMM) as Polygonati Odorati Rhizoma in China market. Three species of CMM are confused. For better application, we need to identify these plants accurately. This study use pharmacognosy technique and GC-MS analysis, three species of CMM were authenticated. In macroscopic characteristics, the fruit of Polygonati Odorati Rhizoma is blue-black, while the other two are maroon and dark purple orderly. Nodes of Polygonati Odorati Rhizoma are upward and light uplift, about 1 cm spacing, while the other are not. As for microscopic characteristics, the cortex of Polygonati Odorati Rhizoma only occupies about 1/5 of the radius of the transverse section with inconspicuous endodermis, which is much smaller than others. The type of vascular bundles of Polygonati Odorati Rhizoma is closed collateral, but the other is amphivasal. Raphides of calcium oxalate are scattered, but Raphides of the other two are like brooms and neat rows. GC-MS analysis of essential oil could provide different characteristics to distinguish three species. Twenty-three compounds were identified from essential oil of Polygonati Odorati Rhizoma and the main components were n-hexadecanoic acid (49.45%), while n-hexadecanoic acid of the other two are 23.92% and 9.45%. The content of n-hexadecanoic is strongly different. This research was aimed to establish a method by pharmacognosy and GC-MS analysis to identify three CMM and for providing scientifical data to ensure accuracy of origin of three species.
Xu, Beilei; Zhang, Guijun; Xu, Changhua; Sun, Suqin
Fourier transform infrared spectroscopy (FT-IR) associated with second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2D-IR) are employed to analyze various processed products and different extracts of Rhizoma Coptidis. There is a shift of the peak of 1641 cm-1 of raw Rhizoma Coptidis after processed, which drifts to lower wave number. Peaks at 1508, 1387, 1363, 1332, 1274 and 1234 cm-1 barely change in most samples, except an obvious enhancement of these peaks after processed, suggesting that processed Rhizoma Coptidis may have higher content of berberine than raw material, which is corresponding to the results of correlation coefficients analysis. There are some differences in the absorption peaks in the range of 1800-1000 cm-1 in the SD-IR spectra, which have better resolution, of different processed products. 2D-IR spectra, which elevate the resolution further, can present more differences among the products in the range of 1300-800 cm-1 and 1800-1300 cm-1. Analysis of aqueous, ethanol and petroleum ether extracts of various processed products proves that there are distinctive differences of all auto-peaks in shapes and intensities in all of them. With the advantages of high resolution, high speed and convenience, FT-IR combined with 2D-IR can quickly and precisely distinguish various processed products of Rhizoma Coptidis and can be applied to predict the tendency of transformation of the complicated chemical mixture systems under heat perturbation.
Zhang, Ding-Kun; Zhang, Fang; Lin, Jun-Zhi; Han, Li; Wu, Zhen-Feng; Yang, Ying-Guang; Yang, Ming
In this paper, Rhodiolae Crenulatae Radix et Rhizoma extract,with high hygroscopic,was selected as research model, while lactose was selected as modifiers to study the effect of the grinding modification method on the hygroscopic. Subsequently, particle size distribution, scannin electron microscopy, infrared spectroscopy and surface properties were adopted for a phase analysis. The results showed that the modified extract, prepared by Rhodiolae Crenulatae Radix et Rhizoma extract grinding 5 min with the same amount of lactose UP2, which hygroscopic initial velocity, acceleration, and critical relative humidity moisture were less than that of Rhodiolae Crenulatae Radix et Rhizoma extract and the mixture dramatically. In addition, compared with the mixture, the size distribution of modified extract was much less, the microstructure was also difference, while the infrared spectroscopy and surface properties were similar with that of lactose. It is the main principle that lactose particle adhered to the surface of Rhodiolae Crenulatae Radix et Rhizoma extract after grinding mofication to decress the moisture obviously.
Kang, Suk-Nam; Lee, Jong Seok; Park, Joung-Hyun; Cho, Jae-Hyeon; Park, Jae-Hong; Cho, Kwang-Keun; Lee, Ok-Hwan; Kim, Il-Suk
Drynariae rhizoma has been used to prevent bone loss that occurs with increasing age. However, the chemical compounds in extracts that act on bone metabolism in herbal medicine are poorly understood. This study aimed to investigate and compare the extraction efficacy of polyphenolic compounds, antioxidant activity, and in vitro anti-osteoporosis properties of water extract (DR-DW) and ethanol extract (DR-EtOH) from D. rhizoma. Total phenolics and flavonoids were better extracted with 70% EtOH, and this extraction method also resulted in higher antioxidant activity and in vitro anti-osteoporosis properties in these extracts. In particular, the contents of phloroglucinol, protocatechuic acid ethyl ester, 2-amino-3,4-dimethyl-benzoic acid, 3-(3,5-dimethyl-pyrazol-1-yl)-benzoic acid, chlorogenic acid, syringic acid, trans-ferulic acid, (−)-epigallocatechin, epigallocatechin gallate, quercetin dehydrate, luteolin and emodin in DR-EtOH were higher than those in DR-DW. These results indicated that DR-EtOH could be a good source of natural herbs with anti-osteoporosis properties. PMID:24763116
He, Yanfei; Chen, Siyu; Yu, Hai; Zhu, Long; Liu, Yayun; Han, Chunyang; Liu, Cuiyan
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
He, Yanfei; Chen, Siyu; Yu, Hai; Zhu, Long; Liu, Yayun; Han, Chunyang; Liu, Cuiyan
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.
Kang, Suk-Nam; Lee, Jong Seok; Park, Joung-Hyun; Cho, Jae-Hyeon; Park, Jae-Hong; Cho, Kwang-Keun; Lee, Ok-Hwan; Kim, Il-Suk
Drynariae rhizoma has been used to prevent bone loss that occurs with increasing age. However, the chemical compounds in extracts that act on bone metabolism in herbal medicine are poorly understood. This study aimed to investigate and compare the extraction efficacy of polyphenolic compounds, antioxidant activity, and in vitro anti-osteoporosis properties of water extract (DR-DW) and ethanol extract (DR-EtOH) from D. rhizoma. Total phenolics and flavonoids were better extracted with 70% EtOH, and this extraction method also resulted in higher antioxidant activity and in vitro anti-osteoporosis properties in these extracts. In particular, the contents of phloroglucinol, protocatechuic acid ethyl ester, 2-amino-3,4-dimethyl-benzoic acid, 3-(3,5-dimethyl-pyrazol-1-yl)-benzoic acid, chlorogenic acid, syringic acid, trans-ferulic acid, (-)-epigallocatechin, epigallocatechin gallate, quercetin dehydrate, luteolin and emodin in DR-EtOH were higher than those in DR-DW. These results indicated that DR-EtOH could be a good source of natural herbs with anti-osteoporosis properties.
Shan, Mingqiu; Yu, Sheng; Yan, Hui; Chen, Peidong; Zhang, Li; Ding, Anwei
Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, swelling and pain caused by injuries from falls. In addition, it is a kind of pigment utilized as a food additive and a dye for wool or fiber. This review mainly concentrates on studies of the botany, phytochemistry, pharmacology and toxicology of this Traditional Chinese Medicine. The phytochemical evidences indicated that over a hundred chemical components have been found and isolated from the medicine, such as anthraquinones, naphthoquinones, triterpenoids, cyclic hexapeptides and others. These components are considered responsible for the various bioactivities of the herbal drug, including anti-oxidation, anti-inflammation, immunomodulation, antitumor, effects on coagulation-fibrinolysis system, neuroprotection and other effects. Additionally, based on these existing results, we also propose some interesting future research directions. Consequently, this review should help us to more comprehensively understand and to more fully utilize the herbal medicine Rubiae Radix et Rhizoma.
Wang, Jing; Yuan, Zimin; Kong, Hongwei; Li, Yong; Lu, Xin; Xu, Guowang
Metabolomics was used to explore the mechanism of Rhizoma coptidis in treating type II diabetes mellitus. The rat model of type II diabetes mellitus was constructed by an injection of streptozocin (40 mg/kg), along with diets of fat emulsion. The rats were divided into four groups, the control group, the model group, the Rhizoma coptidis group (10 g/kg) and the metformin group (0.08 g/kg). After the treatment for 30 d, blood samples were collected to test biomedical indexes, and 24 h urine samples were collected for the metabolomics experiment. In the Rhizoma coptidis group, fasting blood glucose (FBG), total cholesterol (TC) and total plasma triglycerides (TG) were significantly decreased by 59.26%, 58.66% and 42.18%, respectively, compared with those in the model group. Based on gas chromatography-mass spectrometry, a urinary metabolomics method was used to study the mechanism of Rhizoma coptidis in treating diabetes mellitus. Based on the principal component analysis, it was found that the model group and control group were separated into two different clusters. The Rhizoma coptidis group was located between the model group and the control group, closer to the control group. Twelve significantly changed metabolites of diabetes mellitus were detected and identified, including 4-methyl phenol, benzoic acid, aminomalonic acid, and so on. After diabetic rats were administered with Rhizoma coptidis, 7 metabolites were significantly changed, and L-ascorbic acid and aminomalonic acid which related with the oxidative stress were significantly regulated to normal. The pharmacological results showed that Rhizoma coptidis could display anti-hyperglycemic and anti-hyperlipidemic effects. The Rhizoma coptidis had antioxidation function in preventing the occurrence of complications with diabetes mellitus to some extent. The work illustrates that the metabolomics method is a useful tool to study the treatment mechanism of traditional Chinese medicine.
Nagajyothi, P C; Sreekanth, T V M; Tettey, Clement O; Jun, Yang In; Mook, Shin Heung
Here, we report a simple, eco-friendly and inexpensive approach for the synthesis of zinc oxide nanoparticles (ZnO NPs) using Coptidis Rhizoma. The ZnO NPs were characterized by UV-visible absorption spectroscopy, FTIR, SEM-EDX, TGA, TEM, SAED and XRD. TEM images confirmed the presence of spherical and rod shaped ZnO NPs in the range of 2.90-25.20 nm. Green synthesized ZnO NPS exhibited moderate antibacterial activity against Gram-positive and Gram-negative bacteria and excellent DPPH free radical scavenging activity. Synthesized ZnO NPs had no toxic effects on the RAW 264.7 cell line.
Qian, Zhi-Gang; Jiang, Long-Fa
In this study, we prepared Rhizoma Phragmites derived oligosaccharides (ROs) by hydrolysis with hydrogen peroxide (H2O2). The ROs yield was affected by reaction time, temperature, and H2O2 concentration. Too long reaction time and too high temperature decreased the ROs yield. Maximum ROs yield (11.26%) was obtained at reaction time 4h, temperature 75 °C, and H2O2 concentration 3.5% (v/v). The oligosaccharides sample contained 93.16% sugar, of which the average degree was approximately 11, was water-soluble, and showed white. The ROs had the highest antibacterial activity against Staphylococcus aureus, followed by Bacillus subtilis and Escherichia coli at the concentration of 100 μg/mL.
Liu, Jing; Man, Shuli; Li, Jing; Zhang, Yang; Meng, Xin; Gao, Wenyuan
Rhizoma Paridis saponin (RPS) had been regarded as the main active components responsible for the anti-tumor effects of the herb Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. In the present research, we set up a rat model of diethylnitrosamine (DEN) induced hepatoma to evaluate antitumor effect of RPS. After 20 weeks treatment, rats were sacrificed to perform histopathological examinations, liver function tests, oxidative stress assays and so forth. As a result, DEN-induced hepatoma formation. RPS alleviated levels of liver injury through inhibiting liver tissues of malondialdehyde (MDA) and nitric oxide (NO) formation, increasing superoxide dismutases (SOD) production, and up-regulating expression of GST-α/μ/π in DEN-induced rats. All in all, RPS would be a potent agent inhibiting chemically induced liver cancer in the prospective application.
Xie, Yong-Chao; Ning, Ning; Zhu, Li; Li, Dan-Ning
Biatractylolide was isolated from ethyl acetate extract of dried Atractylodis Macrocephalae Rhizoma root by multistep chromatographic processing. Structure of biatractylolide was confirmed by 1H-NMR and 13C-NMR. The IC50 on acetylcholinesterase (AChE) activity was 6.5458 μg/mL when the control IC50 value of huperzine A was 0.0192 μg/mL. Molecular Docking Software (MOE) was used to discover molecular sites of action between biatractylolide and AChE protein by regular molecular docking approaches. Moreover, biatractylolide downregulated the expression of AChE of MEF and 293T cells in a dose-dependent manner. These results demonstrated that the molecular mechanisms of inhibitory activities of biatractylolide on AChE are not only through binding to AChE, but also via reducing AChE expression by inhibiting the activity of GSK3β. PMID:27642355
Guo, Ming; Liu, Yue; Shi, Dazhuo
Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011
Luo, Xin; Wang, Xue-jing; Zhao, Yi-wu; Huang, Wen-zhe; Wang, Zhen-zhong; Xiao, Wei
The extracting technology of salidroside, tyrosol, crenulatin and gallic acid from Rhodiolae Crenulatae Radix et Rhizoma was optimized. With extraction rate of salidroside, tyrosol, crenulatin and gallic acid as indexes, orthogonal test was used to evaluate effect of 4 factors on extracting technology, including concentration of solvent, the dosage of solvent, duration of extraction, and frequency of extraction. The results showed that, the best extracting technology was to extract in 70% alcohol with 8 times the weight of herbal medicine for 2 times, with 3 hours once. High extraction rate of salidroside, tyrosol, crenulatin and gallic acid were obtained with the present technology. The extracting technology was stable and feasible with high extraction rate of four compounds from Rhodiolae Crenulatae Radix et Rhizoma, it was suitable for industrial production.
Yang, Fan; Liang, Yuqiong; Xu, Li; Ji, Leilei; Yao, Nan; Liu, Ruonan; Shi, Le; Liang, Tao
Rhizoma Dioscorea bulbifera, the tuber of Dioscorea bulbifera L., has been used to treat various diseases. However, the clinical application has been limited for its hepatotoxicity. In this study, we explored the cascade working mechanisms of time-dependent hepatotoxicity induced by total saponins extracted from Rhizoma Dioscorea bulbifera (TSRD). Animals were orally administered with TSRD for indicated time period. The adverse effects were determined by histopathology and biochemistry. Similar hepatic index was analyzed in L-O2 cells exposed to dioscin for different durations. We found that TSRD could initially cause cell damage and cholestasis in rats. With the treatment going on, oxidative stress injury and up-regulation of Cytochromes P450 (CYPs) were observed both in vitro and in vivo. Eventually, TSRD induced mitochondrial permeability results in apoptosis or necrosis. Taken together, we provided evidence for the time-dependent hepatotoxicity of TSRD and created a 3-step injury model to clarify its cascade working mechanisms.
Ma, Bing-Liang; Yin, Chun; Zhang, Bo-Kai; Dai, Yan; Jia, Yi-Qun; Yang, Yan; Li, Qiao; Shi, Rong; Wang, Tian-Ming; Wu, Jia-Sheng; Li, Yuan-Yuan; Lin, Ge; Ma, Yue-Ming
Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products.
Wei, Jinxia; Jiang, Zhen; Cui, Zhi; Guo, Xingjie
The objective of this study was to develop a rapid and reliable homogenate extraction (HGE) and ultra high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous analysis of eight bioactive oxoisoaporphine alkaloids (including two new alkaloids) in Rhizoma Menispermi. HGE was optimized by response surface methodology (RSM) to obtain the maximum extraction efficiency of eight alkaloids. Separation was achieved on a Waters ACQUITY UPLC® BEH C18 column (50 × 2.1 mm(2), 1.7 μm) using gradient elution with a mobile phase consisting of acetonitrile and 0.2% formic acid in water. Quantification was performed with multiple reaction monitoring (MRM) mode using positive ESI as an interface. This is the first report of the simultaneous analysis of eight oxoisoaporphine alkaloids in Rhizoma Menispermi using a UPLC-MS/MS method; this analysis afforded good linearity, precision, and accuracy. Then, the method was successfully applied to determine the alkaloids in Rhizoma Menispermi from different sources.
Ma, Bing-Liang; Yin, Chun; Zhang, Bo-Kai; Dai, Yan; Jia, Yi-Qun; Yang, Yan; Li, Qiao; Shi, Rong; Wang, Tian-Ming; Wu, Jia-Sheng; Li, Yuan-Yuan; Lin, Ge; Ma, Yue-Ming
Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of Coptidis Rhizoma extract after purification. The water solubility, in vitro absorption, and plasma exposure of berberine (the major active compound) in the Coptidis Rhizoma extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products. PMID:26822920
Chrubasik, S; Pittler, M H; Roufogalis, B D
Zingiberis rhizoma is used as a broadspectrum antiemetic. We, therefore, conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular plant material. Although clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. Meta-analyses could not demonstrate the postoperative antiemetic effectiveness, and effect in motion sickness or nausea/vomiting of other ethiology. It also remains to be confirmed that proprietary ginger preparations are clinically useful to alleviate osteoarthritic or other pain, although there is no doubt that ginger constituents interfere with the inflammatory cascade and the vanilloid nociceptor. Ginger exerts in vitro antioxidative, antitumorigenic and immunomodulatory effects and is an effective antimicrobial and antiviral agent. Animal studies demonstrate effects on the gastrointestinal tract, the cardiovascular system, on experimental pain and fever, antioxidative, antilipidemic and antitumor effects, as well as central and other effects. The most relevant human pharmacological studies require a confirmatory study to exclude interaction of ginger preparations with platelet aggregation. Pharmacokinetic data are only available for -gingerol and zingiberene. Preclinical safety data do not rule out potential toxicity, which should be monitored especially following ginger consumption over longer periods.
Chen, Fang-Fang; Wang, Guo-Ying; Shi, Yan-Ping
Molecularly imprinted polymers (MIPs) had been prepared by precipitation polymerization method using acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, acetonitrile as the porogen solvent and protocatechuic acid (PA), one of phenolic acids, as the template molecule. The MIPs were characterized by scanning electron microscopy and Fourier transform infrared, and their performance relative to non-imprinted polymers was assessed by equilibrium binding experiments. Six structurally similar phenolic acids, including p-hydroxybenzoic acid, gallic acid, salicylic acid, syringic acid, vanillic acid, ferulic acid were selected to assess the selectivity and recognition capability of the MIPs. The MIPs were applied to extract PA from the traditional Chinese medicines as a solid-phase extraction sorbent. The resultant cartridge showed that the MIPs have a good extraction performance and were able to selectively extract almost 82% of PA from the extract of Rhizoma homalomenae. Thus, the proposed molecularly imprinted-solid phase extraction-high performance liquid chromatography method can be successfully used to extract and analyse PA in traditional Chinese medicines.
Dong, Ge; Wang, Junsong; Guo, Pingping; Wei, Dandan; Yang, Minghua; Kong, Lingyi
Arisaematis Rhizoma (AR), a famous traditional Chinese medicine, has been widely used in Asia over thousands of years. Documented with noticeable toxicity in ancient books, AR has been used to treat various diseases in the clinic. Therefore, it is important to assess the toxicity of AR dynamically and holistically. In this study, a (1)H NMR-based metabolomics approach complemented with serum chemistry and histopathology has been applied to investigate the toxicity of AR. Rats were intragastrically administered with AR (0, 0.5 and 1 g kg(-1) body weight) for 30 days, and serum and urine samples were collected. Their (1)H NMR profiles were analyzed by multivariate pattern recognition techniques to denote metabolic variations induced by AR, and 13 metabolites in urine and 6 metabolites in serum were significantly altered, which suggested that disturbances in energy metabolism, perturbation of the gut microflora environment, membrane damage, folate deficiency and injury of kidneys are produced by AR. Histopathology showed a slight vacuolization of the glomerular matrix and edema of renal tubular epithelial cells in kidneys of AR administered rats, which were evidenced by increased levels of blood urea nitrogen and creatinine in serum chemistry. Our results indicated that oral administration of crude AR was found to induce slight renal toxicity. Therefore, precautions should be made to monitor the potential nephrotoxicity of AR in clinical use. The metabolomics approach provided a promising tool for the study and better understanding of TCM-induced toxicity dynamically and holistically.
Choi, Sung-Ho; Kim, Sung-Jin
Background: Atractylodis Rhizoma Alba (ARA) has been used in Korean folk medicine for constipation, dizziness, and anticancer agent. In the present study, we performed to test whether the methanolic extract of ARA has antioxidant and antiosteoclastogenesis activity in RAW 264.7 macrophage cells. Materials and Methods: Antioxidant capacities were tested by measuring free radical scavenging activity, nitric oxide (NO) levels, reducing power, and inducible nitric oxide synthase (iNOS) expression in response to lipopolysaccharides (LPS). Antiosteoclastogenesis activity was evaluated by performing tartrate-resistant acid phosphatase assay in RAW 264.7 macrophage cells. Results: The extract exerted significant 1,1-diphenyl-2-picrylhydrazyl and NO radical scavenging activity, and it exerted dramatic reducing power. Induction of iNOS and NO by LPS in RAW 264.7 cells was significantly inhibited by the extract, suggesting that the ARA extract inhibits NO production by suppressing iNOS expression. Strikingly, the ARA extracts substantially inhibited the receptor activator of NF-κB ligand-induced osteclastic differentiation of LPS-activated RAW 264.7 cells. The ARA extract contains a significant amount of antioxidant components, including phenolics, flavonoids and anthocyanins. Conclusion: These results suggest that the methanolic extract of ARA exerts significant antioxidant activities potentially via inhibiting free radicals and iNOS induction, thereby leading to the inhibition of osteoclastogenesis. PMID:25298665
Guo, Changrun; Ding, Gang; Huang, Wenzhe; Wang, Zhenzhong; Meng, Zhaoqing; Xiao, Wei
Background Diabetic nephropathy has become the most common cause of morbidity and mortality in diabetic patients. Therefore, there is an urgent need for more effective and safer drugs for use in this condition. Purpose The aims of this study were to investigate the ameliorative effects of total saponin of Dioscoreae hypoglaucae rhizoma (TSD) on diabetic nephropathy and to explore the potential underlying mechanism(s). Methods Rats with streptozotocin-induced diabetes were orally treated with TSD at 40, 80, and 160 mg/kg/d for 12 weeks. At the end of the treatment, blood, urine, and kidneys were collected for biochemical and histological examination. Results The results demonstrated that TSD significantly decreased the fasting blood glucose, glycosylated hemoglobin, urinary protein, serum creatinine, and blood urea nitrogen levels in diabetic rats. The results of histological examinations showed that TSD ameliorated glomerular and tubular pathological changes in diabetic rats. Furthermore, TSD significantly prevented oxidative stress and reduced the renal levels of advanced glycation end products, transforming growth factor-β1, connective tissue growth factor, and tumor necrosis factor-α. Conclusion This study demonstrated the renoprotective effects of TSD in experimental diabetic nephropathy via a number of different mechanisms. PMID:26966352
Guo, Ava J Y; Xie, Heidi Q; Choi, Roy C Y; Zheng, Ken Y Z; Bi, Cathy W C; Xu, Sherry L; Dong, Tina T X; Tsim, Karl W K
Acetylcholinesterase (AChE) inhibitors are widely used for the treatment of Alzheimer's disease (AD). Several AChE inhibitors, e.g. rivastigmine, galantamine and huperzine are originating from plants, suggesting that herbs could potentially serve as sources for novel AChE inhibitors. Here, we searched potential AChE inhibitors from flavonoids, a group of naturally occurring compounds in plants or traditional Chinese medicines (TCM). Twenty-one flavonoids, covered different subclasses, were tested for their potential function in inhibiting AChE activity from the brain in vitro. Among all the tested flavonoids, galangin, a flavonol isolated from Rhizoma Alpiniae Officinarum, the rhizomes of Alpiniae officinarum (Hance.) showed an inhibitory effect on AChE activity with the highest inhibition by over 55% and an IC(50) of 120 microM and an enzyme-flavonoid inhibition constant (K(i)) of 74 microM. The results suggest that flavonoids could be potential candidates for further development of new drugs against AD.
Lee, Won Ho; Choi, Seong Hun; Kang, Su Jin; Song, Chang Hyun; Park, Soo Jin; Lee, Young Joon; Ku, Sae Kwang
Persicariae Rhizoma (PR) has been used as an anti-inflammatory and detoxification agent in Korea, and contains the biologically active dyes purple indirubin and blue indigo. Despite synthetic indigo showing genotoxic potential, thorough studies have not been carried out on the genotoxicity of PR. The potential genotoxicity of an aqueous extract of PR containing indigo (0.043%) and indirubin (0.009%) was evaluated using a standard battery of tests for safety assessment. The PR extract did not induce any genotoxic effects under the conditions of this study. The results of a reverse mutation assay in four Salmonella typhimurium strains and one Escherichia coli strain indicated that PR extract did not increase the frequency of revertant colonies in any strain, regardless of whether S9 mix was present or not. The PR extract also did not increase chromosomal aberrations in the presence or absence of S9 mix. Although slight signs of diarrhea were restrictedly detected in the mice treated with 2,000 mg/kg PR extract, no noteworthy changes in the frequency of micronucleated polychromatic erythrocytes were observed at doses ≤2,000 mg/kg in a bone marrow micronucleus test. These results indicate the potential safety of the PR extract, particularly if it is consumed in small amounts compared with the quantities used in the genotoxicity tests.
Fan, Qimeng; Chen, Chaoyin; Huang, Zaiqiang; Zhang, Chunmei; Liang, Pengjuan; Zhao, Shenglan
Rhizoma Gastrodiae (Tianma) of different variants and different geographical origins has vital difference in quality and physiological efficacy. This paper focused on the classification and identification of Tianma of six types (two variants from three different geographical origins) using three dimensional synchronous fluorescence spectroscopy (3D-SFS) coupled with principal component analysis (PCA). 3D-SF spectra of aqueous extracts, which were obtained from Tianma of the six types, were measured by a LS-50B luminescence spectrofluorometer. The experimental results showed that the characteristic fluorescent spectral regions of the 3D-SF spectra were similar, while the intensities of characteristic regions are different significantly. Coupled these differences in peak intensities with PCA, Tianma of six types could be discriminated successfully. In conclusion, 3D-SFS coupled with PCA, which has such advantages as effective, specific, rapid, non-polluting, has an edge for discrimination of the similar Chinese herbal medicine. And the proposed methodology is a useful tool to classify and identify Tianma of different variants and different geographical origins.
LEE, WON HO; CHOI, SEONG HUN; KANG, SU JIN; SONG, CHANG HYUN; PARK, SOO JIN; LEE, YOUNG JOON; KU, SAE KWANG
Persicariae Rhizoma (PR) has been used as an anti-inflammatory and detoxification agent in Korea, and contains the biologically active dyes purple indirubin and blue indigo. Despite synthetic indigo showing genotoxic potential, thorough studies have not been carried out on the genotoxicity of PR. The potential genotoxicity of an aqueous extract of PR containing indigo (0.043%) and indirubin (0.009%) was evaluated using a standard battery of tests for safety assessment. The PR extract did not induce any genotoxic effects under the conditions of this study. The results of a reverse mutation assay in four Salmonella typhimurium strains and one Escherichia coli strain indicated that PR extract did not increase the frequency of revertant colonies in any strain, regardless of whether S9 mix was present or not. The PR extract also did not increase chromosomal aberrations in the presence or absence of S9 mix. Although slight signs of diarrhea were restrictedly detected in the mice treated with 2,000 mg/kg PR extract, no noteworthy changes in the frequency of micronucleated polychromatic erythrocytes were observed at doses ≤2,000 mg/kg in a bone marrow micronucleus test. These results indicate the potential safety of the PR extract, particularly if it is consumed in small amounts compared with the quantities used in the genotoxicity tests. PMID:27347027
Investigation of the Chemical Changes from Crude and Processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma Herbal Pair Extracts by Using Q Exactive High-Performance Benchtop Quadrupole-Orbitrap LC-MS/MS
Cao, Gang; Li, Qinglin; Cai, Hao; Tu, Sicong; Cai, Baochang
The Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair is mainly used for regulating the functions of liver and spleen, benefiting qi, and nourishing blood. However, the bioactive compounds for the pharmacological activities of the crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair extracts are still unclear to date. In the present study, Q Exactive high-performance benchtop quadrupole-Orbitrap LC-MS/MS was applied to identify the complicated components from crude and processed Paeoniae Radix Alba, crude and processed Atractylodis Macrocephalae Rhizoma, and their crude and processed herbal pair extracts. 123 and 101 compounds were identified in crude and processed Paeoniae Radix Alba samples, respectively. Meanwhile, 32 and 26 compounds were identified in crude and processed Atractylodis Macrocephalae Rhizoma samples, respectively. In the crude and processed Paeoniae Radix Alba-Atractylodis Macrocephalae Rhizoma herbal pair extracts, co-decoction could significantly change the chemical composition of Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma in solution. The developed method may provide a scientific foundation for deeply elucidating the processing and compatibility mechanism of Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma. PMID:24876867
Xie, De-mei; Liu, Guang-xue; Xu, Feng; Shang, Ming-ying; Zhang, Zi-wei; Wang, Xuan; Cai, Shao-qing
To develop an analytic method for qualitative and quantitative analysis of dodecatetraenamides A, B in 42 samples of two official species of Asari Radix et Rhizoma( ARR) (37 samples of Asarum heterotropoides var. mandshuricum with different collection time and 5 samples of Asarum sieboldiivar. seoulense). The HPLC-IT-TOF-MS/MS methods for the qualitative and UPLC-PDA methods for the quantitative analysis were established. Dodecatetraenamides A, B were identified by comparing the retention time, UV absorption spectrum and quasi-molecular ion peak [ M + H]+ with the reference compound using HPLC-IT-TOF-MS/MS. The content of dodecatetraenamides A and B in ARR were determined by UPLC-PDA. The separation was successfully carried out on a ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 µm) column eluted with mobile phases of water (A) and acetonitrile (B) in gradient program (0-3 min, 35% B; 3-5 min, 35%-36% B; 5-6 min, 36%-43% B; 6 min-11 min 43% B; 11-12 min, 43%-100% B). The column temperature was 45 °C, and the detection wavelength was set at 254 nm. The flow rate was 0.6 mL · min(-1). On one level mass spectrometry scanning, the results showed that the quasi-molecular ion [M + H] + of both dodecatetraenamides A and B were m/z 248.20. The quantitative method with UPLC-PDA has made the baseline separation of the constituents, which were reported as mixtures in the most literatures. The average recovery of dodecatetraenamides A and B were 97.90% and 99.86%, the relative standard deviation were 0.4% and 1.1%, respectively. The contents of dodecatetraenamides A, B in all ARR samples was in the range of 0.11-3.89 and 0.24-6.65 mg · g(-1). Their contents reduced with the extension of storage time. Compared with the samples of 2013, the average content of the two constituents in the samples collected in year 2002-2003 reduced 34% and 36%, respectively (P < 0.05). Compared the A. sieboldii var. seoulense and A. heterotropoides var. mandshuricum with the same collective time
Jiang, Zhen-Yu; Deng, Hai-Ying; Yu, Zhi-Jun; Ni, Jun-Yan; Kang, Si-He
Background: The dosage of herb ultrafine particle (UFP) depended on the increased level of its dissolution, toxicity, and efficacy. Objective: The dissolution, antibacterial activity, and cytotoxicity of Coptidis rhizoma (CR) UFP were compared with those of traditional decoction (TD). Materials and Methods: The dissolution of berberine (BBR) of CR TD and UFP was determined by high-performance liquid chromatography. The antibacterial activity of CR extract was assayed by plate-hole diffusion and broth dilution method; the inhibitory effect of rat serums against bacteria growth was evaluated after orally given CR UFP or TD extract. The cytotoxicity of CR extract was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay. Results: The dissolution amount of BBR from CR UFP increased 6–8-folds in comparison to TD at 2 min, the accumulative amount of BBR in both UFP and TD group increased in a time-dependent manner. The minimal inhibitory concentrations and minimal bactericidal concentrations of CR UFP extract decreased to 1/2~1/4 of those of TD extract. The inhibitory effect of rat serums against bacteria growth decreased time-dependently, and no statistical difference was observed between two groups at each time point. The 50% cytotoxic concentrations of UFP extract increased 1.66~1.97 fold than those of TD. Conclusions: The antibacterial activity and cytotoxicity of CR UFP increased in a dissolution-effect manner in vitro, the increased level of cytotoxicity was lower than that of antibacterial activity, and the inhibitory effect of rat serums containing drugs of UFP group did not improve. SUMMARY Ultrafine grinding process caused a rapid increase of BBR dissolution from CR.The antibacterial activity and cytotoxicity of UFP extract in vitro increased in a dissolution-effect manner, but the cytotoxicity increased lower than the antibacterial activity.The antibacterial activity of rat serums of UFP group did not improve in comparison to that
Song, Kee Jae; Shin, Young-June; Lee, Kang Ro; Lee, Eun Jung; Suh, Yun Suk
Purpose This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals. Materials and Methods The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement. Results The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25±3.14) and cough inhibition (61.25±5.36) than the individual use of each extracts [phenol red secretion; HH 13.39±4.22 (p=0.000), RC 20.78±2.50 (p=0.010), cough inhibition; HH 9.89±4.14 (p=0.010), RC 30.25±7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner. Conclusion This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases. PMID:25837191
Lee, Bombi; Yang, Chae Ha; Hahm, Dae-Hyun; Choe, Eun Sang; Lee, Hye-Jung; Pyun, Kwang-Ho; Shim, Insop
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
Effect of polysaccharides extract of rhizoma atractylodis macrocephalae on thymus, spleen and cardiac indexes, caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein and mRNA expression levels in aged rats.
Guo, Ling; Sun, Yong Le; Wang, Ai Hong; Xu, Chong En; Zhang, Meng Yuan
This study was designed to determine the possible protective effect of polysaccharides extract of rhizoma atractylodis macrocephalae on heart function in aged rats. Polysaccharides extract of rhizoma atractylodis macrocephalae was administered to aged rats. Results showed that thymus, spleen and cardiac indexs were significantly increased, whereas caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein expression, Smac/DIABLO and HtrA2/Omi mRNA expression levels were markedly reduced. It can be concluded that polysaccharides extract of rhizoma atractylodis macrocephalae may enhance immunity and improve heart function in aged rats.
Zhang, Jue; Yang, Yixi; Lei, Lei; Tian, Mengliang
Background As a traditional Chinese medicine herb, Chonglou (Paris polyphylla var. chinensis) has been used as anticancer medicine in China in recent decades, as it can induce cell cycle arrest and apoptosis in numerous cancer cells. The saponins extract from the rhizoma of Chonglou [Rhizoma Paridis saponins (RPS)] is known as the main active component for anticancer treatment. However, the molecular mechanism of the anticancer effect of RPS is unknown. Material/Methods The present study evaluated the effect of RPS in non-small-cell lung cancer (NSCLC) A549 cells using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Subsequently, the expression of several genes associated with cell cycle and apoptosis were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting. Results RPS was revealed to inhibit cell growth, causing a number of cells to accumulate in the G 1 phase of the cell cycle, leading to apoptosis. In addition, the effect was dose-dependent. Moreover, the results of qRT-PCR and Western blotting showed that p53 and cyclin-dependent kinase 2 (CDK2) were significantly downregulated, and that BCL2, BAX, and p21 were upregulated, by RPS treatment. Conclusions We speculated that the RPS could act on a pathway, including p53, p21, BCL2, BAX, and CDK2, and results in G1 cell cycle arrest and apoptosis in NSCLC cells. PMID:26311066
Xing, Rongrong; Hu, Shuang; Chen, Xuan; Bai, Xiaohong
A novel graphene-sensitized microporous membrane/solvent microextraction method named microporous membrane/graphene/solvent synergistic microextraction, coupled with high-performance liquid chromatography and UV detection, was developed and introduced for the extraction and determination of three cinnamic acid derivatives in Rhizoma Typhonii. Several factors affecting performance were investigated and optimized, including the types of graphene and extraction solvent, concentration of graphene dispersed in octanol, sample phase pH, ionic strength, stirring rate, extraction time, extraction temperature, and sample volume. Under optimized conditions, the enrichment factors of cinnamic acid derivatives ranged from 75 to 269. Good linearities were obtained from 0.01 to 10 μg/mL for all analytes with regression coefficients between 0.9927 and 0.9994. The limits of quantification were <1 ng/mL, and satisfactory recoveries (99-104%) and precision (1.1-10.8%) were also achieved. The synergistic microextraction mechanism based on graphene sensitization was analyzed and described. The experimental results showed that the method was simple, sensitive, practical, and effective for the preconcentration and determination of cinnamic acid derivatives in Rhizoma Typhonii.
Background Growing evidence shows that herb medicines have some anti-osteoporotic effects, the mechanism underlying is unknown. This study aims to investigate the therapeutic effect of Chinese herb supplements on rats that had osteoporosis-like symptom induced by ovariectomy (OVX). Methods OVX or sham operations were performed on virgin Wistar rats at three-month old, which were randomly divided into eight groups: sham (sham); OVX control group (OVX); OVX rats with treatments [either diethylstilbestrol (DES) or Semen Astragali Complanati decoction (SACD) or Rhizoma Cibotii decoction (RCD) or Herba Cistanches decoction (HCD) or Semen Allii Tuberosi decoction (SATD)]. Non-surgical rats were served as a normal control (NC). The treatments began 4 weeks after surgery, and lasted for 12 weeks. Bone mass and its turnover were analyzed by histomorphometry. Levels of protein and mRNA of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization. Results Compared to OVX control, TBV% in both SACD and RCD groups was increased significantly, while TRS%, TFS%, MAR, and mAR were decreased remarkably in the SACD group, only TRS% decreased dramatically in the RCD group. No significant changes in bone formation were observed in either HCD or SATD groups. OPG levels in both protein and mRNA were reduced consistantly in OB and bMSC from OVX control rats, in contrast, RANKL levels in both protein and mRNA were increased significantly. These effects were substantially reversed by treatments with either DES or SACD or RCD. No significant changes in both OPG and RANKL expression were observed in OB and bMSC from OVX rats treated with SATD and HCD. Conclusions Our study showed that SACD and RCD increased bone formation by stimulating OPG expression and downregulating RANKL expression in OB and bMSC. This suggests that SACD and RCD may be
Xu, Feng; Wu, Hongmei; Wang, Xiangpei; Yang, Ye; Wang, Yuanmin; Qian, Haibing; Zhang, Yanyan
With the aim of characterizing the active ingredients lupenone and β-sitosterol in Rhizoma Musae samples a reversed-phase HPLC method for the separation of these two compounds in Rhizoma Musae samples was developed (regression coefficient>0.9996). The method was further applied to quantify lupenone and β-sitosterol content in Rhizoma Musae samples cultured in different growth environments. Different variables such as geographical location, growth stage, and harvest time, demonstrated differential effects on lupenone and β-sitosterol levels. Moreover, we determined the optimum conditions for cultivation and harvesting of Rhizoma Musae herbs. Lupenone administration caused a significant reduction in fasting blood glucose (FBG) levels in diabetic rats at doses of 1.78, 5.33, and 16.00 mg·kg⁻¹·day⁻¹ for 14 days, the glycated hemoglobin (HbA1c) levels of diabetic rats also significantly reduced at doses of 5.33, and 16.00 mg·kg⁻¹·day⁻¹, indicating a robust antidiabetic activity. To our knowledge, this is the first report of an optimized HPLC method successfully applied to quantify lupenone and β-sitosterol, and its applicability in optimizing Rhizoma Musae growth. Animal experiments also showed for the first time that lupenone from Rhizoma Musae has anti-diabetic activity.
Zi-min, Yuan; Yue, Chen; Hui, Gao; Jia, Lv; Gui-rong, Chen; Wang, Jing
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
Li, Yang; Cai, Fanfan; Zhang, Min; Zhang, Hongyang; Wang, Yuerong; Hu, Ping
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.
