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Qi Y, Wu XJ, Shi JB, Shi XW, Zhao N, Xiong Y, Wang LP. Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism. Chin J Integr Med 2024; 30:1080-1089. [PMID: 37930511 DOI: 10.1007/s11655-023-3555-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/19/2023] [Indexed: 11/07/2023]
Abstract
OBJECTIVE To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.
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Affiliation(s)
- Ying Qi
- School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China
- Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China
| | - Xin-Jie Wu
- School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China
- Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China
| | - Jing-Bin Shi
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiao-Wei Shi
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Na Zhao
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yang Xiong
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Li-Pei Wang
- School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, 311121, China.
- Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou, 311121, China.
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Chang CH, Wang SC, Lee CY, Su CH, Lai YJ, Lin WD, Hsu YM. Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection. ENVIRONMENTAL TOXICOLOGY 2024; 39:4298-4307. [PMID: 38717028 DOI: 10.1002/tox.24322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 04/08/2024] [Accepted: 04/27/2024] [Indexed: 08/09/2024]
Abstract
Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1β levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.
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Affiliation(s)
- Chiung-Hung Chang
- Department of Traditional Chinese Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
- Department of Traditional Chinese Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shu-Chiu Wang
- Department of Traditional Chinese Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Chia-Ying Lee
- Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Chiu-Hsian Su
- Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan
| | - Yen-Ju Lai
- Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan
| | - Wei-De Lin
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
- School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yuan-Man Hsu
- Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
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Tandoro Y, Chen BK, Ali A, Wang CK. Review of Phytochemical Potency as a Natural Anti- Helicobacter pylori and Neuroprotective Agent. Molecules 2023; 28:7150. [PMID: 37894629 PMCID: PMC10609179 DOI: 10.3390/molecules28207150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023] Open
Abstract
Phytochemicals are plant secondary metabolites that show health benefits for humans due to their bioactivity. There is a huge variety of phytochemicals that have already been identified, and these compounds can act as antimicrobial and neuroprotection agents. Due to their anti-microbial activity and neuroprotection, several phytochemicals might have the potency to be used as natural therapeutic agents, especially for Helicobacter pylori infection and neurodegenerative disease, which have become a global health concern nowadays. According to previous research, there are some connections between H. pylori infection and neurodegenerative diseases, especially Alzheimer's disease. Hence, this comprehensive review examines different kinds of phytochemicals from natural sources as potential therapeutic agents to reduce H. pylori infection and improve neurodegenerative disease. An additional large-scale study is needed to establish the connection between H. pylori infection and neurodegenerative disease and how phytochemicals could improve this condition.
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Affiliation(s)
- Yohanes Tandoro
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan; (Y.T.); (B.-K.C.); (A.A.)
- Faculty of Agricultural Technology, Widya Mandala Catholic University Surabaya, Surabaya 60265, Indonesia
| | - Bo-Kai Chen
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan; (Y.T.); (B.-K.C.); (A.A.)
| | - Asif Ali
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan; (Y.T.); (B.-K.C.); (A.A.)
| | - Chin-Kun Wang
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan; (Y.T.); (B.-K.C.); (A.A.)
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Yang Y, Liu Q, Lu X, Ma J, Mei D, Chen Q, Zhao T, Chen J. Sanhuang decoction inhibits autophagy of periodontal ligament fibroblasts during orthodontic tooth movement by activating PI3K-Akt-mTOR pathway. Biomed Pharmacother 2023; 166:115391. [PMID: 37677964 DOI: 10.1016/j.biopha.2023.115391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 08/08/2023] [Accepted: 08/26/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Orthodontic tooth movement (OTM) is a typical treatment that corrects malaligned teeth by applying mechanical forces. However, mechanical overload often leads to damage of PDL fibroblasts. Sanhuang decoction (SHD) is commonly used to inhibit inflammation and oxidative stress. However, the mechanism of SHD for OTM treatment is still unclear. Therefore, this study attempts to explore the underlying mechanism through relevant experiments. METHODS In the present paper, we established a OTM rat model and further explored the effects of SHD on the PDL of OTM rats. The OTM model and effects of SHD were determined by micro-CT, and the PDL pathological changes, PDL width and capillaries in PDL were observed by H&E staining. Subsequently, the ROS levels in PDL was determined using flow cytometry analysis with DCFH-DA staining, MDA contents and antioxidative enzymes activities were also measured using commercial kits. Furthermore, the autophagy of PDL fibroblasts and proteins in the PI3K/Akt/mTOR pathway were detected using immunoluminescence, qPCR and western blotting assays. RESULTS The results showed SHD treatment can alleviate the decrease of PDL cells and capillaries induced by OTM, and improve the MDA and ROS levels in PDL, as well as enhance the activities of SOD and GSH-Px. Further experiments indicated SHD decreased the autophagy levels of PDL fibroblasts via promoting the phosphorylation levels of mTOR, PI3K and Akt proteins. CONCLUSION SHD inhibited autophagy of periodontal ligament fibroblasts during orthodontic tooth movement by inhibiting oxidative stress via activating PI3K-Akt-mTOR pathway. Our present findings suggested SHD treatment would be useful for management of the possible disorders occurs in orthodontic tooth movement therapy.
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Affiliation(s)
- Yiqiang Yang
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Qi Liu
- Department of Prosthodontics, Yinchuan Stomatological Hospital, Yinchuan 750004, PR China
| | - Xun Lu
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Jing Ma
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Donglan Mei
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Qi Chen
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Tian Zhao
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China
| | - Jia Chen
- Department of Orthodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China.
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Chen D, Chen X, He C, Xiao C, Chen Z, Chen Q, Chen J, Bo H. Sanhuang xiexin decoction synergizes insulin/PI3K-Akt/FoxO signaling pathway to inhibit hepatic glucose production and alleviate T2DM. JOURNAL OF ETHNOPHARMACOLOGY 2023; 306:116162. [PMID: 36646159 DOI: 10.1016/j.jep.2023.116162] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/29/2022] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sanhuang Xiexin Decoction (SHXXD) is a classic prescription for the treatment of diabetes. Excessive hepatic glucose production (HGP) is a major determinant of the occurrence and development of diabetes. Inhibition of HGP can significantly improve type 2 diabetes mellitus (T2DM). AIM OF THE STUDY To investigate the mechanism by which SHXXD inhibits HGP. MATERIALS AND METHODS First, a mouse model of T2DM was established through high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection to determine the pharmacodynamic effect of SHXXD in T2DM mice. Then, the possible pathways induced by SHXXD in the treatment of T2DM were predicted by network pharmacology combined with transcriptomics (including target prediction, network analysis and enrichment analysis). Finally, the specific mechanism of SHXXD was elucidated by in vitro experiments. RESULTS In vivo experiments showed that SHXXD reduced fasting blood glucose and alleviated weight loss in T2DM mice. Improved glucose clearance rates and insulin sensitivity improve dyslipidemia, liver tissue structural abnormalities and inflammatory cell infiltration as well as increase glycogen storage in T2DM mice. The results of network pharmacology and transcriptome analysis showed that SHXXD contained 378 compounds and 2625 targets. In total, 292 intersection targets were identified between the differentially expressed genes (DEGs) of the liver tissue insulin resistance (IR) related dataset GSE23343. KEGG enrichment analysis showed that the insulin/PI3K-Akt/FoxO signaling pathway may be related to SHXXD-mediated improvements in T2DM. In vitro experimental results showed that SHXXD increased glucose consumption by HepG2-IR cells and improved their insulin sensitivity. RT‒qPCR and Western blotting results showed that SHXXD inhibited hepatic gluconeogenesis through the insulin/PI3K-Akt/FoxO signaling pathway by promoting IGFIR, PIK3R1 and AKT2 expression and subsequently inhibiting PEPCK and FBP1 expression via phosphorylation of Foxo1. In addition, PI3K/Akt deactivated p-GSK3β through phosphorylation, thereby promoting GS expression and increasing glycogen synthesis. CONCLUSIONS SHXXD can target the liver to cooperate with the insulin/PI3K-Akt/FoxO signaling pathway to inhibit HGP to alleviate T2DM.
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Affiliation(s)
- Dan Chen
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Xiao Chen
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Cai He
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Chuntao Xiao
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Zelin Chen
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Qizhu Chen
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Jun Chen
- College of Pharmacy, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China
| | - Huaben Bo
- School of Bioscience and Biopharmaceutics, Guangdong Province, Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China.
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Zhu K, Wang MY, Li HF, Dong ZL, Li WW, Liu C, Zhang L, Jiang S, Shang EX, Qian DW, Duan JA. Investigation of the Material Basis of Xiexin Tang to Alleviate Type 2 Diabetes Mellitus Based on Spectrum-Effect Analysis by UPLC-Q-TOF/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1221:123691. [PMID: 37011544 DOI: 10.1016/j.jchromb.2023.123691] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 03/16/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023]
Abstract
Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-β-D-glucose might be the main effective basis of XXT to improve T2DM.
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The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients. Cancers (Basel) 2023; 15:cancers15041213. [PMID: 36831555 PMCID: PMC9953925 DOI: 10.3390/cancers15041213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 01/21/2023] [Accepted: 01/29/2023] [Indexed: 02/17/2023] Open
Abstract
Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.
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Li B, Wang M, Chen S, Li M, Zeng J, Wu S, Tu Y, Li Y, Zhang R, Huang F, Tong X. Baicalin Mitigates the Neuroinflammation through the TLR4/MyD88/NF- κB and MAPK Pathways in LPS-Stimulated BV-2 Microglia. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3263446. [PMID: 36408278 PMCID: PMC9668451 DOI: 10.1155/2022/3263446] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/22/2022] [Indexed: 09/25/2023]
Abstract
Baicalin (BA) is a major flavone from Scutellaria baicalensis Georgi and has showed significant curative effects in Parkinson's and Alzheimer's diseases. In the present study, we investigated the effects of BA on antineuroinflammation and related signaling cascade in lipopolysaccharide- (LPS-) induced BV-2 microglial model. The results showed that BA significantly attenuated inflammatory mediators (NO, iNOS, IL-1β, COX-2, and PGE2) and suppressed the expression of miR-155. More crucially, BA could regulate the expression of related proteins in Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor κB (NF-κB) pathway and suppress the phosphorylation of mitogen-activated protein kinase (MAPK) family. In addition, molecular docking analysis indicated that BA binds to the amino acids Lie 63 and Tyr 65 of TLR4 by π-σ and π-π T-shaped interaction. Thus, BA suppressed the LPS-stimulated neuroinflammation in BV-2 microglia by blocking the TLR4-mediated signal transduction through TLR4/MyD88/NF-κB and MAPK pathways and inhibiting the miR-155 expression. Our findings demonstrated that BA could be a valuable therapeutic for the treatment of neuroinflammation and neurodegenerative diseases.
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Affiliation(s)
- Baojing Li
- The First Affiliated Hospital of Yunnan University of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Mingming Wang
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Shuai Chen
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Manping Li
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Jing Zeng
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Saichun Wu
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Yuanqing Tu
- College of Pharmacy, Jinan University, Guangzhou, China
| | - Yanping Li
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Rongping Zhang
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Feng Huang
- The First Affiliated Hospital of Yunnan University of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Xiaoyun Tong
- The First Affiliated Hospital of Yunnan University of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
- Yunnan Key Laboratory of Southern Medicinal Utilization, College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China
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Han Z, Tan X, Sun J, Wang T, Yan G, Wang C, Ma K. Systems pharmacology and transcriptomics reveal the mechanisms of Sanhuang decoction enema in the treatment of ulcerative colitis with additional Candida albicans infection. Chin Med 2021; 16:75. [PMID: 34376226 PMCID: PMC8353752 DOI: 10.1186/s13020-021-00487-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/02/2021] [Indexed: 01/16/2023] Open
Abstract
Background Ulcerative colitis (UC) is an important inflammatory phenotype in bowel disease (IBD), which is caused by multiple potential factors, including fungal dysbiosis. Candida albicans (C. albicans) was confirmed to be an important factor promoting the occurrence and development of UC. Sanhuang decoction (SHD) has been used for UC therapy in China for thousand of years, although its core active constituents and pharmacological mechanism remain undefined. Methods In this work, a murine model of UC with C. albicans colonization was established with dextran sodium sulfate (DSS) and C. albicans intragastric administration. The major bioactive constituents and potential mechanism of SHD against UC with fungal dysbiosis were comprehensively examined by combining systems pharmacology and in vivo transcriptomics. Results SHD attenuated C. albicans burden, reduced DAI, increased mucosal integrity and relived systemic inflammation in UC mice. Systems pharmacology analysis identified 9 core bioactive ingredients and 45 hub targets of SHD against UC. Transcriptomics analysis confirmed 370 differentially expressed genes (DEGs) after SHD treatment, which were mainly enriched in inflammatory and immune response related signaling pathways. Toll-like receptor and PI3K-Akt signaling pathway were screened out as the candidate targets involved in the action of SHD on fungal dysbiosis-associated UC, which were consistent with the findings in systems pharmacology. The expression of TLR4, IL-1β, NF-κB, PI3K and Akt proteins were stimulated by C. albicans, and partially reversed by SHD in UC mice. Conclusion These findings suggested SHD could be a candidate for the treatment of fungal dysbiosis-associated UC via TLR4-NF-κB and PI3K-Akt signaling pathways. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00487-2.