Li, Chen; Xu, Feng; Cao, Chen; Shang, Ming-Ying; Zhang, Cui-Ying; Yu, Jie; Liu, Guang-Xue; Wang, Xuan; Cai, Shao-Qing
Traditional Chinese medicines (TCM) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. In this paper, electronic nose, headspace gas chromatography-mass spectrometry (GC-MS) and chemometrics methods were applied to differentiate two species of Asari Radix et Rhizoma by their odors. The samples used were the dried roots and rhizomes of Asarum heterotropoides var. mandshuricum (AH) and Asarum sieboldii (AS). The electronic nose was used to determine the odors of the samples and enabled rapid differentiation of AH and AS when coupled with principal component analysis. Headspace GC-MS was utilized to reveal the differences between the volatile constituents of AH and AS. In all, 54 volatile constituents were identified, and 9 major constituents (eucalyptol, eucarvone, 3,5-dimethoxytoluene, 3,4,5-trimethoxytoluene, methyleugenol, 2,3,5-trimethoxytoluene, croweacin, pentadecane and asaricin) could be used as chemical markers to distinguish these two species. AH contained higher relative contents of eucarvone (1.79-16.76%), 3,5-dimethoxytoluene (6.64-26.52%), 3,4,5-trimethoxytoluene/methyleugenol (6.43-31.67%) and 2,3,5-trimethoxytoluene (1.64-6.66%), whereas AS had higher relative contents of eucalyptol (14.06-24.95%), croweacin (5.64-13.55%), pentadecane (8.44-20.82%) and asaricin (7.03-13.45%). Moreover, AH and AS could be distinguished according to the contents of either all 54 identified volatile constituents or only the 9 major constituents by employing cluster analysis. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two species of Asari Radix et Rhizoma by their odors.
Song, Chengwu; Huang, Xiaofei; Lu, Kungang; Peng, Min; Yu, Shanggong; Fang, Nianbai
Alismatis Rhizoma Decoction (ARD) is a classical Traditional Chinese Medicine (TCM) formula for treatment of vertigo with its long history of successful clinical effect. Since vertigo is a symptom of hyperlipidemia, this study aimed at evaluating the hypolipidemic effect of ARD in hyperlipidemic mice induced by high fat diet (HFD) and investigated the rationality of formula combination of Alismatis Rhizoma (AR) and Atractylodis Macrocephalae Rhizoma (AMR). Compared with control group, hyperlipidemic mice in AR and ARD groups displayed a reduction of the following parameters: body weight, liver and serum total cholesterol, triglyceride concentration, liver and spleen coefficients, activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT); whereas the serum HDL-cholesterol levels were significantly elevated in both AR and ARD groups. AR and ARD treatments significantly down regulated the expressions of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoA reductase) and sterol regulatory element binding factor-2 (SREBF-2). These findings clearly provided evidences that the suppression on biosynthesis of cholesterol in liver may in part contribute to the hypolipidemic effects of ARD and AR. Since no significantly hypolipidemic effect of AMR was observed, the more prominent effect of ARD than that of AR indicated synergistic effects of AR and AMR, and confirmed the rationality of ARD formula.
The ethanolic extracts of some Chinese traditional herb drugs, reported by Hong-Fu Wang et al. in China, could inhibit platelet aggregation as well as protect against radiation damage in mice, rat and rabbits. The inhibitory effects of the extracts of five Chinese drugs on the rate of platelet aggregation were observed in both in vitro and in vivo tests, averaging 23--53% in vitro and 46--69% in vivo. Antiradiation tests on mice vs. 7.5--8.0 Gy of [gamma]-radiation, using the herb drug extracts as protective agents, showed increasing survival rates by 8--50%. Based on Hong-Fu Wang's report, a search for the active constituents of these herb drugs in inhibiting platelet aggregation and protecting animals against radiation damage was started. In this research program, a Chinese traditional drug, Rhizoma Chuanxiong (rhizome of Ligusticum chuanxiong Hort.) was chosen. Three types of chemicals present in Rhizoma Chuanxiong, appeared promising for testing: 1-(5-hydroxymethyl-2-furyl)-9H-pyrido-(3,4-b)indole, 4-hydroxyl-3-butylidenephthalide and 5-hydroxyl-3-butylidenephthalide, and 4-hydroxyl-3-methoxycinnamyl 4-hydroxyl-3-methoxycinnamate. A total of 56 compounds of these derivatives has been synthesized and 30 were synthesized for the first time. The structure elucidation of these compounds was based on IR, [sup 1]H NMR and elemental analysis. From this research program, a very mild dehydrogenation method was developed. It was by using 2,3-dichloro-5,6-dicyanobenzoquinone in acetonitrile at ice bath temperature to dehydrogenate 1-(5-hydroxymethyl-2-furyl)-1,2,3,4-tetrahydro-9H-pyrido-(3,4-b)indole into 1-(5-hydroxymethyl-2-furyl)-9H-pyrido-(3,4-b)indole. This project showed for the first time that harmanoid alkaloids have the activity of inhibition of plate aggregation by 4 to 23 times that of aspirin. These results aid in establishing a relation between radiation protection in animals and prevention of platelet hyperaggregation.
Qiu, Zuo-Cheng; Dong, Xiao-Li; Dai, Yi; Xiao, Gao-Keng; Wang, Xin-Luan; Wong, Ka-Chun; Wong, Man-Sau; Yao, Xin-Sheng
Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk. PMID:27999266
Li, Zhenhao; Liu, Ting; Liao, Jie; Ai, Ni; Fan, Xiaohui; Cheng, Yiyu
In this study, we propose an integrated strategy for the efficient identification and quantification of herbal constituents using liquid chromatography with mass spectrometry. First, liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the chemical profiling of herbs, where a targeted following nontargeted approach was developed to detect trace constituents by using structural correlations and extracted ion chromatograms. Next, ion pairs and parameters of MS(2) of quadrupole time-of-flight mass spectrometry were selected to design multiple reaction monitoring transitions for the identified compounds on liquid chromatography with triple quadrupole mass spectrometry. The relative concentration of each constituent was then calculated using a semiquantitative calibration curve. The proposed strategy was applied in a study of chemical interactions between Glycyrrhizae Radix and Coptidis Rhizoma. A total of 140 compounds were identified or tentatively characterized from the herbs, 132 of which were relatively quantified. The visualized quantitative results clearly showed codecoction produced significant constituent concentration variations especially for those with a low polarity. The case study also indicated that the present methodology could provide a reliable, accurate, and labor-saving solution for chemical studies of herbal medicines.
Pan, Tai-Long; Wang, Pei-Wen; Huang, Chun-Hsun; Leu, Yann-Lii; Wu, Tung-Ho; Wu, Yun-Ru; You, Jyh-Sheng
The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases.
Pan, Tai-Long; Wang, Pei-Wen; Huang, Chun-Hsun; Leu, Yann-Lii; Wu, Tung-Ho; Wu, Yun-Ru; You, Jyh-Sheng
The bioactive components extracted from Scutellariae radix and Rhei rhizoma (SR) have been commonly used to treat liver diseases. The aim of this study was to verify the underlying mechanisms and antifibrotic effects of ethanol extract from the herbal combinatorial formula (SRE) in a dimethylnitrosamine (DMN)-administered rat model, with functional proteome tools. Our results indicated that the hepatic collagen content and alpha-smooth muscle actin expression were obviously alleviated by treatment with SRE. Comprehensive proteomics revealed global protein changes, and the network analysis implied that SRE application would attenuate oxidative stress and cytoskeleton dysregulation caused by DMN exposure. Next, marked downregulation of antioxidant enzymes mediated by DMN treatment was restored in the presence of SRE, while SRE treatment contributed to decreased MDA content. Moreover, protein carbonylation and DNA adduction induced by oxidative stress finally leading to liver injury were also reduced under SRE administration. These findings demonstrate that SRE could effectively prevent hepatic fibrosis mainly through regulating the redox status, and subsequently modulating the modification of intracellular molecules. Our experiments might help in developing novel therapeutic strategies against oxidation-caused liver diseases. PMID:26133262
Zhang, Luyan; Zhang, Wei; Chen, Gang
This report describes the fabrication and the application of a novel carbon nanotube (CNT)-epoxy composite electrode as a sensitive amperometric detector for the capillary electrophoresis (CE). The composite electrode was fabricated on the basis of the in situ polycondensation of a mixture of CNTs and 1,2-ethanediamine-containing bisphenol A epoxy resin in the inner bore of a piece of fused silica capillary under heat. It was coupled with CE for the separation and detection of arbutin and bergenin in Bergeniae Rhizoma, a traditional Chinese medicine, to demonstrate its feasibility and performance. The two phenolic constituents were well separated within 10min in a 45cm capillary length at a separation voltage of 12kV using a 50mM borate buffer (pH 9.2). The CNT-based detector offered higher sensitivity, significantly lower operating potential, satisfactory resistance to surface fouling, and lower expense of operation, indicating great promise for a wide range of analytical applications. It showed long-term stability and reproducibility with relative standard deviations of less than 5% for the peak current (n=15).
Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling
Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.
de la Peña, June Bryan I; Lee, Hye Lim; Yoon, Seo Young; Kim, Gun Hee; Lee, Yong Soo; Cheong, Jae Hoon
The present study seeks to evaluate the sedative and anxiolytic effects of the 70% ethanol extract of Sinomeni Caulis et Rhizoma (SR). The extract was orally administered to mice at dosages of 25, 50, 100, 200 or 400 mg/kg. The mice were then subjected to an array of behavioral tests to assess the sedative (open-field, rota-rod, and thiopental sodium-induced sleeping test) and anxiolytic (elevated plus maze test) effects of the substance. SR (100, 200 mg/kg) significantly reduced locomotor activity, decreased rota-rod performance, and potentiated thiopental sodium-induced sleeping in mice, all indicative of its sedative effects. SR (50, 100 mg/kg) also produced anxiolytic effects, as shown by an increase in entries and staying time on the open arm of the plus maze. SR's sedative and anxiolytic effects were comparable to that of the benzodiazepine, diazepam. Moreover, to identify SR's probable mechanism of action, intracellular Cl⁻ ion influx was observed in cultured human neuroblastoma cells. SR dose-dependently increased Cl⁻ influx, which was blocked by co-administration of the GABAA receptor competitive antagonist, bicuculline. Among the major constituents of SR, only magnoflorine showed a similar increment in Cl⁻ influx, which was also blocked by bicuculline. Altogether, the present results suggest that SR has sedative and anxiolytic effects, probably mediated by magnoflorine through a GABAergic mechanism of action.
Cao, Feng; Peng, Wei; Li, Xiaoli; Liu, Ming; Li, Bin; Qin, Rongxin; Jiang, Weiwei; Cen, Yanyan; Pan, Xichun; Yan, Zifei; Xiao, Kangkang; Zhou, Hong
This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6'-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography - electrospray ionization - tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane.
Qian, Ping; Yang, Xiu-Wei
A new indoloquinazoline alkaloid, 10-methoxywuchuyuamide I (1), three new benzylisoquinoline alkaloids, named as coptichic aldehyde (2), coptichine (3) and 13-carboxaldehyde-8-oxocoptisine (4), and a new isoindoline alkaloid, named as coptichinamide (5), together with two known alkaloids, wuchuyuamide I (6) and 8-oxocoptisine (7) were isolated from the Coptidis Rhizoma-Euodiae Fructus couple. Their chemical structures were determined by extensive spectroscopic analyses, including IR, UV, EI-MS, HRESI-MS, 1D and 2D NMR data ((1)H NMR, (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC). Cytotoxicities of the isolated alkaloids against NCI-N87 and Caco-2 cell lines were evaluated. Four benzylisoquinoline alkaloids 2-4 and 7 showed inhibitory activities against NCI-N87 cell with IC50 values range from 8.92 to 35.98 μM. The alkaloid 3 was a new antiproliferation compound against NCI-N87 cells. The results provided valuable information for further investigation of alkaloid 3 as a chemopreventive agent.
Kang, Su Jin; Lee, Eun Kyung; Han, Chang Hyun; Lee, Bong Hyo; Lee, Young Joon; Ku, Sae Kwang
Persicariae Rhizoma (PR) is the dried stem parts of Persicaria tinctoria H. Gross (Polygonaceae), and has been traditionally used as anti-inflammatory and detoxifying agent. In the present study, the effects of PR aqueous extracts on ligation-induced experimental periodontitis (EPD) and associated alveolar bone loss in rats were examined. Following the induction of EPD in rats, PR extracts were orally administered once a day for 10 days, and the changes and gains in body weight, alveolar bone loss and total aerobic bacterial counts of buccal gingiva were observed with histopathological analysis. In addition, anti-inflammatory effects were evaluated by monitoring myeloperoxidase (MPO) activities, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α contents, and anti-oxidant effects were investigated by measuring inducible nitric oxide synthase (iNOS) activities and malondialdehyde (MDA) levels. Bacterial proliferation, periodontitis and associated alveolar bone loss induced by ligature placement were significantly and dose-dependently inhibited by the treatment with PR extracts. The inhibitory effects of 200 mg/kg PR were similar to those of 5 mg/kg indomethacin on ligation-induced periodontitis and associated alveolar bone losses in this study. The results suggest that PR effectively inhibits ligature placement-induced periodontitis and alveolar bone loss in rats via antibacterial, antioxidative and anti-inflammatory activities. PMID:27588077
Sim, Yeomoon; Choi, Jin Gyu; Gu, Pil Sung; Ryu, Byeol; Kim, Jeong Hee; Kang, Insug; Jang, Dae Sik; Oh, Myung Sook
Cyperi Rhizoma (CR), the rhizome of Cyperus rotundus L., exhibits neuroprotective effects in in vitro and in vivo models of neuronal diseases. Nevertheless, no study has aimed at finding the neuroactive constituent(s) of CR. In this study, we identified active compounds in a CR extract (CRE) using bioactivity-guided fractionation. We first compared the anti-oxidative and neuroprotective activities of four fractions and the CRE total extract. Only the ethyl acetate (EA) fraction revealed strong activity, and further isolation from the bioactive EA fraction yielded nine constituents: scirpusin A (1), scirpusin B (2), luteolin (3), 6′-acetyl-3,6-diferuloylsucrose (4), 4′,6′ diacetyl-3,6-diferuloylsucrose (5), p-coumaric acid (6), ferulic acid (7), pinellic acid (8), and fulgidic acid (9). The activities of constituents 1–9 were assessed in terms of anti-oxidative, neuroprotective, anti-inflammatory, and anti-amyloid-β activities. Constituents 1, 2, and 3 exhibited strong activities; constituents 1 and 2 were characterized for the first time in this study. These results provide evidence for the value of CRE as a source of multi-functional neuroprotectants, and constituents 1 and 2 may represent new candidates for further development in therapeutic use against neurodegenerative diseases. PMID:27350341
Maiwulanjiang, Maitinuer; Bi, Cathy W C; Lee, Pinky S C; Xin, Guizhong; Miernisha, Abudureyimu; Lau, Kei M; Xiong, Aizhen; Li, Ning; Dong, Tina T X; Aisa, Haji A; Tsim, Karl W K
Nardostahyos Radix et Rhizoma (NRR; the root and rhizome of Nardostachys jatamansi DC.) is a widely used medicinal herb. Historically, NRR is being used for the treatment of cardiovascular and neurological diseases. To search for active ingredients of NRR, we investigated the vascular benefit of NRR volatile oil in (i) the vasodilation in rat aorta ring, and (ii) the release of nitric oxide (NO) and the phosphorylation of endothelial NO synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVECs). By measuring the fluorescence signal in cultures, application of NRR volatile oil resulted in a rapid activation of NO release as well as the phosphorylation of eNOS: both inductions were markedly reduced by L-NAME. In parallel, the phosphorylation level of Akt kinase was markedly increased by the oil treatment, which was partially attenuated by PI3K/Akt inhibitor LY294002. This inhibitor also blocked the NRR-induced NO production and eNOS phosphorylation. In HUVECs, application of NRR volatile oil elevated the intracellular Ca(2+) level, and BAPTA-AM, a Ca(2+) chelator, reduced the Ca(2+) surge: the blockage were also applied to NRR-induced eNOS phosphorylation and NO production. These findings suggested the volatile oil of NRR was the major ingredient in triggering the vascular dilatation, and which was mediated via the NO production.
Lee, A Yeong; Park, Jun Yeon; Chun, Jin Mi; Moon, Byeong Cheol; Kang, Byoung Kab; Seo, Young Bae; Shin, Hyeun-Kyoo; Kim, Ho Kyoung
Alismatis Rhizoma is a perennial herb originating from the rhizomes of Alisma orientalis (Sam) Juzep and the same species which have been used to treat seborrheic dermatitis, eczema, polydipsia, and pedal edema. We aimed to determine the concentrations of the compounds alisol B and alisol B acetate present in a sample of the herb using high-performance liquid chromatography coupled with a photodiode array detector. We selected methanol as the optimal solvent considering the structures of alisol B and alisol B acetate. We estimated the proportion of alisol B and alisol B acetate in a standard extract to be 0.0434% and 0.2365% in methanol, respectively. To optimize extraction, we employed response surface methodology to determine the yields of alisol B and alisol B acetate, which mapped out a central composite design consisting of 15 experimental points. The extraction parameters were time, concentration, and sample weight. The predicted concentration of alisol B derivatives was estimated to be 0.2388% under the following conditions: 81 min of extraction time, 76% of methanol concentration, and 1.52g of sample weight. PMID:23335845
Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling
Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR. PMID:27698376
Xiang, Li; Xu, Youdong; Zhang, Yan; Meng, Xianli; Wang, Ping
Alzheimer's disease (AD) is an age-related neurodegenerative disease. Extensive in vitro and in vivo experiments have proved that the decreased activity of the cholinergic neuron is responsible for the memory and cognition deterioration. The alpha7 nicotinic acetylcholine receptor (α7-nAChR) is proposed to a drug target of AD, and compounds which acting as α7-nAChR agonists are considered as candidates in AD treatment. Chinese medicine CoptidisRhizoma and its compounds are reported in various anti-AD effects. In this study, virtual screening, docking approaches and hydrogen bond analyses were applied to screen potential α7-nAChR agonists from CoptidisRhizome. The 3D structure of the protein was obtained from PDB database. 87 reported compounds were included in this research and their structures were accessed by NCBI Pubchem. Docking analysis of the compounds was performed using AutoDock 4.2 and AutoDock Vina. The images of the binding modes hydrogen bonds and the hydrophobic interaction were rendered with PyMOL220.127.116.11. and LigPlot+ respectively. Finally, N-tran-feruloyltyramine, isolariciresinol, flavanone, secoisolariciresinol, (+)-lariciresinol and dihydrochalcone, exhibited the lowest docking energy of protein-ligand complex. The results indicate these 6 compounds are potential α7 nAChR agonists, and expected to be effective in AD treatment.
Maiwulanjiang, Maitinuer; Bi, Cathy W. C.; Lee, Pinky S. C.; Xin, Guizhong; Miernisha, Abudureyimu; Lau, Kei M.; Xiong, Aizhen; Li, Ning; Dong, Tina T. X.; Aisa, Haji A.; Tsim, Karl W. K.
Nardostahyos Radix et Rhizoma (NRR; the root and rhizome of Nardostachys jatamansi DC.) is a widely used medicinal herb. Historically, NRR is being used for the treatment of cardiovascular and neurological diseases. To search for active ingredients of NRR, we investigated the vascular benefit of NRR volatile oil in (i) the vasodilation in rat aorta ring, and (ii) the release of nitric oxide (NO) and the phosphorylation of endothelial NO synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVECs). By measuring the fluorescence signal in cultures, application of NRR volatile oil resulted in a rapid activation of NO release as well as the phosphorylation of eNOS: both inductions were markedly reduced by L-NAME. In parallel, the phosphorylation level of Akt kinase was markedly increased by the oil treatment, which was partially attenuated by PI3K/Akt inhibitor LY294002. This inhibitor also blocked the NRR-induced NO production and eNOS phosphorylation. In HUVECs, application of NRR volatile oil elevated the intracellular Ca2+ level, and BAPTA-AM, a Ca2+ chelator, reduced the Ca2+ surge: the blockage were also applied to NRR-induced eNOS phosphorylation and NO production. These findings suggested the volatile oil of NRR was the major ingredient in triggering the vascular dilatation, and which was mediated via the NO production. PMID:25643147
Huang, Tao; Xiao, Yubo; Yi, Lin; Li, Ling; Wang, Meimei; Tian, Cheng; Ma, Hang; He, Kai; Wang, Yue; Han, Bing; Ye, Xiaoli; Li, Xuegang
Colorectal cancer is one of the most common causes of cancer-related death in humans. Coptisine (COP) is a natural alkaloid from Coptidis Rhizoma with unclear antitumor mechanism. Human colon cancer cells (HCT-116) and xenograft mice were used to systematically explore the anti-tumor activity of COP in this study. The results indicated that COP exhibited remarkably cytotoxic activities against the HCT-116 cells by inducing G1-phase cell cycle arrest and increasing apoptosis, and preferentially inhibited the survival pathway and induced the activation of caspase proteases family of HCT-116 cells. Experimental results on male BALB/c nude mice confirmed that orally administration of COP at high-dose (150 mg/kg) could suppress tumor growth, and may reduce cancer metastasis risk by inhibiting the RAS-ERK pathway in vivo. Taken together, the results suggested that COP may be potential as a novel anti-tumor candidate in the HCT-116 cells-related colon cancer, further studies are still needed to suggest COP for the further use. PMID:28165459
Wei, Shi-chao; Xu, Li-jun; Zou, Xin; Li, Jing-bin; Jiang, Shu-jun; Xu, Xiao-hu; Huang, Rui; Lu, Fu-er
This article focused on a comparative analysis on the pharmacokinetic and pharmacodynamic characteristics of berberine (BER) and jateorhizine(JAT) in Coptidis Rhizoma powder (HL-P) and their monomeric compounds (BER + JAT, BJ) in type 2 diabetic (T2D) rats to explore the beneficial. effect of HL-P in the treatment of T2D. The T2D rats were treated with HL-P, BER, JAT and BJ, respectively for 63 d. The pharmacokinetic parameters, dynamic changes in blood glucose level and blood lipid values were measured. The results showed that, compared with other corresponding group, t(max), T(½ka) of BER and JAT in HL-P group were reduced, while C(max), AUC(inf), AUC(last), V(L)/F were significantly increased; compared with model group, blood glucose levels were decreased significantly in HL-P group since the 18th day, while those in BER or BJ group were reduced since the 36th day, however, blood glucose levels showed no obvious changes in JAT group; compared with model group, FFA values in all treatment group were decreased significantly. Moreover, TG, HDL and LDL value in HL-P group, LDL value in BER group and HDL value in BJ group were improved significantly. The above results showed that Coptidis Rhizoma powder showed excellent pharmacokinetic characteristics and excellent activity of lowering blood glucose and lipid. It provided a scientific basis for oral application of Coptidis Rhizoma powder in the treatment of T2D.
Ono, Masateru; Oda, Satoko; Yasuda, Shin; Mineno, Tomoko; Okawa, Masafumi; Kinjo, Junei; Miyashita, Hiroyuki; Yoshimitsu, Hitoshi; Nohara, Toshihiro; Miyahara, Kazumoto
Four hexaglycosides of methyl 3S,12S-dihydroxyhexadecanoate (1-4) were provided after treatment of the crude convolvulin fraction from Rhizoma Jalapae Braziliensis (the root of Ipomoea operculata (GOMES) MART., Convolvulaceae) with indium(III) chloride in methanol. The structures of 1-4 were elucidated on the basis of spectroscopic and chemical methods. Their sugar moieties were partially acylated with organic acids including (3S,9R)-3,6:6,9-diepoxydecanoic (exogonic) acid, (E)-2-methylbut-2-enoic (tiglic) acid, and isovaleric acid.
Zheng, Zhao-Guang; Duan, Ting-Ting; He, Bao; Tang, Dan; Jia, Xiao-Bin; Wang, Ru-Shang; Zhu, Jia-Xiao; Xu, You-Hua; Zhu, Quan; Feng, Liang
A cell-permeable membrane, as typified by Transwell insert Permeable Supports, permit accurate repeatable invasion assays, has been developed as a tool for screening immunological active components in Smilacis Glabrae Rhizoma (SGR). In this research, components in the water extract of SGR (ESGR) might conjugate with the receptors or other targets on macrophages which invaded Transwell inserts, and then the eluate which contained components biospecific binding to macrophages was identified by HPLC-ESI-MS(n) analysis. Six compounds, which could interact with macrophages, were detected and identified. Among these compounds, taxifolin (2) and astilbin (4) were identified by comparing with the chromatography of standards, while the four others including 5-O-caffeoylshikimic acid (1), neoastilbin (3), neoisoastilbin (5) and isoastilbin (6), were elucidated by their structure clearage characterizations of tandem mass spectrometry. Then compound 1 was isolated and purified from SGR, along with 2 and 4, was applied to the macrophage migration and adhesion assay in HUVEC (Human Umbilical Vein Endothelial Cells) -macrophages co-incultured Transwell system for immunological activity assessment. The results showed that compounds 1, 2 and 4 with concentration of 5μM (H), 500nM (M) and 50nM (L) could remarkably inhibit the macrophage migration and adhesion (Vs AGEs (Advanced Glycation End Produces) group, 1-L, 2-H and 4-L groups: p<0.05; other groups: p<0.01). Moreover, 1 and 4 showed satisfactory dose-effect relationship. In conclusion, the application of macrophage biospecific extraction coupled with HPLC-ESI-MS(n) analysis is a rapid, simple and reliable method for screening immunological active components from Traditional Chinese Medicine.
Huang, Ping; Qian, Xiaocui; Li, Junsong; Cui, Xiaobing; Chen, Lihua; Cai, Baochang; Tan, Shanzhong
A high-performance liquid chromatography method coupled with photo array diode detector has been developed and validated for simultaneous quantification of 11 active alkaloids in Rhizoma Coptidis (R.C.). The analysis was performed on a Benetnach-C18 column (250 × 4.6 mm, i.d., 5 μm) using binary gradient elution with 30 mmol/L ammonium bicarbonate water containing 0.7% ammonia solution and 0.1% triethylamine (A) and acetonitrile (B) at a flow rate of 1 mL/min, a column temperature of 35°C and UV detection at 275 nm. All calibration curves showed good linear regression (r > 0.9993) in the range of 6.94-111.03, 0.625-10.10, 6.27-100.14, 31.88-510.50, 16.25-260.70, 19.88-18.20, 3.13-50.70, 0.125-2.14, 16.44-263, 62.5-1,000, 0.125-2.14 μg/mL for magnoflorine, noroxyhydrastinine, jatrorrhizine, columbamine, epiberberine, coptisine, berberubine, worenine, palmatine, berberine, oxyberberine, respectively. It also showed good precision, repeatability and stability for quantification of these 11 alkaloids. The limit of detections and limit of quantitations for the analytes ranged from 0.031 to 0.423 μg/mL and from 0.094 to 1.27 μg/mL, respectively. This method was effective and rapid. The optimized method, which was applied to the determination of alkaloids in crude and wine-processed R.C. samples, was found to be feasible, reliable and suitable for their routine quality control.
Liang, Xiu-Jun; Guo, Ya-Chun; Sun, Tong-You; Song, Hong-Ru; Gao, Ya-Xian
Rheumatoid arthritis (RA) is a common chronic autoimmune and incurable disease. The aim of the present study was to investigate the therapeutic effect and mechanism of the total saponins of Rhizoma Dioscorea nipponica (TSRDN) in RA. A collagen induced-arthritis (CIA) rat model was established. CIA rats were randomly divided into three groups and lavaged with an equal volume of solvent (CIA group), TSRDN (25 mg/kg/day, RDN group) and tripterygium (TP; 12 mg/kg/day, TP group) for 21 days, respectively. Normal rats served as a control group. Hematoxylin-eosin (HE) staining was used to observe the histopathological injury of synovial tissues. The level of CD31, which used for marking and counting, micro vessel density (MVD) and the expression levels of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) were detected by immunohistochemical analysis. Additionally, the DNA-binding activity of nuclear factor-κB (NF-κB) was determined using an ELISA kit. HE staining showed obvious synovial hyperplasia, inflammatory cell infiltration, pannus formation, cartilage and bone erosion in the CIA group rats. In addition, compared with control group, the level of MVD, the expression of VEGF and STAT3, and the DNA-binding activity of NF-κB were all increased in CIA group rat synovial tissue (all P<0.01); however, TSRDN or tripterygium were able to inhibit these changes (all P<0.01). It was speculated that TSRDN may prevent angiogenesis by inhibiting the expression of STAT3 and the DNA-binding activity of NF-κB p65, thereby potentially improving CIA. PMID:27698704
Wei, Jinxia; Fang, Linlin; Liang, Xinlei; Su, Dan; Guo, Xingjie
A sensitive and selective liquid chromatography-tandem mass spectrometry method has been developed and validated for simultaneous quantitation of 10 alkaloids (dauricine, daurisoline, N-desmethyldauricine, dauricicoline, dauriporphinoline, bianfugecine, dauricoside, stepholidine, acutumine and acutumidine) from Rhizoma Menispermi in rat plasma. After addition of internal standard (verapamil), plasma samples were pretreated by a single-step protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters BEH C18 column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The analytes were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The validated method exhibited good linearity over a wide concentration range (r≥0.9914), and the lower limits of quantification were 0.01-5.0 ng/mL for all the analytes. The intra-day and inter-day precisions (RSD) at three different levels were both less than 13.4% and the accuracies (RE) ranged from -12.8% to 13.5%. The mean extraction recoveries of analytes and IS from rat plasma were all more than 77%. The validated method was successfully applied to a comparative pharmacokinetic study of 10 alkaloids in rat plasma after oral administration of Rhizoma Menispermi extract.
Guo, Yizhen; Lv, Beiran; Wang, Jingjuan; Liu, Yang; Sun, Suqin; Xiao, Yao; Lu, Lina; Xiang, Li; Yang, Yanfang; Qu, Lei; Meng, Qinghong
As complicated mixture systems, active components of Chuanxiong Rhizoma are very difficult to identify and discriminate. In this paper, the macroscopic IR fingerprint method including Fourier transform infrared spectroscopy (FT-IR), the second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR), was applied to study and identify Chuanxiong raw materials and its different segmented production of HPD-100 macroporous resin. Chuanxiong Rhizoma is rich in sucrose. In the FT-IR spectra, water eluate is more similar to sucrose than the powder and the decoction. Their second derivative spectra amplified the differences and revealed the potentially characteristic IR absorption bands and combined with the correlation coefficient, concluding that 50% ethanol eluate had more ligustilide than other eluates. Finally, it can be found from 2DCOS-IR spectra that proteins were extracted by ethanol from Chuanxiong decoction by HPD-100 macroporous resin. It was demonstrated that the above three-step infrared spectroscopy could be applicable for quick, non-destructive and effective analysis and identification of very complicated and similar mixture systems of traditional Chinese medicines.
Chinese hamster ovary-sphingomyelin synthase2 biospecific extraction and liquid chromatography with tandem mass spectrometry analysis for the prediction of bioactive components of Rhizoma Polygoni Cuspidati.
Xue, Ying; Dong, Jibin; Liang, Jianying
A novel strategy for predicting bioactive components in traditional Chinese medicines using Chinese hamster ovary-sphingomyelin synthase2 (CHO-SMS2 ) cell biospecific extraction and high-performance liquid chromatography with diode array detection and tandem mass spectrometry analysis was proposed. The hypothesis is that when cells are incubated with the extract of traditional Chinese medicines, the potential bioactive components in the traditional Chinese medicines should selectively combine with the cells, while the cell-combining components would be detectable in the extract of denatured cells. The identities of the cell-combining components could be determined by liquid chromatography with tandem mass spectrometry. Using the proposed approach, the potential bioactive components of Rhizoma Polygoni Cuspidati, a commonly used traditional Chinese medicine for atherosclerosis, were detected and identified. Eight compounds in the extract of Rhizoma Polygoni Cuspidati were detected as the components selectively combined with CHO-SMS2 cells, which is a stable cell line that highly expresses sphingomyelin synthases, it was found that piceid, resveratrol, emodin-8-β-d-glucoside, physcion-8-β-d-glucoside, emodin, physcion, 3,5,4'-trihydroxystilbene-3-O-(6"-galloyl)-glucoside, and emodin-1-O-glucoside combined specifically with CHO-SMS2 cells. The results indicate that the proposed approach may be applied to predict the bioactive candidates in traditional Chinese medicines.
Valencia, E; Williams, M J; Chase, C C; Sollenberger, L E; Hammond, A C; Kalmbacher, R S; Kunkle, W E
In Florida, rhizoma peanut (RP; Arachis glabrata Benth.), a tropical legume, combines the attributes of excellent nutritive value, competitive ability with tropical grasses, and high animal performance. The objective of this study was to determine the effects of spring N fertilization (0 vs 35 kg/ha) and summer stocking rate (1.5 and 2.5 bulls/ha) on herbage mass, nutritive value, herbage allowance, and diet botanical composition of grazed RP-grass swards and their interaction with growth and development of bulls (Senepol, and Brahman or Angus). The study was conducted in 1995 and 1996 at the USDA, ARS, Subtropical Agriculture Research Station in Brooksville, FL. Nitrogen was applied in April of each year, and all pastures were stocked with 1.5 bulls/ha until approximately July of each year, when stocking rate was increased on half the pastures to 2.5 bulls/ha. Herbage mass (HM, kg/ha), herbage allowance (HA, kg/kg BW), nutritive value (CP and in vitro organic matter digestibility [IVOMD]), and diet botanical composition (fecal microhistological) readings were determined. Animal measurements included total and seasonal (spring vs summer), ADG, hip height (cm), scrotal circumference (SC, cm), and plasma urea nitrogen (PUN, mg/dL). Herbage mass (3.0 +/- 0.12 Mg/ha and 3.4 +/- 0.13 Mg/ha in 1995 and 1996, respectively) was not affected by nitrogen fertilization or stocking rate but was affected by season (P < 0.05) due to increased plant growth rate associated with summer rainfall. Stocking rate did affect herbage availability, but it never fell below 3 kg/kg BW, indicating herbage availability was never limiting. Crude protein (200 to 140 g/kg) and IVOMD (650 to 540 g/kg) were not affected by treatment, but declined (P < 0.001) from spring until fall. Treatments also had no effect on diet botanical composition. Summer ADG averaged about 0.2 kg/d lower than spring ADG, due, in part, to seasonal declines in nutritive value. Because herbage allowance was never limiting
Simultaneous fingerprint, quantitative analysis and anti-oxidative based screening of components in Rhizoma Smilacis Glabrae using liquid chromatography coupled with Charged Aerosol and Coulometric array Detection.
Yang, Guang; Zhao, Xin; Wen, Jun; Zhou, Tingting; Fan, Guorong
An analytical approach including fingerprint, quantitative analysis and rapid screening of anti-oxidative components was established and successfully applied for the comprehensive quality control of Rhizoma Smilacis Glabrae (RSG), a well-known Traditional Chinese Medicine with the homology of medicine and food. Thirteen components were tentatively identified based on their retention behavior, UV absorption and MS fragmentation patterns. Chemometric analysis based on coulmetric array data was performed to evaluate the similarity and variation between fifteen batches. Eight discriminating components were quantified using single-compound calibration. The unit responses of those components in coulmetric array detection were calculated and compared with those of several compounds reported to possess antioxidant activity, and four of them were tentatively identified as main contributors to the total anti-oxidative activity. The main advantage of the proposed approach was that it realized simultaneous fingerprint, quantitative analysis and screening of anti-oxidative components, providing comprehensive information for quality assessment of RSG.
Yoshida, Ichiro; Ito, Chihiro; Matsuda, Shinya; Tsuji, Akihiko; Yanaka, Noriyuki; Yuasa, Keizo
To develop new whitening agents from natural products, we screened 80 compounds derived from crude drugs in Kampo medicine in a melanin synthesis inhibition assay using murine B16 melanoma cells. The screen revealed that treatment with alisol B, a triterpene from Alismatis rhizoma, significantly decreased both melanin content and cellular tyrosinase activity in B16 cells. However, alisol B did not directly inhibit mushroom tyrosinase activity in vitro. Therefore, we investigated the mechanism underlying the inhibitory effect of alisol B on melanogenesis. Alisol B suppressed mRNA induction of tyrosinase and its transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, alisol B reduced the phosphorylation of CREB and maintained the activation of ERK1/2. These results suggest that the reduction in melanin production by alisol B is due to the downregulation of MITF through the suppression of CREB and activation of ERK and that alisol B may be useful as a new whitening agent.
Bennett, L L; Hammond, A C; Williams, M J; Kunkle, W E; Johnson, D D; Preston, R L; Miller, M F
Steers (n = 156) finished on rhizoma peanut (Arachis glabrata Benth.)-tropical grass pasture in Florida and slaughtered at Central Packing, Center Hill were compared with steers (n = 152) finished on a concentrate diet in Texas and slaughtered at Excel, Plainview. Average daily gain during the growing and finishing periods was lower (P < .001) for forage-finished steers (.49 and .94 kg/d, respectively) than for concentrate-finished steers (.78 and 1.33 kg/d, respectively). Forage-finished steers had less fat over the ribeye (8.3 vs 11.4 mm; P < .01), lighter hot carcass weight (280 vs 346 kg; P < .001), and smaller longissimus muscle area (70.8 vs 86.6 cm2; P < .001) than concentrate-finished steers. Yield grade was not different (2.7 vs 2.6; P > .10), but quality grade was slightly better (low Select vs mid Select; P < .01) for concentrate-finished steers. Lean color of forage-finished steers was darker (P < .001) and fat of forage-finished steers had a creamier color (P < .001), but carcasses were not discounted due to yellow fat color. Shear force values were higher (6.8 vs 4.0 kg; P < .001) for forage-finished than for concentrate-finished steers. Off-flavors were detected by trained sensory panelists in 36% of forage-finished and 14% of concentrate-finished carcasses, but all at barely detectable levels. This research indicates that steers can be finished on rhizoma peanut-tropical grass pastures, but with some reduction in quality grade relative to concentrate-finished steers.(ABSTRACT TRUNCATED AT 250 WORDS)
Yan, Shu; Tian, Shuxia; Kang, Qingwei; Xia, Yafei; Li, Caixia; Chen, Qing; Zhang, Shukun; Li, Zhigang
Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1 mg/kg) for 10 weeks. RPS (350 mg/kg or 100 mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.
Yan, Shu; Tian, Shuxia; Kang, Qingwei; Xia, Yafei; Li, Caixia; Chen, Qing; Zhang, Shukun; Li, Zhigang
Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1mg/kg) for 10 weeks. RPS (350 mg/kg or 100mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer. PMID:26147856
ZHU, MEIFEN; WANG, NING; TSAO, SAI-WAH; YUEN, MAN-FUNG; FENG, YIGANG; WAN, THOMAS S.K.; MAN, KWAN; FENG, YIBIN
Coptidis rhizoma (CR; Huanglian in Chinese) has been used for the treatment of cancer in Chinese medicine, and recent studies have supported its use in cancer therapy. MicroRNAs (miRNAs) play an important role in the pathophysiology of human cancers. We examined alterations in the miRNA profile of hepatocellular carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract (CRAE). An on-chip microarray method was used to detect alterations in the expression profile of miRNAs in human HCC MHCC97-L cells after exposure to 175 μg/ml CRAE. Altered expression of several miRNAs was detected in the MHCC97-L cells after treatment with 175 μg/ml CRAE. The microarray results were validated by quantitative real-time PCR (qRT-PCR). Consistent results were obtained; qRT-PCR confirmed that both miR-21 and miR-23a were significantly up-regulated. TargetScan and PicTar microRNA databases were used to predict the possible target genes of the altered miRNAs. The results showed that the altered miRNAs after CRAE treatment may serve as markers for the therapy of liver cancer. To the best of our knowledge, this is the first report on the up-regulation of miRNAs, miR21 and miR23a in human liver cancer cells treated with CRAE. Our results suggest that CRAE targets miR-21 and miR-23a in liver cancer cells supporting the potential application of CRAE in the treatment of HCC. PMID:22977465
Wang, Yue; Han, Yulong; Chai, Fangni; Xiang, Hongmei; Huang, Tao; Kou, Shuming; Han, Bing; Gong, Xiaobao; Ye, Xiaoli
The aim of this study was to investigate the antihypercholesterolemic activity and potential molecular mechanism of columbamine (COL) that was prepared by extraction from Rhizoma Coptidis in hamsters and HepG2 cells. The results displayed that the COL from Rhizoma Coptidis was a safe natural compound with a LD50 0f 1524.6mg/kg and no detectable toxic symptoms during the observation of chronic toxicity. COL dose-dependently reversed the abnormal lipid levels induced by HFHC diet. Specifically, COL(M) and COL(H) significantly reduced the blood lipid levels(TC, TG and LDL-c) and enhanced the fecal contents of TBA by 21.8% and 25.1% respectively in hamsters. COL up-regulated the genes of CYP8B1, CYP7A1 and LDLR in mRNA and protein level, and down-regulated those of HMGCR to a different degree. Especially, CYP7A1 were significantly up-regulated by COL in hamsters (p<0.01). Further analysis indicated that COL obviously activated the mRNA and protein expression of the transcription factors FTF, HNF-4α, and inhibited those of SHP. Promoter luciferase assay showed that COL induced the expression of FTF and HNF-4α, further transactivating CYP7A1, which accelerated the conversion of liver cholesterol to bile acids. It concluded that the COL showed high lipid-lowering activities through indirectly transactivating CYP7A1 by upregulating FTF and HNF-4α, and directly activating CYP7A1 catalytic activity by strongly interacting with receptor and ligand, therefore promoting cholesterol catabolism and accelerating the excretion of bile acids.
Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by LC-MS: application to a comparative pharmacokinetic study in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract.
Zhao, Xu; Ma, Tiancheng; Zhang, Chenning; Shi, Shaohuai; Cui, Sijiao; Bi, Kaishun; Jia, Ying
A selective liquid chromatographic-mass spectrometric method has been developed and validated for simultaneous determination of senkyunolide I (SEI) and senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Kromasil C18 column (250 × 4.6 mm, 5 µm), with methanol-water (55:45, v/v) as mobile phase. The linear range was 0.05-25 µg/mL for SEI and 0.01-5.0 µg/mL for SEH, with lower limits of quantitation of 0.05 and 0.01 µg/mL, respectively. Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0-86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was successfully applied to a comparative pharmacokinetic study of SEI and SEH in normal and migrainous rats after oral administration of Chuanxiong Rhizoma extract. The results indicated that there were obvious differences between normal and migrainous rats in the pharmacokinetic behavior after oral administration of Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly increased in migrainous rats compared with normal rats.
Wang, Jing-Hua; Bose, Shambhunath; Kim, Hyung-Gu; Han, Kyung-Sun; Kim, Hojun
Accumulating evidence suggests the anti-inflammatory and anti-obesity activities of Rhizoma Atractylodis Macrocephalae (RAM). Here, we evaluated the anti-obesity impact of unfermented (URAM) versus fermented RAM (FRAM) using both in vitro and in vivo models. Both URAM and FRAM exhibited marked anti-inflammatory, anti-adipogenic, and anti-obesity activities, and modulation of the gut microbial distribution. However, FRAM, compared to URAM, resulted in more efficient suppression of NO production and normalization of transepithelial electrical resistance in LPS-treated RAW 264.7 and HCT 116 cells, respectively. Compared to URAM, FRAM more effectively reduced the adipose tissue weight; ameliorated the serum triglyceride and aspartate transaminase levels; restored the serum HDL level and intestinal epithelial barrier function in the LPS control group. The relative abundance of Bifidobacterium and Akkermansia as well as Bacteriodetes/Firmicutes ratio in the gut of the LPS control group was significantly enhanced by both URAM and FRAM. However, FRAM, but not URAM, resulted in a significant increase in the distribution of Bacteriodetes and Lactobacillus in the gut of the HFD + LPS group. Our results suggest that FRAM with probiotics can exert a greater anti-obesity effect than URAM, which is probably mediated at least in part via regulation of the intestinal microbiota and gut permeability. PMID:25684573
Choi, Jae Joon; Oh, Eun-Hye; Lee, Mi Kyeong; Chung, Youn Bok; Hong, Jin Tae; Oh, Ki-Wan
This research was designed to identify whether Gastrodiae Rhizoma ethanol extract (GREE) enhances pentobarbital-induced sleep via γ-aminobutyric acid- (GABA-) ergic systems and modulated sleep architectures in animals. GREE (25, 50, and 100 mg/kg, p.o.) inhibited locomotor activity in mice, in a dose-dependent manner. GREE not only prolonged total sleep time, but also reduced sleep latency time in pentobarbital (42 mg/kg)-treated mice. Subhypnotic pentobarbital (28 mg/kg, i.p.) also increased the number of total sleeping animals in concomitant administration of GREE. GREE (100 mg/kg) alone reduced the count of sleep-wake cycles in electroencephalogram. Furthermore, GREE increased total sleep time and rapid eye movement (REM) sleep. From the in vitro experiments, GREE increased intracellular chloride level in primary cultured cerebellar granule cells. Protein expressions of glutamine acid decarboxylase (GAD) and GABAA receptors subtypes by western blot were increased. Therefore, our study suggested that GREE enhances pentobarbital-induced sleeping behaviors and increased REM via the activation of GABAA-ergic transmission in rodents. PMID:25614750
Liu, Qi; Zhou, Jianda; Yu, Jingang; Xie, Yixi; Jiang, Xinyu; Yang, Hua; Chen, Xiaoqing
A counter-current chromatography (CCC)-solid phase extraction (SPE)-CCC system with high preparative capacity was used to realize rapid one-run systematic separation of natural products, in which two six-port valves and the SPE cartridge served as the interface. In the orthogonal separation system, equal column volumes of TEB-300A and TEB-300B were employed for the first dimension (1st-D) and second dimension (2nd-D), respectively. An optimized solid-phase column (25 mm × 10 mm i.d.) packed with Oasis HLB materials acted as the trapping SPE column. The analyte-focusing effect of the trapping column associated with the considerable preparative capacities of 1st-D and 2nd-D using totally different solvent systems significantly facilitated this one-run systematic separation of natural product. Therefore, this proposed approach was successfully applied to isolate chemical compounds from the crude extract of Rhizoma Chuanxiong. As a result, 11 compounds with widely different polarities were separated by running CCC for only one time. More importantly, this hyphenated strategy could serve as a rapid and efficient systematic pathway for the separation of natural products.
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
Yu, Sen; Pang, Xiaoyan; Deng, Yuanxiong; Liu, Li; Liang, Yan; Liu, Xiaodong; Xie, Lin; Wang, Guangji; Wang, Xinting
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.
Li, Yerui; Liu, Bowen; Geng, Shu; Kim, Sungchan; Jin, Ye; Liu, Xuesong; Luan, Lianjun; Wu, Yongjiang; Chen, Yong
Raw material examination is a critical process in the industrial production of traditional Chinese medicine (TCM); high accuracy and minimal time consumption are both required. In this study, near-infrared (NIR) spectroscopy was applied to improve the quality control efficiency of Rhizoma paridis. Partial least squares regression (PLSR) was first used to develop quantitative calibration models, and the discriminant analysis model was established to qualitatively discriminate the qualified samples from the unqualified samples. These two established NIR models were applied for real-time release testing (RTRT) of R. paridis. R. paridis saponins (RPS) ≥ 0.6% and moisture ≤ 12% were used as the quantitative releasing criteria of RTRT according to the Chinese Pharmacopoeia. Qualified samples classified by the discriminant analysis model were deemed to meet the qualitative releasing criterion of RTRT. Using the established quantitative model, 24 samples were allowed to be released to the subsequent production processes with 100% accuracy. For the qualitative RTRT analysis, three samples were misclassified as the unqualified class and were released unsuccessfully, the accuracy of the qualitative RTRT was 90%. Therefore, the quantitative RTRT was more feasible for actual manufacturing processes. Based on this study, a rapid and effective quantitative NIR spectroscopic method was proposed for the RTRT of R. paridis. The combination of RTRT and NIR spectroscopy could be a potential tool to improve the quality control efficiency of R. paridis.
Dai, Weiquan; Zhao, Weiquan; Gao, Fangyuan; Shen, Jingjing; Lv, Diya; Qi, Yunpeng; Fan, Guorong
Rhizoma Smilacis Glabrae (RSG) is a well-known herbal medicine with the homology of medicine and food. In this study, simultaneous chemical fingerprint and quantitative analysis of the bioactive flavonoid components of RSG were developed using accelerated solvent extraction and high-performance liquid chromatography coupled with ion trap tandem mass spectrometry. The operational parameters of accelerated solvent extraction including extraction solvent, extraction temperature, static extraction time, solid-to-liquid ratio, and extraction cycles were optimized. Hierarchical cluster analysis, similarity analysis, and principal component analysis were performed to evaluate the similarity and variation of the samples collected from several provinces in China. Subsequently, high-performance liquid chromatography fingerprints were established for the discrimination of 16 batches of RSG samples, and the major six flavonoids, namely, toxifolin, neoastilbin, astilbin, neoisoastilbin, isoastilbin, and engeletin were then quantitatively determined. The calibration curves for all the six analytes showed good linearity (r(2) > 0.999), and the limits of detection and quantification were less than 0.10 and 0.27 μg·mL(-1) , respectively. Therefore, the proposed extraction and determination methods were proved to be robust and reliable for the quality control of RSG.
Lu, Fang; Liu, Lei; Yu, Dong-hua; Li, Xu-zhao; Zhou, Qi; Liu, Shu-min
Rhizoma Dioscoreae Nipponicae (RDN) is a widely used traditional Chinese herb, which is used to treat arthroncus, arthrodynia and arthritis. As is known to us, inflammatory mechanisms have played an important role in the occurrence, course and prognosis of gouty arthritis (GA). The aim of this study was to determine the characteristic expressed proteins of synovium in GA rat and synovial cell. The rat model of GA was induced by monosodium urate (MSU) crystal. Tissue samples were assayed by immunohistochemical method. The effects of RDN on Stromal cell-derived factor 1 (SDF-1), CXCR 4 and p38 mitogen-activated protein kinase (MAPK) were investigated in MSU crystal-induced rat. The levels of SDF-1 and mitogen-activated kinase kinase (MKK) 3/6 were measured by Western Blot in interleukin-1β (IL-1β) incubated fibroblast-like synoviocytes (FLS). A significant increase in the levels of SDF-1, CXCR 4 and p38 MAPK were observed in MSU crystal-induced rat. The increased SDF-1 and MKK 3/6 levels were observed in IL-1β incubated FLS. With the treatment of RDN, the above changes were reverted back to near normal levels. RDN might have some therapeutic effects on GA through SDF-1/CXCR 4 and p38 MAPK pathway, and dioscin may be the active compound in RDN to exert therapeutic effect on GA.
Yao, Li; Dong, Wanru; Lu, Fang; Liu, Shumin
Rhizoma Dioscoreae nipponicae (RDN) is an herbal medicine. In the theories of Traditional Chinese Medicine (TCM), the function of RDN is to expel wind and remove dampness. Inflammatory mechanisms play an important role in the pathological process and prognosis of acute gouty arthritis (AGA). The aim of this study was to determine the specially expressed proteins through testing the proteins of the synovium in rats with AGA. The animal model of AGA was set up by Monosodium urate crystal (MSU) combined with hypoxanthine (HX), which was ameliorated in our previous experiment. Blood samples for measurement of serum uric acid were collected prior to sacrifice. Outcomes were assessed (two days after injection) by histological stain and protein quantitation. Three chips of RayBio® Human Label-based Antibody Array I were applied to detect 90 proteins in the synovium tissue of AGA rats. 14 differently expressed proteins were found in the synovium of AGA rats, and nine of them were first found in this model. There were seven up-regulated and seven down-regulated proteins, both TRAIL and Neuropilin-2 could be identified as key contributors to the pathomechanism of AGA.
Kamino, Takuya; Shimokura, Toshihiro; Morita, Yusuke; Tezuka, Yasuhiro; Nishizawa, Mikio; Tanaka, Ken
During the development of natural herbal medicines in Japan, Glehniae Radix cum Rhizoma (Hamabofu in Japanese) has been used as a substitute for Saposhnikoviae Radix (Bofu). Bofu and Hamabofu are blended differently in several Kampo formulae. For example, Bofu is included in Jumihaidokuto by a manufacturer, whereas Hamabofu is included instead of Bofu in the same formula by other manufacturers. Although both Bofu and Hamabofu are used for their expected anti-inflammatory effects, differences in their medicinal properties are not well characterized. In addition, there have been very few reports comparing the pharmacological activities of the constituents in Bofu and Hamabofu. In the present study, we investigated the anti-inflammatory effects of the extracts of Bofu and Hamabofu by monitoring levels of the inflammatory mediator nitric oxide (NO) produced in rat hepatocytes. Moreover, the chemical constituents responsible for the activity were investigated. Our results showed that ethyl acetate fractions of Bofu and Hamabofu extracts contain different compounds, although both fractions suppressed NO production in rat hepatocytes. The linear dihydropyranochromones from the Bofu extract (i.e., 3'-O-angeloylhamaudol, ledebouriellol and hamaudol) suppressed NO production, whereas the coumarins from the Hamabofu extract (i.e., umbelliferone and scopoletin) also suppressed NO production. These results suggest that linear dihydropyranochromones and coumarins are responsible for the anti-inflammatory effects of Bofu and Hamabofu. It is plausible that Bofu and Hamabofu are blended differently in several Kampo formulae due to many constituents with as yet unidentified pharmacological activity.
Tan, Bo; Ma, Yueming; Shi, Rong; Wang, Tianming
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
Wei, Yun; Hu, Jia; Li, Hao; Liu, Jiangang
Three active compounds, senkyunolide-I, senkyunolide-H and ferulic acid (FA), were successfully isolated and purified from the extracts of Rhizoma Chuanxiong by counter-current chromatography (CCC). Based on the principle of the partition coefficient values (k) for target compounds and the separation factor (α) between target compounds, the two-phase solvent system that contains n-hexane-ethyl acetate-methanol-water at an optimized volume ratio of 3:7:4:6 v/v was selected for the CCC separation, and the lower phase was employed as the mobile phase in the head-to-tail elution mode. In a single run, 400 mg of the crude extract yielded pure senkyunolide-I (6.4 mg), senkyunolide-H (1.7 mg) and FA (4.4 mg) with the purities of 98, 93 and 99%, respectively. The CCC fractions were analyzed by high-performance liquid chromatography, and the structures of the three active compounds were identified by MS and (1)H NMR.
Evaluation of In Vitro Anti-Inflammatory Activities and Protective Effect of Fermented Preparations of Rhizoma Atractylodis Macrocephalae on Intestinal Barrier Function against Lipopolysaccharide Insult
Bose, Shambhunath; Kim, Hojun
Lipopolysaccharide (LPS), a potent inducer of systemic inflammatory responses, is known to cause impairment of intestinal barrier function. Here, we evaluated the in vitro protective effect of an unfermented formulation of Rhizoma Atractylodis Macrocephalae (RAM), a traditional Chinese herbal medicine widely used in the treatment of many digestive and gastrointestinal disorders, and two fermented preparations of RAM, designated as FRAM-1 (prepared in Luria-Bertani broth) and FRAM-2 (prepared in glucose), on intestinal epithelial cells (IECs) against LPS insult. In general, fermented formulations, especially FRAM-2, but not unfermented RAM, exerted an appreciable protective effect on IECs against LPS-induced perturbation of membrane resistance and permeability. Both fermented formulations exhibited appreciable anti-inflammatory activities in terms of their ability to inhibit LPS-induced gene expression and induced production of a number of key inflammatory mediators and cytokines in RAW 264.7 macrophage cells. However, in most cases, FRAM-2 exhibited stronger anti-inflammatory effects than FRAM-1. Our findings also suggest that suppression of nuclear factor-κβ (NF-κβ) activity might be one of the possible mechanisms by which the fermented RAM exerts its anti-inflammatory effects. Collectively, our results highlight the benefits of using fermented products of RAM to protect against LPS-induced inflammatory insult and impairment in intestinal barrier function. PMID:23573125
Simultaneous quantification of chrysophanol and physcion in rat plasma by ultra fast liquid chromatography-tandem mass spectrometry and application of the technique to comparative pharmacokinetic studies of Radix et Rhei Rhizoma extract alone and Dahuang Fuzi Decoction.
Liu, Xiao; Li, Huan; Wu, Li; Xing, Jiangwa; Poh, Yanhong; Cai, Hao; Cai, Bao Chang
Most herbal medicines are prescribed in combination based on the theory of TCM to obtain synergistic effects or diminish the possible adverse reactions. Compatibility refers to the combination of two or more herbs based on the clinical settings and the properties of herbs. Chrysophanol and physcion are the main effective compounds in Radix et Rhizoma Rhei and Dahuang Fuzi Decoction which is the combination of Radix et Rhizoma Rhei, Radix Aconiti Lateralis Praeparata and Radix et Rhizoma Asari. However, chrysophanol and physcion are difficult to detect in vivo because of their low concentration and interference from endogenous compounds. The aim of this study is to develop a rapid, specific and sensitive ultra high performance liquid chromatography-triple quadrupole tandem mass method to simultaneously quantify chrysophanol and physcion in rat plasma, in order to better understand the pharmacokinetics and compatibility mechanism of Dahuang Fuzi Decoction for the first time. Multiple reaction monitoring (MRM) mode was applied for the quantitation at [M-H](-)m/z 253.0→m/z 225.1 for chrysophanol, [M-H](-) for m/z 283.1→m/z 240.0 physcion and [M-H](-)m/z 239.0→m/z 211.0 for IS. The analytes were separated on an Agilent Eclipse plus C18 column (100mm×2.1mm, 1.8μm) column within a total running time of 6.5min using a mixture of 3mM ammonium acetate in water and methanol (95:5, v/v) with a time program flow gradient according to the "plus gradient chromatography" theory. The inclusion of the ammonium acetate in the UFLC mobile phase dramatically improved the detection limit of the tested compounds and decreased the interference by matrix effects, which have been referred to as "LC-electrolyte effects". Finally, we demonstrated the application of a validated method in a comparative pharmacokinetic study of rats receiving an oral dose of Dahuang Fuzi Decoction or Radix et Rhei Rhizoma, the monarch drug in the prescription. Pharmacokinetic parameters showed
Allen, Leon Hartwell; Albrecht, Stephan L; Boote, Kenneth J; Thomas, Jean M G; Newman, Yoana C; Skirvin, Katherine W
Carbon sequestration in soils might mitigate the increase of carbon dioxide (CO2) in the atmosphere. Two contrasting subtropical perennial forage species, bahiagrass (BG; Paspalum notatum Flügge; C4), and rhizoma perennial peanut (PP; Arachis glabrata Benth.; C3 legume), were grown at Gainesville, Florida, in field soil plots in four temperature zones of four temperature-gradient greenhouses, two each at CO2 concentrations of 360 and 700 micromol mol(-1). The site had been cultivated with annual crops for more than 20 yr. Herbage was harvested three to four times each year. Soil samples from the top 20 cm were collected in February 1995, before plant establishment, and in December 2000 at the end of the project. Overall mean soil organic carbon (SOC) gains across 6 yr were 1.396 and 0.746 g kg(-1) in BG and PP, respectively, indicating that BG plots accumulated more SOC than PP. Mean SOC gains in BG plots at 700 and 360 micromol mol(-1) CO2 were 1.450 and 1.343 g kg(-1), respectively (not statistically different). Mean SOC gains in PP plots at 700 and 360 micromol mol(-1) CO2 were 0.949 and 0.544 g kg(-1), respectively, an increase caused by elevated CO2. Relative SON accumulations were similar to SOC increases. Overall mean annual SOC accumulation, pooled for forages and CO2 treatments, was 540 kg ha(-1) yr(-1). Eliminating elevated CO2 effects, overall mean SOC accumulation was 475 kg ha(-1) yr(-1). Conversion from cropland to forages was a greater factor in SOC accumulation than the CO2 fertilization effect.
Xie, Weidong; Gu, Dayong; Li, Jianna; Cui, Kai; Zhang, Yaou
Gut microbes play important roles in regulating fat storage and metabolism. Rhizoma coptidis (RC) and its main active compound, berberine, have either antimicrobial or anti-obesity activities. In the present study, we hypothesize that RC exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes and berberine may be a key compound of RC. Gut microbes and glucose and lipid metabolism in high-fat diet-fed C57BL/6J (HFD) mice in vivo are investigated after RC and berberine treatments. The results show that RC (200 mg/kg) and berberine (200 mg/kg) significantly lower both body and visceral adipose weights, and reduce blood glucose and lipid levels, and decrease degradation of dietary polysaccharides in HFD mice. Both RC and berberine significantly reduce the proportions of fecal Firmicutes and Bacteroidetes to total bacteria in HFD mice. In the trial ex vivo, both RC and berberine significantly inhibit the growth of gut bacteria under aerobic and anaerobic conditions. In in vitro trials, both RC and berberine significantly inhibit the growth of Lactobacillus (a classical type of Firmicutes) under anaerobic conditions. Furthermore, both RC and berberine significantly increase fasting-induced adipose factor (Fiaf, a key protein negatively regulated by intestinal microbes) expressions in either intestinal or visceral adipose tissues. Both RC and berberine significantly increase mRNA expressions of AMPK, PGC1α, UCP2, CPT1α, and Hadhb related to mitochondrial energy metabolism, which may be driven by increased Fiaf expression. These results firstly suggest that antimicrobial activities of RC and berberine may result in decreasing degradation of dietary polysaccharides, lowering potential calorie intake, and then systemically activating Fiaf protein and related gene expressions of mitochondrial energy metabolism in visceral adipose tissues. Taken together, these action mechanisms may contribute to significant anti-obesity effects
Ma, Hang; Hu, Yinran; Zou, Zongyao; Feng, Min; Ye, Xiaoli; Li, Xuegang
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.
Sakumoto, Hitoshi; Yokota, Yumiko; Ishibashi, Gakushi; Maeda, Shouta; Hoshi, Chihiro; Takano, Haruyo; Kobayashi, Miki; Yahagi, Tadahiro; Ijiri, Soichiro; Sakakibara, Iwao; Hara, Akiyoshi
The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL-100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM-100 μM and 10 nM-100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1-100 μM) but not at lower concentrations (1-100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM-1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.
Lin, Li-Yun; Shen, Kun-Hung; Yeh, Xiang-Yü; Huang, Bou-Yü; Wang, Hui-Er; Chen, Kuan-Chou; Peng, Robert Y
Rhizoma Alpinia officinarum (Hance) Farw, Zingiberaceae (AO), a ginger family herb exhibiting stimulant and a carminative bioactivity, is widely used in European and Asian countries as spicy condiment and medicinal uses. Allyl isothiocyanate (AITC) is the main pungent taste of native Wasabi (Wasabia japonica). The cytotoxicity of AITC has been implicated in thymus, adrenals, and white blood cells. Considering food safety, apparently a safer substitute for wasabi is worthy commercialized. Previously, we found AO crude paste to be rather feasible for use as a "Wasabi-substitute" in fresh meat and cold salads. A process linking cold ethyl acetate (EtAc) extraction with silica gel adsorption and reversed phase high-performance liquid chromatography (RP-HPLC) (mobile phase, 75% methanol) was used to isolate galangal acetate, the Wasabi-like taste constituent. AO contained abundant galangal acetate (3.84 ± 0.07%) compared to A. galangal (0.57 ± 0.16%), and as already confirmed by thin layer chromatography (TLC), gas chromatography (GC)/mass spectrometry (MS)/MS and Nuclear Magnetic Resonance Spectroscopy (NMR), galangal acetate was particularly thermally labile. The steam distilled essential oil (SDEO) of AO (0.14% on wet basis) contained 80 compounds (number of component, %): monoterpene hydrocarbon (21, 13.83%); oxygenated monoterpene (17, 27.08%); sesquiterpene hydrocarbon (20, 31.03%), and oxygenated sesquiterpene (20, 21.85%), respectively. However, no spicy wasabi-like constituent remained in SDEO. Alternatively, n-hexane, EtAc, and methanol extracts of AO all showed potent DPPH- and superoxide anion-scavenging activity. Conclusively, SDEO although contains 80 volatiles, galangal acetate is absent due to thermal instability. Galangal acetate exhibits pleasant "Wasabi-like taste" for which we have successively developed an integrated process for mass production.
Cao, Yang; Bei, Weijian; Hu, Yinming; Cao, Le; Huang, Lihua; Wang, Laiyou; Luo, Duosheng; Chen, Yuanyuan; Yao, Xi; He, Wei; Liu, Xiaobo; Guo, Jiao
This study is to investigate the cholesterol-lowering effect and the new mode of action of coptis alkaloids on high lipid diet-induced hyperlipidemic rats. Coptis alkaloids extract (CAE) was prepared by alcohol extraction from Rhizoma Coptidis that have been quality-controlled according to the protocol. The cholesterol-lowering effect of CAE was evaluated on SD rats fed with high-lipid diet. Serum level of lipid, Bile acid and cholesterol in the liver and feces of the rats were measured using colorimetric assay kit. RT-PCR and Western blot were used to analyze the mRNA and protein expression of cholesterol metabolism-related genes including cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptor-alpha (PPARα) and farnesoid X receptor (FXR) in the livers of the rats. A HPLC analysis was used to assess the activity of CYP7A1. The results showed that CAE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C). CYP7A1 gene expression and its activity was up-regulated dose-dependently accompanying with the increased level of bile acid and the reduced cholesterol level in the livers of the CAE treated hyperlipidemic rats. Meanwhile, the mRNA expression of PPARα was also up-regulated in dose-dependent way accompanying the down-modulation of the FXR mRNA expression in the livers of the CAE treated hyperlipidemic rats. The results indicate that the cholesterol-lowering effect of coptis alkaloid extract is at least partly attributed to its promoting the cholesterol conversion into bile acids by up-regulating the gene expression of CYP7A1 and thus increasing its activity in the liver of the hyperlipidemic rats, which might related to the positive regulation of PPARα and the negative modulation of FXR.
Park, InSil; Ryuk, JinAh; Lee, HyeWon; Go, Hiroe; Ko, ByoungSeob
Curcumae Radix (CR) and Glycyrrhizae Radix et Rhizoma (GR) extracts have been used as health supplements in traditional medicine. This study was performed to evaluate the effects of combined CR and GR extracts (CR+GR) on metabolic complications related menopausal symptoms. We found a significant results that CR+GR extracted using ethanol stimulated the growth of MCF-7 cells in estrogen activity and was attenuated in lipid deposition of HepG2 cells treated with MβCD compared to CR and GR treatments each. To investigate the situation, an experimental menopause rat model with dyslipidemia was induced by surgical bilateral ovariectomy (OVX) and high fat high cholesterol (HFHC) diet in female rats. OVX rats fed HFHC (OVX-HFHC) showed a shift in weight gain, elevated serum cholesterol, altered liver enzymatic parameters and enhanced liver injury compared to the NC and HFHC groups. However, administration of CR+GR, in particular 200 or 450 mg/kg/day, inhibited the increase in body weight gain and lipid metabolic disturbances, lowering total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) compared to the OVX-HFHC group. Furthermore, CR+GR (200 or 450 mg/kg/day) ameliorated the serum levels of the liver enzymes aspartate aminotransferase (AST) and alanine transaminase (ALT) compared to the OVX-HFHC group. Moreover, CR+GR (200 or 450 mg/kg/day) attenuated not only hepatic steatosis but also larger adipocytes. Our study demonstrated that combined treatment with CR and GR attenuated metabolic complications induced by OVX and HFHC diet, suggesting that this effect may regulate and prevent the acceleration of cardiovascular disease (CVD) after menopause. PMID:26628991
Chemical differentiation of volatile compounds in crude and processed Atractylodis Macrocephalae Rhizoma by using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry combined with multivariate data analysis.
Cao, Gang; Cai, Hao; Jiang, Jianping; Yao, Linjiang; Tu, Sicong; Wang, Lin; Ma, Xiaoqing; Cai, Baochang
In the present study, comprehensive 2D GC-TOF-MS combined with multivariate data analysis was applied to analyze the differences of the volatile components in crude and processed Atractylodis Macrocephalae Rhizoma (AMR) samples. As a result, 26 compounds that were found in crude AMR samples disappeared in processed AMR samples, and 19 compounds were newly generated and identified in AMR after processing with wheat bran. Meanwhile, principal component analysis demonstrated that there were significant chemical differences between crude and processed AMR samples, and processing procedure caused obvious quantitative and qualitative changes of volatile components in AMR. The established method could be used to explain the chemical differentiation between crude and processed AMR, and to further understand the processing mechanism of herbal medicines.
Fo shou san, an ancient herbal decoction prepared from angelicae sinensis radix and chuanxiong rhizoma, induces erythropoietin expression: a signaling mediated by the reduced degradation of hypoxia-inducible factor in cultured liver cells.
Bi, Cathy W C; Xu, Li; Zhang, Wendy L; Zhan, Janis Y X; Fu, Qiang; Zheng, Ken Y Z; Chen, Vicky P; Lau, David T W; Choi, Roy C Y; Wang, Tie J; Dong, Tina T X; Tsim, Karl W K
Fo Shou San (FSS) is an ancient herbal decoction composed of Angelicae Sinensis Radix (ASR; Danggui) and Chuanxiong Rhizoma (CR; Chuanxiong) in a ratio of 3:2. FSS is mainly prescribed for patients having a deficiency of blood supply, and it indeed has been shown to stimulate the production of erythropoietin (EPO) in cultured cells. In order to reveal the mechanism of this FSS-induced EPO gene expression, the upstream regulatory cascade, via hypoxia-induced signaling, was revealed here in cultured hepatocellular carcinoma cell line Hep3B. The induction of EPO gene expression, triggered by FSS, was revealed in cultured hepatocytes by: (i) the increase of EPO mRNA; and (ii) the activation of the hypoxia response element (HRE), an upstream regulator of the EPO gene. The FSS-induced EPO gene expression was triggered by an increased expression of hypoxia-inducible factor-1 α (HIF-1 α) protein; however, the mRNA expression of HIF-1 α was not altered by the treatment of FSS. The increased HIF-1 α was a result of reduced protein degradation after the FSS treatment. The current results therefore provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.
Fu, Jinfeng; Wang, Min; Guo, Huimin; Tian, Yuan; Zhang, Zunjian; Song, Rui
Introduction: Rhizoma et Radix Polygoni Cuspidati (Huzhang in Chinese, HZ) is a traditional medicinal plant in China. Many of the components of HZ have been proved to be bioactive while it is difficult to conduct a comprehensive chemical profiling of HZ as a consequence of the absence of efficient separation system and sensitive detective means. We developed a simple and effective method for comprehensive characterization of constituents in HZ. Objective: To develop a simple and effective method to characterize the components in HZ and provide useful information for subsequent metabolic studies of HZ. Materials and Methods: The components in HZ aqueous extract were characterized by using high performance liquid chromatography with UV diode-array detector (HPLC-DAD) and ion trap/time-of-flight mass spectrometric detection (HPLC-IT/TOF). Stilbenes, anthraquinones, gallates and tannins, naphthalenes and some other compounds were identified and confirmed by diagnostic fragment ions with accurate mass measurements, characteristic fragmentation pathways and relevant published literatures. Results: Among the 238 constituents detected in HZ, a total number of 74 constituents were identified unambiguously or tentatively, including 29 compounds reported for the first time in HZ. Conclusion: The identification and structure elucidation of these chemicals provided essential data for quality control and further in vivo metabolic studies of HZ. Key words: Polygonum cuspidatum, HPLC-DAD, HPLC-IT/TOF, qualitative analysis. PMID:26246723
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.
Fan, Hui; Chen, Yuan-Yuan; Bei, Wei-Jian; Wang, Lai-You; Chen, Bao-Tian; Guo, Jiao
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.
Trace enrichment and characterization of polyphenols in Bistort Rhizoma using weak anion-exchange solid phase extraction and high performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
Wang, Shao-Teng; Yang, Hua; Gao, Wen; Li, Hui-Jun; Li, Ping
The analysis of trace constituents in herbal medicines has always been a challenge due to complex matrices and structural diversities. In this work, a pH-sensitive solid phase extraction (SPE) procedure capable of enriching trace polyphenols in Bistort Rhizoma (BR) was proposed and preliminary chemical characterization was accomplished by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS). A weak anion-exchange SPE column packed with divinylbenzene/vinylpyrrolidone bonding quaternary amine group was employed for anionic extraction, and the target fraction was obtained by eluting with acidic methanol (apparent pH 1.9). On the other hand, the MS/MS fragmentation rules of four reference polyphenols in negative ion mode were outlined. Using these rules, a total of 31 polyphenols including 20 benzoyl derivatives and 11 caffeoyl derivatives were screened out from BR extract, of which 26 trace members were found for the first time in this herb. Those findings demonstrated that the anion-exchange SPE could enhance the detection capability and selectivity for plant polyphenols in the LC-MS analysis and the strategy for deducing structures could be applied for analysis of polyphenols in BR and other herbal medicines.
Park, Jinbong; Jeon, Yong-Deok; Kim, Hye-Lin; Kim, Dae-Seung; Han, Yo-Han; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; Yoon, Daeyeon; Jeong, Mi-Young; Lee, Jong-Hyun; Hong, Seung-Heon; Lee, Junhee; Um, Jae-Young
This study was performed in order to investigate the antiobese effects of the ethanolic extract of Veratri Nigri Rhizoma et Radix (VN), a herb with limited usage, due to its toxicology. An HPLC analysis identified jervine as a constituent of VN. By an Oil Red O assay and a Real-Time RT-PCR assay, VN showed higher antiadipogenic effects than jervine. In high-fat diet- (HFD-) induced obese C57BL/6J mice, VN administration suppressed body weight gain. The levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), adipocyte fatty-acid-binding protein (aP2), adiponectin, resistin, and LIPIN1 were suppressed by VN, while SIRT1 was upregulated. Furthermore, VN activated phosphorylation of the liver kinase B1- (LKB1-) AMP-activated protein kinase alpha- (AMPKα-) acetyl CoA carboxylase (ACC) axis. Further investigation of cotreatment of VN with the AMPK agonist AICAR or AMPK inhibitor Compound C showed that VN can activate the phosphorylation of AMPKα in compensation to the inhibition of Compound C. In conclusion, VN shows antiobesity effects in HFD-induced obese C57BL/6J mice. In 3T3-L1 adipocytes, VN has antiadipogenic features, which is due to activating the LKB1-AMPKα-ACC axis. These results suggest that VN has a potential benefit in preventing obesity. PMID:27143989
Park, Jinbong; Jeon, Yong-Deok; Kim, Hye-Lin; Kim, Dae-Seung; Han, Yo-Han; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; Yoon, Daeyeon; Jeong, Mi-Young; Lee, Jong-Hyun; Hong, Seung-Heon; Lee, Junhee; Um, Jae-Young
This study was performed in order to investigate the antiobese effects of the ethanolic extract of Veratri Nigri Rhizoma et Radix (VN), a herb with limited usage, due to its toxicology. An HPLC analysis identified jervine as a constituent of VN. By an Oil Red O assay and a Real-Time RT-PCR assay, VN showed higher antiadipogenic effects than jervine. In high-fat diet- (HFD-) induced obese C57BL/6J mice, VN administration suppressed body weight gain. The levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), adipocyte fatty-acid-binding protein (aP2), adiponectin, resistin, and LIPIN1 were suppressed by VN, while SIRT1 was upregulated. Furthermore, VN activated phosphorylation of the liver kinase B1- (LKB1-) AMP-activated protein kinase alpha- (AMPKα-) acetyl CoA carboxylase (ACC) axis. Further investigation of cotreatment of VN with the AMPK agonist AICAR or AMPK inhibitor Compound C showed that VN can activate the phosphorylation of AMPKα in compensation to the inhibition of Compound C. In conclusion, VN shows antiobesity effects in HFD-induced obese C57BL/6J mice. In 3T3-L1 adipocytes, VN has antiadipogenic features, which is due to activating the LKB1-AMPKα-ACC axis. These results suggest that VN has a potential benefit in preventing obesity.
Quality assessment of a formulated Chinese herbal decoction, Kaixinsan, by using rapid resolution liquid chromatography coupled with mass spectrometry: A chemical evaluation of different historical formulae.
Zhu, Kevin Y; Fu, Q; Xie, Heidi Q; Xu, Sherry L; Cheung, Anna W H; Zheng, Ken Y Z; Luk, Wilson K W; Choi, Roy C Y; Lau, David T W; Dong, Tina T X; Jiang, Zhi Y; Chen, Ji J; Tsim, Karl W K
Kaixinsan is an ancient Chinese herbal decoction mainly prescribed for patients suffering from mental depression. This decoction was created by Sun Si-miao of Tang Dynasty (A.D. 600) in ancient China, and was composed of four herbs: Radix and Rhizome Ginseng, Radix Polygalae, Rhizoma Acori Tatarinowii and Poria. Historically, this decoction has three different formulations, each recorded at a different point in time. In this study, the chemical compositions of all three Kaixinsan formulae were analyzed. By using rapid resolution LC coupled with a diode-array detector and an ESI triple quadrupole tandem MS (QQQ-MS/MS), the Radix and Rhizome Ginseng-derived ginsenosides including Rb(1), Rd, Re, Rg(1), the Radix Polygalae-derived 3,6'-disinapoyl sucrose, the Rhizoma Acori Tatarinowii-derived α- and β-asarone and the Poria-derived pachymic acid were compared among the three different formulations. The results showed variations in the solubility of different chemicals between one formula and the others. This systematic method developed could be used for the quality assessment of this herbal decoction.
One- and two-dimensional gas chromatography-mass spectrometry and high performance liquid chromatography-diode-array detector fingerprints of complex substances: a comparison of classification performance of similar, complex Rhizoma Curcumae samples with the aid of chemometrics.
Ni, Yongnian; Mei, Minghua; Kokot, Serge
Many complex natural or synthetic products are analysed either by the GC-MS (gas chromatography-mass spectrometry) or HPLC-DAD (high performance liquid chromatography-diode-array detector) technique, each of which produces a one-dimensional fingerprint for a given sample. This may be used for classification of different batches of a product. GC-MS and HPLC-DAD analyses of complex, similar substances represented by the three common types of the TCM (traditional Chinese medicine), Rhizoma Curcumae were analysed in the form of one- and two-dimensional matrices firstly with the use of PCA (Principal component analysis), which showed a reasonable separation of the samples for each technique. However, the separation patterns were rather different for each analytical method, and PCA of the combined data matrix showed improved discrimination of the three types of object; close associations between the GC-MS and HPLC-DAD variables were observed. LDA (linear discriminant analysis), BP-ANN (back propagation-artificial neural networks) and LS-SVM (least squares-support vector machine) chemometrics methods were then applied to classify the training and prediction sets. For one-dimensional matrices, all training models indicated that several samples would be misclassified; the same was observed for each prediction set. However, by comparison, in the analysis of the combined matrix, all models gave 100% classification with the training set, and the LS-SVM calibration also produced a 100% result for prediction, with the BP-ANN calibration closely behind. This has important implications for comparing complex substances such as the TCMs because clearly the one-dimensional data matrices alone produce inferior results for training and prediction as compared to the combined data matrix models. Thus, product samples may be misclassified with the use of the one-dimensional data because of insufficient information.