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Affiliation(s)
- Zhijun Han
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Xiaofen Tan
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Juan Sun
- Anhui Provincial Key Laboratory of New Manufacturing Technology for Chinese Medicinal Decoction Pieces, Anhui University of Chinese Medicine, Hefei, 230012, China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, China
| | - Tianming Wang
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China.,Anhui Provincial Key Laboratory of New Manufacturing Technology for Chinese Medicinal Decoction Pieces, Anhui University of Chinese Medicine, Hefei, 230012, China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, China
| | - Guiming Yan
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China.,Anhui Provincial Key Laboratory of New Manufacturing Technology for Chinese Medicinal Decoction Pieces, Anhui University of Chinese Medicine, Hefei, 230012, China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, China
| | - Changzhong Wang
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China.,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China.,Anhui Provincial Key Laboratory of New Manufacturing Technology for Chinese Medicinal Decoction Pieces, Anhui University of Chinese Medicine, Hefei, 230012, China.,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, China
| | - Kelong Ma
- College of Integrated Chinese and Western Medicine, College of Life Science, Anhui University of Chinese Medicine, Hefei, 230012, China. .,Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China. .,Anhui Provincial Key Laboratory of New Manufacturing Technology for Chinese Medicinal Decoction Pieces, Anhui University of Chinese Medicine, Hefei, 230012, China. .,Key Laboratory of Xin'An Medicine, Ministry of Education, Anhui Academy of Chinese Medicine, Hefei, 230012, China.
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Chen M, Liu C, Shen Y, Zou J, Zhang Z, Wan Y, Yang L, Jiang S, Qian D, Duan J. A Powerful HPLC-ELSD Method for Simultaneous Determination of Fecal Bile Acids in T2DM Rats Interfered by Sanhuang Xiexin Tang. J Chromatogr Sci 2021; 59:871-876. [PMID: 33524991 DOI: 10.1093/chromsci/bmaa144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Indexed: 11/13/2022]
Abstract
Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2 ≥ 0.99). The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.
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Affiliation(s)
- Mengjun Chen
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Chen Liu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Yumeng Shen
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Junfeng Zou
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Zhimiao Zhang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Yue Wan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Lei Yang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
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Wang X, Li S, Wang Y, Hu R. HPLC-DAD-Q-TOF/MS-Based Screening and Analysis of the Multiple Absorbed Bioactive Components in Rat Serum after Oral Administration of Xiexin Tang. CURR PHARM ANAL 2020. [DOI: 10.2174/1573412915666190314130053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Xiexin Tang (XXT) is a classic Traditional Chinese Medicine (TCM) formula
that has been used in herbal clinics for more than 1800 years. Recently, many studies have investigated
the pharmacological effects and chemical composition of XXT. However, there is little information
about systematic studies on the material basis of its efficacy. In the present study, the serum pharmacochemistry
technique and HPLC-DAD-Q-TOF/MS were performed to screen and analyze the multiple
absorbed bioactive components and metabolites of orally dosed XXT in rat serum.
Methods:
Bio-samples and herbal extracts were analyzed and detected by HPLC-DAD-Q-TOF/MS.
Upon comparison of the chromatograms of the single-constituent decoctions with that of the XXT formulation,
the peak quantity and peak intensity of the formulated decoction showed some variation from
those of the single-constituent decoctions.
Results:
Twenty-one serum-adsorbed constituents were identified after intragastric administration of
herbal extracts, of which 8 originated from Rhei Radix et Rhizoma (RRR), 5 from Coptidis Rhizoma
(CR), and 8 from Scutellariae Radix (SR). The results showed that the main adsorbed constituents in the
serum were anthraquinones, anthrones, chromones, and butyrophenones, alkaloids, and flavonoids.
Conclusion:
The results demonstrate that an effective and reliable analytical method is set up for
screening the bioactive components of Chinese herbal medicine, which provided a meaningful basis for
further pharmacology and active mechanism research of XXT.
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Affiliation(s)
- Xiaoyu Wang
- Department of Pharmacology, Shaanxi University of Chinese Medicine, Shaanxi Xianyang 712046, China
| | - Shujiao Li
- Center of Scientific Research, Nanyang Medical College, Nanyang 473061, China
| | - Yuqing Wang
- Center of Scientific Research, Nanyang Medical College, Nanyang 473061, China
| | - Rui Hu
- Department of Pharmacology, Shaanxi University of Chinese Medicine, Shaanxi Xianyang 712046, China
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13
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Peng WY, Tsai TH. Scanning Electron Microscopy and Liquid Chromatography for Physical and Chemical Inspection of Industrial Pharmaceutical Traditional Chinese Herbal Medicine. ACS OMEGA 2020; 5:11563-11569. [PMID: 32478246 PMCID: PMC7254810 DOI: 10.1021/acsomega.0c00809] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 04/28/2020] [Indexed: 05/03/2023]
Abstract
Multiherbal preparation of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma is a well-known herbal formula, which is widely used in the prescription for relieving heat toxicity, inflammation of the intestine, and eczema. However, little is known about the characteristics of the physical and chemical qualities of industrial pharmaceutical products. The aim of the study is to develop a liquid chromatography system to examine the quality and quantity of pharmaceutical products. Besides scanning electron microscopy, light microscopy photographs with Congo red staining and iodine-KI staining were used for physical examination of the quality of the pharmaceutical products. A reverse-phase C18 column was used to separate the analytes of baicalin, berberine, rhein, and p-hydroxybenzoate (internal standard) with a gradient eluent mobile phase of acetonitrile and 10 mM NaH2PO4 (pH 3.0, adjusted by orthophosphoric acid). The results demonstrated that a large variety of content range presents among the testing herbal pharmaceutical products. The contents of rhein, baicalin, and berberine were around 0.22-22.46, 0.44-50.79, and 0.41-2.48 mg/g, respectively. The physical examination data demonstrated that different brands of industrial pharmaceutical products have different shapes of granules or rods. In summary, to ensure the clinical efficacy of complicated herbal medicine, both quality and quantity controls are all very important. This study provides a reference standard operating procedure guide for the quality control (QC) with chemical and physical examination for the Chinese herbal pharmaceutical products of San-Huang-Xie-Xin-Tang (SHXXT).
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Affiliation(s)
- Wen-Ya Peng
- Institute
of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan
| | - Tung-Hu Tsai
- Institute
of Traditional Medicine, School of Medicine, National Yang-Ming University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan
- Graduate
Institute of Acupuncture Science, China
Medical University, Taichung 40402, Taiwan
- School
of Pharmacy, College of Pharmacy, Kaohsiung
Medical University, Kaohsiung 80708, Taiwan
- Department
of Chemical Engineering, National United
University, Miaoli 36063, Taiwan
- . Tel: (886-2) 2826 7115. Fax: (886-2) 2822 5044
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Pan L, Ding Y, Ni X, Wang CZ, Jiang B, Zhang Y, Jiang N, Tang Y, Chen L, Yuan CS. Modeling rapid and selective capture of nNOS–PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal–organic frameworks. RSC Adv 2020; 10:7671-7681. [PMID: 35492204 PMCID: PMC9049783 DOI: 10.1039/c9ra10537a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 02/05/2020] [Indexed: 12/12/2022] Open
Abstract
Novel and highly selective molecularly imprinted polymers based on the surface of metal–organic frameworks, NH2-MIL-101(Cr) (MIL@MIPS), were successfully fabricated to capture neuronal nitric oxide synthase–postsynaptic density protein-95 (nNOS–PSD-95) uncouplers from Sanhuang Xiexin Decoction (SXD) for stroke treatment. The resultant polymers were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffraction. The performance tests revealed that MIL@MIPs had a large binding capacity, fast kinetics, and excellent selectivity. Then the obtained polymers were satisfactorily applied to solid-phase extraction coupled with high-performance liquid chromatography to selectively capture nNOS–PSD-95 uncouplers from SXD. Furthermore, the biological activities of components obtained from SXD were evaluated in vivo and in vitro. As a consequence, the components showed a potent neuroprotective effect from the MTS assay and uncoupling activity from the co-immunoprecipitation experiment. In addition, the anti-ischemic stroke assay in vivo was further investigated to determine the effect of reducing infarct size and ameliorating neurological deficit by the active components. Therefore, this present study contributes a valuable new method and new tendency to selectively capture active components for stroke treatment from SXD and other natural medicines. Novel MIL@MIPs were prepared to rapidly capture nNOS–PSD-95 uncouplers from Sanhuang Xiexin decoction, coupled with SPE and HPLC.![]()
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Affiliation(s)
- Linli Pan
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Yingying Ding
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Xiaoting Ni
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research
- Department of Anesthesia & Critical Care
- University of Chicago
- Chicago
- USA
| | - Bo Jiang
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Yu Zhang
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Nan Jiang
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Yulin Tang
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Lina Chen
- School of Pharmacy
- Nanjing Medical University
- Nanjing
- China
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research
- Department of Anesthesia & Critical Care
- University of Chicago
- Chicago
- USA
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15
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Xiao S, Zhang Z, Chen M, Zou J, Jiang S, Qian D, Duan J. Xiexin Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energy metabolism. JOURNAL OF ETHNOPHARMACOLOGY 2019; 241:112032. [PMID: 31220598 DOI: 10.1016/j.jep.2019.112032] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 06/16/2019] [Accepted: 06/16/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional herbal medicine has been taken as a new and effective approach to treat many chronic diseases. Xiexin Tang (XXT), a compound recipe composed of Dahuang (Rheum palmatum L.), Huangqin (Scutellaria baicalensis Georgi) and Huanglian (Coptis chinensis Franch.), has been reported to have hypoglycemic and hypolipidemic effects, but its mechanism remains unclear. Our previous study found that Xiexin Tang markedly ameliorated the composition of the gut microbiota, especially for some short chain fatty acids (SCFAs) producing bacteria, and then notably increased SCFAs production. However, the mechanism of XXT on the fermentation of gut bacteria and further improvement of obesity is not yet clear. AIM OF THE STUDY This study aimed to unravel the molecular mechanism of XXT on the amelioration of obesity. MATERIALS AND METHODS Here, high-fat diet-induced obese rat model was established to investigate the intervention efficacy following oral administration of XXT. Additionally, the expressions of key enzymes of gut microbe-derived SCFAs biosynthesis and key targets in the signaling pathway of energy metabolism were investigated by ELISA and qPCR analysis. RESULTS Results showed that XXT could notably correct lipid metabolism disorders, alleviate systematic inflammation, improve insulin sensitivity and reduce fat accumulation. Additionally, XXT could increase gut microbiota-derived SCFAs-producing capacity by enhancing mRNA levels and activities of SCFA-synthetic key enzymes such as acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD), butyryl-CoA: acetate CoA transferase (BUT) and butyrate kinase (BUK), which markedly decreased the adenosine triphosphate (ATP) contents, elevated adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels and further lowered the energy charge (EC) in obese rats via activating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/uncoupling protein-2 (UCP-2) signaling pathway. What's more, XXT could notably ameliorate dyslipidemia via increasing the gene expression of 5'-AMP-activated protein kinase (AMPK) and blocking mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSIONS Taken together, our data provided a novel insight into the role of XXT in losing weight from energy metabolism regulation, which unraveled the molecular mechanism of XXT on the alleviation of dyslipidemia and fat heterotopic accumulation. The study provided useful information for XXT in clinical application to treat obesity.
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Affiliation(s)
- Suwei Xiao
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Zhimiao Zhang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Mengjun Chen
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Junfeng Zou
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
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16
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Zhai Q, Li J. Effectiveness of traditional Chinese herbal medicine, San-Huang-San, in combination with enrofloxacin to treat AHPND-causing strain of Vibrio parahaemolyticus infection in Litopenaeus vannamei. FISH & SHELLFISH IMMUNOLOGY 2019; 87:360-370. [PMID: 30630050 DOI: 10.1016/j.fsi.2019.01.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 12/31/2018] [Accepted: 01/06/2019] [Indexed: 06/09/2023]
Abstract
The effects of oral administration of enrofloxacin (ENR) and San-Huang-San (SHS), singly or in combination, on the survival performance, disease resistance, and immunity of Litopenaeus vannamei were investigated. After challenge with an AHPND-causing strain of Vibrio parahaemolyticus (VPAHPND), shrimp were immediately fed a drug-free diet, diets containing only ENR (20 mg·kg-1) or SHS (500 mg·kg-1) or diets containing low-dose (10 mg·kg-1 ENR + 250 mg ·kg-1 SHS), medium-dose (20 mg·kg-1 ENR + 500 mg ·kg-1 SHS), and high-dose (40 mg·kg-1 ENR + 1000 mg ·kg-1 SHS) drug combinations for 5 days. The cumulative shrimp mortality over 5 days after injection of VPAHPND in the ENR + SHS combination groups was significantly lower than that in the ENR or SHS alone groups (p < 0.05). Immune parameters, including the vibrio density, total hemocyte counts (THCs), hemocyanin (HEM) concentration, antibacterial activity, activity levels of lysozyme (LZM), acid phosphatase (ACP), alkaline phosphatase (AKP), and phenoloxidase (PO) in cell-free hemolymph, and the expression levels of the immune-related genes anti-lipopolysaccharide factor (ALF), cathepsin B (catB), crustin, lectin (Lec), lysozyme (LZM), and Toll-like receptor (TLR) in hemocytes were determined in the shrimp. The results showed that the shrimp in drug combination groups cleared more VPAHPND than that in the ENR or SHS group in the same time. The values for other immune parameters in the drug combination groups were higher than those in the ENR or SHS group (p < 0.05). Finally, in the histological examinations, the histological structural alignment and integrity of the hepatopancreatic tubules in the drug combination groups were better than that in the ENR and SHS groups. Under the experimental conditions, compared with ENR or SHS used alone, the combination use of ENR and SHS could improve immunity and disease resistance in shrimp after VPAHPND infection, and could reduce the use of ENR when the better therapeutic effect was achieved.