Qian, Xiao-Cui; Zhang, Liang; Tao, Yi; Huang, Ping; Li, Jun-Song; Chai, Chuan; Li, Wen; Di, Liu-Qing; Cai, Bao-Chang
Rhizoma coptidis (R.C.), a widely used traditional Chinese medicine, has been used for centuries in the treatment of hypertension, inflammation, dysentery and liver diseases, etc. Wine-processing is a specialized technology by sautéing crude herbal medicine using Chinese rice wine. This paper was designed to establish a simultaneous quantitative method of ten alkaloids (berberine, coptisine, palmatine, jatrorrhizine, epiberberine, magnoflorine, columbamine, noroxyhydrastinine, oxyberberine and 8-oxocoptisine) in rat plasma. Furthermore, the pharmacokinetics of those alkaloids after administration of crude and wine-processed R.C. aqueous extracts was compared. As a result, a ultra high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method was developed and validated for the first time. Chromatographic separation was achieved on a C18 column using gradient elution with the mobile phase consisting of acetonitrile and water (containing 0.2% formic acid) at a flow rate of 0.2 ml/min. The validated method showed good linearity over a wide concentration range (r>0.99), and lower limits of quantification less than 5.46 ng/ml for the each analyte. The intra- and inter-day assay variability was below 9.9% and 10.5% for all analytes, respectively. The extraction recovery of those alkaloids and I.S. ranged from 65.3% to 90.7%. The validated method has been successfully applied to pharmacokinetic comparison after administration of crude and wine-processed R.C. aqueous extracts. Pharmacokinetic comparative study showed that Cmax of coptisine and 8-oxocoptisine and AUC0-t of coptisine, palmatine and 8-oxocoptisine were increased significantly (p<0.05) after wine-processing, while other compounds didn't show significant difference, which suggested that wine-processing exerted limited effects on the absorption of alkaloids. These results might be helpful for R.C.' clinical reasonable application and further studies on its wine
Ren, Jixiang; Zhou, Xiangyu; Wang, Jian; Zhao, Jianjun; Zhang, Pengguo
This study established a rat model of cerebral hemorrhage by injecting autologous anticoagulated blood. Rat models were intragastrically administered 5, 10, 20 g/kg Poxue Huayu and Tianjing Busui Decoction, supplemented with Hirudo, raw rhubarb, raw Pollen Typhae, gadfly, Fructrs Trichosanthis, Radix Notoginseng, Rhizoma Acori Talarinowii, and glue of tortoise plastron, once a day, for 14 consecutive days. Results demonstrated that brain water content significantly reduced in rats with cerebral hemorrhage, and intracerebral hematoma volume markedly reduced after treatment. Immunohistochemical staining revealed that brain-derived neurotrophic factor, tyrosine kinase B and vascular endothelial growth factor expression noticeably increased around the surrounding hematoma. Reverse transcription-PCR revealed that brain-derived neurotrophic factor and tyrosine kinase B mRNA expression significantly increased around the surrounding hematoma. Neurologic impairment obviously reduced. These results indicated that Poxue Huayu and Tianjing Busui Decoction exert therapeutic effects on cerebral hemorrhage by upregulating the expression of brain-derived neurotrophic factor. PMID:25206512
Han, Li-Qin; Dong, Shun-Fu; Liu, Jian-Hua
There is an intimate connection between trace elements and body healthiness, trace elements and organism depend on each other, and each trace element exists with certain proportion, which preserve physio-function. If the balance is of maladjustment, diseases may occur or develop. The trace elements were determined in 16 kinds of Chinese herbal medicines by atomic absorption spectrometry. The medicines include lilium brownii, herba houttuyniae, licorice root, radices isatidis seu baphicacanthi, Sehizandra sinensis Bail, Scutellaria baicalensis Georgi, Beimu, Polygonum multiflorum Thunb, Lithospermum officinalel, Rhizoma acori gramjnoi, Pinellia ternate Breit, Salisburia adiantifolia, Lonicera japonica, Radices puerarire, Bupleurum falcatum and Ligusticum wallichii, all of which could be bought on the market. Sixteen kinds of Chinese herbal medicines commonly used to treat respiratroy system diseases in clinic were selected, dried and powdered, completely mixed, 1.000 0 g was weighed accurately with analytical balance, and 3 portions were used for each kind of sample. The atomic absorption spectrometry was used to determine the contents of trace elements (Cu, Zn, Fe, Cr, Ni and Mn), and the content discrepancy of the trace elements in different medicines was observed the results shows that the contents of the trace elements were rich in the 16 kinds of Chinese herbal medicines, there were more contents of Fe, Zn and Mn, but they were different in different medicines. And there were more trace elements in Salisburia adiantifolia, Polygonum multiflorum Thunb, Bupleurum falcatum, Sehizandra sinensis Bail, Pinellia ternate Breit and Lithospermum officinalel, and lower trace elements in Radices puerarire, Rhizoma acori gramjnoi and Radices isatidis seu baphicacanthi. The analytic results provided useful data for using Chinese herbal medicines and provided theoretical basis for studying Chinese herbal medicines theory.
Okuda, Jun; Noro, Yukio; Ito, Shiro
The origin of Yakushi buddha (Bhaisajyaguru in Sanscrit, buddha of healing) is not clearly known. It has been proposed the original statue of Yakushi buddha may have been conceived from Varna, a god in Brahminism, believed to be a god of justice who possessed medicines and prolonged life. It is believed that Yakushi buddha appeared in Japan when the buddhism was imported from Korea and China in VI century, Yakushi buddha was believed more profoundly in Japan, compared with Korea and China.The reasons are probably as follows: Yakushi buddha is buddha of healing, Emperor Temmu (672-685) built Yakushi-ji temple in Nara, Emperor Shomu (724-749) built Kokubun-ji temples at principal towns. The principal statues of buddha in these temples are Yakushi buddha. In Japan, there are 252 Yakushi Buddha statues in Buddhistical Temples, which are listed in Important Cultural Property including 14 National Treasures. Belief in Yakushi Buddha was especially prevalent from the 7th to the 13th centuries in Japan. The oldest wooden Yakushi Buddha statue is in the Horin-ji temple in Nara. Among the 252 Yakushi Buddha statues, 224 are in wood, 15 are in copper, 6 are in picture and etc. 212 (84,1%) have medicinal pots (or rarely, a bowl) on the palm of left hand. However, these medicinal containers are wooden blocks. Very recently, it was found that Yakushi Buddha statue in the Suho-Kokubun-ji temple (Yamaguchi Prefecture, Japan) has a medicinal pot on the palm of the left hand in which an offering (220 g materials) was found. The date on the reverse side of lid places the offering at October 12, 1699. The offering is composed of five cereals (rice, barley, wheat, soybean, adzuki bean), five medicinal plants (Acori Graminei, Acori Calami, Radix Ginseng, Flos Caryophylli, Lignum Santali Albi), and five minerals (rock crystals, purple and blue glasse, CaCO3, particles, silver and golden foils). DNA analysis proved those three randomly selected seeds of rice all belongs to the template
Han, Jianping; Pang, Xiaohui; Liao, Baosheng; Yao, Hui; Song, Jingyuan; Chen, Shilin
Adulterant herbal materials are a threat to consumer safety. In this study, we used DNA barcoding to investigate the proportions and varieties of adulterant species in traditional Chinese medicine (TCM) markets. We used a DNA barcode database of TCM (TCMD) that was established by our group to investigate 1436 samples representing 295 medicinal species from 7 primary TCM markets in China. The results indicate that ITS2 barcodes could be generated for most of the samples (87.7%) using a standard protocol. Of the 1260 samples, approximately 4.2% were identified as adulterants. The adulterant focused on medicinal species such as Ginseng Radix et Rhizoma (Renshen), Radix Rubi Parvifolii (Maomeigen), Dalbergiae odoriferae Lignum (Jiangxiang), Acori Tatarinowii Rhizoma (Shichangpu), Inulae Flos (Xuanfuhua), Lonicerae Japonicae Flos (Jinyinhua), Acanthopanacis Cortex (Wujiapi) and Bupleuri Radix (Chaihu). The survey revealed that adulterant species are present in the Chinese market, and these adulterants pose a risk to consumer health. Thus, regulatory measures should be adopted immediately. We suggest that a traceable platform based on DNA barcode sequences be established for TCM market supervision. PMID:26740340
Yan, Lu; Hu, Qinghua; Mak, Marvin S. H.; Lou, Jianshu; Xu, Sherry L.; Bi, Cathy W. C.; Zhu, Yue; Wang, Huaiyou; Dong, Tina T. X.; Tsim, Karl W. K.
Kai-Xin-San (KXS), a Chinese herbal decoction for anti-depression, is a combination of paired-herbs, i.e. Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The make-up of the paired-herbs has been commonly revised according to syndrome differentiation and treatment variation of individual. Currently, an optimized KXS (KXS2012) was prepared by functional screening different combination of GR-PR and ATR-PO. The aim of this study was to verify the effect and underlying mechanism of KXS2012 against depression in chronic mild stress (CMS)-induced depressive rats and in primary cultures of neurons and astrocytes. In rat model, the CMS-induced depressive symptoms were markedly alleviated by the treatment with KXS2012. The CMS-suppressed neurotransmitter amounts were restored in the presence of KXS2012. And the expressions of neurotropic factors and its corresponding receptors were increased under KXS2012 administration. In cultured neurons, application of KXS2012 could promote neurogenesis by inducing the expression of synaptotagmin and dendritic spine density. Moreover, application of KXS2012 in cultured astrocytes, or in H2O2-stressed astrocytes, induced the expressions of neurotrophic factors: the increase might be associated with the modification of Erk1/2 and CREB phosphorylation. Our current results fully support the therapeutic efficacy of KXS2012 against depression in cell and animal models. PMID:27444820
Li, Guangyan; Song, Xiangwen; Han, Bangxing; Fang, Shiying
Shancigu (Rhizome Pleionis) was first recorded in the Ben cao shiyi (Supplements to Chinese Materia Medica). The source of the strain of this medicinal was unclear because of its too simple description in the medical books in the Tang and Song dynasties. Its original plant could be Cremastra appendiculata (D.Don) Makino, Tulipa edulis (Miq.) Baker and so on. The original plant of Shanciguwas Tulipaedulis since the Ming dynasty to the Republican period. The name of "Guangcigu" began to appear in the Republican period because of the changes of its processing method. The original plants evolved into Cremastra appendiculata, Pleione bulbocodioides (Franch.) Rolfe and Pleione yunnanensis Rolfe, with Tulipa edulisas the original plant of Guangcigu (Bulbus of Tulipasedulis). It is found that only the Tulipaedulis is the unequivocal origin with the longest medicinal history through sorting out of the original plants of Shancigu. Hence, it is suggested that Tulipa edulis should be recovered as the original strain of Shancigu.
Li, Yong-Guo; Song, Long; Liu, Mei; Hu, Zhi-Bi; Wang, Zheng-Tao
This review summarizes the recent advances in the chemical analysis of Danshen and its finished products, including the introduction of the identified bioactive components, analytical methods for quantitative determination of target analytes and fingerprinting authentication, quality criteria of Danshen crude herb and its preparations, as well as the pharmacokinetic and pharmacodynamic studies on the active components of Danshen and its finished products. Danshen contains mainly two types of constituents, the hydrophilic depsides and lipophilic diterpenoidal quinones and both of them are responsible for the pharmacological activities of Danshen. In order to monitor simultaneously both types of components which have different physicochemical properties, numerous analytical methods have been reported using various chromatographic and spectrophotometric technologies. In this review, 110 papers on analysis of Danshen are discussed, various analytical methods and their chromatographic conditions are briefly described and their advantages/disadvantages are compared. For obtaining a quick, accurate and applicable analytical approach for quality evaluation and establishing a harmonized criteria of Danshen and its finished products, the authors' suggestion and opinions are given, including the reasonable selection of marker compounds with high concentration and commercial availability, a simple sample preparation procedure with high recoveries of both the hydrophilic phenols and lipophilic tanshinones, and an optimized chromatographic condition with ideal resolutions of all the target components. The chemical degradation and transformation of the predominant constituent salvianolic acid B in Danshen during processing and manufacturing are also emphasized in order to assure the quality consistency of Danshen containing products.
Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease. PMID:25386946
Razmovski-Naumovski, Valentina; Kam, Antony; Low, Mitchell; Chan, Kelvin
Aims. This study aims to investigate the possible synergistic interactions of the Danshen-Sanqi combination on vascular disease via their anti-inflammatory activities. Methods. Nine combination ratios of Danshen-Sanqi extracts were screened in the RAW264.7 cell line and their anti-inflammatory effects were examined in lipopolysaccharide- (LPS-) induced nitric oxide (NO), tumor necrosis factor (TNF), and monocyte chemoattractant protein-1 (MCP-1) generation pathways. The interaction between Danshen and Sanqi on each target was analysed using combination index (CI) and isobologram models. Additionally, the anti-inflammatory activities of key bioactive compounds from Danshen and Sanqi were tested using the same models. The compounds from each herb that exerted the most potent activity were combined to evaluate their possible synergistic/antagonistic interactions. Results. Danshen-Sanqi 8 : 2 was found to be the optimal ratio and exerted a synergistic effect in inhibiting NO, TNF, and MCP-1 when the concentrations were higher than 1.24, 1.89, and 2.17 mg/mL, respectively. Although dihydrotanshinone I (DT) and ginsenoside Rd (Rd) from Danshen and Sanqi, respectively, exhibited the greatest individual bioactivity in the assays, antagonistic effects were observed for the DT-Rd combination 7 : 3. Conclusion. This study provided scientific evidence to support the traditional use of the Danshen-Sanqi combination for vascular disease through their synergistic interactions on anti-inflammatory pathways. PMID:27830149
Lin, Mei; Xia, Bairong; Yang, Meng; Gao, Shu; Huo, Yanqiu; Lou, Ge
Two acidic polysaccharides (MDP-A1 and MDP-A2) were isolated from the rhizome of Menispermum dauricum and their apparent molecular weight are 9.1×10(4) and 5.8×10(4) Da, respectively. Both contained glucose, mannose, galactose, arabinose, glucuronic acid and galacturonic acid, but differed in the molar ratio. We also investigated the antitumor activities and mechanisms of MDP-A1 and MDP-A2 in human ovarian carcinoma SKOV3 cells. The MTT assay showed that MDP-A1 and MDP-A2 were able to inhibit cell proliferation of SKOV3 cells in a bell-shaped concentration-response manner, due to a significant increase in the number of apoptotic cells. Furthermore, treatment with MDP-A1 or MDP-A2 caused significant induction of caspase-3 and caspase-8, but slightly affected caspase-9 activity. In addition, a significant reduction in tumor volume was observed in mice treated with MDP-A1 or MDP-A2. Taken together, these results suggested that MDP-A1 and MDP-A2 had a potential application as natural antitumor drugs.
Lin, Mei; Xia, Bairong; Yang, Meng; Gao, Shu; Huo, Yanqiu; Lou, Ge
The rhizome of Menispermum dauricum DC (Menispermaceae) is one of the most commonly used traditional Chinese medicines officially listed in Chinese Pharmacopeia. In present study, we purified a water-soluble polysaccharide (WMDP) from this plant and investigated its physicochemical properties. WMDP was a homogeneous polysaccharide, with an average molecular weight of approximately 3.5×10(4)Da, as determined by high-performance gel-permeation chromatography (HPGPC). Gas chromatography (GC) analysis identified that WMDP was composed of Glc, Gal, Xyl, Rha, Ara and Man in the ratio of 2.45:2.13:1.05:1.29:1.63:1.45. The interreaction between Gongo Red and WMDP in NaOH solutions resulted in the shift of maximum absorption, indicating WMDP had a triple-helix conformation. We also investigated the antitumor activities and mechanisms of WMDP in human ovarian carcinoma SKOV3 cells. The experimental evidence showed that WMDP significantly inhibited cell proliferation and DNA synthesis in SKOV3 cells in a concentration-dependent manner, due to a significant increase in the number of apoptotic cells. Furthermore, treatment with WMDP caused a rapid loss of intracellular glutathione (GSH) content and stimulation of reactive oxygen species (ROS). In addition, nuclear factor-kappa B (NF-κB) in SKOV3 cells received WMDP treatment was inactivated. Taken together, induction of apoptosis on SKOV3 cells by WMDP was mainly associated with ROS production, GSH depletion and NF-κB inactivation.
Sano, Tomoko; Matsumura, Ikue; Nakamura, Rie; Yamaji, Hiroki; Hashimoto, Kazunori; Takeda, Osami; Kiuchi, Fumiyuki; Takeda, Tadahiro
Boi and its original plant Sinomenium acutum from Japan were compared with Seifuto and its botanical origins from China in terms of their internal transcribed spacer (ITS) sequences and major chemical components. Boi, Seifuto, and their botanical origins overall showed seven variable sites in the ITS sequence and six genotypes. Japanese S. acutum and Boi had one nucleotide variation at position 593 to show two genotypes (J1 and J2) and their heterozygote (J3). Seifuto samples and their botanical origins, S. acutum and S. acutum var. cinereum from China, showed three genotypes (C1, C2, and C3), which did not agree with the botanical classification, indicating that they cannot be distinguished according to their ITS sequences. All Seifuto samples from Henan market showed the same ITS genotype (C1). The Japanese and Chinese genotypes differed in the nucleotide position 424, which can be used to distinguish the country of origin of these materials. In the HPLC analysis of six major components, sinomenine (1), magnoflorine (2), menisperine (3), 6-O-methyllaudanosoline glucoside (4), liriodendrin (5), and menisdaurin (6), all were detected in Boi, whereas five (all except for menisdaurin) were detected in Seifuto. The main component in the rhizome of Seifuto was sinomenine, whereas magnoflorine was the main component in the rhizome and the climbing stem of Boi. The content of sinomenine in Seifuto was almost twice that in Boi. Although the individual content of alkaloids 1-4 differed between Boi and Seifuto, the total contents of these alkaloids were comparable between them both in the climbing stem and rhizome.
Wang, Xinsheng; Wu, Yanfang; Chen, Guangyun; Yue, Wei; Liang, Qiaoli; Wu, Qinan
The present study reports on the extraction of phenolic compounds from sparganii rhizome. Box-Behnken Design (BBD), a widely used form of response surface methodology (RSM), was used to investigate the effect of process variables on the ultrasound-assisted extraction (UAE). Three independent variables including ethanol concentration (%), extraction time (min) and solvent-to-material ratio (mL/g) were studied. The results showed that the optimal UAE condition was obtained with an ethanol concentration of 75.3%, an extraction time of 40min and a solvent-to-material ratio of 19.21mL/g for total phenols, and an ethanol concentration of 80%, an extraction time of 33.54min and solvent-to-material ratio of 22.72mL/g for combination of ρ-hydroxybenzaldehyde, ρ-coumaric acid, vanillic acid, ferulic acid, rutin and kaempferol. The experimental values under optimal conditions were in good consistent with the predicted values, which suggested UAE is more efficient process as compared to solvent extraction.
Okuda, T; Umezawa, Y; Ichikawa, M; Hirata, M; Oh-i, T; Koga, M
We report a case of drug eruption caused by the crude drug Boi. A 41-year-old female patient had been diagnosed with chronic rheumatoid arthritis in the department of internal medicine. After ingestion of a decoction of the crude drug Boi for the alleviation of arthralgia, a slight fever developed, which was followed by systemic edematous erythema with itching. HPLC showed that the main components of the crude drug Boi are sinomenine and magnoflorine. The results of patch tests were negative for all oral drugs that the patient had been taking. Oral ingestion tests showed that the patient showed positive reactions to the as-is Boi boiling-water decoction and 1/10-volume sinomenine. Based on this, the drug eruption was judged to be caused by sinomenine. It is considered the first time that the causative component of a drug eruption was confirmed by oral ingestion tests with components of a crude drug of Kampo medicine (Sino-Japanese traditional medicine).
Chen, T; Li, J; Cao, J; Xu, Q; Komatsu, K; Namba, T
From the rhizome of Smilax glabra Roxb., a new flavanone was isolated and named as smitilbin (1), together with 6 known compounds, engeletin (2), astilbin (3), dihydroquercetin (4), eurryphin (5), resveratrol (6), and 5-O-caffeoylshikimic acid (7). These compounds were applied to the assay of liver nonparenchymal cells (NPC) against hepatocytes (HC) isolated from mice with an immunological liver injury. Against the NPC-caused elevation of ALT (alanine transminase) in culture supernatant from HC, the pretreatment of NPC with flavanoids (1-3) dose-dependently blocked the ALT release while 4, the aglycone of 3, did not. The chromone 5 showed a much stronger inhibition. Compound 6 also showed the activity. However, 1-7 did not show any suppression of NPC or CCl4-induced ALT release when they were used to pretreat HC. These results suggest that compounds 1-3, 5, and 6 could protect the hepatocyte damage from NPC through selectively producing the dysfunction of NPC with an essential requirement of rhamnose, and the chromone part in their structures may be critical for exhibiting the activity rather than through protecting the hepatocyte membranes.
Nian, Sihui; Liu, Ehu; Fan, Yong; Alolga, Raphael N; Li, Huijun; Li, Ping
The green and efficient preparation of natural products from biomass is considered an important area of interest in pharmaceutical applications. In this study, we aimed to provide a practical example with a popular traditional Chinese medicine, Anemarrhenae Rhizome, and showcase the orthogonal use of column chromatography with polyamide and macroporous adsorption resins to selectively concentrate and efficiently purify four bioactive compounds: neomangiferin (NMF), mangiferin (MF), timosaponin B-II (TS B-II), and timosaponin A-III (TS A-III). First, polyamide T60-100 was employed to fractionalize the crude extracts of Anemarrhenae Rhizome. Macroporous resin HPD400 was subsequently used to purify the xanthones and steroidal saponins. Under the optimized conditions, 2.31 g of NMF, 4.10 g of MF, 12.87 g of TS B-II, and 2.78 g of TS A-III were prepared from 1 kg of crude materials, and their purities were 90.0, 92.15, 90.8, and 92.61%, respectively. The results of this study indicate that the combined column chromatography with polyamide and macroporous adsorption resins can be referenced as a green and efficient alternative for large-scale purification of bioactive ingredients from herbal raw materials.
Yin, Xingbin; Lin, Longfei; Shen, Mingrui; Zhai, Yujing; Cao, Sali; Fu, Jing; Li, Xuechun; Yang, Chunjing; Xia, Zhenwen; Zhao, Yang; Li, Shangxin; Bai, Ying; Xue, Dan; Ni, Jian
A highly sensitive, rapid assay method has been developed and validated for the analysis of polyphyllin H in beagle dog plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of polyphyllin H and ginsenoside Re (IS) from beagle dog plasma. Chromatographic separation was carried out on an Agilent Zorbax XDB-C18 (100 × 2.1 mm, 1.8μm) column by isocratic elution with acetonitrile and water (50:50, v/v) at a flow rate of 0.25 mL/min with a total run time of 2.5 min. The MS/MS ion transitions monitored were m/z 869.60 → 869.60 for polyphyllin H and m/z 969.60 → 969.60 for IS. [corrected] Linear responses were obtained for polyphyllin H ranging from 1 to 50 ng/mL. The intra-and inter-day precisions (RSDs) <1.77 and 3.39% and the extraction recovery ranged from 91.89 to 93.33% with RSD <2.68%. Stability studies showed that polyphyllin H was stable in the preparation and analytical process. The results indicated that the validated method was successfully used to determine the concentration-time profiles of polyphyllin H.
Huang, Hongzhang; Xuan, Xueyi; Xu, Liyuan; Yang, Jianrui; Gao, Chongkai; Li, Ning
In this study, we have proposed and developed a novel, environmental-friendly and simple method for separation of nine hydrophilic and hydrophobic components in Danshen using microemulsion liquid chromatography. The proposed method was optimized via the preliminary screening experiment and the experimental design. The following factors were investigated in preliminary screening experiment: pH of mobile phase, column type, the nature of surfactant, the nature of oil phase and additives. In order to simultaneously optimize resolution and analysis time, the chromatographic optimization function (COF) was adopted to evaluate chromatograms. The central composite design (CCD) was used to create the matrix of experiments for mapping the chromatographic response surface. Finally, the COF values were fitted into a second order polynomial model and the response surface methodology (RSM) was employed to find the optimal eluent constituents. The reliability of the established model was confirmed by the good agreement obtained between experimental data and predictive values. Based on the results from the preliminary screening experiment and the CCD optimization, the optimal mobile phase was identified as a solution consisting of 6.68% (w/w) polyoxyethylene lauryl ether (Brij35), 0.84% (w/w) cyclohexane, 6.92% (w/w) n-butanol, 85.56% (w/w) phosphate buffer (pH 6.60) and 8mM cetyltrimethyl ammonium bromide (CTAB).
Yin, Xiang-jun; He, Qing-yong
To analyze the compatibility regularity of compound traditional Chinese medicine (TCM) patents for treating dyslipidemia, and provide basis for the clinical development and research of new TCM for treating dyslipidemia. Totally 243 compound traditional Chinese medicine patents for treating dyslipidemia were collected from the national patent database from September 1985 to March 2014 and analyzed by using drug frequency, association rules, complex network and entropy method of Traditional Chinese Medicine Inheritance System (V1.1). The commonest single medicine in the treatment of dyslipidemia is Crataegi Fructus 109 (44.86%). The commonest pair medicine is Crataegi Fructus-Salviae Miltiorrhizae Radix et Rhizoma 53 (21.81%). The commonest corner drug is Crataegi Fructus-Cassiae Semen-Polygoni Multiflori Radix 25 (10.29%). The common prescriptions on basis of association rules are Prunellae Spica-->Salviae Miltiorrhizae Radix et Rhizoma (0.833), Rhei Radix et Rhizoma, Alismatis Rhizoma-->Polygoni Multiflori Radix (1.00), Salviae Miltiorrhizae Radix et Rhizoma, Cassiae Semen, Alismatis Rhizoma-->Polygoni Multiflori Radix (0.929). The core drugs based on complex networks are Salviae Miltiorrhizae Radix et Rhizoma and Crataegi Fructus. The new prescriptions extracted by entropy method are Atractylodis Macrocephalae Rhizoma-Glycyrrhizae Radix et Rhizoma-Platycladi Semen-Stephaniae Tetrandrae Radix; Citri Reticulatae Pericarpium-Poria-Coicis Semen-Pinelliae Rhizoma. This study shows the regularity in the compatibility of compound TCM patents treating dyslipidemia, suggesting that future studies on new traditional Chinese medicines treating dyslipidemia should focus on the following six aspects: (1) Single medicine should be preferred: e. g. Crataegi Fructus; (2) Pair medicines should be preferred: e. g. Crataegi Fructus-Salviae Miltiorrhizae Radix et Rhizoma; (3) Corner drugs should be preferred: e. g. Crataegi Fructus, Cassiae Semen, Polygoni Multiflori Radix; (4) The
Neuroprotective effect and underlying mechanism of sodium danshensu [3-(3,4-dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae = Danshen] against cerebral ischemia and reperfusion injury in rats.
Guo, Chao; Yin, Ying; Duan, Jialin; Zhu, Yanrong; Yan, Jiajia; Wei, Guo; Guan, Yue; Wu, Xiaoxiao; Wang, Yanhua; Xi, Miaomaio; Wen, Aidong
Sodium danshensu (SDSS), the sodium salt of danshensu (DSS), has the same pharmacological effects as DSS. In the present study, we aimed to investigate the neuroprotective effect and possible mechanism of SDSS against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were randomly divided into four groups: sham, control, 30 mg/kg and 60 mg/kg SDSS. Cerebral ischemia was induced by 2 h of middle cerebral artery occlusion (MCAO). Neurological functional deficits were evaluated according to the modified neurological severity score (mNSS); cerebral infarct volume and histological damage were measured by TTC or H-E staining. In addition, the number of apoptotic cells and caspase 3/7 activity were assessed by TUNEL or Caspase-Glo assay. And the expression of apoptosis-regulatory proteins and the PI3K/Akt pathway were investigated by western blotting. Our results showed that treatment with SDSS for 5 days after MCAO remarkably improved neurologic deficits and survival rate, reduced infarct volume and the number of dead neurons. SDSS also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that treatment with SDSS also increased the level of p-Akt and p-GSK-3β. Taken together, our results suggest that SDSS has the neuroprotective effect against cerebral I/R injury, and the potential mechanism might to inhibition of apoptosis through activating the PI3K/Akt signal pathway.
Sanae, F; Komatsu, Y; Chisaki, K; Kido, T; Ishige, A; Hayashi, H
San'o-shashin-to, composed of Scutellariae Radix, Coptidis Rhizoma and Rhei Rhizoma (volume ratio = 1:1:1), reduced an increase in arterial blood pressure of anesthetized rats induced by theophylline (5 mg/kg, i.v.). The hypotensive effect of San'o-shashin-to was produced in a dose dependent manner and was maximum at its 0.5 g/kg. Then the constituent herbal medicines were examined for their possible hypotensive effect. Scutellariae Radix of 0.2 g/kg slightly decreased in the blood presure. Rhei Rhizoma of 0.2 g/kg decreased in the blood pressure and the hypotensive effect was significantly produced even at the dose of 0.05 g/kg, while Coptidis Rhizoma had little effect. Among fractions of San'o-shashin-to separated by Diaion HP-20 column chromatography, the 50% methanol-eluted fraction had a large hypotensive effect. The 50% methanol-eluted fraction of Scutellariae Radix and Rhei Rhizoma were also effective and, especially, that of Rhei Rhizoma had a large hypotensive effect. In isometric tension study, Scutellariae Radix and Rhei Rhizoma (10-30 microg/ml) slightly exerted contractile and relaxant effects, respectively, on the phenylephrine-contracted endothelium-intact rat thoracic aorta. Coptidis Rhizoma (1-10 microg/ml) caused both endothelium-dependent and -independent relaxantion. These results suggest that the hypotensive effect of San'o-shashin-to is not mediated by the direct action on blood vessel but by other actions. Some components in Scutellariae Radix and Rhei Rhizoma, especially in the latter may play a main role in the hypotensive effect.
Zhai, Yu-yao; Guo, Bao-lin; Huang, Wen-hua
Plant growth retardant as one of plant growth regulator can inhibit the cell division, elongation and growth rate in shoot apical meristem (SAM), which can be reversed by gibberellin regulate the product of photosynthesis transfer to the root and rhizome part. As commonly used plant growth retardant, paclobutrazol, uniconazole, chlorocholine chloride, mepiquat chloride, choline chloride and daminozide are used to promote the growth of root and rhizome, call as "zhuanggenling", "pengdasu", "pengdaji" etc. Single or recombination of plant growth regulator is registered as pesticide, and called as pesticide "zhuanggenling" in this paper. Growth regulator which registered as a foliar fertilizer or fertilization was called agricultural fertilizer "zhuanggenling" in this paper. The author investigate the usage of "zhuanggenling" in the root and rhizome of medicinal plants cultivation from 2012 to 2014 in Sichuan province, Huangyuan town, Mianyang (Ophiopogonis Radix); Pengzhou Aoping town (Chuanxiong Rhizoma); Pengshan Xiejia town (Alismatis Rhizoma); Jiangyou Taiping town and Zhangming town (Aconiti Lateralis Radix Praeparata); Yunnan Wenshan (Notoginseng Radix et Rhizoma); Henan province, Wuzhidafeng Town (Rehmanniae Radix, Achyranthis Bidentatae Radix, Dioscoreae Rhizoma); Gansu Min county (Codonopsis Radix, Angelicae Sinensis Radix); Gansu Li county (Rhei Radix et Rhizoma). The result showed that "zhuanggenling" were applied in the most medicinal plant cultivation except Rhei Radix et Rhizoma. It has been applied widespreadly in Ophiopogonis Radix, Alismatis Rhizoma, Achyranthis Bidentatae Radix, Codonopsis Radix; Rehmanniae Radix, commonly in Angelicae Sinensis Radix application, and occasionally in Chuanxiong Rhizoma, Aconiti Lateralis Radix Praeparata, Notoginseng Radix et Rhizoma and Dioscoreae Rhizoma. In 53 collected sample from plantation areas, fifteen (28%) were pesticide "zhuanggenling", thirty-eight (72%) were pesticide "zhuanggenling". UPLC analysis
Huo, Jiege; Qin, Fengxia; Cai, Xueting; Ju, Jianming; Hu, Chunping; Wang, Zhigang; Lu, Wuguang; Wang, Xiaoning; Cao, Peng
Weikang Keli (constitutes of Root of Codonopsis pilosula, Rhizoma Atractylodis Macrocephalae, Rhizoma Curcumae Aeruginosae, Rhizoma Pinelliae, Actinidia chinensis Planch, and Rhodiola rosea) is a well known Chinese herbal formula for gastric cancer therapy in clinical treatment. However, the detailed molecular mechanisms involved are still not fully understood. In this study, we found that Weikang Keli could induce patterns of autophagy in SGC-7901 cells, including intracellular vacuole formation, microtubule-associated protein 1 light chain 3 (LC3) conversion. Hoechst 33258 staining and Western blot analysis of apoptosis-related proteins showed that WK induced SGC-7901 cell death was not through apoptosis. In vivo study also revealed that i.g. administration of Weikang Keli once a day for 25 days could significantly reduce tumor volumes by about 50%. Collectively, the current data indicated that Weikang Keli induced gastric cancer cell death by autophagy effects.
Chan, Lai Wah; Cheah, Emily LC; Saw, Constance LL; Weng, Wanyu; Heng, Paul WS
Background Eight medicinal plants were tested for their antimicrobial and antioxidant activities. Different extraction methods were also tested for their effects on the bioactivities of the medicinal plants. Methods Eight plants, namely Herba Polygonis Hydropiperis (Laliaocao), Folium Murraya Koenigii (Jialiye), Rhizoma Arachis Hypogea (Huashenggen), Herba Houttuyniae (Yuxingcao), Epipremnum pinnatum (Pashulong), Rhizoma Typhonium Flagelliforme (Laoshuyu), Cortex Magnoliae Officinalis (Houpo) and Rhizoma Imperatae (Baimaogen) were investigated for their potential antimicrobial and antioxidant properties. Results Extracts of Cortex Magnoliae Officinalis had the strongest activities against M. Smegmatis, C. albicans, B. subtilis and S. aureus. Boiled extracts of Cortex Magnoliae Officinalis, Folium Murraya Koenigii, Herba Polygonis Hydropiperis and Herba Houttuyniae demonstrated greater antioxidant activities than other tested medicinal plants. Conclusion Among the eight tested medicinal plants, Cortex Magnoliae Officinalis showed the highest antimicrobial and antioxidant activities. Different methods of extraction yield different spectra of bioactivities. PMID:19038060
Pan, X; Hu, C; Zeng, F; Zhang, S; Xu, J
The alkaloids of rhizoma of Menispermum dauricum DC growing in Xianning have been subjected to isolation and identification. The results showed that its two major constituents, which are only next of dauricine in content, are dauricinoline and daurinoline, instead of the commonly found daurisoline in the same plant materials from North China.
Peanuts or groundnuts (Arachis hypogaea L.) are a valuable oilseed crop, but other than the seed, the rest of the plant is of minimal value. Plant material including the leaves is used as mulch or as animal feed. Perennial peanut (Arachis glabrata Benth) known as forage or rhizoma peanut produces...
Chang, Lin-Chau; Sun, Shao-Wen
Coptidis Rhizoma, Scutellariae Radix, and Rhei Rhizoma are three common Chinese herbs. There are many herbal formulas which contain either two or all three of the herbs mentioned above. Their bioactive components have already been identified, respectively. However, there is no report about separation of the 13 bioactive constituents of the three herbs at the same time. In order to assess these constituents of related Chinese herbal preparations, a micellar electrokinetic chromatography method was developed. While buffer pH and surfactant concentration affected the resolution of separation, acetonitrile percentage was found to significantly influence the resolution, peak shape, and elution window. Optimum separation of 13 compounds was achieved at pH 7.3 using a buffer mixture of 70% (v/v) 3 mM di-sodium tetraborate, 10 mM sodium dihydrogen phosphate, and 50 mM sodium deoxycholate with 30% (v/v) acetonitrile. When applying the developed method to analyze a model preparation, San-huang-xie-xin-tang, which contains all three herbs, 8 of the 13 bioactive constituents, could be determined. The present study proposed a method to assess San-huang-xie-xin-tang within short analysis time and also provided a possible starting point to evaluate related herbal preparations containing Coptidis Rhizoma, Scutellariae Radix, and Rhei Rhizoma.
Bennett, L L; Hammond, A C; Williams, M J; Chase, C C; Kunkle, W E
Two methods of determining diet botanical composition, microhistological (MH), and stable carbon isotope ratio (CR) analyses were used to determine botanical composition of ingesta and fecal grab samples in steers grazing rhizoma peanut-mixed tropical grass pastures. Three pastures were used over two grazing seasons, 1992 and 1993, in Brooksville, FL. A weighted-disc double-sampling technique was used to determine forage mass and botanical composition, percentage of rhizoma peanut (Arachis glabrata), grass (Paspalum notatum and Cynodon dactlyon), and forb (primarily Chenopodium ambrosioides) on offer every 28 d throughout the grazing seasons. There was an effect of sampling date (P<.001), sampling date x pasture (P<.001), and sampling date x year (P<.001) on forage mass on offer. There was a pasture x year x sampling date interaction (P<.001) for all botanical components. In 1992 and 1993, using cannulated steers sampled every 56 d, there were interactions with year for rhizoma peanut and forb (P<.05), but not for grass with MH analysis (components: rhizoma peanut, grass, and forb). Ingesta and fecal rhizoma peanut (r = .73 and .92 for 1992 and 1993, respectively) and ingesta and fecal forb (r = .86 and .98 for 1992 and 1993, respectively) were positively correlated (P<.001). Ingesta and fecal grass were positively correlated (r = .52, P<.001), but the correlation was not as high. With the CR analysis (components: Calvin cycle [C3] plants and C4-dicarboxylic acid pathway [C4] plants), ingesta and corrected fecal (corrected for in vitro organic matter digestibility [IVOMD]) C3 plants were positively correlated (r = .62; P<.001). Diet composition of fecal grab samples from noncannulated steers, collected on the same sampling schedule as for hand-clipped pasture samples, differed at times due to the complexity of the sward (both rhizoma peanut and forb constituted a single component, C3, in the CR analysis). Based on these results, if there is a substantial
Li, Lin-Yan; Cao, Fen-Fang; Su, Zhi-Jian; Zhang, Qi-Hao; Dai, Xiao-Yong; Xiao, Xue; Huang, Ya-Dong; Zheng, Qing; Xu, Hua
Rhizoma Atractylodes macrocephala, Radix Isatidis, Coptis chinensis and Flos Genkwa are common herbal remedies used by pregnant woman in China. In this study, their potential embryotoxicity was assessed using the embryonic stem cell test (EST) and a prediction model. The potential embryotoxicity of the herbs was based on three endpoints: the concentrations of the compounds that inhibited the proliferation of 50% of embryonic stem cells (ESCs) (IC50ES), the concentrations that inhibited 50% of 3T3 cells (IC503T3), and the concentrations that inhibited the differentiation of 50% of ESCs (ID50ES). The results revealed that Rhizoma Atractylodes macrocephala and Radix Isatidis are non-embryotoxic compounds. Coptis chinensis extracts appeared to demonstrated weak embryotoxicity, and Flos Genkwa exhibited strong embryotoxicity. These results may be useful in guiding the clinical use of these herbs and in expanding the application of the EST to the field of traditional Chinese medicine.
Wu, Min; Liu, Meixia; Guo, Gang; Zhang, Wengao; Liu, Longtao
Rhizoma Polygoni Cuspidati, a Chinese herbal medicine, has been widely used in traditional Chinese medicine for a long time. Polydatin, one of the major active ingredients in Rhizoma Polygoni Cuspidati, has been recently shown to possess extensive cardiovascular pharmacological activities. In present study, we examined the effects of Polydatin on the formation of peritoneal macrophage-derived foam cells in Apolipoprotein E gene knockout mice (ApoE−/−) and explored the potential underlying mechanisms. Peritoneal macrophages were collected from ApoE−/− mice and cultured in vitro. These cells sequentially were divided into four groups: Control group, Model group, Lovastatin group, and Polydatin group. Our results demonstrated that Polydatin significantly inhibits the formation of foam cells derived from peritoneal macrophages. Further studies indicated that Polydatin regulates the metabolism of intracellular lipid and possesses anti-inflammatory effects, which may be regulated through the PPAR-γ signaling pathways. PMID:26557864
Ma, Feng; Chen, Ye; Li, Jing; Qing, He-Ping; Wang, Ji-De; Zhang, Ya-Li; Long, Bei-Guo; Bai, Yang
AIM: To evaluate the anti-Helicobacter pylori (H. pylori) activity of 50 traditional Chinese herbal medicines in order to provide the primary evidence for their use in clinical practice. METHODS: A susceptibility test of water extract from 50 selected traditional Chinese herbal medicines for in vitro H. pylori Sydney strain 1 was performed with broth dilution method. Anti-H. pylori activity of the selected Chinese herbal medicines was evaluated according to their minimum inhibitory concentration (MIC). RESULTS: The water extract from Rhizoma Coptidis, Radix Scutellariae and Radix isatidis could significantly inhibit the H. pylori activity with their MIC less than 7.8 mg/mL, suggesting that traditional Chinese herbal medicines have anti-inflammatory and antibacterial effects and can thus be used in treatment of H. pylori infection. CONCLUSION: Rhizoma Coptidis, Radix Scutellariae and Radix isatidis are the potential sources for the synthesis of new drugs against H. pylori. PMID:21105198
Rhizoma bolbostemmae was the earliest applied fritillaria species during the period of pre-Qin to Han Dynasties in China. In the period of Wei-Jin, the fritillaria species presented diversities, with Zhejiang-fritillary also appeared for the first time. During the period of the Tang Dynasty to late Ming Dynasty, the fritillaria species kept expanding, Fritillaria hupehensis and Zhejiang-fritillary were deemed authentic species all the time. To the end of the Ming Dynasty, Fritillaria hupehensis withdrew from the stage of history gradually, Fritillaria cirrhosa came into being and then Fritillaria cirrhosa and Zhejiang-fritillary both appeared and became two important species of medicinal fritillarias after late Ming dynasty until today. In the period of the Qing Dynasty, the cognition of Fritillaria cirrhosa, Zhejiang-fritillary and rhizoma bolbostemmae became more and more clear. The fritillaria species continued to expand, and counterfeit and local species began to appear in large numbers.
also diligently organize the gathering, processing and purchasing of Chinese medicinal herbs such as licorice root [Radix Geycyrrhizae], rhizome of...wind-weed [Rhizoma Ane- marrhenae], and Chinese caterpillar fungus [Cordyceps chinensis], as well as wild growing cash crops to increase the masses...unchanged for com- modities including grain and edible oil, sugar, coal, matches, soap, and washing powder supplies rationed to city and town residents
Choi, Jae Sue; Kim, Ji-Hye; Ali, Md Yousof; Min, Byung-Sun; Kim, Gun-Do; Jung, Hyun Ah
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.