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Affiliation(s)
- Qianqian Zhai
- Key Laboratory for Sustainable Utilization of Marine Fisheries Resources, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, PR China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, PR China
| | - Jian Li
- Key Laboratory for Sustainable Utilization of Marine Fisheries Resources, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, PR China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, PR China.
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17
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Anti- Helicobacter pylori effect of various extracts of ixeris chinensis on inflammatory markers in human gastric epithelial AGS cells. J Herb Med 2018. [DOI: 10.1016/j.hermed.2017.08.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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18
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Wei X, Tao J, Xiao S, Jiang S, Shang E, Zhu Z, Qian D, Duan J. Xiexin Tang improves the symptom of type 2 diabetic rats by modulation of the gut microbiota. Sci Rep 2018; 8:3685. [PMID: 29487347 PMCID: PMC5829262 DOI: 10.1038/s41598-018-22094-2] [Citation(s) in RCA: 181] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 02/13/2018] [Indexed: 12/22/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM), a chronic metabolic disease which severely impairs peoples' quality of life, currently attracted worldwide concerns. There are growing evidences that gut microbiota can exert a great impact on the development of T2DM. Xiexin Tang (XXT), a traditional Chinese medicine prescription, has been clinically used to treat diabetes for thousands of years. However, few researches are investigated on the modulation of gut microbiota community by XXT which will be very helpful to unravel how it works. In this study, bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Results indicated that XXT could notably shape the gut microbiota. T2DM rats treated with XXT exhibited obvious changes in the composition of the gut microbiota, especially for some short chain fatty acids producing and anti-inflammatory bacteria such as Adlercreutzia, Alloprevotella, Barnesiella, [Eubacterium] Ventriosum group, Blautia, Lachnospiraceae UCG-001, Papillibacter and Prevotellaceae NK3B31 group. Additionally, XXT could also significantly ameliorate hyperglycemia, lipid metabolism dysfunction and inflammation in T2DM rats. Moreover, the correlation analysis illustrated that the key microbiota had a close relationship with the T2DM related indexes. The results probably provided useful information for further investigation on its active mechanism and clinical application.
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Affiliation(s)
- Xiaoyan Wei
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Jinhua Tao
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Suwei Xiao
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Erxin Shang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Zhenhua Zhu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
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19
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Xinjie Y, Yan L. Effect of modified Sanhuang Xiexin Tang plus additional herbs combined with “standard triple therapy” on Helicobacter pylori eradication. J TRADIT CHIN MED 2018. [DOI: 10.1016/j.jtcm.2018.02.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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20
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Comparative pharmacokinetics of six major bioactive components in normal and type 2 diabetic rats after oral administration of Sanhuang Xiexin Decoction extracts by UPLC-TQ MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2017; 1061-1062:248-255. [DOI: 10.1016/j.jchromb.2017.07.026] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 07/12/2017] [Accepted: 07/14/2017] [Indexed: 12/23/2022]
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21
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Wang YQ, Li SJ, Zhuang G, Geng RH, Jiang X. Screening free radical scavengers in Xiexin Tang by HPLC-ABTS-DAD-Q-TOF/MS. Biomed Chromatogr 2017; 31. [DOI: 10.1002/bmc.4002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 04/25/2017] [Accepted: 05/03/2017] [Indexed: 11/11/2022]
Affiliation(s)
- Yu-Qing Wang
- The center for Scientific Research; Nanyang Medical College; Nanyang China
| | - Shu-Jiao Li
- The center for Scientific Research; Nanyang Medical College; Nanyang China
| | - Guo Zhuang
- The center for Scientific Research; Nanyang Medical College; Nanyang China
| | - Rong-Hui Geng
- The center for Scientific Research; Nanyang Medical College; Nanyang China
| | - Xu Jiang
- The center for Scientific Research; Nanyang Medical College; Nanyang China
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22
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Lee MJ, Choi JH, Lee SJ, Cho IH. Oriental Medicine Samhwangsasim-tang Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Th1 Cell Responses and Upregulating Treg Cell Responses. Front Pharmacol 2017; 8:192. [PMID: 28458638 PMCID: PMC5394181 DOI: 10.3389/fphar.2017.00192] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 03/24/2017] [Indexed: 01/09/2023] Open
Abstract
Oriental medicine Samhwangsasim-tang (SHSST) has traditionally been used in East Asia to treat hypertension and its complications. However, little is known about its potential value regarding the treatment of chronic inflammatory diseases such as multiple sclerosis (MS). In this study, we investigated whether SHSST has a beneficial effect in treating myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Onset-treatment with SHSST was found to alleviate neurological symptoms as well as demyelination and glial activation in the spinal cords from the EAE mice. The SHSST also attenuated the mRNA or protein expression of pro-inflammatory cytokines (interleukin-1beta and tumor necrotic factor-alpha); chemokines (RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha); inducible nitric oxide synthase; and cyclooxygenase-2 in correspondence with the down-regulation of the nuclear factor-kappa B and mitogen-activated protein kinases signal pathways in the spinal cords from EAE mice. Interestingly, the protective effect of the SHSST was related to a decreased number of Th1 cells and an increased number of Treg cells in spinal cords from EAE mice. Taken together, our finding firstly suggested that SHSST could delay or mitigate EAE with a wide therapeutic time-window by suppressing Th1 cell responses and upregulating Treg cell responses. Also, our findings are strong enough to warrant further investigation of SHSST as a treatment for chronic autoimmune diseases including MS.
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Affiliation(s)
- Min J Lee
- Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee UniversitySeoul, South Korea.,Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee UniversitySeoul, South Korea
| | - Jong H Choi
- Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee UniversitySeoul, South Korea.,Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee UniversitySeoul, South Korea
| | - Sung J Lee
- Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National UniversitySeoul, South Korea
| | - Ik-Hyun Cho
- Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee UniversitySeoul, South Korea.,Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee UniversitySeoul, South Korea.,Institute of Korean Medicine, College of Korean Medicine, Kyung Hee UniversitySeoul, South Korea
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Wu J, Hu Y, Xiang L, Li S, Yuan Y, Chen X, Zhang Y, Huang W, Meng X, Wang P. San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review. Front Pharmacol 2016; 7:448. [PMID: 27965575 PMCID: PMC5124576 DOI: 10.3389/fphar.2016.00448] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/09/2016] [Indexed: 12/29/2022] Open
Abstract
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.