Shen, Ning; Li, Cai-Na; Huan, Yi; Shen, Zhu-Fang
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.
Aromatic herbs have been used as carminatives. Oxygen free radicals are generated in ischaemia/reperfusion injury in the stomach, and induce lipid peroxidation or protein oxidative modification. Several aromatic herbs were shown to have inhibitory effects on the generation of oxygen free radicals. It was shown that several aromatic herbs, Caryophylli Flos, Cinnamomi Cortex, Foeniculi Fructus and Zedoariae Rhizoma, have inhibitory effects on lipid peroxidation or protein oxidative modification by copper.
Deng, Xianmei; Yu, Jiangyong; Zhao, Ming; Zhao, Bin; Xue, Xingyang; Che, ChunTao; Meng, Jiang; Wang, Shumei
A sensitive, simple, and validated high-performance liquid chromatography with diode array detection and mass spectrometry detection method was developed for three ginger-based traditional Chinese herbal drugs, Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata. Chemometrics methods, such as principal component analysis, hierarchical cluster analysis, and analysis of variance, were also employed in the data analysis. The results clearly revealed significant differences among Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata, indicating variations in their chemical compositions during the processing, which may elucidate the relationship of the thermal treatment with the change of the constituents and interpret their different clinical uses. Furthermore, the sample consistency of Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata can also be visualized by high-performance liquid chromatography with diode array detection and mass spectrometry analysis followed by principal component analysis/hierarchical cluster analysis. The comprehensive strategy of liquid chromatography with mass spectrometry analysis coupled with chemometrics should be useful in quality assurance for ginger-based herbal drugs and other herbal medicines.
Li, Jia; Zhang, Hong-Fei; Shi, Yan-Ping
A method involving simultaneous extraction and sample clean-up procedure: hollow fiber sorptive microextraction, coupled with gas chromatography-mass spectrometric detection for quantification of seven organochlorine pesticides in Radix et Rhizoma Rhei is described. SiO(2) hollow fiber with porous structure was synthesized for the first time. The internal diameter of SiO(2) hollow fiber is 380 microm and average wall thickness is 100 microm. Aggregated SiO(2) particles deposited on the surface of the hollow fiber in a regular array lead to porous structure. SiO(2) hollow fiber was applied to the determination of organochlorine pesticides in Radix et Rhizoma Rhei to avoid sample clean-up and minimize the matrix effects. Extraction solvent, extraction temperature and equilibration time were optimized. Fiber to fiber repeatability over the concentration ranges were less than 10%. Recoveries were satisfactory (between 63% and 115%) for most of organochlorine pesticides at spiking levels. Furthermore, the proposed method was also applied to determine seven organochlorine pesticides in 43 commercial Radix et Rhizoma Rhei samples, in which the selected pesticides were found in eight samples. The results have been further confirmed by solvent extraction methods according to China Pharmacopoeia (2005).
Lam, Puiyan; Cheung, Fan; Tan, Hor Yue; Wang, Ning; Yuen, Man Fung; Feng, Yibin
The liver is intimately connected to inflammation, which is the innate defense system of the body for removing harmful stimuli and participates in the hepatic wound-healing response. Sustained inflammation and the corresponding regenerative wound-healing response can induce the development of fibrosis, cirrhosis and eventually hepatocellular carcinoma. Oxidative stress is associated with the activation of inflammatory pathways, while chronic inflammation is found associated with some human cancers. Inflammation and cancer may be connected by the effect of the inflammation-fibrosis-cancer (IFC) axis. Chinese medicinal herbs display abilities in protecting the liver compared to conventional therapies, as many herbal medicines have been shown as effective anti-inflammatory and anti-oxidative agents. We review the relationship between oxidative stress and inflammation, the development of hepatic diseases, and the hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and composite formulae, which have been commonly used for preventing and treating hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu-tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective effects with focus on their anti-oxidative and ant-inflammatory activities. This review aims to provide new insight into how Chinese medicinal herbs work in therapeutic strategies for liver diseases.
Yu, Xiao; Zhao, Xiao-Dong; Bao, Rong-Qi; Yu, Jia-Yu; Zhang, Guo-Xing
Sera from the rats with different drug treatments (atorvastatin, Tiaozhi granule, or its extracts) were collected. LO-2 cells or HepG2 cells were pretreated with different sera as the following groups randomly: (1) blank control group, (2) positive control group (atorvastatin group), (3) Tiaozhi granule water extract groups, (4) Tiaozhi granule alcohol extract groups, and (5) alcohol extracts for each component: Pollen Typhae Angustifoliae, Curcuma longa L., and Rhizoma Alismatis. LO-2 cells were cotransfected with plasmid carrying SR-BI and pRL-TK promoter genes. Promoter activity was measured by the luciferase reporter gene assay. The mRNA and protein expressions of SR-BI were examined using real-time PCR and western blot analyses. Our results show that promoter activity and mRNA and protein expression levels of the SR-BI were significantly upregulated by Tiaozhi granules alcohol or water extracts in a dose-dependent manner. Pollen Typhae Angustifoliae alcohol extract with a high dosage could also increase SR-BI activity and expression, but not the extracts from Curcuma longa L. and Rhizoma Alismatis. Both Tiaozhi granule alcohol and water extracts can upregulate SR-BI gene expression. Among the components, Pollen Typhae Angustifoliae are important for the regulatory effect coordinating with Curcuma longa L. and Rhizoma Alismatis. PMID:28050195
Lam, Puiyan; Cheung, Fan; Tan, Hor Yue; Wang, Ning; Yuen, Man Fung; Feng, Yibin
The liver is intimately connected to inflammation, which is the innate defense system of the body for removing harmful stimuli and participates in the hepatic wound-healing response. Sustained inflammation and the corresponding regenerative wound-healing response can induce the development of fibrosis, cirrhosis and eventually hepatocellular carcinoma. Oxidative stress is associated with the activation of inflammatory pathways, while chronic inflammation is found associated with some human cancers. Inflammation and cancer may be connected by the effect of the inflammation-fibrosis-cancer (IFC) axis. Chinese medicinal herbs display abilities in protecting the liver compared to conventional therapies, as many herbal medicines have been shown as effective anti-inflammatory and anti-oxidative agents. We review the relationship between oxidative stress and inflammation, the development of hepatic diseases, and the hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and composite formulae, which have been commonly used for preventing and treating hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu-tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective effects with focus on their anti-oxidative and ant-inflammatory activities. This review aims to provide new insight into how Chinese medicinal herbs work in therapeutic strategies for liver diseases. PMID:27043533
Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test.
Hatip-Al-Khatib, Izzettin; Egashira, Nobuaki; Mishima, Kenichi; Iwasaki, Katsunori; Iwasaki, Kiyo; Kurauchi, Kouji; Inui, Keiichiro; Ikeda, Tomoaki; Fujiwara, Michihiro
The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-beta-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol.
Jiang, Chenxue; Bian, Yali; Fan, Xinsheng
The allegation of "Glycyrrhiza antagonistic to Sargassum, Euphorbia Pekinensis, Kansui, and Genkwa", being one of the hypotheses of "18 antagonisms" in TCM pharmacology, is referring to the antagonistic action among the Radix et Rhizoma Glycyrrhiza and Radix Euphorbiae Kansui, Radix Euphorbiae Pekinensis, Flos Genkwa, and Sargassum when compounded together in a single recipe. By reviewing its history concerted with modern knowledge, it can be found that the theory of "seven emotions" was originated from Shennong's Classic of Materia Medica; while the Variorum of the Classic of Materia Medica firstly and definitely records that Radix et Rhizoma Glycyrrhizae is forbidden to be used with Radix Kansui, Flos Genkwa, Radix Euphorbiae Pekinensis, Sargassum together in a single formula. It was summarized into a Chinese poetic sentence as above-mentioned later. In the works of later ages, including Chinese Pharmacopoeia, A Great Dictionary of Chinese Materia Medica, and China's Herbology, etc., all enhance the understanding of the prohibited combination of Radix et Rhizoma Glycyrrhizae and its incompatible herbs. Nevertheless, there are discrepancies between the results of modern experimental and clinical studies on this problem, which, needless to say, should be resolved by further investigations.
Wu, Jia-rui; Guo, Wei-xian; Zhang, Xiao-meng; Yang, Bing; Zhang, Bing; Zhao, Meng-di; Sheng, Xiao-guang
The prescriptions including Polygoni Multiflori Caulis that built by Pro. Yan were collected to build a database based on traditional Chinese medicine (TCM) inheritance assist system. The method of association rules with apriori algorithm was used to achieve frequency of single medicine, frequency of drug combinations, association rules between drugs and core drug combinations. The datamining results indicated that in the prescriptions that including Polygoni Multiflori Caulis, the highest frequency used drugs were parched Ziziphi Spinosae Semen, Ostreae Concha, Ossis Mastodi Fossilia, Salviae Miltiorrhizae Radix Et Rhizoma, Paeoniae Rubra Radix, and so on. The most frequent drug combinations were "Polygoni Multiflori Caulis-parched Ziziphi Spinosae Semen", "Ostreae Concha-Polygoni Multiflori Caulis", and "Polygoni Multiflori Caulis-Ossis Mastodi Fossilia". The drug association rules of confidence coefficient 1 were "Ostreae Concha-->Polygoni Multiflori Caulis", "Poria-->Polygoni Multiflori Caulis", "parched Ziziphi Spinosae Semen-->Polygoni Multiflori Caulis", and "Paeoniae Alba Radix-->Polygoni Multiflori Caulis". The core drug combinations in the treatment of insomnia were Ossis Mastodi Fossilia, Polygoni Multiflori Caulis, Salviae Miltiorrhizae Radix et Rhizoma, Ostreae Concha, Polygalae Radix, Margaritifera Concha, Poria, and parched Ziziphi Spinosae Semen. And the core drug combinations in the treatment of obstruction of Qi in chest were Salviae Miltiorrhizae Radix Et Rhizoma, Polygoni Multiflori Caulis, parched Ziziphi Spinosae Semen, Trichosanthis Fructus, Allii Macrostemonis Bulbus, and Paeoniae Rubra Radix.
Cai, Qing; Li, Yuanyuan; Mao, Jianxin; Pei, Gang
α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 μM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis. PMID:28018174
Fike, J H; Staples, C R; Sollenberger, L E; Macoon, B; Moore, J E
Objectives were to evaluate effects of forage species, stocking rate, and supplementation rate on performance and physiology of grazing lactating Holstein cows under intensive rotational stocking management during summer. Eight treatments were arranged in a 2 x 2 x 2 factorial design. Animals (n = 62) grazed pastures of Tifton 85 bermudagrass or Florigraze rhizoma peanut, a tropical legume. Low and high stocking rates were 7.5 and 10.0 cows/ha for bermudagrass and 5.0 and 7.5 cows/ha for rhizoma peanut. Within each forage-stocking rate combination, cows were fed supplement at 0.33 or 0.5 kg of supplement (as-fed basis)/kg daily milk production. Cows grazing rhizoma peanut pastures produced more milk (16.9 vs. 15.4 kg/d) but had higher rectal temperatures (39.4 vs. 39.1 degrees C). Milk production per cow was improved at the higher stocking rate for bermudagrass but was reduced at the higher stocking rate for peanuts. Increasing supplementation rate boosted plasma glucose, milk production, and milk protein percent. Increased supplementation rate had a greater positive impact on milk production of cows grazing bermudagrass compared to rhizoma peanut (21.9 vs. 10.6% increase) due to a lower substitution of grain for forage intake. Organic matter intakes of forage, supplement, and total diet were greatest by cows grazing rhizoma peanut pastures and averaged 12.4, 6.1, and 18.5 kg/d compared to 9.2, 5.4, and 14.6 kg/d for cows grazing bermudagrass. Despite lower individual feed intake and performance, production per unit land area was 29% greater (112 vs. 90 kg of milk/ha per d) for cows grazing bermudagrass due to the greater stocking rate possible with that forage. Only cows supplemented at the high rate and kept at the high stocking rate on bermudagrass maintained body weight. Cows on other treatments lost body weight. Tifton 85 bermudagrass appears to be an excellent summer forage for dairy cows grazing in the southeastern U.S. given its nutritive value
Pan, X P
A new phenolic dauricine-type alkaloid together with the know dauricine were isolated from the rhizoma of Menispermum dauricum DC cultivated in Xianning district, Hubei province. Dauricine was obtained as the major alkaloid and was confirmed by comparison with authentic sample. The new alkaloid is an unstable white powder: Based on spectrometric analysis (UV, IR, FAB-MS and 1HNMR) and N-methylation which offered dauricine dimethiodide (V), the structure was elucidated as RR, N-desmethyldauricine (II), which was isolated for the first time from nature.
Song, Nan; Zhao, Zhihu; Ma, Xinlong; Sun, Xiaolei; Ma, Jianxiong; Li, Fengbo; Sun, Lei; Lv, Jianwei
Postmenopausal osteoporosis is characterized by a reduction in the number of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion. Thus, osteogenesis and angiogenesis are coupled in the process of osteoporosis formation and fracture healing. Naringin is the main ingredient of the root Rhizoma Drynariae, a traditional Chinese medicine, and it has potential effects on promoting fracture healing. However, whether naringin stimulates angiogenesis in the process of bone healing is unclear. Here, we show that naringin promotes fracture healing through stimulating angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats.
Mu, Qingchun; Liu, Pengfei; Hu, Xitong; Gao, Haijun; Zheng, Xu; Huang, Haiyan
Among the various treatment methods for stroke, increasing attention has been paid to traditional Chinese medicines. Buyang Huanwu decoction is a commonly used traditional Chinese medicine for the treatment of stroke. This paper summarizes the active components of the Chinese herb, which is composed of Huangqi (Radix Astragali seu Hedysari), Danggui (Radix Angelica sinensis), Chishao (Radix Paeoniae Rubra), Chuanxiong (Rhizoma Ligustici Chuanxiong), Honghua (Flos Carthami), Taoren (Semen Persicae) and Dilong (Pheretima), and identifies the therapeutic targets and underlying mechanisms that contribute to the neuroprotective properties of Buyang Huanwu decoction. PMID:25368650
Ma, Xiaoli; Guo, Xiaoyu; Song, Yuelin; Qiao, Lirui; Wang, Wenguang; Zhao, Mingbo; Tu, Pengfei; Jiang, Yong
Clarification of the chemical composition of traditional Chinese medicine formulas (TCMFs) is a challenge due to the variety of structures and the complexity of plant matrices. Herein, an integrated strategy was developed by hyphenating ultra-performance liquid chromatography (UPLC), quadrupole time-of-flight (Q-TOF), hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS), and the novel post-acquisition data processing software UNIFI to achieve automatic, rapid, accurate, and comprehensive qualitative and quantitative analysis of the chemical components in TCMFs. As a proof-of-concept, the chemical profiling of Baoyuan decoction (BYD), which is an ancient TCMF that is clinically used for the treatment of coronary heart disease that consists of Ginseng Radix et Rhizoma, Astragali Radix, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, and Cinnamomi Cortex, was performed. As many as 236 compounds were plausibly or unambiguously identified, and 175 compounds were quantified or relatively quantified by the scheduled multiple reaction monitoring (sMRM) method. The findings demonstrate that the strategy integrating the rapidity of UNIFI software, the efficiency of UPLC, the accuracy of Q-TOF-MS, and the sensitivity and quantitation ability of Qtrap-MS provides a method for the efficient and comprehensive chemome characterization and quality control of complex TCMFs.
Takizawa, Yukiho; Nishimura, Hiroaki; Morota, Takashi; Tomisawa, Hiroki; Takeda, Shuichi; Aburada, Masaki
TJ-8117 (Onpi-to) is an herbal medicine extracted from a mixture of five crude medicinals (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active components of TJ-8117, was labeled with tritium and added to TJ-8117. Pharmacokinetics in plasma, tissue distribution and excretion of radioactivity were investigated following a single oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in rats and dogs. 1. Following oral administration of [3H]TJ-8117, radioactivity exhibited linear pharmacokinetics in Cmax. Linearity of AUC(0-72 h) was lost at the highest dose of [3H]TJ-8117. Cmax and AUC(0-72 h) were higher in female rats than in male rats, a finding which suggested a sex difference in rats. Plasma levels of radioactivity displayed curves with one peak in dogs, which suggested a species difference between rats and dogs. 2. No accumulation was observed in any tissues in male rats. 3. Within 168 h after administration of [3H]TJ-8117 to male rats, 18.7%, 84.1% and 0.9% of the dose was excreted in urine, feces and expired air, respectively. Data from bile-duct cannulated rats indicated that at least 18.4% of the dose was absorbed.
Kim, Young-Suk; Jung, Eun-Ah; Shin, Ji-Eun; Chang, Jong-Chul; Yang, Hyung-Kil; Kim, Nam-Jae; Cho, Ki-Ho; Bae, Hyung-Sup; Moon, Sang-Kwan; Kim, Dong-Hyun
To evaluate the antihyperlipidemic activities of Orengedokuto (OT) and Daio-Orengedokuto (DOT), the inhibitory effects of these polyprescriptions on HMG-CoA reductase and pancreatic lipase and on the rat hyperlipidemic model induced by Triton WR-1339 were measured. OT potently inhibited HMG-CoA reductase but did not inhibit lipase. Among their ingredients, Coptidis Rhizoma was the most potent inhibitor, followed by Rhei Rhizoma. The HMG-CoA reductase-inhibitory activity of 80% EtOH extract was superior to that of water extract. However, DOT potently inhibited HMG CoA-reductase as well as pancreatic lipase. In the rat hyperlipidemic model induced by Triton WR-1339, OT and DOT decreased serum total cholesterol and low-density lipoprotein cholesterol levels. DOT also decreased serum triglyceride levels, but OT did not decrease it. These results suggest that the antihyperlipidemic activity of DOT may originate from the inhibition of pancreatic lipase as well as HMG-CoA reductase.
Ma, Xiaoli; Guo, Xiaoyu; Song, Yuelin; Qiao, Lirui; Wang, Wenguang; Zhao, Mingbo; Tu, Pengfei; Jiang, Yong
Clarification of the chemical composition of traditional Chinese medicine formulas (TCMFs) is a challenge due to the variety of structures and the complexity of plant matrices. Herein, an integrated strategy was developed by hyphenating ultra-performance liquid chromatography (UPLC), quadrupole time-of-flight (Q-TOF), hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS), and the novel post-acquisition data processing software UNIFI to achieve automatic, rapid, accurate, and comprehensive qualitative and quantitative analysis of the chemical components in TCMFs. As a proof-of-concept, the chemical profiling of Baoyuan decoction (BYD), which is an ancient TCMF that is clinically used for the treatment of coronary heart disease that consists of Ginseng Radix et Rhizoma, Astragali Radix, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, and Cinnamomi Cortex, was performed. As many as 236 compounds were plausibly or unambiguously identified, and 175 compounds were quantified or relatively quantified by the scheduled multiple reaction monitoring (sMRM) method. The findings demonstrate that the strategy integrating the rapidity of UNIFI software, the efficiency of UPLC, the accuracy of Q-TOF-MS, and the sensitivity and quantitation ability of Qtrap-MS provides a method for the efficient and comprehensive chemome characterization and quality control of complex TCMFs.
Statistical quality control of total ash, acid-insoluble ash, loss on drying, and hazardous heavy metals contained in the component medicinal herbs of "Ssanghwatang", a widely used oriental formula in Korea.
Kim, Donggyu; Kim, Bogsoon; Yun, Eunsun; Kim, Junghun; Chae, Youngzoo; Park, Seungkook
To investigate the current quality control status of raw materials in "Ssanghwatang", a widely used oriental formula effective for fatigue recovery in Korea, 1024 samples of 9 herbs available in Seoul area markets were collected, and the contents of quality inspection items such as total ash, acid-insoluble ash, loss on drying, and hazardous heavy metals (Pb, As, Cd, Hg) were examined. Medicinal herbs requiring quality control, which may not meet the specifications and standards set by the Korea Food and Drug Administration, were selected using robust z-scores, a random variable. Among the quality control items, control of total ash content was required for the Ssanghwatang raw materials Cinnamomi Cortex, Rehmanniae Radix Preparata, Zingiberis Rhizoma, and Zizyphi Fructus; loss on drying for Cinnamomi Cortex; and heavy metal (Cd) for Angelicae Gigantis Radix, Cinnamomi Cortex, and Zingiberis Rhizoma. Additionally, acid-insoluble ash content revealed how many fine soil and sand particles are present in commercial medicinal herbs, which were correlated with heavy metals such as Pb (r = 0.528) and As (r = 0.342) in Rehmanniae Radix Preparata (p < 0.01).
Zhan, Changsen; Xiong, Aizhen; Shen, Danping; Yang, Li; Wang, Zhengtao
Danning Tablets are a traditional Chinese formula showing broad clinical applications in hepatobiliary diseases and containing a diversity of bioactive chemicals. However, the chemical profiling of the formula, which serves as the material foundation of its efficacy, is really a big challenge as Danning Tablets consist of seven herbs from different origins. An ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (UPLC-DAD-ESI-MS/MS) approach was developed to characterize the principal polyphenol constituents in the formula. As a result, a total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified based on their retention time, UV absorption and MS/MS fragmentation patterns. The sources of these compounds were also illustrated. Most of the bioactive anthraquinone derivatives were found in Rhei Radix et Rhizoma or Polygoni Cuspidati Rhizoma et Radix, which are the Emperor drugs in the formula for its clinic usage. These findings indicate the merit of using this integrated UPLC-DAD-ESI-MS/MS approach to rapidly illustrate the chemical foundation of complex formulas. The present study will facilitate the quality control of Danning Tablet formulas as well as the individual herbs.
Exploring processing adjuvants’ influence on traditional Chinese medicine compatibility of Aconiti Radix Cocta and Pinelliae rhizome using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry
Wang, Yuming; Li, Yubo; Zhang, Xiuxiu; Xu, Yanyan; Wang, Hui; Zhang, Yanjun
Background: It is known that when crude Pinelliae rhizome and Pinelliae rhizoma preparatum are combined with Aconiti Radix Cocta respectively, the toxicity of the combination varies. However, the component's transformation between different compatibility have remained unclear. Objective: In this paper, a novel approach using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with multivariate statistical analysis was established for exploring the influence of processing adjuvants (PAs) on the compatibility of Aconiti Radix Cocta and Pinelliae rhizome. Materials and Methods: In order to obtain information about the representative markers between different groups, an exhaustive study of different protocols based on adding or removing different PAs step by step was carried out and the influence of PAs on compatibility was investigated. Results: It was found that lime can facilitate diester diterpenoid alkaloids with high toxicity in Aconiti Radix Cocta to be converted into low-toxic or non-toxic derivatives. Glycyrrhizae Radix et Rhizoma had no remarkable effect on the process. Conclusion: The established method in this study will be of great significance to process research mechanism and study on traditional Chinese Medicine compatibility and clinical application. PMID:25422550
Wong, Lailai; Liang, Zhitao; Chen, Hubiao; Zhao, Zhongzhen
Authentication of Chinese Materia Medica (CMM) decoction dregs is important for ensuring the efficacy and safety of CMM when they are used in decoction. If someone got worse or poisoned after taking a decoction while the formula is appropriate, the authentication of CMM dregs is the effective method to explore the reasons. Therefore, a systematic study on the authentication of CMM dregs was carried out. In this study, two pairs of easily confused CMM dregs, Fenge (Puerariae Thomsonii Radix) and Shanyao (Dioscoreae Rhizoma), Dihuang (Rehmanniae Radix) and Huangjing (Polygonati Rhizoma), which mostly comprise storage tissues, were investigated by comparing the morphological and microscopic characteristics. Fenge and Shanyao contain abundant starch granules. After decoction their dregs were hard, nonstarchy and horn-like. Fully gelatinized starch granules were found in the powder of Fenge dregs while incompletely gelatinized starch granules were occasionally found in the Shanyao dregs. In contrast, Dihuang and Huangjing contain water-soluble sugars. After decoction, their dregs were hard and brittle. Their parenchymatous cells were shrunken and unknown crystals were found under microscope. Hence, the morphological and microscopic characteristics of CMM before and after decoction were different, and different changes in the CMM dregs can be illustrated by the different nature of their ergastic substance. These differences could be used to authenticate CMM dregs.
Wong, Lailai; Liang, Zhitao; Chen, Hubiao; Zhao, Zhongzhen
Chinese Materia Medica (CMM) decoction dregs are the residues of medicinal materials after decoction. Accurate identification of CMM in decoction dregs will be helpful for exploring the causes of poisoning or other medical incidents arising after the ingestion of CMM decoctions. To determine how decoction affects the characteristics used to authenticate specific CMM, a systematic study was carried out. In this study, two pairs of Materia Medica that are commonly confused-namely, Baizhu (Atractylodis Macrocephalae Rhizoma) and Cangzhu (Atractylodis Rhizoma), Baishao (Paeoniae Alba Radix) and Chishao (Paeoniae Rubra Radix)-were chosen for investigation. Each pair of Materia Medica has similar morphology in appearance, but they have different functions in Chinese clinic. After decoction, with regard to gross morphological characters, the results showed that bark and wood could be easily distinguished. The striation of vessels and fibers became more prominent because of the contraction of parenchymatous cells, but the lignified cells did not. As for the microscopic characteristics, the cells with thickened walls, such as stone cells and fibers, were basically stable. Most of the parenchymatous cells were broken. Crystals of calcium oxalate showed no changes as they were insoluble in water. Starch granules were gelatinized and aggregated in parenchymatous cells. Inulins were substantially reduced in number as they dissolved in water during decoction. According to these changes in morphological and microscopic characteristics after decoction, the dregs of two pairs of Materia Medica could be distinguished.
Law, Betty Yuen Kwan; Mok, Simon Wing Fai; Wu, An Guo; Lam, Christopher Wai Kei; Yu, Margaret Xin Yi; Wong, Vincent Kam Wai
Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.
Shi, Min; Sun, Guoxiang
Danshen tablet, which consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Borneolum syntheticum, has been widely used in the therapy of cardiovascular disease. The aim of this study was to develop comprehensive evaluation methods for the quality control of Danshen tablet. First, five-wavelength fusion fingerprint was established to avoid one-sidedness of a single wavelength. Then, the ultraviolet spectrum fingerprint was applied to reflect the information of unsaturated bond and conjugated system of chemical substances in Danshen tablet. The similarity analyses of these two fingerprints were performed by systematic quantified fingerprint method in terms of qualitative and quantitative aspects. After that, the evaluation results of high-performance liquid chromatography and ultraviolet fingerprints were integrated by the mean algorithm, which could reduce the error caused by single method. The integrated evaluation results showed that 30 batches of samples were classified into seven grades. Finally, the fingerprint-efficacy relationship was established using an on-line antioxidant system and partial least squares model to explore the connection between chemical components and antioxidant activities. The methods established in this paper had proven to be suitable for the analysis of Danshen tablet. This article is protected by copyright. All rights reserved.
Ma, Xiaoli; Guo, Xiaoyu; Song, Yuelin; Qiao, Lirui; Wang, Wenguang; Zhao, Mingbo; Tu, Pengfei; Jiang, Yong
Clarification of the chemical composition of traditional Chinese medicine formulas (TCMFs) is a challenge due to the variety of structures and the complexity of plant matrices. Herein, an integrated strategy was developed by hyphenating ultra-performance liquid chromatography (UPLC), quadrupole time-of-flight (Q-TOF), hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS), and the novel post-acquisition data processing software UNIFI to achieve automatic, rapid, accurate, and comprehensive qualitative and quantitative analysis of the chemical components in TCMFs. As a proof-of-concept, the chemical profiling of Baoyuan decoction (BYD), which is an ancient TCMF that is clinically used for the treatment of coronary heart disease that consists of Ginseng Radix et Rhizoma, Astragali Radix, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, and Cinnamomi Cortex, was performed. As many as 236 compounds were plausibly or unambiguously identified, and 175 compounds were quantified or relatively quantified by the scheduled multiple reaction monitoring (sMRM) method. The findings demonstrate that the strategy integrating the rapidity of UNIFI software, the efficiency of UPLC, the accuracy of Q-TOF-MS, and the sensitivity and quantitation ability of Qtrap-MS provides a method for the efficient and comprehensive chemome characterization and quality control of complex TCMFs. PMID:27924825
Wang, Caiyun; Chen, Xuan; Hu, Shuang; Bai, Xiaohong
A novel stirrer-liquid/solid microextraction method was developed for the separation and enrichment of trace levels of curcumin, bisdemethoxycurcumin, and demethoxycurcumin in Rhizoma Curcumae Longae, Radix Curcumae, and Rhizoma Curcumae before their analysis by high-performance liquid chromatography with ultraviolet detection. In the proposed approach, a magnetic stirrer was immersed in decanol to coat its surface completely with decanol, which was used as an extraction platform. The stirrer coated with decanol is not only a power to agitate the sample solution to constantly update the sample on the stirrer surface but also it can adsorb and extract the target analytes. Some effective parameters, including suitable superficial area of stirrer, extraction solvent, sample phase pH, NaCl concentration, stirring rate, extraction time, sample phase volume, were analyzed and selected. Under the optimal conditions, the linearities are 0.0044-2.20 μg/mL, detection limits are 0.3-0.6 ng/mL, and the extraction content per unit length and enrichment factors of the target analytes are 6.24-9.71/mm and 589-917, respectively. Also, the stirrer-liquid/solid microextraction mechanism for the extraction and enrichment of the target analytes was analyzed and expounded. The results showed that stirrer-liquid/solid microextraction is a simple, rapid sample pretreatment approach with a high enrichment factor.
Guo, Jianming; Shang, Erxin; Zhao, Jinlong; Fan, Xinsheng; Duan, Jinao; Qian, Dawei; Tao, Weiwei; Tang, Yuping
Liquorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L., Leguminosae. Licorice is described as 'National Venerable Master' in Chinese medicine and plays paradoxical roles, i.e. detoxification/strengthen efficacy and inducing/enhancing toxicity. Therefore, licorice was called "Two-Face" herb in this paper. The aim of this study is to discuss the paradoxical roles and the perspective usage of this "Two-Face" herb using data mining and frequency analysis. More than 96,000 prescriptions from Chinese Formulae Database were selected. The frequency and the prescription patterns were analyzed using Microsoft SQL Server 2000. Data mining methods (frequent itemsets) were used to analyze the regular patterns and compatibility laws of the constituent herbs in the selected prescriptions. The result showed that licorice (Radix glycyrrhizae) was the most frequently used herb in Chinese Formulae Database, other frequently used herbs including Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), etc. Toxic herbs such as Radix aconiti lateralis praeparata (Fu zi), Rhizoma pinelliae (Ban xia) and Cinnabaris (Zhu sha) are top 3 herbs that most frequently used in combination with licorice. Radix et rhizoma ginseng (Ren shen), Poria (Fu ling), Radix Angelicae Sinensis (Dang gui) are top 3 nontoxic herbs that most frequently used in combination with licorice. Moreover, Licorice was seldom used with sargassum (Hai Zao), Herba Cirsii Japonici (Da Ji), Euphorbia kansui (Gan Sui) and Flos genkwa (Yuan Hua), which proved the description of contradictory effect of Radix glycyrrhizae and these herbs as recorded in Chinese medicine theory. This study showed the principle pattern of Chinese herbal drugs used in combination with licorice or not. The principle patterns and special compatibility laws reported here could be useful and instructive for scientific usage of licorice in clinic application. Further pharmacological and chemical researches are
Lin, Li-Yun; Peng, Chiung-Chi; Yeh, Xian-Yü; Huang, Bor-Yü; Wang, Hui-Er; Chen, Kuan-Chou; Peng, Robert Y
Rhizoma A. officinarum (Hance) Farw, synonymously is called rhizoma galangae or smaller galangal (hereafter abbreviated as AO). Numerous studies reported that AO possesses anti-inflammatory, anticancer, chemoprotective, antibacterial, antifungal and diuretic properties. To understand whether AO exhibits antihyperlipidemic bioactivity and what is the mechanism of action, we performed chemical and animal studies using hamsters (age: 4 weeks, body weight: 45 ± 4 g). The grouping of the animals was as follows: control, high fat (HF) diet, HF + AO2%, HF + AO4%, HF + AO6%, HF + AO8% and HF + AO10%. AO contained curcumin 5.67 mg g(-1) (on wet basis), crude fiber 1.3% ± 0.0%, soluble diet fiber 92 ± 2 mg g(-1), insoluble diet fiber 502 ± 5 mg g(-1), and phytosterols 63.9 ± 1.6 mg/100 g. Its methanolic extract consisted of high polyphenolics 4927.8 ± 101.1 mgGAE/100 g and flavonoids 593.2 ± 22.2 mgQE/100 g. The enlarged organs, including liver, kidney, and spleen, which were elicited by HF were completely alleviated by AO supplement diets. Levels of serum cholesterol, triglyceride, LDL-C, HDL-C and LDL-C/HDL-C ratio for the control originally were 138 ± 6, 98 ± 4, 40 ± 5, 168 ± 7 mg dL(-1) and 0.24, which were elevated by HF to 319 ± 12, 223 ± 13, 108 ± 11, 194 ± 6 mg dL(-1) and 0.05, and alleviated completely by HF + AO8% and HF + AO10%. In vitro, AO extracts showed potent DPPH free radical-scavenging and superoxide anion scavenging capabilities. In vivo, AO (at dose ≥8%) dose-dependently alleviated levels of superoxide dismutase, catalase, GSH, and MDA to 117 ± 6.9 U mL(-1), 32.9 ± 3.7 U mL(-1), 7.0 ± 1.7 μmol mL(-1) and 1.8 ± 0.4 nmol L(-1), respectively, exhibiting the remarkable antioxidative and antihyperlipidemic effects of AO. Conclusively, we are the first to report the occurrence of curcumin in rhizoma A. officinarum. Curcumin synergistically elicits promising anti-dyslipidemic bioactivity with coexisting total polyphenolics, dietary fibers
Tan, Lihua; Li, Cailan; Chen, Hanbin; Mo, Zhizhun; Zhou, Jiangtao; Liu, Yuhong; Ma, Zhilin; Xu, Yuyao; Yang, Xiaobo; Xie, Jianhui; Su, Ziren
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
Qu, Cheng; Wang, Lin-Yan; Jin, Wen-Tao; Tang, Yu-Ping; Jin, Yi; Shi, Xu-Qin; Shang, Li-Li; Shang, Er-Xin; Duan, Jin-Ao
The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) are the major bioactive components of many formulae comprised of safflower. In this study, selective knock-out of target components such as HSYA and ASYB by using preparative high performance liquid chromatography (prep-HPLC) followed by antiplatelet and anticoagulation activities evaluation was used to investigate the roles of bioactive ingredients in safflower series of herb pairs. The results showed that both HSYA and ASYB not only played a direct role in activating blood circulation, but also indirectly made a contribution to the total bioactivity of safflower series of herb pairs. The degree of contribution of HSYA in the safflower and its series herb pairs was as follows: Carthami Flos-Ginseng Radix et Rhizoma Rubra (CF-GR) > Carthami Flos-Sappan Lignum (CF-SL) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Astragali Radix (CF-AR) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Glycyrrhizae Radix et Rhizoma (CF-GL) > Carthami Flos-Salviae Miltiorrhizae Radix et Rhizoma (CF-SM) > Carthami Flos (CF), and the contribution degree of ASYB in the safflower and its series herb pairs: CF-GL > CF-PS > CF-AS > CF-SL > CF-SM > CF-AR > CF-GR > CF. So, this study provided a significant and effective approach to elucidate the contribution of different herbal components to the bioactivity of the herb pair, and clarification of the variation of herb-pair compatibilities. In addition, this study provides guidance for investigating the relationship between herbal compounds and the bioactivities of herb pairs. It also provides a scientific basis for reasonable clinical applications and new drug
Ni, Wei-Jian; Ding, Hai-Hua; Tang, Li-Qin
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.
Zhang, Qing; Li, Yan; Chen, Lei
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.
Chen, Guang; Lu, Fuer; Xu, Lijun; Dong, Hui; Yi, Ping; Wang, Fang; Huang, Zhaoyi; Zou, Xin
Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years. To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs. In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin. The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively. The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined. The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated. The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW.
Deng, Xiao-Wei; Xie, Ning
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.
Liu, Shumin; Lu, Fang; Wang, Xijun; Sun, Wenjun; Chen, Pingping; Dong, Wanru
This study describes the metabonomics of fevers in animal models and the therapeutic effects of Rhizoma coptidis extract (RCE) on them. The rat urinary samples were analyzed by UPLC/ ESI-Q-TOF/MS, combined with principal component analysis (PCA). Nine ions were chosen to characterize the similarities and differences in the responses to fever. The ion at m/z 206.0278 was unambiguously identified to be xanthurenic acid. This study demonstrated that the metabonomic approach can readily distinguish between febrile and healthy individuals. This data support the contention that the metabonomic approach represents a promising new technology for the development of rapid-throughput in vivo fever screening. Furthermore, this approach can detect the interfering effects of RCE. This investigation has led the authors to believe that metabonomics is a valid approach for explaining the therapeutic effects of traditional Chinese medicine on fevers.
Kalveniene, Zenona; Savickas, Arūnas; Svambaris, Liudvinas; Briedis, Vitalis; Bernatonis, Domininkas
The article deals with the production of the complex tincture of Hyperici herba 80.0 g, Cinnamomi cortex 20.0 g, Rosmarini folium 20.0 g, Lavandulae flos 20.0 g, Zingiberis rhizoma 60.0 g and the selection of an extracting liquid phase, and the choice of extraction method. The experimentally determined optimal conditions for tincture preparation were as follows: concentration of ethanol--70% (V/V), the particle size of the leaves, herb, flowers--2.0-3.0 mm, for the bark and the roots--0.3-0.5 mm, the extraction method--percolation. The quality of the tincture was evaluated by analyzing the sum of flavonoids (recalculated into equivalent amount of rutin), dry residue, the concentration of ethanol, density of the extractive preparation, and microbial contamination. Also the overall appearance was checked, the identification of flavonoids was performed by color reactions and high-pressure liquid chromatography.
Jo, Sung Kee; Lee, Hae June; Kim, Se Ra; Kim, Jong Choon; Bae, Chun Sik; Jung, Uhee; Park, Hae Ran; Jang, Jong Sik; Kim, Sung Ho
This study evaluated a new herbal preparation, HemoHIM, for its antiinflammatory activity against carrageenan-induced edema, the formation of granulation tissues by cotton pellet and experimental colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The HemoHIM was prepared by adding its ethanol-insoluble polysaccharide fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. The preparation (4 mg of solids/mL of drinking water, p.o., 50-100 mg/kg of body weight, i.p.) produced a dose-related inhibition of carrageenan-induced paw edema and cotton pellet-induced granuloma in rats. In addition, HemoHIM also reduced the degree of TNBS-induced colitis and improved the gross and histological changes such as thickening, dilatation, ulceration, and infiltration by polymorphonuclear leukocytes and multiple erosive lesions. These results demonstrate that the HemoHIM has a potent antiinflammatory effect.
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
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
Li, Juan; Wang, Ru-feng; Yang, Li; Wang, Zheng-tao
Notoginseng Radix et Rhizoma (Sanqi), the underground part of Panax notoginseng (Burk.) F. H. Chen (Araliaceae) is commonly used in Chinese medicine for treatment of haemorrhage, haemostasis, swelling, etc. The aerial part including leaves, flowers and fruits are also applied for similar functions. Triterpenoid saponins are considered to be responsible for the biological activities of Sanqi. Up to date, more than 100 saponins have been isolated from theroots, rhizomes, leaves, flowers and fruits of P. notoginseng. The reported saponins can be classified into protopanaxadiol (PPD), protopanaxatriol (PPT), C17 side-chain varied and other types, according to the skeletons of the aglycons. The present review summarizes the saponins isolated from P. notoginseng and their distribution in different medicinal organs, as well as the pharmacological actions on cardiovascular system.