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Affiliation(s)
- Jiasi Wu
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Yingfan Hu
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Li Xiang
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Sheng Li
- Chengdu Institute of Biology, Chinese Academy of Sciences Chengdu, China
| | - Yi Yuan
- Chengdu University of Traditional Chinese MedicineChengdu, China; Chengdu Institute of Biology, Chinese Academy of SciencesChengdu, China
| | | | - Yan Zhang
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Wenge Huang
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Xianli Meng
- Chengdu University of Traditional Chinese Medicine Chengdu, China
| | - Ping Wang
- Chengdu University of Traditional Chinese Medicine Chengdu, China
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Wu TY, Chang FR, Liou JR, Lo IW, Chung TC, Lee LY, Chi CC, Du YC, Wong MH, Juo SHH, Lee CC, Wu YC. Rapid HPLC Quantification Approach for Detection of Active Constituents in Modern Combinatorial Formula, San-Huang-Xie-Xin-Tang (SHXXT). Front Pharmacol 2016; 7:374. [PMID: 27812335 PMCID: PMC5071620 DOI: 10.3389/fphar.2016.00374] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 09/27/2016] [Indexed: 01/24/2023] Open
Abstract
San-Huang-Xie-Xin-Tang (SHXXT), one of the most important traditional Chinese medicinal formulas, is comprised by three herbal medicines, the rhizome of Rheum officinale [or Rheum tanguticum (Polygonaceae) (Dahuang in Chinese)], the root of Scutellaria baicalensis (Labiatae) (Huangqin in Chinese), and the rhizome of Coptis chinensis (Ranunculaceae) (Huanglian in Chinese) in the ratios of 2:1:1 or 1:1:1. This study is aimed to quantitate and qualify of SHXXT, by a rapid, convenient, and effective HPLC-PDA approach associated with LC-MS technique. Of which method, nine chosen major bioactive components in SHXXT, including aloe-emodin (Ale), baicalin (Ba), berberine (Be), coptisine (Co), palmatine (Pa), resveratroloside (Res), rhein (Rh), sennoside A (Se-A), and wogonin (Wo), were evaluated within 30 min. The nine chemical markers were monitored in a high sensitivity with a low detection limit of 0.01−0.55 μg/mL and the correlation coefficient of the regression curve revealed a good linearity with R2 > 0.99. Moreover, the extraction solution system and the HPLC elution conditions were also optimized in the present study. This present developed protocol was then successfully applied to quantify nine chemical markers of 10 SHXXT products from eight Taiwanese TCM pharmaceutical companies. In quantitative results, Res was found as the major compound in SHXXT-1~5 and 8 with significantly higher amounts than those in other products, indicating the products SHXXT-1~5 and 8 may use R. tanguticum as the raw material, which possessed a higher concentration of the bioactive composition Res, instead of R. officinale. Simultaneously, Ale, Rh, and Wo were < 2% in these 10 products. Different chemical profiles of commercial products indicated that, probably, each product with the same named formula might be regarded as a sole medicine and need to be investigated individually. Importantly, it is never too much to emphasize the importance of quality control in TCM development.
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Affiliation(s)
- Tung-Ying Wu
- Chinese Medicine Research and Development Center, China Medical University Hospital Taichung, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical UniversityKaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical UniversityKaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University HospitalKaohsiung, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical UniversityKaohsiung, Taiwan
| | - Jing-Ru Liou
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan
| | - I-Wen Lo
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan
| | - Tang-Chia Chung
- Department of Pharmacy, Kaohsiung Medical University Hospital Kaohsiung, Taiwan
| | - Li-Yao Lee
- Department of Pharmacy, Kaohsiung Medical University Hospital Kaohsiung, Taiwan
| | - Chun-Chen Chi
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan
| | - Ying-Chi Du
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan
| | - Man-Hon Wong
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan
| | - Suh-Hang Hank Juo
- Graduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan
| | - Chun-Chen Lee
- Department of Pharmacy, Kaohsiung Medical University Hospital Kaohsiung, Taiwan
| | - Yang-Chang Wu
- Chinese Medicine Research and Development Center, China Medical University HospitalTaichung, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical UniversityKaohsiung, Taiwan; School of Pharmacy, College of Pharmacy, China Medical UniversityTaichung, Taiwan; Research Center for Chinese Herbal Medicine, China Medicinal UniversityTaichung, Taiwan; Center for Molecular Medicine, China Medical University HospitalTaichung, Taiwan
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Chen GY, Shu YC, Chuang DY, Wang YC. Inflammatory and Apoptotic Regulatory Activity of Tanshinone IIA in Helicobacter pylori-Infected Cells. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2016; 44:1187-1206. [PMID: 27627918 DOI: 10.1142/s0192415x1650066x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori infections induce host cell inflammation and apoptosis, however, they are conflicting. Tanshinone IIA is an active compound of Salvia miltiorrhiza Bge. In this study, we investigated the regulatory effects of tanshinone IIA on H. pylori-induced inflammation and apoptosis in vitro. Tanshinone IIA treatments (13.6-54.4[Formula: see text][Formula: see text]M) significantly decreased nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) [p-38 and C-terminal Jun-kinase 1/2 (JNK1/2)] protein expressions and inflammatory substance [cyclooxygenase-2 (COX-2), 5-lipooxygenase (5-LOX), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1[Formula: see text] (IL-1[Formula: see text], IL-6, and IL-8] production in the H. pylori-infected cells. In contrast, tanshinone IIA treatments significantly increased apoptotic relevant protein [Bcl-2-associated X protein (Bax) and caspase 9] expressions and increased mitochondrial transmembrane potential ([Formula: see text] disruption, mitochondrial cytochrome [Formula: see text] (cyt [Formula: see text] release, and caspase cascades. Tanshinone IIA treatments effectively decreased H. pylori-induced inflammation and significantly promoted H. pylori-induced intrinsic apoptosis through NF-kB and MAPK (p-38 and JNK) pathways. Tanshinone IIA has great potential as a candidate to protect host cells from H. pylori-induced severe inflammation and gastric cancer.
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Affiliation(s)
- Guan-Yu Chen
- * Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C
| | - Yu-Chieh Shu
- * Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C
| | - Duen-Yau Chuang
- † Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan, R.O.C
| | - Yuan-Chuen Wang
- * Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.,‡ Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan, R.O.C
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Aribi M, Meziane W, Habi S, Boulatika Y, Marchandin H, Aymeric JL. Macrophage Bactericidal Activities against Staphylococcus aureus Are Enhanced In Vivo by Selenium Supplementation in a Dose-Dependent Manner. PLoS One 2015; 10:e0135515. [PMID: 26340099 PMCID: PMC4560415 DOI: 10.1371/journal.pone.0135515] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 07/22/2015] [Indexed: 11/27/2022] Open
Abstract
Background Dietary selenium is of fundamental importance to maintain optimal immune function and enhance immunity during infection. To this end, we examined the effect of selenium on macrophage bactericidal activities against Staphylococcus aureus. Methods Assays were performed in golden Syrian hamsters and peritoneal macrophages cultured with S. aureus and different concentrations of selenium. Results Infected and selenium-supplemented animals have significantly decreased levels of serum nitric oxide (NO) production when compared with infected but non-selenium-supplemented animals at day 7 post-infection (p < 0.05). A low dose of 5 ng/mL selenium induced a significant decrease in macrophage NO production, but significant increase in hydrogen peroxide (H2O2) levels (respectively, p = 0.009, p < 0.001). The NO production and H2O2 levels were significantly increased with increasing concentrations of selenium; the optimal macrophage activity levels were reached at 20 ng/mL. The concentration of 5 ng/mL of selenium induced a significant decrease in the bacterial arginase activity but a significant increase in the macrophage arginase activity. The dose of 20 ng/mL selenium induced a significant decrease of bacterial growth (p < 0.0001) and a significant increase in macrophage phagocytic activity, NO production/arginase balance and S. aureus killing (for all comparisons, p < 0.001). Conclusions Selenium acts in a dose-dependent manner on macrophage activation, phagocytosis and bacterial killing suggesting that inadequate doses may cause a loss of macrophage bactericidal activities and that selenium supplementation could enhance the in vivo control of immune response to S. aureus.
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Affiliation(s)
- Mourad Aribi
- Laboratory of Applied Molecular Biology and Immunology, Department of Biology, University of Tlemcen, 13000, Tlemcen, Algeria
- * E-mail:
| | - Warda Meziane
- Laboratory of Applied Molecular Biology and Immunology, Department of Biology, University of Tlemcen, 13000, Tlemcen, Algeria
| | - Salim Habi
- Laboratory of Applied Molecular Biology and Immunology, Department of Biology, University of Tlemcen, 13000, Tlemcen, Algeria
| | - Yasser Boulatika
- Laboratory of Applied Molecular Biology and Immunology, Department of Biology, University of Tlemcen, 13000, Tlemcen, Algeria
| | - Hélène Marchandin
- Université Montpellier 1, UMR 5569 HydroSciences Montpellier, Équipe Pathogènes Hydriques Santé Environnements, 34093, Montpellier, Cedex 5, France
- Centre Hospitalier Régional Universitaire, Laboratoire de Bactériologie, 34295, Montpellier, Cedex 5, France
| | - Jean-Luc Aymeric
- UM2-INRA, UMR1333, Laboratoire Diversité, Génomes et Interactions Microorganismes Insectes, Université de Montpellier, Bataillon, 34095, Montpellier, Cedex 05, France
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Yu XD, Zheng RB, Xie JH, Su JY, Huang XQ, Wang YH, Zheng YF, Mo ZZ, Wu XL, Wu DW, Liang YE, Zeng HF, Su ZR, Huang P. Biological evaluation and molecular docking of baicalin and scutellarin as Helicobacter pylori urease inhibitors. JOURNAL OF ETHNOPHARMACOLOGY 2015; 162:69-78. [PMID: 25557028 DOI: 10.1016/j.jep.2014.12.041] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 09/07/2014] [Accepted: 12/22/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. AIM OF THE STUDY To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. MATERIALS AND METHODS The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. RESULTS Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of Helicobacter pylori urease, since thiol reagents (L,D-dithiothreitol, L-cysteine and glutathione) abolished the inhibitory action and competitive active site Ni(2+) binding inhibitors (boric acid and sodium fluoride) carried invalid effect. Molecular docking study further supported the structure-activity analysis and indicated that baicalin and scutellarin interacted with the key residues Cys321 located on the mobile flap through S-H·π interaction, but did not interact with active site Ni(2+). Moreover, Baicalin (at 0.59-1.05 mM concentrations) and scutellarin (at 0.23-0.71 mM concentrations) did not exhibit significant cytotoxicity to GES-1. CONCLUSIONS Baicalin and scutellarin were non-competitive inhibitors targeting sulfhydryl groups especially Cys321 around the active site of Helicobacter pylori urease, representing potential to be good candidate for future research as urease inhibitor for treatment of Helicobacter pylori infection. Furthermore, our work gave additional scientific support to the use of Scutellaria baicalensis in traditional Chinese medicine (TCM) to treat gastrointestinal disorders.
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Affiliation(s)
- Xiao-Dan Yu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Rong-Bo Zheng
- Guangzhou Wanglaoji Pharmaceutical Company Limited, Guangzhou, Guangdong 510450, P.R. China
| | - Jian-Hui Xie
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China
| | - Ji-Yan Su
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Xiao-Qi Huang
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, P.R. China
| | - Yong-Hong Wang
- Guangdong Institute of Microbiology, Guangzhou 510006, P.R. China
| | - Yi-Feng Zheng
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Zhi-Zhun Mo
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Xiao-Li Wu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Dian-Wei Wu
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Ye-er Liang
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China
| | - Hui-Fang Zeng
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, P.R. China.
| | - Zi-Ren Su
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou, University of Chinese Medicine, Dongguan 523000, P.R. China
| | - Ping Huang
- College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China.
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Hwang MW, Ahn TS, Hong NR, Jeong HS, Jung MH, Ha KT, Kim BJ. Effects of traditional Chinese herbal medicine San-Huang-Xie-Xin-Tang on gastrointestinal motility in mice. World J Gastroenterol 2015; 21:1117-1124. [PMID: 25632184 PMCID: PMC4306155 DOI: 10.3748/wjg.v21.i4.1117] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 08/05/2014] [Accepted: 09/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of San-Huang-Xie-Xin-Tang (SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal (GI) motility in mice. METHODS The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates (ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). RESULTS In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT (0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT (0.1-1 g/kg). CONCLUSION These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.
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Chen H, Gao Y, Wu J, Chen Y, Chen B, Hu J, Zhou J. Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies. Cancer Lett 2014; 354:5-11. [PMID: 25128647 DOI: 10.1016/j.canlet.2014.08.003] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Revised: 07/31/2014] [Accepted: 08/01/2014] [Indexed: 12/31/2022]
Abstract
Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.