Hou, Jingyi; Li, Geng; Wei, Yingqin; Lu, Heng; Jiang, Chao; Zhou, Xiaoteng; Meng, Fanyun; Cao, Jun; Liu, Jinxin
In this paper, surfactant-coated multi-walled carbon nanotubes (SC-MWNTs) have been proposed as a novel pseudostationary phase (PSP) to enhance the separation of isoquinoline alkaloids in nonaqueous capillary electrophoresis (NACE). Several parameters affecting NACE separation were studied including the MWNT concentration, the electrolyte concentration, pH* and the separation voltage. In comparison to conventional NACE, the addition of an MWNT dispersion using surfactant solutions in the electrolyte produced an important enhancement in the resolution due to the π-π interactions between the analytes and the surface of the carbon nanotubes. Using SC-MWNTs (6μgmL(-1)) as a PSP in the background electrolyte (BGE) (i.e., 20mM sodium acetate in methanol-acetonitrile (80:20, v/v)) provided the complete separation of five alkaloids. Finally, the developed method has been successfully applied to the detection and quantification of the tested compounds of Rhizoma Coptidis.
Wang, Zhaohui; Han, Dongyue; Qie, Lili; Liu, Chang; Wang, Fuchun
Clinical literature of bronchial asthma treated with acupoints application from January 2000 to March 2014 in modern periodicals databases was retrieved through computer. With cluster analysis and frequency analysis methods of data mining, acupoints selecting and medication rules of bronchial asthma treated with acupoints application were analyzed. Total 38 articles were included eventually, including 25 acupoints and 42 medicines. The results indicate that on acupoints selecting, Feishu (BL 13) is used as the main acupoint and 3 groups of bladder meridian and conception vessel acupoints are applied alternately and on medicines, Baijiezi (Brassica alba Boiss), Xixin (Radix et Rhizoma Asari), Gansui (Radix Kansui), Yanhusuo (Corydalis) and Mahuang (Radix et Rhizonma Ephedrae) are primarily adopted, epispastic medicines being the main medicines; medicines mostly belong to lung meridian, main medicines being unchanged mostly with Shengjiang as guiding drug.
Quantitative and chemical fingerprint analysis for the quality evaluation of Isatis indigotica based on ultra-performance liquid chromatography with photodiode array detector combined with chemometric methods.
Shi, Yan-Hong; Xie, Zhi-Yong; Wang, Rui; Huang, Shan-Jun; Li, Yi-Ming; Wang, Zheng-Tao
A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.
Cao, Gang; Xu, Zhiwei; Wu, Xin; Li, Qingli; Chen, Xiaocheng
This work aimed to investigate the volatile components in crude and processed herbal medicines (HMs). Using Atractylodis Macrocephalae Rhizoma (AMR) as a model HM, the volatile components were captured through on-line purge and trap technique and identified by using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS) system. A total of 224 and 171 volatile compounds were identified in crude and processed AMR samples, respectively. After frying with honey-bran, 52 compounds which were found in crude AMR samples disappeared in processed AMR samples, and 15 compounds were newly generated in processed AMR. The established method can be applied in different research areas such as HM and food processing.
Zou, Kun; Li, Zhao; Zhang, Yong; Zhang, Hao-yue; Li, Bo; Zhu, Wei-liang; Shi, Ji-ye; Jia, Qi; Li, Yi-ming
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
Ding, Shi-Ping; Li, Ji-Cheng; Xu, Jian; Mao, Lian-Gen
AIM: To study the mechanism of Chinese herbal medicine (CHM, the prescription consists of Radix Salviae Miltiorrhizae, Radix Codonopsitis Pilosulae, Rhizoma Atractylodis Alba and Rhizoma Alismatis, Leonurus Heterophyllus Sweet, etc) on the regulation of the peritoneal lymphatic stomata and the ascites drainage. METHODS: The mouse model of live fibrosis was established with the application of intragastric installations of carbon tetrachloride once every three days; scanning electron microscope and computer image processing were used to detect the area and the distributive density of the peritoneal lymphatic stomata; and the concentrations of urinary ion and NO in the serum were analyzed in the experiment. RESULTS: Two different doses of CHM could significantly increase the area of the peritoneal lymphatic stomata, promote its distributive density and enhance the drainage of urinary ion such as sodium, potassium and chlorine. Meanwhile, the NO concentration of two different doses of CHM groups was 133.52 ± 23.57 μmol/L, and 137.2 ± 26.79 μmol/L respectively. In comparison with the control group and model groups (48.36 ± 6.83 μmol/L, and 35.22 ± 8.94 μmol/L, P < 0.01), there existed significantly marked difference, this made it clear that Chinese herbal medicine could induce high endogenous NO concentration. The effect of Chinese herbal medicine on the peritoneal lymphatic stomata and the drainage of urinary ion was altered by adding NO donor(sodium nitropurruside, SNP) or NO synthase (NOS) inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) to the peritoneal cavity. CONCLUSION: There existed correlations between high NO concentration and enlargement of the peritoneal lymphatic stomata, which result in enhanced drainage of ascites. These data supported the hypothesis that Chinese herbal medicine could regulate the peritoneal lymphatic stomata by accelerating the synthesis and release of endogenous NO. PMID:11833101
Wu, Jiasi; Hu, Yingfan; Xiang, Li; Li, Sheng; Yuan, Yi; Chen, Xiaomei; Zhang, Yan; Huang, Wenge; Meng, Xianli; Wang, Ping
Inflammatory disorders underlie varieties of human diseases. San-Huang-Xie-xin-Tang (SHXXT), composed with Rhizoma Rhei (Rheum palmatum L.), Rhizoma Coptidis (Coptis chinensis Franch), and Radix Scutellaria (Scutellaria baicalensis Georgi), is a famous formula which has been widely used in the fight against inflammatory abnormalities. Mutual reinforcement is one of the basic theories of traditional Chinese medicine. Here this article reviewed and analyzed the recent research on (1) How the main constituents of SHXXT impact on inflammation-associated signaling pathway molecules. (2) The interaction between the main constituents and efflux pumps or intestinal transporters. The goal of this work was to, (1) Provide evidence to support the theory of mutual reinforcement. (2) Clarify the key targets of SHXXT and suggest which targets need further investigation. (3) Give advice for the clinical use of SHXXT to elevated the absorption of main constituents and eventually promote oral bioavailability. We search literatures in scientific databases with key words of "each main SHXXT constituent," in combination with "each main inflammatory pathway target molecule" or each main intestinal transporter, respectively. We report the effect of five main constituents on target molecules which lies in three main inflammatory signaling pathways, we as well investigate the interaction between constituents and intestinal transporter. We conclude, (1) The synergistic effect of constituents at both levels confirm the mutual reinforcement theory of TCM as it is proven in this work. (2) The effect of main constituents on downstream targets in nuclear need more further investigation. (3) Drug elevating the absorption of rhein, berberine and baicalein can be employed to promote oral bioavailability of SHXXT.
Wang, Chunfei; Feng, Liang; Ma, Liang; Chen, Haifeng; Tan, Xiaobin; Hou, Xuefeng; Song, Jie; Cui, Li; Liu, Dan; Chen, Juan; Yang, Nan; Wang, Jing; Liu, Ying; Zhao, Bingjie; Wang, Gang; Zhou, Yuanli; Jia, Xiaobin
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are abundant in Rhizoma alismatis. In the present study, we evaluated the induction of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal tubular (HK-2) cells by activating autophagy and also explored its regulation on PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were considered to be new bioindicators of nephrotoxicity. Interestingly, the protein expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B and 24A in vivo and in vitro. Furthermore, cell apoptosis could be triggered by 23B and 24A via significantly decreasing the protein expression and mRNA levels of Bcl-2 and Bcl-xl. Autophagy of HK-2 cells could be induced by both 23B and 24A via significantly enhancing the ratio of LC3II/LC3I, the protein expression of Beclin-1 as well as the mRNA levels of LC3 and Beclin-1. Meanwhile, PI3K/Akt/mTOR signaling pathway could be inhibited by these two compounds. An autophagy inhibitor, 3-methyladenine, could partially reverse cell viability and conversely change the ratio of LC3II/LC3I and the protein expression of Bcl-2 and Kim-1. Thus this study helped to understand that 23B and 24A induced autophagy resulted in apoptosis and nephrotoxicity through inhibiting PI3K/Akt/mTOR signaling pathway, facilitating further studies for nephrotoxicity induced by these two compounds and could be beneficial for safe use of Rhizoma alismatis in clinic.
Wu, Jiasi; Hu, Yingfan; Xiang, Li; Li, Sheng; Yuan, Yi; Chen, Xiaomei; Zhang, Yan; Huang, Wenge; Meng, Xianli; Wang, Ping
Inflammatory disorders underlie varieties of human diseases. San-Huang-Xie-xin-Tang (SHXXT), composed with Rhizoma Rhei (Rheum palmatum L.), Rhizoma Coptidis (Coptis chinensis Franch), and Radix Scutellaria (Scutellaria baicalensis Georgi), is a famous formula which has been widely used in the fight against inflammatory abnormalities. Mutual reinforcement is one of the basic theories of traditional Chinese medicine. Here this article reviewed and analyzed the recent research on (1) How the main constituents of SHXXT impact on inflammation-associated signaling pathway molecules. (2) The interaction between the main constituents and efflux pumps or intestinal transporters. The goal of this work was to, (1) Provide evidence to support the theory of mutual reinforcement. (2) Clarify the key targets of SHXXT and suggest which targets need further investigation. (3) Give advice for the clinical use of SHXXT to elevated the absorption of main constituents and eventually promote oral bioavailability. We search literatures in scientific databases with key words of “each main SHXXT constituent,” in combination with “each main inflammatory pathway target molecule” or each main intestinal transporter, respectively. We report the effect of five main constituents on target molecules which lies in three main inflammatory signaling pathways, we as well investigate the interaction between constituents and intestinal transporter. We conclude, (1) The synergistic effect of constituents at both levels confirm the mutual reinforcement theory of TCM as it is proven in this work. (2) The effect of main constituents on downstream targets in nuclear need more further investigation. (3) Drug elevating the absorption of rhein, berberine and baicalein can be employed to promote oral bioavailability of SHXXT. PMID:27965575
Yin, Jun; Zhang, Hanjie; Ye, Jianping
In management of metabolic syndrome, the traditional Chinese medicine (TCM) is an excellent representative in alternative and complementary medicines with a complete theory system and substantial herb remedies. In this article, basic principle of TCM is introduced and 22 traditional Chinese herbs are reviewed for their potential activities in the treatment of metabolic syndrome. Three herbs, ginseng, rhizoma coptidis (berberine, the major active compound) and bitter melon, were discussed in detail on their therapeutic potentials. Ginseng extracts made from root, rootlet, berry and leaf of Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng), are proved for anti-hyperglycemia, insulin sensitization, islet protection, anti-obesity and anti-oxidation in many model systems. Energy expenditure is enhanced by ginseng through thermogenesis. Ginseng-specific saponins (ginsenosides) are considered as the major bioactive compounds for the metabolic activities of ginseng. Berberine from rhizoma coptidis is an oral hypoglycemic agent. It also has anti-obesity and anti-dyslipidemia activities. The action mechanism is related to inhibition of mitochondrial function, stimulation of glycolysis, activation of AMPK pathway, suppression of adipogenesis and induction of low-density lipoprotein (LDL) receptor expression. Bitter melon or bitter gourd (Momordica charantia) is able to reduce blood glucose and lipids in both normal and diabetic animals. It may also protect β cells, enhance insulin sensitivity and reduce oxidative stress. Although evidence from animals and humans consistently supports the therapeutic activities of ginseng, berberine and bitter melon, multi-center large-scale clinical trials have not been conducted to evaluate the efficacy and safety of these herbal medicines. PMID:18537696
Fung, Hau-Yee; Lang, Yan; Ho, Hing-Man; Wong, Tin-Long; Ma, Dik-Lung; Leung, Chung-Hang; Han, Quan-Bin
Sanhuang Tablet (SHT) is a Chinese patented drug commonly used for the treatment of inflammations of the respiratory tract, gastrointestinal tract, and skin. It contains a special medicinal composition including the single compound berberine hydrochloride, extracts of Scutellariae Radix and Rhei Radix et Rhizoma, as well as the powder of Rhei Radix et Rhizoma. Despite advances in analytical techniques, quantitative evaluation of a Chinese patented drug like SHT remains a challenge due to the complexity of its chemical profile. In this study, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to simultaneously quantify 29 non-sugar small molecule components of SHT (11 flavonoids, two isoflavonoids, one flavanone, five anthraquinones, two dianthranones, five alkaloids, two organic acids and one stilbene). Three major saccharide components, namely fructose, glucose, and sucrose, were also quantitatively determined using high performance liquid chromatography-charged aerosol detector (HPLC-CAD) on an Asahipak NH₂P-50 4E amino column. The established methods were validated in terms of linearity, sensitivity, precision, accuracy, and stability, and then successfully applied to analyze 27 batches of commercial SHT products. A total of up to 57.61% (w/w) of SHT could be quantified, in which the contents of the determined non-saccharide small molecules varied from 5.91% to 16.83% (w/w) and three saccharides accounted for 4.41% to 48.05% (w/w). The results showed that the quality of the commercial products was inconsistent, and only four of those met Chinese Pharmacopoeia criteria.
Wang, Mingfeng; Wang, Jia; Tan, Rui; Wu, Qin; Qiu, Hongmei; Yang, Junqing; Jiang, Qingsong
Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor- α (PPAR α )/nitric oxide (NO) signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L) and insulin (0.1 μ mol/L) (HGI) was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS) was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPAR α and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μ mol/L), fenofibrate (0.3 μ mol/L), or L-arginine (100 μ mol/L). MK886 (0.3 μ mol/L), a selective PPAR α antagonist, could abolish the effects of berberine and fenofibrate. N (G) -nitro-L-arginine-methyl ester (100 μ mol/L), a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPAR α /NO signaling pathway.
Sigua, Gilbert C; Chase, Chad C; Albano, Joseph
Grazing can accelerate and alter the timing of nutrient transfer, and could increase the amount of extractable phosphorus (P) cycle from soils to plants. The effects of grazing management and/or forage type that control P cycling and distribution in pasture's resources have not been sufficiently evaluated. Our ability to estimate the levels and changes of soil-extractable P and other crop nutrients in subtropical beef cattle pastures has the potential to improve our understanding of P dynamics and nutrient cycling at the landscape level. To date, very little attention has been paid to evaluating transfers of extractable P in pasture with varying grazing management and different forage type. Whether or not P losses from grazed pastures are significantly greater than background losses and how these losses are affected by soil, forage management, or stocking density are not well understood. The objective of this study was to evaluate the effect of grazing management (rotational versus "zero" grazing) and forage types (FT; bahiagrass, Paspalum notatum, Flugge versus rhizoma peanuts, Arachis glabrata, Benth) on the levels of extractable soil P and degree of P saturation in beef cattle pastures. This study (2004-2007) was conducted at the Subtropical Agricultural Research Station, US Department of Agriculture-Agricultural Research Service located 7 miles north of Brooksville, FL. Soil (Candler fine sand) at this location was described as well-drained hyperthermic uncoated Typic Quartzipsamments. A split plot arrangement in a completely randomized block design was used and each treatment was replicated four times. The main plot was represented by grazing management (grazing vs. no grazing) while forage types (bahiagrass vs. perennial peanut) as the sub-plot treatment. Eight steel exclosures (10 × 10 m) were used in the study. Four exclosures were placed and established in four pastures with bahiagrass and four exclosures were established in four pastures with rhizoma
Kitagawa, Hiroyuki; Munekage, Masaya; Ichikawa, Kengo; Fukudome, Ian; Munekage, Eri; Takezaki, Yuka; Matsumoto, Takashi; Igarashi, Yasushi; Hanyu, Haruo; Hanazaki, Kazuhiro
Context Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia. Objective To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers. Design, Setting, and Participants A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012. Interventions Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period. Main Outcome Measure Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE). Results The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650–1.98 ng/mL and 0.138–0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975–1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72–1.95 h for GM and 2.47–3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7–108 ng/mL, 8.00–8.01 h, and 9.39–12.3 h, respectively. Conclusion We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS. Trial Registration Japan Pharmaceutical Information Center JAPIC CTI-121811 PMID:26151135
Yang, Mei; Zou, Juan; Zhu, Hongmei; Liu, Shanling; Wang, He; Bai, Peng; Xiao, Xue
The clinical applications of Rhizoma paridis in traditional Chinese medicine are well known. However, the therapeutic potential of Rhizoma paridis and its active component such as Paris saponin I (polyphyllin D) and Paris saponin II (PSII) (formosanin C) in cancer treatments have not yet been fully explored. Recent studies have demonstrated that PSII and chemoagents exhibit comparable inhibitory affects against human ovarian cancer cell growth. Since NF-κB, a ubiquitous transcription factor that plays an important role in cancer biology, is often associated with gynecological cancers, in the present study, we evaluated the possibility that PSII modulates NF-κB activity and VEGF-mediated angiogenesis and elucidated the molecular mechanisms underlying such effects. We assessed the effects of PSII on NF-κB activity in SKOV3 tumor cells and on tumor cell induced-angiogenesis using standardized angiogenesis in vitro, ex vivo and in vivo assays, western blot analysis and kinase assay. We also assessed the effect of the super-engineered repressor of IĸBα and its effect, in combination with PSII treatment on tumor growth and angiogenesis in xenograft athymic mouse models of ovarian cancer (SKOV3 and SKOV3/mutant IĸBα cells) using color Doppler ultrasound and traditional immunohistochemistry. We showed that PSII suppressed NF-κB activation as a result of the reduction in IKKβ kinase activity on its substrate IκBα and the expression of IKKβ. Compromising NF-κB activation reduced the expression of NF-κB-downstream targets such as VEGF, Bcl-2 and Bcl-xL. Such inhibitory effects at molecular levels appear to compromise tumor growth and angiogenesis. Most importantly, the combination of PSII treatment and constitutive repression of IĸBα activity exhibited marked inhibitory effects against human ovarian cancer cell growth in a xenograft mouse model of ovarian cancer. For the first time, we provide evidence showing that PSII potently inhibits angiogenesis
Wen, Chih-Chun; Shyur, Lie-Fen; Jan, Jia-Tsrong; Liang, Po-Huang; Kuo, Chih-Jung; Arulselvan, Palanisamy; Wu, Jin-Bin; Kuo, Sheng-Chu; Yang, Ning-Sun
Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix ( lóng dǎn; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma ( shān yào; the tuber of Dioscorea batatas), Cassiae Semen ( jué míng zǐ; the dried seed of Cassia tora) and Loranthi Ramus ( sāng jì shēng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii ( gǒu jǐ; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50) and 50% of viral replication (EC50) were determined. The resulting selective index values (SI = CC50/EC50) of the most effective extracts CBE, GSH, DBM, CTH and TCH were > 59.4, > 57.5, > 62.1, > 59.4, and > 92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39 μg/ml and 44 μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics.AbbreviationsSARS,severe acute respiratory syndromeCoV,coronavirusCPE,cytopathogenic effectTCM,traditional Chinese medicine.
Wen, Chih-Chun; Shyur, Lie-Fen; Jan, Jia-Tsrong; Liang, Po-Huang; Kuo, Chih-Jung; Arulselvan, Palanisamy; Wu, Jin-Bin; Kuo, Sheng-Chu; Yang, Ning-Sun
Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (龍膽 lóng dǎn; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma (山藥 shān yào; the tuber of Dioscorea batatas), Cassiae Semen (決明子 jué míng zǐ; the dried seed of Cassia tora) and Loranthi Ramus (桑寄生 sāng jì shēng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii (狗脊 gǒu jǐ; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50) and 50% of viral replication (EC50) were determined. The resulting selective index values (SI = CC50/EC50) of the most effective extracts CBE, GSH, DBM, CTH and TCH were > 59.4, > 57.5, > 62.1, > 59.4, and > 92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39 μg/ml and 44 μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics. Abbreviations SARS, severe acute respiratory syndrome CoV, coronavirus CPE, cytopathogenic effect TCM, traditional Chinese medicine PMID:24716104
Jin, Hao; Jin, Xin; Cao, Boran; Wang, Wenbo
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
Yu, Mingxiang; Chen, Xianying; Lv, Chaoyang; Yi, Xilu; Zhang, Yao; Xue, Mengjuan; He, Shunmei; Zhu, Guoying; Wang, Hongfu
Highlights: • Curcumol suppresses osteoclasts differentiation in vitro. • Curcumol impairs JNK/AP-1 signaling pathway. • Curcumol may be used for treating osteoclast related diseases. - Abstract: Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.
Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei
Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.
Zhan, Janis Y X; Zheng, Ken Y Z; Zhu, Kevin Y; Zhang, Wendy L; Bi, Cathy W C; Chen, J P; Du, Crystal Y Q; Dong, Tina T X; Lau, David T W; Tsim, Karl W K
Si Wu Tang (Four Agents Decoction), a traditional Chinese decoction composed of Angelica Sinensis Radix, Chuanxiong Rhizoma, Paeoniae Radix Alba, and Rehmanniae Radix Praeparata in a ratio of 1 : 1 : 1 : 1, has been used to treat women's diseases for more than a thousand years. According to the original description of Si Wu Tang, Angelica Sinensis Radix should be treated with wine. However, the importance of this wine-treated Angelica Sinensis Radix in Si Wu Tang's function has not been identified. In this article, the chemical and biological properties of two decoctions processed in different ways (Si Wu Tang with crude Angelica Sinensis Radix and Si Wu Tang with wine-treated Angelica Sinensis Radix) were compared for examination. The herbal decoction Si Wu Tang prepared from wine-treated Angelica Sinensis Radix contained much different amounts of its active compounds. Compared with Si Wu Tang using crude Angelica Sinensis Radix, Si Wu Tang prepared from wine-treated Angelica Sinensis Radix had better biological responses. Therefore, these findings accentuate the functional importance of herbs treated with wine in the Chinese decoction.
Ma, Rufeng; Zhu, Ruyuan; Wang, Lili; Guo, Yubo; Liu, Chenyue; Liu, Haixia; Liu, Fengwei; Li, Hongjun; Li, Yu; Fu, Min
Aim. The incidence of diabetic osteoporosis (DOP) is increasing due to lack of effective management over the past few decades. This review aims to summarize traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical and preclinical management of DOP. Methods. Literature sources used were from Medline (Pubmed), CNKI (China Knowledge Resource Integrated Database), and CSTJ (China Science and Technology Journal Database) online databases. For the consultation, keywords such as diabetic osteoporosis (DOP), TCM, clinical study, animal experiment, toxicity, and research progress were used in various combinations. Around 100 research papers and reviews were visited. Results. Liver-spleen-kidney insufficiency may result in development of DOP. 18 clinical trials are identified to use TCM compound prescriptions for management of patients with DOP. TCM herbs and their active ingredients are effective in preventing the development of DOP in streptozotocin (STZ) and alloxan as well as STZ combined with ovariectomy insulted rats. Among them, most frequently used TCM herbs in clinical trials are Radix Astragali, Radix et Rhizoma Salviae Miltiorrhizae, Radix Rehmanniae Preparata, and Herba Epimedii. Some of TCM herbs also exhibit toxicities in clinical and preclinical research. Conclusions. TCM herbs may act as the novel sources of anti-DOP drugs by improving bone and glucolipid metabolisms. However, the pathogenesis of DOP and the material base of TCM herbs still merit further study. PMID:27698674
Zheng, Ken Yu-Zhong; Zhang, Zhen-Xia; Guo, Ava Jiang-Yang; Bi, Cathy Wen-Chuang; Zhu, Kevin Yue; Xu, Sherry Li; Zhan, Janis Ya-Xian; Lau, David Tai-Wei; Dong, Tina Ting-Xia; Choi, Roy Chi-Yan; Tsim, Karl Wah-Keung
Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance to mountain sickness in preventing hypoxia; however, the functional ingredient responsible for this adaptogenic effect has not been revealed. Here, we have identified salidroside, a glycoside predominantly found in Rhodiola, is the chemical in providing such anti-hypoxia effect. Cultured human embryonic kidney fibroblast (HEK293T) and human hepatocellular carcinoma (HepG2) were used to reveal the mechanism of this hematopoietic function mediated by salidroside. The application of salidroside in cultures induced the expression of erythropoietin (EPO) mRNA from its transcription regulatory element hypoxia response element (HRE), located on EPO gene. The application of salidroside stimulated the accumulation of hypoxia-inducible factor-1α (HIF-1α) protein, but not HIF-2α protein: the salidroside-induced HIF-1α protein was via the reduction of HIF-1α degradation but not the mRNA induction. The increased HIF-1α could account for the activation of EPO gene. These results supported the notion that hematopoietic function of Rhodiola was triggered, at least partially, by salidroside.
Li, Fengbo; Sun, Xiaolei; Ma, Jianxiong; Ma, Xinlong; Zhao, Bin; Zhang, Yang; Tian, Peng; Li, Yanjun; Han, Zhe
Highlights: • Naringin possesses many pharmacological activities, promotes the proliferation of osteoblast. • Undecalcified histological obtain dynamic parameters of callus formation and remodeling. • Naringin regulate osteoclast apoptosis by mitochondrial pathway. - Abstract: Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.
Haris, P; Mary, Varughese; Aparna, P; Dileep, K V; Sudarsanakumar, C
Curcumin is a natural phytochemical from the rhizoma of Curcuma longa, the popular Indian spice that exhibits a wide range of pharmacological properties like antioxidant, anticancer, anti-inflammatory, antitumor, and antiviral activities. In the published literatures we can see different studies and arguments on the interaction of curcumin with DNA. The intercalative binding, groove binding and no binding of curcumin with DNA were reported. In this context, we conducted a detailed study to understand the mechanism of recognition of dimethylsulfoxide-solubilized curcumin by DNA. The interaction of curcumin with calf thymus DNA (ctDNA) was confirmed by agarose gel electrophoresis. The nature of binding and energetics of interaction were studied by Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC), UV-visible, fluorescence and melting temperature (Tm) analysis. The experimental data were compared with molecular modeling studies. Our investigation confirmed that dimethylsulfoxide-solubilized curcumin binds in the minor groove of the ctDNA without causing significant structural alteration to the DNA.
Chen, Deying; Su, Xiaoling; Wang, Nan; Li, Yunong; Yin, Hua; Li, Liang; Li, Lanjuan
We report a chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) method generally applicable for tracking metabolomic changes from samples collected in an animal model for studying disease development and treatment. A rat model of surgically induced osteoarthritis (OA) was used as an example to illustrate the workflow and technical performance. Experimental duplicate analyses of 234 plasma samples were carried out using dansylation labeling LC-MS targeting the amine/phenol submetabolome. These samples composed of 39 groups (6 rats per group) were collected at multiple time points with sham operation, OA control group, and OA rats with treatment, separately, using glucosamine/Celecoxib and three traditional Chinese medicines (Epimedii folium, Chuanxiong Rhizoma and Bushen-Huoxue). In total, 3893 metabolites could be detected and 2923 of them were consistently detected in more than 50% of the runs. This high-coverage submetabolome dataset could be used to track OA progression and treatment. Many differentiating metabolites were found and 11 metabolites including 2-aminoadipic acid, saccharopine and GABA were selected as potential biomarkers of OA progression and OA treatment. This study illustrates that CIL LC-MS is a very useful technique for monitoring incremental metabolomic changes with high coverage and accuracy for studying disease progression and treatment in animal models. PMID:28091618
Li, Ying-hong; Wang, Xu-sheng; Chen, Xiao-lin; Jin, Yu; Chen, Hong-bo; Jia, Xiu-qin; Zhang, Yong-feng; Wu, Zheng-zhi
Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.
Bose, Shambhunath; Han, Kyung-Wan; Lee, Myeong-Jong
Disturbance in the gut microbial niche by antibiotics like neomycin produces gastrointestinal (GI) disorders. Here, we evaluated the impact of a mixture of extracts of three herbs (Atractylodis Rhizoma Macrocephalae, Massa Medicata Fermentata, and Dolichoris Semen) with known GI protective activities, either laboratory unfermented (herbal formulation-1 (HF-1)) or fermented/re-fermented (herbal formulation-2 (HF-2)) on neomycin-treated rats using a commercial Lactobacillus probiotic as a reference. Treatment with neomycin augmented stool water content, decreased fecal population of Lactobacillus spp., changed the histology of intestine without inducing inflammation, reduced the colonic expression of zonula occludens-1 (ZO-1) and claudin-1, and elevated the serum C-reactive protein (CRP) and interferon-gamma (IFN-γ) levels. Coadministration of either HF-2 or probiotic, but not HF-1, restored the fecal content of Lactobacillus spp., normalized the serum CRP level, and significantly increased the colonic expression of ZO-1 and claudin-1 in neomycin-treated rats. The combined treatment with any of the above agents ameliorated the histological changes of cecum and colon in neomycin-treated rats, and the magnitude of this effect was probiotic > HF-2 > HF-1. Our study revealed the intestinal protective effect of a mixture of three herbs against neomycin insult, which is mediated through multiple mechanisms and is potentiated upon prior fermentation/refermentation of the herbs. PMID:23690835
Yan, Dan; Li, Junxian; Xiong, Yin; Zhang, Congen; Luo, Jiaoyang; Han, Yumei; Wang, Ruiling; Jin, Cheng; Qian, Hong; Li, Jiangyu; Qiu, Lingling; Peng, Cheng; Lin, Yuling; Song, Xueai; Xiao, Xiaohe
To identify major active constituents and measure their levels in a typical medicinal herb–Rhizoma coptidis, we applied the concept of removing and adding, taking inspiration from functional genetic methods. As this herb has bacteriostatic properties and is used to treat bacterial diarrhea, we examined the effects of individual constituents (berberine, palmatine, coptisine, epiberberine, jateorrhizine and columbamine) on the growth of Shigella dysenteriae with microcalorimetry. The removing and adding procedures revealed that berberine and coptisine were the main antibacterial constituents of R. coptidis, with bacteriostatic activities of 54.10% and 39.75%, respectively. The relative levels of berberine and coptisine in R. coptidis were 8.08%–31.92% and 4.05%–14.45%, respectively. On the basis of whole effect, the method of constituents removing and adding, coupled with a bioassay, is a useful strategy to identify the active constituents and measure their levels in herbal medicines, which may provide reference to other natural products. PMID:24413194
Zhong, Zhang-Feng; Qiang, Wen-An; Wang, Chun-Ming; Tan, Wen; Wang, Yi-Tao
Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anti-cancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ERα-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ERα protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ERα-positive MCF-7 cells. Actually, ERα-knockdown cells were more sensitive than ERα positive cells to furanodiene on the cytotoxicity effect. So the anti-cancer effects of furanodiene and non-steroidal agent in breast cancer cells still requires further investigation. Our results showed that furanodiene exposure could enhance growth inhibitory effects of doxorubicin in ERα-negative MDA-MB-231 cells and ERα-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ERα-positive breast cancer cells, non-tumorigenic breast epithelial cells, macrophage cells, hepatocytes cells, pheochromocytoma cells and cardiac myoblasts cells. Furanodiene enhances the anti-cancer effects of doxorubicin in ERα-negative breast cancer cells through suppressing cell viability via inducing apoptosis in mitochondria-caspases-dependent and reactive oxygen species-independent manners. These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future.
Emanuele, S M; Staples, C R
An in vitro technique and an in situ technique were used to measure release of Ca, Mg, P and Zn over time from hand-clipped alfalfa (Medicago sativa L.). Maximal release of P and Zn was greater using the in situ technique. 'Florida 77' alfalfa (Medicago sativa L.), 'Florigraze' rhizoma peanut (Arachis glabrata Benth.), 'Mott' dwarf elephantgrass (Pennisetum purpureum Schum.), 'Tifton 78' bermudagrass (Cynodon dactylon (L) Pers.), 'Pensacola' bahiagrass (Paspalum notatum Flugge) and 'Floralta' limpograss (Hemarthria altissima (Poir.) Stapf and Hubbard) were used to examine the ruminal release of Ca, Mg, P, K, Cu and Zn by means of the in situ technique. Minerals were ranked from highest to lowest for extent of immediate and maximal release in the rumen. Averaged across forage species, ranking was K at 100% and 100%, Mg at 82% and 95%, Cu at 71% and 84%, P at 66% and 80%, Zn at 26% and 69% and Ca at 29% and 70%. A large proportion of Ca was associated with the plant cell wall, based on the duration of incubation time needed to maximize its release and the large fractinal amount of Ca slowly released. A large portion of the Zn was released slowly as well (mean, 43.8%), but release of Zn was maximal in less than 24 h. Most of the Mg, K, P and Cu probably reside in the cell contents. Forages with high NDF concentrations can have high release coefficients for their minerals.
Lee, Kuo-Hsiung; Morris-Natschke, Susan L; Yang, Xiaoming; Huang, Rong; Zhou, Ting; Wu, Shou-Fang; Shi, Qian; Itokawa, Hideji
This article will review selected herbal products used in traditional Chinese medicine, including medicinal mushrooms ( bā xī mó gū; Agaricus blazei, yún zhī; Coriolus versicolor, líng zhī; Ganoderma lucidum, xiāng xùn; shiitake, Lentinus edodes, niú zhāng zhī; Taiwanofungus camphoratus), Cordyceps ( dōng chóng xià cǎo), pomegranate ( shí liú; Granati Fructus), green tea ( lǜ chá; Theae Folium Non Fermentatum), garlic ( dà suàn; Allii Sativi Bulbus), turmeric ( jiāng huáng; Curcumae Longae Rhizoma), and Artemisiae Annuae Herba ( qīng hāo; sweet wormwood). Many of the discussed herbal products have gained popularity in their uses as dietary supplements for health benefits. The review will focus on the active constituents of the herbs and their bioactivities, with emphasis on the most recent progress in research for the period of 2003 to 2011.
Ni, Jin; Romero-Weaver, Ana L.; Kennedy, Ann R.
Si-Wu-Tang (SWT) is a decoction consisting of a mixture of ingredients of Rehmanniae Radix, Angelica Radix, Chuanxiong Rhizoma and Paeoniae Radix. As a traditional Chinese herbal decoction, SWT has been widely used for the treatment of diseases characterized as blood and/or energy deficit. The present study was performed to evaluate the effects of SWT on the different populations of circulating white blood cells (WBCs) and gastrointestinal changes in γ-ray irradiated mice. Female mice were treated daily with orally administered SWT seven days before irradiation, until one day before irradiation or until one day before sample collection. WBC counts were determined from peripheral blood samples taken from the mice at different times post-irradiation. Hematoxylin and eosin (H&E) staining, as well as immunohistochemical analysis of fibrinogen, were utilized to evaluate the effects of SWT in the intestines of mice after radiation exposure. The results of the present studies demonstrate that SWT has protective effects against radiation damage to circulating WBCs, specifically to lymphocytes, and to the gastrointestinal tract of the irradiated animals. PMID:25324699
Jiang, Shiyu; Ling, Chunhua; Li, Wei; Jiang, Hongxin; Zhi, Qiaoming; Jiang, Min
Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.
ZHU, YU; MA, NAN; LI, HUI-XIANG; TIAN, LIN; BA, YU-FENG; HAO, BIN
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
Fu, Kaiqiang; Lv, Xiaopei; Li, Weishi; Wang, Yu; Li, Huatao; Tian, Wenru; Cao, Rongfeng
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.
Yu, Chao; Tan, Shanjun; Zhou, Chunyu; Zhu, Cuilin; Kang, Xin; Liu, Shuai; Zhao, Shuang; Fan, Shulin; Yu, Zhen; Peng, Ai; Wang, Zhen
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.
Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian
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.
Bao, Jiaolin; Huang, Borong; Zou, Lidi; Chen, Shenghui; Zhang, Chao; Zhang, Yulin; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao; He, Chengwei
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.
Mishan, M A; Ahmadiankia, N; Matin, M M; Heirani-Tabasi, A; Shahriyari, M; Bidkhori, H R; Naderi-Meshkin, H; Bahrami, A R
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.
Tang, Li-Qin; Wei, Wei; Chen, Li-Ming; Liu, Sheng
Berberine is the major active constituent of Rhizoma coptidis. The present study was carried out to investigate the effect of berberine on diabetes in rats and its possible mechanisms. Diabetes was induced by tail vein injection with alloxan in Wistar rats. The amount of alloxan administered was 55 mg/kg. Diabetic rats were fed with a high-cholesterol diet. The fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), nitric oxide (NO) levels in serum and malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-px) contents in heart tissue were assayed by spectrophotometry. Pancreas samples collected after 3 weeks of alloxan treatment were stained with hematoxylin-eosin (HE) and examined under a light microscope, and scored. Intragastric administration of berberine (100 and 200 mg/kg) significantly decreased fasting blood glucose levels, serum content of TC, TG, LDL-c, and effectively increased HDL-c, NO level in diabetic rats. Furthermore, berberine treatment significantly blocked the increase of MDA, increased SOD and GSH-px levels in diabetic rats. Histopathological scores showed that berberine had restored the damage of pancreas tissues in rats with diabetes mellitus. The results showed berberine significantly inhibited the progression of diabetes induced by alloxan, and the inhibitory effect of berberine on diabetes might be associated with its hypoglycemic effect, modulating lipids metabolic effects and its ability to scavenge free radical.
Shen, Ning; Huan, Yi; Shen, Zhu-fang
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.
Kwon, Mihwa; Choi, Young A; Choi, Min-Koo; Song, Im-Sook
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.
Wang, Juan; Huang, Fengxiang; Bai, Zhun; Chi, Bixia; Wu, Jiacai; Chen, Xu
Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK), which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose) polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy. PMID:26307972
Wang, Juan; Huang, Fengxiang; Bai, Zhun; Chi, Bixia; Wu, Jiacai; Chen, Xu
Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK), which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose) polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.
Mohammadi, Ali; Mansoori, Behzad; Baradaran, Behzad
MicroRNAs' expression profiles have recently gained major attention as far as cancer research is concerned. MicroRNAs are able to inhibit target gene expression via binding to the 3' UTR of target mRNA, resulting in target mRNA cleavage or translation inhibition. MicroRNAs play significant parts in a myriad of biological processes; studies have proven, on the other hand, that aberrant microRNA expression is, more often than not, associated with the growth and progression of cancers. MicroRNAs could act as oncogenes (oncomir) or tumor suppressors and can also be utilized as biomarkers for diagnosis, prognosis, and cancer therapy. Recent studies have shown that such herbal extracts as Shikonin, Sinomenium acutum, curcumin, Olea europaea, ginseng, and Coptidis Rhizoma could alter microRNA expression profiles through inhibiting cancer cell development, activating the apoptosis pathway, or increasing the efficacy of conventional cancer therapeutics. Such findings patently suggest that the novel specific targeting of microRNAs by herbal extracts could complete the restriction of tumors by killing the cancerous cells so as to recover survival results in patients diagnosed with malignancies. In this review, we summarized the current research about microRNA biogenesis, microRNAs in cancer, herbal compounds with anti-cancer effects and novel strategies for employing herbal extracts in order to target microRNAs for a better treatment of patients diagnosed with cancer.
Lee, Kuo-Hsiung; Morris-Natschke, Susan L.; Yang, Xiaoming; Huang, Rong; Zhou, Ting; Wu, Shou-Fang; Shi, Qian; Itokawa, Hideji
This article will review selected herbal products used in traditional Chinese medicine, including medicinal mushrooms (巴西蘑菇 bā xī mó gū; Agaricus blazei, 雲芝 yún zhī; Coriolus versicolor, 靈芝 líng zhī; Ganoderma lucidum, 香蕈 xiāng xùn; shiitake, Lentinus edodes, 牛樟芝 niú zhāng zhī; Taiwanofungus camphoratus), Cordyceps (冬蟲夏草 dōng chóng xià cǎo), pomegranate (石榴 shí liú; Granati Fructus), green tea (綠茶 lǜ chá; Theae Folium Non Fermentatum), garlic (大蒜 dà suàn; Allii Sativi Bulbus), turmeric (薑黃 jiāng huáng; Curcumae Longae Rhizoma), and Artemisiae Annuae Herba (青蒿 qīng hāo; sweet wormwood). Many of the discussed herbal products have gained popularity in their uses as dietary supplements for health benefits. The review will focus on the active constituents of the herbs and their bioactivities, with emphasis on the most recent progress in research for the period of 2003 to 2011. PMID:24716120
Man, Sui Cheung; Chan, Kam Wa; Lu, Jia-Hong; Durairajan, Siva Sundara Kumar; Liu, Liang-Feng; Li, Min
We present a systematic review of existing research that aims to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (OM), mainly comprised of cholinesterase inhibitors, for vascular dementia (VaD). We included 47 studies conducted in mainland China, each testing different HM. Of 43 HM monotherapy studies, 37 reported HM to be significantly better than OM or placebo; six reported similar efficacy between HM and OM. All four HM adjuvant studies reported significant efficacy. No major adverse events for HM were reported. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies suggested that HM can be a safe and effective treatment for VaD, either alone or in conjunction with OM. However, methodological flaws in the design of the studies limited the extent to which the results could be interpreted. Thirty most commonly used herbal constituents, including Rhizoma Chuanxiong (Chuanxiong in Chinese), Radix Polygoni Multiflori (Heshouwu in Chinese) and Radix Astragali (Huangqi in Chinese). were ranked. Further multi-center trials with large sample sizes, high methodological quality and standardized HM ingredients are necessary for clinical recommendations to be made. PMID:22235231
Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho
Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.
Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung-Tae
The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans.
Qualitative and quantitative analysis of multiple components for quality control of Deng-Zhan-Sheng-Mai capsules by ultra high performance liquid chromatography tandem mass spectrometry method coupled with chemometrics.
Jiang, Pin; Lu, Yan; Chen, Daofeng
Deng-Zhan-Sheng-Mai capsules are a well-known traditional Chinese patent medicine that was developed in China for the treatment of ischemic stroke. Its quality control focuses on Erigerontis Herba but ignores the contributions of Ginseng Radix et Rhizoma, Schisandrae Chinensis Fructus, and Ophiopogonis Radix. To improve the quality standards for this medicine, this work reports the application of a systematic ultra high performance liquid chromatography tandem mass spectrometric method coupled with chemometrics. Three qualitative and quantitative parameters are established for the evaluation of quality: chemical profiling, the relationship between the contents of 18 compounds and the antioxidant activity, and chemometric analysis. A total of 55 compounds, including 20 phenolic acids, 10 flavonoids, 15 saponins, and 10 lignans, were identified. The method for the quantitative determination of the aforementioned 18 compounds was validated. The limit of quantification ranged from 0.13 to 9.60 ng/mL. The overall recoveries ranged from 95.31 to 103.54%. Hierarchical cluster analysis and principal component analysis were applied to the data of 18 components in ten batches of samples. Nine compounds, including scutellarin, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ophiopogonin D, schisandrin, and schisandrol B, are suggested as chemical markers for evaluating the quality.
Dong, Hui; Yan, Guang-Li; Han, Ying; Sun, Hui; Zhang, Ai-Hua; Li, Xian-Na; Wang, Xi-Jun
Chuanwu (CW), a famous traditional Chinese medicine (TCM) from the mother roots of Aconitum carmichaelii Debx.. (Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao (Radix Glyeyrrhizae, CG), Baishao (Radix Paeoniae Alba, CS) and Ganjiang (Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.
Zhang, Qian; Wang, Junsong; Liao, Shanting; Li, Pei; Xu, Dingqiao; Lv, Yan; Yang, Minghua; Kong, Lingyi
Optimal drug proportions and mechanism deciphering of multicomponent drugs are critical for developing novel therapies to cope with complex diseases, such as stroke. In the present study, orthogonal experimental design was applied to explore the optimal proportion of the four component herbs in Huang-Lian-Jie-Du-Decoction (HLJDD) on the treatment of ischemic stroke. The treatment efficacies and mechanisms were assessed using global and amino acids (AAs) targeted metabolomics, as well as correlation network analysis. The global NMR metabolomics results revealed that AAs metabolism was significantly perturbed in middle cerebral artery occlusion rats. The levels of 23 endogenous AAs were then subjected to HPLC-QTOF-MS/MS analysis. These results complemented with neurobehavioral evaluations, cerebral infarct assessments, biochemical evaluations, histological inspections and immunohistochemistry observations strongly demonstrated that HLJDD with optimal proportion of 6 (Rhizoma coptidis): 4 (Radix scutellariae): 1 (Cortex phellodendr): 3 (Fructus Gardeniae) had the best efficacy on ischemic stroke, which could be ascribed to its modulation on AA metabolism. This integrated metabolomics approach showed the potential and applicable in deciphering the complex mechanisms of traditional Chinese medicine formulae on the treatment of complicated diseases, which provided new means to assess the treatment effects of herb combinations and to further development of drugs or therapies based on these formulae.
Chen, Deying; Su, Xiaoling; Wang, Nan; Li, Yunong; Yin, Hua; Li, Liang; Li, Lanjuan
We report a chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) method generally applicable for tracking metabolomic changes from samples collected in an animal model for studying disease development and treatment. A rat model of surgically induced osteoarthritis (OA) was used as an example to illustrate the workflow and technical performance. Experimental duplicate analyses of 234 plasma samples were carried out using dansylation labeling LC-MS targeting the amine/phenol submetabolome. These samples composed of 39 groups (6 rats per group) were collected at multiple time points with sham operation, OA control group, and OA rats with treatment, separately, using glucosamine/Celecoxib and three traditional Chinese medicines (Epimedii folium, Chuanxiong Rhizoma and Bushen-Huoxue). In total, 3893 metabolites could be detected and 2923 of them were consistently detected in more than 50% of the runs. This high-coverage submetabolome dataset could be used to track OA progression and treatment. Many differentiating metabolites were found and 11 metabolites including 2-aminoadipic acid, saccharopine and GABA were selected as potential biomarkers of OA progression and OA treatment. This study illustrates that CIL LC-MS is a very useful technique for monitoring incremental metabolomic changes with high coverage and accuracy for studying disease progression and treatment in animal models.
Iizuka, Norio; Hamamoto, Yoshihiko
Constipation is characterized by a variety of bowel symptoms such as difficulty passing stool, hard stool, and a feeling of incomplete evacuation. The multifactorial causes of constipation limit the clinical efficacy of current conventional treatments that use a single drug that acts through only one pathway. To complement the shortcomings of the current Western medical model and provide a complete holistic approach, herbal medicines capable of targeting multiple organs and cellular sites may be used. In Japan, many herbs and herbal combinations have traditionally been used as foods and medicines. Currently, Japanese physicians use standardized herbal combinations that provide consistent and essential quality and quantity. This review highlights representative Japanese herbal medicines (JHMs), Rhei rhizoma-based JHMs including Daiokanzoto and Mashiningan, and Kenchuto-based JHMs including Keishikashakuyakuto and Daikenchuto, which coordinate the motility of the alimentary tract. This review provides a framework to better understand the clinical and pharmacological efficacies of JHMs on constipation according to the unique theory of Japanese traditional medicine, known as Kampo medicine. PMID:25904866
Hou, Jipeng; He, Xin; Xu, Xuefang; Shi, Xiaoyan; Xu, Yanyan; Liu, Changxiao
The aim of this study was to evaluate the oral absorption of two chemicals simultaneously using a drug dissolution/absorption simulating system (DDASS), and to establish a correlation between DDASS and in vivo absorption to clarify the prediction of this in vitro model. Ferulic acid (FA) and tetrahydropalmatine (THP), the components of Angelicae Sinensis Radix and Corydalis Yanhusuo Rhizoma, respectively, were chosen as model compounds. Three groups including FA, THP, and FA and THP together (FA + THP) were studied in DDASS. The corresponding in vivo pharmacokinetics study was performed in rats. Then the correlation was analysed between DDASS permeation in vitro and rat absorption data in vivo. A strong level A correlation (r > 0.84) was obtained after a correlation coefficient test (p < 0.05 or 0.01). Moreover, when FA and THP were used together in DDASS, the cumulative permeation of FA increased by 38.5%, while THP permeation decreased by 25.8%. In rats, the area under the concentration-time curve from time to infinity for FA increased 2.6-fold, while THP decreased 19.6%. The changes in rat intestinal permeation modeled by the DDASS were consistent with the absorption changes in rats. We conclude that DDASS is a valid in vitro model to evaluate oral absorption of two drug components simultaneously and reflect the in vivo characteristics of drug absorption accurately.
Lou, Jian-Shu; Yan, Lu; Bi, Cathy W. C.; Chan, Gallant K. L.; Wu, Qi-Yun; Liu, Yun-Le; Huang, Yun; Yao, Ping; Du, Crystal Y. Q.; Dong, Tina T. X.; Tsim, Karl W. K.
Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP)-resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug-resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling. PMID:27558312
Bhutada, Pravinkumar; Mundhada, Yogita; Bansod, Kuldeep; Hiware, Rahul; Rathod, Sumit; Dixit, Pankaj; Mundhada, Dharmendra
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.
Zhu, Yu; Ma, Nan; Li, Hui-Xiang; Tian, Lin; Ba, Yu-Feng; Hao, Bin
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.
Kim, Sung-Ho; Lee, Song-Eun; Oh, Heon; Kim, Se-Ra; Yee, Sung-Tae; Yu, Young-Beob; Byun, Myung-Woo; Jo, Sung-Kee
We evaluated the effect of bu-zhong-yi-qi-tang, a prescription of traditional Oriental medicine, and its major ingredients on protection of the intestine and hematopoietic organs against radiation damage in this study. The jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells were investigated in mice irradiated with high and low doses of gamma-rays. bu-zhong-yi-qi-tang administration before irradiation protected the jejunal crypts (p < 0.0001), increased the formation of the endogenous spleen colony (p < 0.05) and reduced the frequency of radiation-induced apoptosis (p < 0.05). In experiments on the effects of the individual ingredient of bu-zhong-yi-qi-tang, Rensan (Radix Ginseng), Danggui (Radix Angelicae gigantis), Shengma (Rhizoma Cimicifugae) and Chaihu (Radix Bupleuri) might have major radioprotective effects, and each might have different degrees of effect on these three endpoints. These results indicated that bu-zhong-yi-qi-tang might be a better agent than any one of its ingredients to satisfy all three endpoints. Although the mechanisms of this inhibitory effect remain to be elucidated, these results indicated that bu-zhong-yi-qi-tang might be a useful radioprotector, especially since it is a relatively non-toxic natural product. Further studies are needed to better characterize the protective nature of bu-zhong-yi-qi-tang extract and its ingredients.
Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei
Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.
Haris, P.; Mary, Varughese; Aparna, P.; Dileep, K. V.; Sudarsanakumar, C.
Curcumin is a natural phytochemical from the rhizoma of Curcuma longa, the popular Indian spice that exhibits a wide range of pharmacological properties like antioxidant, anticancer, anti-inflammatory, antitumor, and antiviral activities. In the published literatures we can see different studies and arguments on the interaction of curcumin with DNA. The intercalative binding, groove binding and no binding of curcumin with DNA were reported. In this context, we conducted a detailed study to understand the mechanism of recognition of dimethylsulfoxide-solubilized curcumin by DNA. The interaction of curcumin with calf thymus DNA (ctDNA) was confirmed by agarose gel electrophoresis. The nature of binding and energetics of interaction were studied by Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC), UV-visible, fluorescence and melting temperature (Tm) analysis. The experimental data were compared with molecular modeling studies. Our investigation confirmed that dimethylsulfoxide-solubilized curcumin binds in the minor groove of the ctDNA without causing significant structural alteration to the DNA.
The Profiling and Identification of the Absorbed Constituents and Metabolites of Guizhi Decoction in Rat Plasma and Urine by Rapid Resolution Liquid Chromatography Combined with Quadrupole-Time-of-Flight Mass Spectrometry
Xiang, Hongjun; Zhang, Lishi; Song, Jiannan; Fan, Bin; Nie, Yinglan; Bai, Dong; Lei, Haimin
Guizhi decoction (GZD), a well-known traditional Chinese medicine (TCM) prescription consisting of Ramulus Cinnamomi, Radix Paeoniae Alba, Radix Glycyrrhizae, Fructus Jujubae and Rhizoma Zingiberis Recens, is usually used for the treatment of common colds, influenza, and other pyretic conditions in the clinic. However, the absorbed ingredients and metabolic compounds of GZD have not been reported. In this paper, a method incorporating rapid resolution liquid chromatography (RRLC) with quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) was used to identify ingredients after oral administration of GZD. Identification of the primary components in GZD, drug-containing serum and urine samples was carried out in order to investigate the assimilation and metabolites of the decoction in vivo. By comparing the total ion chromatograms (TICs) of GZD, a total of 71 constituents were detected or characterized. By comparing TICs of blank and dosed rat plasma, a total of 15 constituents were detected and identified as prototypes according to their retention time (tR) and MS, MS/MS data. Based on this, neutral loss scans of 80 and 176 Da in samples of rat plasma and urine helped us to identify most of the metabolites. Results showed that the predominant metabolic pathways of (epi) catechin and gallic acid were sulfation, methylation, glucuronidation and dehydroxylation; the major metabolic pathways of flavone were hydrolysis, sulfation and glucuronidation. Furthermore, degradation, oxidation and ring fission were found to often occur in the metabolism process of GZD in vivo. PMID:27626411
Zhao, Huai-Bin; Hong, Yan-Long; Wang, You-Jie; Shen, Lan; Wu, Fei; Feng, Yi; Ruan, Ke-Feng
The paper is to report the establishment of an HPLC specific chromatogram of Glycyrrhiza in Sini decoctions and the influence of combination on the specific chromatogram. The RP-HPLC method was used with a Phenomenex Gemini C18 column (250 mm x 4.6 mm ID, 5 microm), and acetonitrile-0.05% trifluoroacetic acid (gradient elution) as mobile phase. Flow rate was 0.8 mL x min(-1) and the detection wavelength was set at 232 nm. The temperature of column was 30 degrees C. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions. Twenty peaks were selected as specific peaks in Sini Decoction with liquiritin peak as the reference peak. Six of them were from Glycyrrhiza and the other 6 peaks were from both Glycyrrhiza and Ganjiangfuzi Decoction. The areas of specific peaks of Sini Decoctions were smaller than those in the chromatogram of Glycyrrhiza. The specific chromatogram of Glycyrrhiza in Sini Decoctions is markedly influenced by Radix Aconiti Carmichaeli and Rhizoma Zingiberis. The areas of the specific peaks in Sini Decoctions were reduced obviously. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions.
Bi, Cathy W C; Xu, Li; Tian, Xiao Yu; Liu, Jian; Zheng, Ken Y Z; Lau, Chi Wai; Lau, David T W; Choi, Roy C Y; Dong, Tina T X; Huang, Yu; Tsim, Karl W K
Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.
Gong, Xingchu; Li, Yao; Qu, Haibin
The alkaline ethanol precipitation process is investigated as an example of a technique for the removal of tannins extracted from Salviae miltiorrhizae Radix et Rhizoma for the manufacture of Danshen injection. More than 90% of the tannins can be removed. However, the recoveries of danshensu, rosmarinic acid, and salvianolic acid B were less than 60%. Total tannin removal increased as the refrigeration temperature decreased or the amount of NaOH solution added increased. Phenolic compound recoveries increased as refrigeration temperature increased or the amount of NaOH solution added decreased. When operated at a low refrigeration temperature, a relative high separation selectivity can be realized. Phenolic compound losses and tannin removal were mainly caused by precipitation. The formation of phenol salts, whose solubility is small in the mixture of ethanol and water used, is probably the reason for the precipitation. A model considering dissociation equilibrium and dissolution equilibrium was established. Satisfactory correlation results were obtained for phenolic compound recoveries and total tannin removal. Two important parameters in the model, which are the water content and pH value of alkaline supernatant, are suggested to be monitored and controlled to obtain high batch-to-batch consistency.
Yang, Xiao-Yan; Ye, Jing; Sun, Gui-Xia; Xue, Bao-Juan; Zhao, Yuan-Yuan; Miao, Pei-Pei; Su, Jin; Zhang, Yu-Jie
Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.
Wang, Xiaoqing; Yao, Xiao; Zhu, Zhen'an; Tang, Tingting; Dai, Kerong; Sadovskaya, Irina; Flahaut, Sigrid; Jabbouri, Said
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.
Zhang, Juan; Tang, Hongju; Deng, Ruyuan; Wang, Ning; Zhang, Yuqing; Wang, Yao; Liu, Yun; Li, Fengying; Wang, Xiao; Zhou, Libin
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.
Huang, Cheng; Zhang, Yuebo; Gong, Zhenwei; Sheng, Xiaoyan; Li, Zongmeng; Zhang, Wei; Qin, Ying
Berberine (BBR), a compound purified from Cortidis rhizoma, reduces serum cholesterol, triglycerides, and LDL-cholesterol of hypercholesterolemic patients and high fat diet fed animals, and increases hepatic LDLR mRNA and protein levels through a post-transcriptional mechanism. BBR also enhances the hypoglycemic action of insulin in diabetic animal models. Here, we show that BBR inhibits the differentiation of 3T3-L1 preadipocytes induced by DM and suppresses the mitotic clonal expansion of 3T3-L1 preadipocytes in a time- and dose-dependent manner. Gene expression analysis and Western blot analysis reveal that the BBR inhibits the mRNA and protein levels of adipogenesis related transcription factors PPARgamma and C/EBPalpha and their upstream regulator, C/EBPbeta. Reporter gene assays demonstrate that the full-length PPARgamma and alpha transcription activities are inhibited by BBR. Using real-time PCR, we have also found that the PPAR target genes that are involved in adipocyte differentiation, such as aP2, CD36, ACO, LPL, and other adipocyte markers, are suppressed by BBR. These studies suggest that BBR works on multiple molecular targets as an inhibitor of PPARgamma and alpha, and is a potential weight reducing, hypolipidemic, and hypoglycemic drug.
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
Development of an analytical method coupling cell membrane chromatography with gas chromatography-mass spectrometry via microextraction by packed sorbent and its application in the screening of volatile active compounds in natural products.
Li, Miao; Wang, Sicen; He, Langchong
Natural products (NPs) are important sources of lead compounds in modern drug discovery. To facilitate the screening of volatile active compounds in NPs, we have developed a new biochromatography method that uses rat vascular smooth muscle cells (VSMC), which are rich in L-type calcium channels (LCC), to prepare the stationary phase. This integrated method, which couples cell membrane chromatography (CMC) with gas chromatography-mass spectrometry (GC-MS) via microextraction by packed sorbent (MEPS) technology, has been termed VSMC/CMC-MEPS-GC-MS. Methodological validation confirmed its specificity, reliability and convenience. Screening results for Radix Angelicae Dahuricae and Fructus Cnidii obtained using VSMC/CMC-MEPS-GC-MS were consistent with those obtained using VSMC/CMC-offline-GC-MS. MEPS connection plays as simplified solid-phase extraction and replaces the uncontrollable evaporation operation in reported offline connections, so our new method is supposed to be more efficient and reliable than the offline ones, especially for compounds that are volatile, thermally unstable or difficult to purify. In application, senkyunolide A and ligustilide were preliminary identified as the volatile active components in Rhizoma Chuanxiong. We have thus confirmed the suitability of VSMC/CMC-MEPS-GC-MS for volatile active compounds screening in NP.
Background This study was undertaken to evaluate the beneficial effects of a modified prescription of Sutaehwan named Sutaehwan-Gami (SG), created by adding Rhizoma dioscoreae and Carthami semen to Sutaehwan, on menopausal symptoms. Methods To evaluate the estrogenic effect of SG, we first examined estrogen receptor (ER) activation by SG treatment in breast adenocarcinoma cells and confirmed the estrogenic effect of SG in vivo ovariectomized rats. The animals were randomized into four groups: Sham operated group (Sham), saline treated ovariectomized group (OVX), SG treated group (SG) and raloxifene treated group (RLX). Animals were provided with SG at a dose of 500 mg/kg bw/day and RLX at a dose of 5.4 mg/kg bw/day with standard rat pellets for 3 months. Results SG significantly increased ERα phosphorylation, and its downstream effectors, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation in breast adenocarcinoma cells. Treatment with SG reversed ovariectomy-induced uterine weight reduction and weight gain. Decreases in the levels of GOT and GPT were observed in the SG group. The significantly reduced E2β level in OVX rats was raised by treatment with SG. Moreover, SG significantly increased the phosphorylation levels of ERK and Akt in the uterus. Conclusion Taken together, these data indicate that SG has phytoestrogen-like properties through ERK and Akt activation, implying that it could be protective and beneficial for the management of menopausal symptoms. PMID:23173704
Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas
Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan), Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto), Huang Qi Wu Wu Tang (Ogikeishigomotsuto), and Shao Yao Gan Cao Tang (Shakuyakukanzoto). The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN. PMID:23983777
Chung, Ka Fai; Lee, Claire K Y
This study examined the composition of over-the-counter (OTC) sleeping pills in Hong Kong and reviewed the current knowledge about the hypnotic efficacy and safety of their major herbal and dietary supplement constituents. We conducted a cross-sectional survey of OTC sleep aids at drug stores in a residential district of 0.3 million population and literature search using MEDLINE, EMBASE, PsycINFO, China Journal Net, China Biomedical Database and relevant English and Chinese literature. We identified 17 brands of OTC sleeping pill: eleven of them were composed of mixtures of Chinese and Western herbal agents and six brands contained 3 mg of melatonin. The Chinese herbal mixture suanzaorentang, comprising zizyphi spinosi semen, poria cocos, ligusticum wallichii, anemarrhenae rhizoma and glycyrrhizae radix in ratio of 7:5:2:1:1, was the most common OTC sleeping pill available in the survey. Our literature review showed that kava, valerian and melatonin were the better-researched herbs and dietary supplements, however, the data on hypnotic efficacy and safety was inadequate to support their clinical use. More rigorous investigations of the risk-benefit relationship of herbal agents and dietary supplements used for insomnia are needed.
TIAN, YE; TENG, LI-RONG; WANG, ZHEN-ZUO; ZHAO, MIN; MENG, QING-FAN; LU, JIA-HUI; TIAN, JIAN-MING; ZHANG, WEI-WEI; ZHENG, XIAOYI; WANG, DI; TENG, LE-SHENG
Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain. PMID:26136985
Ramachandran, Umamaheswari; Manavalan, Arulmani; Sundaramurthi, Husvinee; Sze, Siu Kwan; Feng, Zhi Wei; Hu, Jiang-Miao; Heese, Klaus
Tianma (Rhizoma gastrodiae) is the dried rhizome of the plant Gastrodia elata Blume (Orchidaceae family). As a medicinal herb in traditional Chinese medicine (TCM) its functions are to control convulsions, pain, headache, dizziness, vertigo, seizure, epilepsy and others. In addition, tianma is frequently used for the treatment of neurodegenerative disorders though the mechanism of action is widely unknown. Accordingly, this study was designed to examine the effects of tianma on the proteome metabolism in differentiated human neuronal SH-SY5Y cells to explore its specific effects on neuronal signaling pathways. Using an iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomics research approach, we identified 2390 modulated proteins, out of which 406 were found to be altered by tianma in differentiated human neuronal SH-SY5Y cells. Based on the observed data, we hypothesize that tianma promotes neuro-regenerative signaling cascades by controlling chaperone/proteasomal degradation pathways (e.g. CALR, FKBP3/4, HSP70/90) and mobilizing neuro-protective genes (such as AIP5) as well as modulating other proteins (RTN1/4, NCAM, PACSIN2, and PDLIM1/5) with various regenerative modalities and capacities related to neuro-synaptic plasticity.
Li, Yan; Zhang, Jingxiao; Zhang, Lilei; Chen, Xuetong; Pan, Yanqiu; Chen, Su-Shing; Zhang, Shuwei; Wang, Zhenzhong; Xiao, Wei; Yang, Ling; Wang, Yonghua
Migraine is the most common neurovascular disorder that imparts a considerable burden to health care system around the world. However, currently there are still no effective and widely applicable pharmacotherapies for migraine patients. Herbal formulae, characterized as multiple herbs, constituents and targets, have been acknowledged with clinical effects in treating migraine, which attract more and more researchers' attention although their exact molecular mechanisms are still unclear. In this work, a novel systems pharmacology-based method which integrates pharmacokinetic filtering, target fishing and network analysis was developed and exemplified by a probe, i.e. Tianshu formula, a widely clinically used anti-migraine herbal formula in China which comprises of Rhizoma chuanxiong and Gastrodia elata. The results exhibit that 20 active ingredients of Tianshu formula possess favorable pharmacokinetic profiles, which have interactions with 48 migraine-related targets to provide potential synergistic therapeutic effects. Additionally, from systematic analysis, we speculate that R. chuanxiong as the monarch herb mediates the major targets like PTGS2, ESR1, NOS2, HTR1B and NOS3 to regulate the vascular and nervous systems, as well as the inflammation and pain-related pathways to benefit migraine patients. Meanwhile, as an adjuvant herb, G. elata may not only assist the monarch herb to improve the outcome of migraine patients, but also regulate multiple targets like ABAT, HTR1D, ALOX15 and KCND3 to modify migraine accompanying symptoms like vomiting, vertigo and gastrointestinal disorders.
Xin, Tianyi; Li, Xiaojin; Yao, Hui; Lin, Yulin; Ma, Xiaochong; Cheng, Ruiyang; Song, Jingyuan; Ni, Lianghong; Fan, Congzhao; Chen, Shilin
The adulteration of herbal products is a threat to consumer safety. Here we surveyed the species composition of commercial Rhodiola products using DNA barcoding as a supervisory method. A Rhodiola dietary supplement DNA barcode database was successfully constructed using 82 voucher samples from 10 Rhodiola species. Based on the DNA barcoding standard operating procedure (SOP), we used this database to identify 100 Rhodiolae Crenulatae Radix et Rhizoma decoction piece samples that were purchased from drug stores and hospitals. The results showed that only 36 decoction piece sequences (40%) were authentic R. crenulata, which is recorded in Chinese Pharmacopeia, whereas the other samples were all adulterants and may indicate a potential safety issue. Among the adulterants, 35 sequences (38.9%) were authenticated as R. serrata, nine sequences (10%) were authenticated as R. rosea, which is documented in the United States Pharmacopeia, and the remaining samples were authenticated as other three Rhodiola species. This result indicates decoction pieces that are available in the market have complex origins and DNA barcoding is a convenient tool for market supervision. PMID:25661009
Li, Rui; Guo, Lin-Xiu; Li, Yi; Chang, Wen-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong
Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments. This metabolomics investigation of RA was conducted in collagen-induced arthritis (CIA) rats. Liquid chromatography/mass spectrometry and multivariate statistical tools were used to identify the alteration of serum and urine metabolites associated with RA and responses to drug treatment. As a result, 45 potential metabolites associated with RA were identified. After treatment, a total of 24 biomarkers were regulated to normal like levels. Among these, PC(18:0/20:4), 9,11-octadecadienoic acid, arachidonic acid, 1-methyladenosine, valine, hippuric acid and pantothenic acid etc, were reversed in Clematis TS and C-AR groups. Tetrahydrocortisol was regulated to normal levels in Clematis TS and TP groups, while 3,7,12-trihydroxycholan-24-oic acid was regulated in C-AR and TP groups. Biomarkers like citric acid, p-cresol glucuronide, creatinine, cortolone were reversed in TP group.
Zhang, Mingyong; Le, Jian; Wen, Jun; Chai, Yifeng; Fan, Guorong; Hong, Zhanying
Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance liquid chromatography (HPLC)-UV detection was applied in rat urine for the extraction and determination of tetrahydropalmatine (THP) and tetrahydroberberine (THB), both active components in Rhizoma corydalis. Various parameters affecting the extraction efficiency, such as the type and volume of extraction and dispersive solvent, pH, etc. were evaluated. Under the optimal conditions (extraction solvent: 37 μL of chloroform, dispersive solvent: 100 μL of methanol, alkaline with 100 μL of 1 mol/L NaOH, and without salt addition), the enrichment factors of THP and THB were more than 30. The extraction recoveries were 69.8-75.8% and 72.7-77.6% for THP and THB in rat urine, respectively. Both THP and THB showed good linearity in the range of 0.025-2.5 μg/mL, and the limit of quantification was 0.025 μg/mL (S/N=10, n=6). The intra-day and inter-day precision of THP and THB were <12.6%. The relative recoveries ranged from 95.5 to 107.4% and 96.8 to 100.9% for THP and THB in rat urine, respectively. The method has been successfully applied to rat urine samples. The results demonstrated that DLLME is a very simple, rapid and efficient method for the extraction and preconcentration of THP and THB from urine samples.
Huang, Chengyi; Yu, Yufeng
Background Cisplatin remains one of the most active agents and is the mainstay of combination chemotherapy regimens against gingival squamous cell carcinoma. However, the efficacy of cisplatin is limited by its high toxicity and the development of drug resistance. β-elemene, isolated from the Chinese herb Rhizoma zedoariahas, is highly effective against malignancies and has low toxicity, but the development of β-elemene sensitizing chemotherapy in targeting the STAT3 signaling pathway remains unexplored in gingival squamous cell carcinoma. The present study was conducted to assess the chemosensitizing effects of β-elemene for enhancing the cytotoxicity of cisplatin in gingival squamous cell carcinoma. Material/Methods The gingival squamous cell carcinoma YD-38 cell line was used. MTT assay, clonogenic assay, annexin V/PI apoptosis assay, Western blot analysis, and xenograft model treatment were carried out in vitro and in vivo. Results β-elemene significantly enhanced proliferative inhibition and cisplatin induced apoptosis in gingival squamous cell carcinoma. Cisplatin combined with β-elemene decreased the expressions of p-STAT3, p-JAK2, and Bcl-2, and increased the expressions of Bax and caspase-3 significantly compared to cisplatin only treatment, as well as in the xenograft model. Conclusions The results indicated that β-elemene promoted the anti-proliferative and apoptotic effect of cisplatin by inhibiting STAT3 and blocking the JAK2-STAT3 signaling pathway in GSCC in vitro and in vivo. PMID:28355175
Kim, Hyeun Bum; Lee, Chul Young; Kim, Sung Jae; Han, Jeong Hee; Choi, Keum Hwa
The objective of this study was to evaluate effects of a combined use of extracts of medicinal herbs Taraxaumi mongolicum, Viola yedoensis Makino, Rhizoma coptidis, and Radix isatidis (MYCI) on porcine epidemic diarrhea (PED). Twenty-two 3-day-old piglets received an oral challenge with 3 × 10(3.5) TCID50 of the virulent PED virus (PEDV) in PBS or PBS only and daily oral administration of 60 mg of the MYCI mixture suspended in milk replacer or the vehicle for 7 days in a 2 × 2 factorial arrangement of treatments. Average daily gain (ADG) increased (p < 0.05) in response to the MYCI treatment in the PEDV-challenged piglets (-18 vs. 7 g for the vehicle- vs. MYCI-administered group), but not in unchallenged animals (27 vs. 28 g). Diarrhea score and fecal PEDV shedding, however, were not influenced by the MYCI treatment. The PEDV challenge caused severe intestinal villus atrophy and crypt hyperplasia, both of which were alleviated by administration of the MYCI mixture as indicated by an increase in the villus height and a decrease in the crypt depth due to the treatment. Overall, medicinal herb extracts used in this study ameliorated impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent PEDV. Therefore, our results suggest that the MYCI mixture could be used as a prophylactic or therapeutic agent against PED.
Song, Mi Young; Kang, Seok Yong; Oh, Tae Woo; Kumar, Rethineswaran Vinoth; Jung, Hyo Won; Park, Yong-Ki
The root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) is a Traditional Korean Medicine and has been commonly used for weight control. Mitochondrial dysfunction appears to be a key contributor to insulin resistance, and therefore mitochondrial targeting drugs represent an important potential strategy for the treatment of insulin resistance and obesity. In this study, the authors investigated the regulatory effects of ARA on mitochondrial function with respect to the stimulation of glucose and lipid metabolism in C2C12 myotubes. After differentiating C2C12 myotubes, cells were treated with or without different concentrations (0.2, 0.5, and 1.0 mg/mL) of ARA extract. ARA extract significantly increased the expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC1α) and the downregulations of its targets, nuclear respiratory factor-1 (NRF-1), transcription factor A (TFAM), and total ATP content in C2C12 myotubes. ARA extract also increased the expressions of PGC1α activator and of the metabolic sensors, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase and sirtuin (SIRT) 1. Furthermore, it significantly increased glucose uptake by enhancing glucose consumption and subsequently decreased FFA contents and increased carnitine palmitoyltransferase (CPT) 1b expression. Our study indicates that ARA has a potential for stimulating mitochondrial function and energy metabolism in muscle. PMID:26617661
Feng, Xue-Feng; Huang, Lu-Qi; Ge, Xiao-Guang; Yang, Lian-Ju; Yang, Jing-Yu
Making textual research on Bencao and documents, this article inquires to the origin and development of genuine medicinal herbs of Shanyao (Rhizoma Dioscoreae) on the points of change of the growing areas and the development of cultivating and processing techniques and clinical uses. The study indicates that the medicinal use of Dioscorea oposita went through several periods: the period of the use of wild D. oposita before Tang dynasty, the period of the mixed use of wild and cultivating D. oposita from Song to the middle of Qing dynasty, and the period of the main use of cultivating D. oposita after the latter stage of Qing dynasty (18th century). It considers that the growing area of genuine medicinal herbs of Shanyao appeared in Ming dynasty and finally formed "Huaishanyao" on the early of 20th century. The acknowledgement of Huaishanyao as genuine medicinal herbs is related closely to its cultivating and processing techniques and clinical uses. The development of cultivating techniques provided the resource of Shanyao, the invention of processing techniques improved its appearance and quality, and the clinical uses and practices by modern and contemporary famous medical men played an important role to the social approval and development of Huaishanyao.
Mu, Yang; Yan, Wen-Jie; Yin, Tai-Lang; Yang, Jing
Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti-inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high-fat diet (HFD)-induced spermatogenesis dysfunction. Sprague-Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B-cell lymphoma (Bcl)-xl, Bcl-associated X protein (Bax) and cleaved-caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved-caspase 3, as well as increased expression of Bcl-xl. In conclusion, the present study revealed that curcumin treatment reduced HFD-induced spermatogenesis dysfunction in male rats. PMID:27600729
Jin, Z C; Qian, J
Effects of 15 kinds of herbal drugs, vegetables and chemicals on lex-dependent sfi-SOS response were determined by micropersistent and/or pulse models induced by 4-Nitroquinoline-N-oxide (4NQO) and Mitomycin C (MMC) in Escherichia coli(E. coli) PQ37 and PQ35, respectively. Results showed the water extract of Rhizoma Polygonati (RP), Fructus Chebulae (FC), Radix Polygoni Multiflori (RPM), Fructus Ligustri Lucidi (FLL), Bulbus Fritillariae Thunbergii (BFT), shell of water chestnut with a pedicle, Chinese chives juice, and solutions of 5-Fluorouracil, Tannic acid and garlicin could inhibit SOS responses with a dose-response relationship and suggested the inhibitory effects took place both inside and outside E. coli cells. Water extract of FC, FLL, BFT, shell of water chestnut with a pedicle, Chinese chives juice and solution of 5-Fluorouracil and Tannic acid could intracellularly inhibit SOS responses induced by MMC in E. coli PQ35, and acetone extract of Grifola Frondosa (GF) could extracellularly inhibit SOS responses in E. coli PQ37 and intracellularly in PQ35 induced by 4NQO or MMC. Water extract of raw hawthorn. Radix Angelicae Duhuricae (RAD), Radix Ophiopogonis (RO), and 5-Fluorodeoxyuridine could extracellularly inhibit SOS responses induced by 4NQO in E coli PQ37. The possible mechanisms of intracellular inhibition and antidamage repair were discussed in the paper.
Yu, Hui; Lu, Cai; Chen, Jun; Gu, Wei
This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique. According to the results, alisol acetates significantly lower the TC, TG, and LDL-C concentrations of hyperlipidemic mice, while raising HDL-C concentrations. Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion, both in vivo and in vitro. Neither of these alisol acetates significantly lower the protein expression of HMG-CoA. This suggests that alisol acetates lower the TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug, which may exhibit an inhibition effect via directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group via molecular simulation. PMID:27872650
Shaw, Lee-Hsin; Lin, Lie-Chwen; Tsai, Tung-Hu
Bu-yang-huan-wu-tang (BYHWT) is one of the most popular formulated traditional Chinese medicine prescriptions, and is widely for prevention of ischemic cardio-cerebral vascular diseases and stroke-induced disability. A specific high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed and validated for simultaneous quantification of the nine main bioactive components, i.e., astragaloside I, astragaloside II, astragaloside IV, formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside, ligustilide and paeoniflorin in rat plasma after oral administration of BYHWT extract. This method was applied to investigate the pharmacokinetics in conscious and freely moving rats. No significant matrix effects were observed. The overall analytical procedure was rapid and reproducible, which makes it suitable for quantitative analysis of a large number of samples. Among them, three astragalosides and four isoflavones in A. membranaceus, ligustilide in Radix Angelicae Sinensis and Rhizoma Ligustici Chuanxiong and paeoniflorin in Radix Paeoniae Rubra were identified. This developed method was then successfully applied to pharmacokinetic studies of the nine bioactive constituents after oral administration of BYHWT extracts in rats. The pharmacokinetic data demonstrated that astragaloside I, astragaloside II, astragaloside IV and ligustilide presented the phenomenon of double peaks. The other herbal ingredients of formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside and paeoniflorin appeared together in a single and plateau absorption phase. These phenomenona suggest that these components may have multiple absorption sites, regulation of enterohepatic circulation or the gastric emptying rate, or there is ingredient-ingredient interaction. These pharmacokinetic results provide a constructive contribution to better understand the absorption mechanism of BYHWT and to support additional clinical evaluation.
Chiang, Su-yin; Lee, Pei-yi; Lai, Ming-tsung; Shen, Li-ching; Chung, Wen-sheng; Huang, Hui-fen; Wu, Kuen-yuh; Wu, Hsiu-ching
Safrole-2',3'-oxide (SAFO) is a reactive electrophilic metabolite of the hepatocarcinogen safrole, the main component of sassafras oil. Safrole occurs naturally in a variety of spices and herbs, including the commonly used Chinese medicine Xi xin (Asari Radix et Rhizoma) and Dong quai (Angelica sinensis). SAFO is the most mutagenic metabolite of safrole tested in the Ames test. However, little or no data are available on the genotoxicity of SAFO in mammalian systems. In this study, we investigated the cytotoxicity and genotoxicity of SAFO in human HepG2 cells and male FVB mice. Using MTT assay, SAFO exhibited a dose- and time-dependent cytotoxic effect in HepG2 cells with TC(50) values of 361.9μM and 193.2μM after 24 and 48h exposure, respectively. In addition, treatment with SAFO at doses of 125μM and higher for 24h in HepG2 cells resulted in a 5.1-79.6-fold increase in mean Comet tail moment by the alkaline Comet assay and a 2.6-7.8-fold increase in the frequency of micronucleated binucleated cells by the cytokinesis-block micronucleus assay. Furthermore, repeated intraperitoneal administration of SAFO (15, 30, 45, and 60mg/kg) to mice every other day for a total of twelve doses caused a significant dose-dependent increase in mean Comet tail moment in peripheral blood leukocytes (13.3-43.4-fold) and in the frequency of micronucleated reticulocytes (1.5-5.8-fold). Repeated administration of SAFO (60mg/kg) to mice caused liver lesions manifested as a rim of ballooning degeneration of hepatocytes immediately surrounding the central vein. Our data clearly demonstrate that SAFO significantly induced cytotoxicity, DNA strand breaks, micronuclei formation both in human cells in vitro and in mice. More studies are needed to explore the role SAFO plays in safrole-induced genotoxicity.
Sigua, G C; Williams, M J; Coleman, S W; Starks, R
Forage-based livestock systems have been implicated as major contributors to deteriorating water quality, particularly for phosphorus (P) from commercial fertilizers and manures affecting surface and ground water quality. Little information exists regarding possible magnitudes of nutrient losses from pastures that are managed for both grazing and hay production and how these might impact adjacent bodies of water. We examined the changes that have occurred in soil fertility levels of rhizoma peanut (Arachis glabrata Benth.)-based beef cattle pastures (n = 4) in Florida from 1988 to 2002. These pastures were managed for grazing in spring followed by haying in late summer and were fertilized annually with P (39 kg P2O5 ha(-1)) and K (68 kg K2O ha(-1)). Additionally, we investigated trends in water quality parameters and trophic state index (TSI) of lakes (n = 3) associated with beef cattle operations from 1993 to 2002. Overall, there was no spatial or temporal buildup of soil P and other crop nutrients despite the annual application of fertilizers and daily in-field loading of animal waste. In fact, soil fertility levels showed a declining trend for crop nutrient levels, especially soil P (y = 146.57 - 8.14 x year; r2= 0.75), even though the fields had a history of P fertilization and the cattle were rotated into the legume fields. Our results indicate that when nutrients are not applied in excess, cow-calf systems are slight exporters of P, K, Ca, and Mg through removal of cut hay. Water quality in lakes associated with cattle production was "good" (30-46 TSI) based on the Florida Water Quality Standard. These findings indicate that properly managed livestock operations may not be major contributors to excess loads of nutrients (especially P) in surface water.
Ahmed, Shakeel; Zhan, Chuansong; Yang, Yanyan; Wang, Xuekui; Yang, Tewu; Zhao, Zeying; Zhang, Qiyun; Li, Xiaohua; Hu, Xuebo
Atractylodes lancea (Thunb.) DC., named “Cangzhu” in China, which belongs to the Asteraceae family. In some countries of Southeast Asia (China, Thailand, Korea, Japan etc.) its rhizome, commonly called rhizoma atractylodis, is used to treat many diseases as it contains a variety of sesquiterpenoids and other components of medicinal importance. Despite its medicinal value, the information of the sesquiterpenoid biosynthesis is largely unknown. In this study, we investigated the transcriptome analysis of different tissues of non-model plant A. lancea by using short read sequencing technology (Illumina). We found 62,352 high quality unigenes with an average sequence length of 913 bp in the transcripts of A. Lancea. Among these, 43,049 (69.04%), 30,264 (48.53%), 26,233 (42.07%), 17,881 (28.67%) and 29,057(46.60%) unigenes showed significant similarity (E-value<1e-5) to known proteins in Nr, KEGG, SWISS-PROT, GO, and COG databases, respectively. Of the total 62,352 unigenes, 43,049 (Nr Database) open reading frames were predicted. On the basis of different bioinformatics tools we identify all the enzymes that take part in the terpenoid biosynthesis as well as five different known sesquiterpenoids via cytosolic mevalonic acid (MVA) pathway and plastidal methylerythritol phosphate (MEP) pathways. In our study, 6, 864 Simple Sequence Repeats (SSRs) were also found as great potential markers in A. lancea. This transcriptomic resource of A. lancea provides a great contribution in advancement of research for this specific medicinal plant and more specifically for the gene mining of different classes of terpenoids and other chemical compounds that have medicinal as well as economic importance. PMID:26990438
Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin. PMID:19292900
Gong, Zipeng; Chen, Ying; Zhang, Ruijie; Yang, Qing; Wang, Yajie; Guo, Yan; Zhou, Bingbing; Weng, Xiaogang; Liu, Xuchen; Li, Yujie; Zhu, Xiaoxin; Dong, Yu
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.
Zhou, Jiyin; Zhou, Shiwen; Tang, Jianlin; Zhang, Kebin; Guang, Lixia; Huang, Yongping; Xu, Ying; Ying, Yi; Zhang, Le; Li, Dandan
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.
Zhou, Ji Yin; Zhou, Shi Wen; Zhang, Ke Bin; Tang, Jian Lin; Guang, Li Xia; Ying, Yi; Xu, Ying; Zhang, Le; Li, Dan Dan
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.
Wu, Duo; Wen, Wei; Qi, Chun-Li; Zhao, Ru-Xia; Lü, Jun-Hua; Zhong, Chun-Yan; Chen, Yi-Yu
Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.
Li, Fen; Zhao, Yun-bin; Wang, Ding-kun; Zou, Xin; Fang, Ke; Wang, Kai-fu
Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor (α7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β (IKκβ) Ser181/IKKβ and the expression of nuclear factor-kappa B (NF-κB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of AChE activity.
Nadjafi, Shabnam; Ebrahimi, Soltan-Ahmad; Rahbar-Roshandel, Nahid
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.
Morita, Yuji; Nakashima, Ken-ichi; Nishino, Kunihiko; Kotani, Kenta; Tomida, Junko; Inoue, Makoto; Kawamura, Yoshiaki
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
Wang, Zhi-Yong; Liu, Jian-Gang; Li, Hao; Yang, Hui-Ming
Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.
Chan, Thomas Y K
In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989-2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989-1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994-1996. In the whole of Hong Kong, the incidence during 2000-June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008-2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures.
Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul
Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD
Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei
Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson's correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role.
Shaw, Lee-Hsin; Lin, Lie-Chwen; Tsai, Tung-Hu
Bu-yang-huan-wu-tang (BYHWT) is one of the most popular formulated traditional Chinese medicine prescriptions, and is widely for prevention of ischemic cardio-cerebral vascular diseases and stroke-induced disability. A specific high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed and validated for simultaneous quantification of the nine main bioactive components, i.e., astragaloside I, astragaloside II, astragaloside IV, formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside, ligustilide and paeoniflorin in rat plasma after oral administration of BYHWT extract. This method was applied to investigate the pharmacokinetics in conscious and freely moving rats. No significant matrix effects were observed. The overall analytical procedure was rapid and reproducible, which makes it suitable for quantitative analysis of a large number of samples. Among them, three astragalosides and four isoflavones in A. membranaceus, ligustilide in Radix Angelicae Sinensis and Rhizoma Ligustici Chuanxiong and paeoniflorin in Radix Paeoniae Rubra were identified. This developed method was then successfully applied to pharmacokinetic studies of the nine bioactive constituents after oral administration of BYHWT extracts in rats. The pharmacokinetic data demonstrated that astragaloside I, astragaloside II, astragaloside IV and ligustilide presented the phenomenon of double peaks. The other herbal ingredients of formononetin, ononin, calycosin, calycosin-7-O-β-d-glucoside and paeoniflorin appeared together in a single and plateau absorption phase. These phenomenona suggest that these components may have multiple absorption sites, regulation of enterohepatic circulation or the gastric emptying rate, or there is ingredient-ingredient interaction. These pharmacokinetic results provide a constructive contribution to better understand the absorption mechanism of BYHWT and to support additional clinical evaluation. PMID:22952787
Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei
Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson’s correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role. PMID:26657159
He, Kai; Ye, Xiaoli; Wu, Hao; Wang, YanZhi; Zou, Zongyao; Ning, Na; Hu, Yinran; Chen, Biao; Fang, Xuedong; Li, Xuegang
Current work was conducted to evaluate the cholesterol-lowering effect of coptisine extracted from Rhizoma coptidis in Syrian golden hamsters. The safety results indicated that coptisine was a safe and low-toxic compound. Coptisine showed a beneficial effect in the abnormal serum lipid levels induced by a high-fat and high-cholesterol diet (HFHC): at a concentration of 70.05 mg/kg, coptisine significantly led to a decrease in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-c) levels by 26.70, 15.38, and 22.22 %, respectively, and high-density lipoprotein cholesterol (HDL-c) was increased by 41.74 % in serum of hamsters (p < 0.01). In addition, total bile acid (TBA) levels in feces of hamsters were elevated after coptisine administration. Further investigation has suggested that the mRNA and protein expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) in the liver of hamsters was down-regulated by high-dosage coptisine treatment (p < 0.05); mRNA and protein expression of low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) were dramatically up-regulated by coptisine administration. The apical sodium-dependent bile salt transporter expression was down-regulated in the coptisine-treated animals, but showed no significant differences from the HFHC groups. Taken together, our results demonstrate that a high dosage of coptisine could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. These findings suggest a critical role for coptisine in anti- hypercholesterolemia, and thus it needs to be considered as a potential natural cholesterol lowering agent.
Gong, Ping; Lu, Zhidan; Xing, Jing; Wang, Na; Zhang, Yu
Paraquat poisoning causes multiple organ injury and high mortality due to severe toxicity and lack of effective treatment. Xuebijing (XBJ) injection, a traditional Chinese medicine preparation of five Chinese herbs (Radix Salviae Miltiorrhiae, Rhizoma Chuanxiong, Flos Carthami, Angelica Sinensis and Radix Paeoniae Rubra), has an anti-inflammatory effect and is widely used in the treatment of sepsis. This retrospective study was designed to evaluate the effects of XBJ combined with conventional therapy on mortality risk of patients with acute paraquat poisoning. Out of 68 patients, 27 were treated with conventional therapy (control group) and 41 were treated with intravenous administration of XBJ (100 ml, twice a day, up to 7 days) plus conventional therapy (XBJ group). Vital organ function, survival time within 28 days and adverse events during the treatment were reviewed. Results indicated that XBJ treatment significantly increased median survival time among patients ingesting 10-30 ml of paraquat (P=0.02) compared with the control group. After adjustment for covariates, XBJ treatment was associated significantly with a lower mortality risk (adjusted HR 0.242, 95% CI 0.113 to 0.516, P=0.001) compared with the control group. Additionally, compared with Day 1, on Day 3 the value of PaO2/FiO2 was significantly decreased, and the values of serum alanine aminotransferase, creatinine and troponin T were significantly increased in the control group (all P<0.05), but these values were significant improved in the XBJ group (all P<0.05). Only one patient had skin rash with itch within 30 minutes after injection and no severe adverse events were found in the XBJ group. In conclusion, XBJ treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning, which may be attributed to improved function of vital organs with no severe adverse events.
Zhang, Qi; Guo, Fei; Fu, Zhi-wen; Zhang, Bing; Huang, Cheng-gang; Li, Yang
Aim: N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. Methods: NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg−1·d−1) or a positive-control drug, fluoxetine (10 mg·kg−1·d−1) for 3 weeks. Behavioral assessments were carried out every week. Results: In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC50 value of 2.8 μmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltage-dependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. Conclusion: YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression. PMID:26687936
Liu, Xiao-qin; Li, Yun-fei; Meng, Wen-ting; Li, Dong-xiang; Sun, Henry; Tong, Ling; Sun, Guo-xiang
The present study is focused on the development of an analytical method for the simultaneous analysis of seventy-four pesticides belonging to different chemical classes (organochlorines, organophosphates, pyrethroids, dinitroanilines, dicarboximides, triazoles, etc.) in Chinese material medica. The samples were extracted according to the acetate QuEChERS protocol. To reduce the amount of co-extracted compounds, n-hexane instead of acetonitrile was employed as the extraction solvent. To improve the overall recoveries of problematic basic and base-sensitive compounds, sodium acetate was used to adjust the pH to a neutral condition, and florisil combined with octadecyl-modified silica (C18) were utilized in the cleanup step. The samples were analysed by GC-MS/MS, and quantified by matrix-matched calibration. The validation study was carried out on two representative herbs, Chuanxiong Rhizoma and Angelica Sinensis Radix. In two matrices, the linearity of the calibration was good between 5 and 250 ng/mL concentration ranges, and the limits of quantification (LOQs) less than 0.01 mg/kg for most pesticides. At the LOQs and ten times the LOQs, the mean recoveries of almost all pesticides were within 70-120%, with relative standard deviations (RSDs) lower than 10%. The method was applied on twenty real samples. Seven batches of Chuanxiong and five batches of Danggui were found to contain the residues. The combination of modified QuEChERS and GC-MS/MS offers low cost of analysis as well as excellent accuracy and sensitivity. This method could be especially useful for trace analysis of pesticide residues in complex matrices.
Han, Dongyue; Liu, Chang; Qie, Lili; Wang, Fuchun; Wang Zhaohui
To make a systematic study on acupoints selection and medication rules for allergic rhinitis treated with acupoint application, literature regarding clinical researches on acupoint application for allergic rhinitis since 2000 has been retrieved; medication and acupoints involved were preprocessed and cluster analysis technique was applied to classify the data. As a result, a total of 37 pieces of literature were included, involving 27 types of herbs and 33 acupoints. The results showed Baijiezi (Brassica alba Boiss), Xixin (Radix et Rhizoma Asari), Gansui (Radix Kansui), Yanhusuo (Corydalis), Jiangzhi (Ginger juice) and Baizhi (Radix angelicae) constituted the main herb prescription, and the layer was increased along with frequency of use. Feishu (BL 13), Dazhui (GV 14), Shenshu (BL 23), Pishu (BL 20), Gaohuang (BL 43), Fengmen (BL 12) constituted the main acupoint prescription, which were clustered into 4 classes; Feishu (BL 13) and Dazhui (GV 14) constituted the first class; Pishu (BL 20) and Shenshu (BL 23) constituted the second class; the first and second class merged into the third class, Including Feishu (BL 13), Dazhui (GV 14), Shenshu (BL 23) and Pishu (BL 20); Gaohuang (BL 43) and Fengmen (BL 12) constituted the fourth class; the fourth class and the third class constituted the whole acupoint prescription. It was showed that for the allergic rhinitis treated with acupoint application, the medication was mainly epispastic herbs with pungent nature that belonged to the lung, spleen and kidney meridian, which presented the principle of simultaneous treatment of principal and subordinate symptoms; also the medication can be selected from core layer to supporting layer based on clinical needs; for the selection of acupoints, acupoints in lung and bladder meridian were mainly selected to assist exterior and resist the pathogenic qi, which could treat allergic rhinitis fundamentally by joint use with acupoints in soleen and kidney meridian.
Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin
Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.
Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin
Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38–0.41 g/g, AWA of 3.7–4.9 g/g, and SS of 280–350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability. PMID:25101624
Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K
Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.
ZHOU, FEI; HAN, SHUYAN; ZHOU, NING; ZHENG, WENXIAN; LI, PINGPING
Aromatase inhibitors (AIs) are widely used in the treatment of hormone-dependent breast cancer and as a result, aromatase inhibitor-associated bone loss (AIBL) has become a major concern amongst patients receiving AI treatment. Modified Shu-Gan-Liang-Xue decoction (mSGLXD), a clinical prescription, has been used for ameliorating AIBL in patients with breast cancer for decades and has achieved good clinical efficacy. However, the mechanism underlying how mSGLXD influences bone homeostasis and alleviates AIBL has remained elusive. In the present study, mSGLXD was supplemented with Rhizoma Drynariae containing phytoestrogens, and the safety of mSGLXD was evaluated. mSGLXD did not possess estrogenic activity and significantly inhibited the proliferation of estrogen receptor-positive breast cancer cell line MCF-7, which suggested that mSGLXD was safe for postmenopausal patients with breast cancer. Subsequently, the effects of mSGLXD alone or in combination with anastrozole on osteoblastic MC3T3-E1 cell proliferation and differentiation were investigated. Cell counting kit-8, reverse transcription-polymerase chain reaction and biochemical methods, such as ELISA and alizarin red S staining, were used in the present study. It was revealed that mSGLXD not only stimulated MC3T3-E1 cell proliferation, but also upregulated alkaline phosphatase and osteocalcin gene and protein expression levels. High concentrations of anastrozole (10 or 100 μmol/l) markedly inhibited MC3T3-E1 cell proliferation, but this inhibitory effect was attenuated by mSGLXD. Furthermore, mSGLXD increased MC3T3-E1 cell mineralization following β-glycerophosphate and ascorbic acid induction. Therefore, the results of the present study suggested that mSGLXD may be a promising adjuvant therapy, with high safety and efficacy, for the prevention and treatment of AIBL in patients with breast cancer who receive AI treatment. PMID:25405542
Lin, Fei-xiang; Du, Shi-xin; Liu, De-zhong; Hu, Qin-xiao; Yu, Guo-yong; Wu, Chu-cheng; Zheng, Gui-zhou; Xie, Da; Li, Xue-dong; Chang, Bo
Naringin is an active compound extracted from Rhizoma Drynariae, and studies have revealed that naringin can promote proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). In this study, we explored whether naringin could promote osteogenic differentiation of BMSCs by upregulating Foxc2 expression via the Indian hedgehog (IHH) signaling pathway. BMSCs were cultured in basal medium, basal medium with naringin, osteogenic induction medium, osteogenic induction medium with naringin and osteogenic induction medium with naringin in the presence of the IHH inhibitor cyclopamine (CPE). We examined cell proliferation by using a WST-8 assay, and differentiation by Alizarin Red S staining (for mineralization) and alkaline phosphatase (ALP) activity. In addition, we detected core-binding factor α1 (Cbfα1), osteocalcin (OCN), bone sialoprotein (BSP), peroxisome proliferation-activated receptor gamma 2 (PPARγ2) and Foxc2 expression by using RT-PCR. We also determined Foxc2 and IHH protein levels by western blotting. Naringin increased the mineralization of BMSCs, as shown by Alizarin red S assays, and induced ALP activity. In addition, naringin significantly increased the mRNA levels of Foxc2, Cbfα1, OCN, and BSP, while decreasing PPARγ2 mRNA levels. Furthermore, the IHH inhibitor CPE inhibited the osteogenesis-potentiating effects of naringin. Naringin increased Foxc2 and stimulated the activation of IHH, as evidenced by increased expression of proteins that were inhibited by CPE. Our findings indicate that naringin promotes osteogenic differentiation of BMSCs by up-regulating Foxc2 expression via the IHH signaling pathway. PMID:27904711
Nafisi, Shohreh; Adelzadeh, Maryam; Norouzi, Zeinab; Sarbolouki, Mohammad Nabi
Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical with a variety of biological activities. The ongoing research and clinical trials have proved that this natural phenolic compound has great and diverse pharmacological potencies. Beside its effective antioxidant, antiinflammatory, and antimicrobial/antiviral properties, curcumin is also considered as a cancer chemopreventive agent. While the antioxidant activity of curcumin is well documented, its interaction with DNA and RNA is not fully investigated. This study was designed to examine the interactions of curcumin with calf thymus DNA and yeast RNA in aqueous solution at physiological conditions, using constant DNA and RNA concentration (6.25 mM) and various curcumin/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, and 1/10. Fourier transform infrared (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of curcumin-DNA and curcumin-RNA complexes in aqueous solution. Spectroscopic evidence showed that curcumin binds to the major and minor grooves of DNA duplex and to RNA bases as well as to the back bone phosphate group with overall binding constants of K(curcumin-DNA) = 4.255 x 10(4) M(-1) and K(curcumin-RNA) = 1.262 x 10(4) M(-1). Major DNA and RNA aggregation occurred at high pigment concentration. No conformational changes were observed upon curcumin interaction with these biopolymers; that is, DNA remains in the B, and RNA retains its A-family structure.
Han, Xue; Zhang, Ding-Kun; Guo, Yu-Ming; Feng, Wu-Wen; Dong, Qin; Zhang, Cong-En; Zhou, Yong-Feng; Liu, Yan; Wang, Jia-Bo; Zhao, Yan-Ling; Xiao, Xiao-He; Yang, Ming
Anti-influenza Chinese herbal medicines (anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most of them could not be compared using the standard evaluation methods for antiviral activity. This situation poses an obstacle to a wide application of anti-flu CHMs. Thus, it was necessary to develop an evaluation method to estimate antiviral activities of anti-flu CHMs. In the present study, we searched for anti-flu CHMs, based on clinic usage, to select study objects from commonly-used patented anti-flu Chinese medicines. Then, a neuraminidase-based bioassay, optimized and verified by HPLC method by our research group, was adopted to detect antiviral activities of selected 26 anti-flu CHMs. Finally, eight of these herbs, including Coptidis Rhizoma, Isatidis Folium, Lonicerae Flos, Scutellaria Radix, Cyrtomium Rhizome, Houttuynia Cordata, Gardeniae Fructus, and Chrysanthemi Indici Flos, were shown to have strong antiviral activities with half maximal inhibitory concentration (IC50) values being 2.02 to 6.78 mg·mL(-1) (expressed as raw materials). In contrast, the IC50 value of positive control peramivir was 0.38 mg·mL(-1). Considering the extract yields of CHMs, the active component in these herbs may have a stronger antiviral activity than peramivir, suggesting that these herbs could be further researched for active compounds. Moreover, the proposed neuraminidase-based bioassay was high-throughput and simple and could be used for evaluation and screening of anti-flu CHMs as well as for their quality control.
Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes: Herbal medicines as a case study.
Yang, Xing-Xin; Xu, Feng; Wang, Dan; Yang, Zhi-Wei; Tan, Huan-Ran; Shang, Ming-Ying; Wang, Xuan; Cai, Shao-Qing
Mitochondria are an important intracellular pharmacological target because damage to this organelle results in a variety of human disorders and because mitochondria are involved in complex processes such as energy generation, apoptosis and lipid metabolism. To expedite the search for natural bioactive compounds targeting mitochondria, we initially developed an efficient mitochondria-based screening method by combining centrifugal ultrafiltration (CU) with liquid chromatography/mass spectrometry (LC/MS), which is called screening method for mitochondria-targeted bioactive constituents (SM-MBC) and is compatible with the search of mitochondria-targeted compounds from complex matrixes such as herbal medicines extracts. Functionally active, structurally intact and pure mitochondria were obtained from rat myocardium using an optimized protocol for mitochondrial isolation comprising organelle release followed by differential and Nycodenz density gradient centrifugation. After evaluating the reliability of the method using thiabendazole (TZ), rotenone (RN), amiodarone (AR) and trimetazidine (TD) as positive controls, this method was successfully applied to screen bioactive constituents from extracts of Polygoni Cuspidati Rhizoma et Radix (PCRR) and Scutellariae Radix (SR). Nineteen active compounds were detected and identified by LC/MS, of which 17 were new mitochondria-targeted compounds. The activity of 9 of the 19 hit compounds was confirmed by in vitro pharmacological trials. These results demonstrate that SM-MBC can be used for the efficient screening of mitochondria-targeted constituents in complex preparations used to treat mitochondrial disorders, such as PCRR and SR. The results may be meaningful for an in-depth understanding of drug mechanism of action and drug discovery from medicinal herbs.
Li, Yan; Kuang, Hongying; Shen, Wenjuan; Ma, Hongli; Zhang, Yuehui; Stener-Victorin, Elisabet; Hung, Ernest; Ng, Yu; Liu, Jianping; Kuang, Haixue; Hou, Lihui; Wu, Xiaoke
Introduction Letrozole is being used as an alternative to clomiphene citrate in women with polycystic ovary syndrome (PCOS) requiring ovulation induction. Berberine, a major active component of Chinese herbal medicine rhizoma coptidis, has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS but there is no study reporting the live birth or its potential as a complementary treatment to letrozole. We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 660 infertile women with PCOS in Mainland China. Methods and analysis This study is a multicentre randomised, double-blind trial. The randomisation scheme is coordinated through the central mechanism and stratified by the participating site. Participants are randomised into one of the three treatment arms: (1) letrozole and berberine, (2) letrozole and berberine placebo, or (3) letrozole placebo and berberine. Berberine is administered three times a day (1.5 g/day) for up to 24 weeks, starting on day 1 after a spontaneous period or a withdrawal bleeding. Either letrozole or letrozole placebo 2.5 mg is given daily from day 3 to day 7 of the first three cycles and the dose is increased to 5 mg/day in the last three cycles, if not pregnant. The primary hypothesis is that the combination of berberine and letrozole results in a significantly higher live birth rate than letrozole or berberine alone. Ethics and dissemination The study was approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Study findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration ClinicalTrials.gov identifier: NCT01116167. PMID:24282248
A practical strategy for characterization of the metabolic profile of chiral drugs using combinatory liquid chromatography-mass spectrometric techniques: application to tetrahydropalmatine enantiomers and their metabolites in rat urine.
Zhang, Yinying; Dong, Xin; Le, Jian; Wen, Jun; Lin, Zebin; Liu, Yinli; Lou, Ziyang; Chai, Yifeng; Hong, Zhanying
The characterization and quantification of the metabolites of chiral drugs still remain a great challenge due to the complexity of the metabolites and most of them are not commercially available. In this study, a practical approach based on the combinatory liquid chromatography-mass spectrometric techniques has been proposed for the evaluation of metabolism profiles and urinary excretion kinetics of chiral drugs and their metabolites. Racemic tetrahydropalmatine (rac-THP), a biologically active ingredient isolated from a traditional Chinese herb Rhizoma Corydalis, was chosen as the model chiral drug. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was applied to characterize the metabolites of THP enantiomers in rat urine after administration of (+)-THP or (-)-THP. Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of these metabolites. More than 30 potential metabolites were found in rat urine, most of which were identified for the first time, and the metabolic pathways in vivo were involved in demethylation, oxidation, glucuronide conjugation and sulfation, etc. And the tridesmethlyzed metabolite and didesmethlyzed coupled with oxidation metabolite were found only in (+)-THP treated rats. Afterwards, a liquid chromatography tandem mass spectrometry (LC-QqQ/MS) assay was developed and validated for the determination of the urine level of THP enantiomers and their metabolites. Semi-quantification of three phase I metabolites and two phase II metabolites were performed. Enantiomeric (-/+) cumulative urinary excretion ratios of THP and its five metabolites were obtained, which indicated the stereoselective aspects of metabolites of THP enantiomers in vivo. The study demonstrated the enormous potential of this strategy for the qualitative characterization, quantitative assay and the stereoselectivity of chiral drugs and their
Liu, Weihua; Liu, Peiqinq; Tao, Sha; Deng, Yanhui; Li, Xuejuan; Lan, Tian; Zhang, Xiaoyan; Guo, Fenfen; Huang, Wenge; Chen, Fengying; Huang, Heqing; Zhou, Shu-Feng
Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus, is a major cause of end-stage renal disease. Berberine is one of the main constituents of Coptidis rhizoma and Cortex phellodendri. In the present study, we examined effects of berberine (BBR) on renal injury in streptozotocin-induced diabetic rats, and on the changes of aldose reductase (AR) and oxidative stress in cultured rat mesangial cells exposed to high glucose. Fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were detected by using the commercially available kits. Cell proliferation, collagen synthesis, aldose reductase (AR), superoxide anion, superoxide dismutase (SOD), and malondialdehyde (MDA) were detected, respectively, by different methods. In streptozotocin-induced diabetic rats, fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were significantly decreased in rats treated with 200 mg/kg berberine for 12 weeks compared with diabetic control rats (P < 0.05). This was accompanied by a reduced AR activity and gene expression at both mRNA and protein levels. In cultured rat mesangial cells exposed to high glucose, incubation of BBR significantly decreased cell proliferation, collagen synthesis and AR activity as well as its mRNA and protein levels compared with control cells (P < 0.05). In vitro, BBR also significantly increased SOD activity and decreased superoxide anion and MDA compared with control cells (P < 0.05). These results suggested that BBR could ameliorate renal dysfunction in DN rats, which may be ascribed to inhibition of AR in mesangium, reduction of oxidative stress, and amelioration of extracellular matrix synthesis and cell proliferation. Further studies are warranted to explore the role of AR in DN and the therapeutic implications by AR inhibitors such as BBR.
Zhu, Tao; Zhang, Wei; Feng, She-jun; Yu, Hua-peng
Inflammation is a defense and protective response to multiple harmful stimuli. Over and uncontrolled inflammation can lead to local tissues or even systemic damages and injuries. Actually, uncontrolled and self-amplified inflammation is the fundament of the pathogenesis of a variety of inflammatory diseases, including sepsis shock, acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Our recent study showed that emodin, the main active component of Radix rhizoma Rhei, could significantly ameliorate LPS-induced ALI/ARDS in mice. However, its underlying signal pathway was not still very clear. Then, the aim of current study was to explore whether emodin could attenuate LPS-induced inflammation in RAW264.7 cells, and its involved potential mechanism. The mRNA and protein expression of ICAM-1, MCP-1 and PPARγ were measured by qRCR and western blotting, the production of TNF-α was evaluated by ELISA. Then, the phosphorylation of NF-κB p65 was also detected by western blotting. And NF-κB p65 DNA binding activity was analyzed by ELISA as well. Meanwhile, siRNA-PPARγ transfection was performed to knockdown PPARγ expression in cells. Our data revealed that LPS-induced the up-regulation of ICAM-1, MCP-1 and TNF-α, LPS-induced the down-regulation of PPARγ, and LPS-enhanced NF-κB p65 activation and DNA binding activity were substantially suppressed by emdoin in RAW264.7 cells. Furthermore, our data also figured out that these effects of emdoin were largely abrogated by siRNA-PPARγ transfection. Taken together, our results indicated that LPS-induced inflammation were potently compromised by emodin very likely through the PPARγ-dependent inactivation of NF-κB in RAW264.7 cells.
Li, Depeng; Zhang, Naisheng; Cao, Yongguo; Zhang, Wen; Su, Gaoli; Sun, Yong; Liu, Zhicheng; Li, Fengyang; Liang, Dejie; Liu, Bo; Guo, Mengyao; Fu, Yunhe; Zhang, Xichen; Yang, Zhengtao
Emodin is an anthraquinone derivative from the Chinese herb Radix et Rhizoma Rhei. It has been reported that emodin possesses a number of biological properties, such as anti-inflammatory, anti-virus, anti-bacteria, anti-tumor, and immunosuppressive properties. However, the effect of emodin on mastitis is not yet known. The aim of this study was to investigate whether emodin has protective effect against lipopolysaccharide (LPS)-induced mastitis in a mouse model. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Emodin was administered intraperitoneally with the dose of 1, 2, and 4 mg/kg respectively 1h before and 12h after induction of LPS. Emodin significantly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), concentration of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), mRNA expression levels of TNF-α, IL-1β and IL-6, which were increased in LPS-induced mouse mastitis. In addition, emodin influenced nuclear factor kappa-B signal transduction pathway by inhibiting activation of nuclear transcription factor-kappaB (NF-κB) p65 and degradation inhibitor of NF-κB α (IκBα), and emodin also influenced mitogen activated protein kinases signal transduction pathway by depression activation of p38, extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). In conclusion, these results indicated that emodin could exert beneficial effects on experimental mastitis induced by LPS and may represent a novel treatment strategy for mastitis.
Satoh, K; Nagai, F; Kano, I
Hinesol, a major component of the crude drug "So-jutsu" (Atractylodis Lanceae Rhizoma), strongly inhibited H+,K+-ATPase activity with a IC50 value of 5.8x10(-5) M. It also inhibited Na+,K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and H+-ATPase activities, although the inhibition rate was lower. No effects on alkaline or acid phosphatase activities were observed. The mechanism by which hinesol inhibited H+,K+-ATPase activity was studied in detail. The inhibition was uncompetitive with respect to ATP, and it increased as the Mg2+ concentration was raised, whereas it was not affected by the K+ concentration. The activity of K+-dependent p-nitrophenyl phosphatase (K+-pNPPase), a partial reaction of H+,K+-ATPase, was inhibited by hinesol noncompetitively with respect to pNPP (IC50 value of 1.6x10(-4) M), and competitively with respect to K+, whereas it was not affected by the Mg2+ concentration. These results suggest that hinesol is a relatively specific inhibitor of H+,K+-ATPase. It appears that hinesol reacts with enzyme in the E1 state in the presence of ATP and Mg2+ and forms the complex hinesol-H+ E1-ATP or hinesol x E1-P, blocking the conformational change to the E2 state. Furthermore, hinesol enhanced the inhibitory effect of omeprazole on H+,K+-ATPase, and the inhibitory site of hinesol was different from that of omeprazole. The effect of So-jutsu as an anti-gastric ulcer agent may be ascribed to the inhibitory effect of hinesol on H+,K+-ATPase activity.
Wang, Ping-Han; Zhao, Li-Xue; Wan, Jing-Yu; Zhang, Liang; Mao, Xiao-Na; Long, Fang-Yi; Zhang, Shuang; Chen, Chu; Du, Jun-Rong
Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.
Guo, K J; Xu, S F; Yin, P; Wang, W; Song, X Z; Liu, F H; Xu, J Q; Zoccarato, I
Many traditional Chinese medicine (TCM) decoctions are proven to have multiple functions in animal production. These decoctions are seldom recognized by the international scientific community because the mechanisms of action are not clearly elucidated. According to TCM theory, Cortex Phellodendri (COP), Rhizoma Atractylodes (RA), Agastache Rugosa (AR), and Gypsum Fibrosum (GF) can be used to formulate a medicinal compound that prevents or cures animal disease caused by heat stress. The aim of this research was to study the regulatory functions of the active components of TCM and to elucidate the effects of different TCM decoctions on antioxidant activity and lipid peroxide content, using in vitro and in vivo models of heat stress. For in vitro experiments, intestinal crypt-like epithelial cell line-6 (IEC-6) cells were employed to evaluate the effects of the active components of COP, RA, AR, and GF. For in vivo experiments, forty-eight 2-mo-old Chinese experimental mini-pigs (7.20 ± 0.02 kg) were randomly assigned to 4 groups: a normal-temperature group (NTG); a high-temperature group (HTG); HTG treated with COP, RA, AR, and GF (1:1:1:1, TCM1); and HTG treated with COP, RA, AR, and GF (1:1:1:0.5, TCM2). Results showed that the active components of the COP, RA, AR, and GF increased (P < 0.05) the proliferation and viability of heat-stressed IEC-6 cells and that the most effective treatment doses of COP alkaloid, RA Aetherolea, Herba Agastachis Aetherolea, and GF water extract were 200, 100, 100, and 200 µg/mL, respectively. All 4 active components increased (P < 0.05) superoxide dismutase, glutathione peroxidase activities, and glutathione content, and decreased (P < 0.05) malondialdehyde content with respect to the heat-stressed group to concentrations similar to those seen in NTG. In vivo experiments demonstrated that TCM1 and TCM2 improved (P < 0.05) the poor growth performance seen in HTG pigs. The superoxide dismutase, glutathione peroxidase activities, and
Meng, Qiang; Duan, Xing-ping; Wang, Chang-yuan; Liu, Zhi-hao; Sun, Peng-yuan; Huo, Xiao-kui; Sun, Hui-jun; Peng, Jin-yong; Liu, Ke-xin
Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with AB23A (15, 30, and 60 mg·kg−1·d−1, ig) for 4 weeks. On the last day, blood samples and livers were collected. Serum liver functional enzymes, inflammatoru markers were assessed. The livers were histologically examined using H&E, Oil Red O, Masson's trichrome and Sirius Red staining. Mouse primary hepatocytes were used for in vitro experiments. The mechanisms underlying AB23A protection were analyzed using siRNA, qRT-PCR, and Western blot assays. AB23A treatment significantly and dose-dependently decreased the elevated levels of serum ALT and AST in MCD diet-fed mice. Furthermore, AB23A treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in the mice. AB23A-induced decreases in serum and hepatic lipids were related to decreased hepatic lipogenesis through decreasing hepatic levels of SREBP-1c, FAS, ACC1 and SCD1 and increased lipid metabolism via inducing PPARα, CPT1α, ACADS and LPL. The reduction in inflammatory cell infiltration corresponded to deceased serum levels of mKC and MCP-1 and decreased hepatic gene expression of MCP-1 and VCAM-1. The reduction in hepatic fibrosis was correlated with decreased hepatic gene expression of fibrosis markers. The protective effects of AB23A were FXR-dependent, because treatment with the FXR agonist CDCA mimicked AB23A-induced hepato-protection in the mice, whereas co-administration of FXR antagonist guggulsterone abrogated AB23A
Zhou, Yun-Xiao; Chen, Jiu; Li, Jian-Ping; Wang, Yan-Li; Jin, Xiao-Dong
The objective of this study was to examine the effects of Chinese medicine formula-Yu Zhang Dan (YZD, composed of Herba Lysimachiae, Rhizoma Polygoni Cuspidati, Radix Curcumae) on the model rats with hepatic fibrosis. Forty male Sprague-Dawley (SD) rats were used in the present study, and they were separated randomly into 4 groups: a normal control group (Group A, n=5), a model control (Group B, n=15), a high dose of YZD (Group C, n=10), and a low dose of YZD (Group D, n=10). Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl(4)). The variation of the serum alanine transaminase (ALT), aspartate aminotransferase (AST), hyaluronate acid (HA), laminin (LN), type • • procollagen peptide (P• •NP), L-Glutathione (GSH) was respectively measured with radioimmunoassay (RIA) and detection of transforming growth factor-beta 1 (TGF-β1) and smooth muscle alpha actin (α-SMA) was conducted with immunohistochemistry. The ALT, AST HA, LN and PIII NP levels in the serum of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the ALT, AST HA, LN and PIII NP levels of the model rats (P<0.05). The TGF-β1 and α-SMA levels of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the TGF-β1 levels of the model rats (P<0.05) , and only the high dose of YZD significantly decreased the α-SMA levels of the model rats (P<0.05). The expression of TGF-β1 and α-SMA in the liver tissues of the rats were in the cytoplasm of the cells. It may be through decreasing the ALT, AST, HA, LN and PIII NP levels in the serum of the model rats and decreasing the expression of TGF-β1 and α-SMA in the liver tissues of the model rats that YZD significantly relieved the hepatic fibrosis.
Cui, Han-Ming; Zhang, Qiu-Yan; Wang, Jia-Long; Chen, Jian-Long; Zhang, Yu-Ling; Tong, Xiao-Lin
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
Pang, Ming-jie; Yang, Zhun; Zhang, Xing-lin; Liu, Zhao-fang; Fan, Jun; Zhang, Hong-ying
Aim: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. Methods: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg−1·d−1, ip) for 30 d. Results: Treatment with physcion (5, 10, and 20 μmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 μmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti
Durairajan, Siva Sundara Kumar; Huang, Ying-Yu; Yuen, Pui-Yee; Chen, Lei-Lei; Kwok, Ka-Yan; Liu, Liang-Feng; Song, Ju-Xian; Han, Quan-Bin; Xue, Lei; K. Chung, Sookja; Huang, Jian-Dong; Baum, Larry; Senapati, Sanjib; Li, Min
Huanglian-Jie-Du-Tang (HLJDT) is a famous traditional Chinese herbal formula that has been widely used clinically to treat cerebral ischemia. Recently, we found that berberine, a major alkaloid compound in HLJDT, reduced amyloid-β (Aβ) accumulation in an Alzheimer’s disease (AD) mouse model. In this study, we compared the effects of HLJDT, four single component herbs of HLJDT (Rhizoma coptidis (RC), Radix scutellariae (RS), Cortex phellodendri (CP) and Fructus gardenia (FG)) and the modified formula of HLJDT (HLJDT-M, which is free of RS) on the regulatory processing of amyloid-β precursor protein (APP) in an in vitro model of AD. Here we show that treatment with HLJDT-M and its components RC, CP, and the main compound berberine on N2a mouse neuroblastoma cells stably expressing human APP with the Swedish mutation (N2a-SwedAPP) significantly decreased the levels of full-length APP, phosphorylated APP at threonine 668, C-terminal fragments of APP, soluble APP (sAPP)-α and sAPPβ-Swedish and reduced the generation of Aβ peptide in the cell lysates of N2a-SwedAPP. HLJDT-M showed more significant APP- and Aβ- reducing effects than berberine, RC or CP treatment alone. In contrast, HLJDT, its component RS and the main active compound of RS, baicalein, strongly increased the levels of all the metabolic products of APP in the cell lysates. The extract from FG, however, did not influence APP modulation. Interestingly, regular treatment of TgCRND8 APP transgenic mice with baicalein exacerbated the amyloid plaque burden, APP metabolism and Aβ production. Taken together, these data provide convincing evidence that HLJDT and baicalein treatment can increase the amyloidogenic metabolism of APP which is at least partly responsible for the baicalein-mediated Aβ plaque increase in the brains of TgCRND8 mice. On the other hand, HLJDT-M significantly decreased all the APP metabolic products including Aβ. Further study of HLJDT-M for therapeutic use in treating AD is
Xiang, Li; Wang, Jingjuan; Zhang, Guijun; Rong, Lixin; Wu, Haozhong; Sun, Suqin; Guo, Yizhen; Yang, Yanfang; Lu, Lina; Qu, Lei
Rhizoma Chuanxiong (CX) and Radix Angelica sinensis (DG) are very important Traditional Chinese Medicine (TCM) and usually used in clinic. They both are from the Umbelliferae family, and have almost similar chemical constituents with each other. It is complicated, time-consuming and laborious to discriminate them by using the chromatographic methods such as high performance liquid chromatography (HPLC) and gas chromatography (GC). Therefore, to find a fast, applicable and effective identification method for two herbs is urged in quality research of TCM. In this paper, by using a three-stage infrared spectroscopy (Fourier transform infrared spectroscopy (FT-IR), the second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2D-IR)), we analyzed and discriminated CX, DG and their different extracts (aqueous extract, alcoholic extract and petroleum ether extract). In FT-IR, all the CX and DG samples' spectra seemed similar, but they had their own unique macroscopic fingerprints to identify. Through comparing with the spectra of sucrose and the similarity calculation, we found the content of sucrose in DG raw materials was higher than in CX raw materials. The significant differences in alcoholic extract appeared that in CX alcoholic extract, the peaks at 1743 cm-1 was obviously stronger than the peak at same position in DG alcoholic extract. Besides in petroleum ether extract, we concluded CX contained much more ligustilide than DG by the similarity calculation. With the function of SD-IR, some tiny differences were amplified and overlapped peaks were also unfolded in FT-IR. In the range of 1100-1175 cm-1, there were six peaks in the SD-IR spectra of DG and the intensity, shape and location of those six peaks were similar to that of sucrose, while only two peaks could be observed in that of CX and those two peaks were totally different from sucrose in shape and relative intensity. This result was consistent with that of the