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Affiliation(s)
- Haijun Chen
- College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China; Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA
| | - Yu Gao
- College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Jianlei Wu
- College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Yingyu Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Buyuan Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Jianda Hu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China.
| | - Jia Zhou
- Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
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Kim BJ, Kim H, Lee GS, So I, Kim SJ. Effects of San-Huang-Xie-Xin-tang, a traditional Chinese prescription for clearing away heat and toxin, on the pacemaker activities of interstitial cells of Cajal from the murine small intestine. JOURNAL OF ETHNOPHARMACOLOGY 2014; 155:744-752. [PMID: 24953035 DOI: 10.1016/j.jep.2014.06.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 06/02/2014] [Accepted: 06/06/2014] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicinal formula composed of Coptidis rhizoma (Coptis chinesis Franch), Scutellariae radix (Scutellaria baicalensis Georgi), and Rhei rhizoma (Rheum officinale Baill) and is widely used in Eastern Asia, especially to ameliorate the symptoms of gastrointestinal (GI) disorders related to gastritis, gastric bleeding, peptic ulcers, and abnormal GI motility AIM OF THE STUDY Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. Because GI disorders, especially abnormal GI motility, are major lifelong problems, the authors investigated the effects of SHXXT on mouse small intestine ICCs, and sought to identify the receptors and the action mechanisms involved. MATERIALS AND METHODS Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials generated by cultured ICCs. RESULTS SHXXT produced membrane depolarization in current-clamp mode, and Y25130 (a 5-HT3 receptor antagonist) and RS39604 (a 5-HT4 receptor antagonist) blocked SHXXT-induced membrane depolarizations, whereas SB269970 (a 5-HT7 receptor antagonist) did not. However, during external Ca2+ free conditions or in the presence of thapsigargin, SHXXT did not exhibit membrane depolarization. Furthermore, the application of flufenamic acid (a nonselective cation channel (NSCC) blocker) or DIDS (a chloride channel blocker) abolished pacemaker potential generation and blocked SHXXT-induced membrane depolarizations. In addition, SHXXT-induced membrane depolarizations, which are dependent on G-protein, in ICCs were blocked by PD 98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Regarding the components of SHXXT, Coptidis rhizome and Rhei rhizoma modulated ICC pacemaking activity, whereas Scutellariae radix did not. CONCLUSION SHXXT modulates pacemaker potentials via 5-HT3 and 5-HT4 receptor-mediated pathways, external Ca2+ influx, and Ca2+ release from internal stores. Furthermore, NSCCs and Cl- channels play important roles in the regulation of pacemaking activity in a MAPK dependent manner in ICCs. The regulation of pacemaking activity by SHXXT may be due to the activity of Coptidis rhizome and Rhei rhizome. The study shows SHXXT can modulate the pacemaking activity of ICCs in the GI tract, and thus, suggests SHXXT has potential pharmacological relevance for the treatment of GI motility disorders.
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Affiliation(s)
- Byung Joo Kim
- Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea.
| | - Hyungwoo Kim
- Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan 626-870, Republic of Korea
| | - Guem San Lee
- Wonkwang University College of Korean Medicine, Iksan 570-749, Republic of Korea
| | - Insuk So
- Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
| | - Seon Jeong Kim
- Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
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Kinetics and mechanism study of competitive inhibition of jack-bean urease by baicalin. ScientificWorldJournal 2013; 2013:879501. [PMID: 24198731 PMCID: PMC3807542 DOI: 10.1155/2013/879501] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 08/27/2013] [Indexed: 11/18/2022] Open
Abstract
Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of Ki = 3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki* = 1.47 × 10−4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases.
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Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:715671. [PMID: 23935673 PMCID: PMC3713598 DOI: 10.1155/2013/715671] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 05/28/2013] [Indexed: 12/01/2022]
Abstract
In Chinese medicine, Xiexin decoction (XXD) has been used for the clinical treatment of diabetes for at least 1700 years. The present study was conducted to investigate the effective ingredients of XXD and their molecular mechanisms of antidiabetic nephropathy in rats. Rats with diabetes induced by high-fat diet and streptozotocin were treated with XXD extract for 12 weeks. XXD significantly improved the glucolipid metabolism disorder, attenuated albuminuria and renal pathological changes, reduced renal advanced glycation end-products, inhibited receptor for advanced glycation end-product and inflammation factors expression, suppressed renal nuclear factor-κB pathway activity, and downregulated renal transforming growth factor-β1. The concentrations of multiple components in plasma from XXD were determined by liquid chromatography and tandem mass spectrometry. Pharmacokinetic/pharmacodynamic analysis using partial least square regression revealed that 8 ingredients of XXD were responsible for renal protective effects via actions on multiple molecular targets. Our study suggests that the renal protective role of XXD with multiple effective ingredients involves inhibition of inflammation through downregulation of the nuclear factor-κB pathway, reducing renal advanced glycation end-products and receptor for advanced glycation end-product in diabetic rats.
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Poudel A, Kim SG, Lamichhane R, Kim YK, Jo HK, Jung HJ. Quantitative assessment of traditional Oriental herbal formulation Samhwangsasim-tang using UPLC technique. J Chromatogr Sci 2013; 52:176-85. [PMID: 23403059 DOI: 10.1093/chromsci/bmt008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
A specific and reliable ultra-performance liquid chromatography-diode array detection method has been developed and validated for the quantitative assessment of a traditional Oriental herbal formulation, Samhwangsasim-tang (SST). A Halo reversed-phase amide column (2.7 µm, 4.6 × 150 mm) was used to separate marker compounds; detection was conducted by ultraviolet absorbance at 250 nm. The column temperature was maintained at 45°C. A mobile phase consisting of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was found to be suitable for the separation, at a flow rate of 1.8 mL/min with gradient elution. Linearity, specificity, precision and recovery were calculated to validate the method and instrumentation. Under the described conditions, all marker compounds (rhaponticin, berberine, palmatine, baicalin, baicalein and wogonin) were collected within 25 min. All calibration curves of components showed good linearity (correlation coefficient > 0.9996). The limit of detection and limit of quantification ranged from 0.08-3.05 and 0.23-8.12 µg/mL, respectively. The relative standard deviation (RSD) and repeatability values of intra-day and inter-day precision were less than 2.30, 2.99 and 1.82%, respectively. In the recovery test, the accuracy ranged from 97.56-103.30% with RSD values less than 2.63%. The developed method was simple, specific, sensitive, accurate, precise and reproducible for the quantification of the active chemical constituents of SST. The simultaneous analysis of the contents of marker compounds in different SST samples prepared by different extraction procedures and different commercial products was successfully evaluated.
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Affiliation(s)
- Amrit Poudel
- 1Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk, South Korea
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Wang Z, Hu H, Chen F, Lan K, Wang A. Reduced system exposures of total rhein and baicalin after combinatory oral administration of rhein, baicalin and berberine to beagle dogs and rats. JOURNAL OF ETHNOPHARMACOLOGY 2013; 145:442-449. [PMID: 23159470 DOI: 10.1016/j.jep.2012.11.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Revised: 10/26/2012] [Accepted: 11/01/2012] [Indexed: 06/01/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhein (Rh), baicalin (BG) and berberine (Be) are important coexisted constituents of San-Huang-Xie-Xin-Tang, which was widely used in traditional Chinese medicine for the treatment of gastritis, hypertension, gastric bleeding and peptic ulcers, etc. AIM OF THE STUDY Based on the extensive phase II conjugation reactions of polyphenols (Rh and BG) in vivo, the aims of the present study were to investigate the effects of combination (Rh, BG and Be) on the system exposures of total Rh and BG involving the phase II conjugates metabolites and its possible mechanism. MATERIALS AND METHODS A 3×3 Latin square single heavy design was used to investigate the pharmacokinetics influence of total Rh and BG after combination of Be by treating plasma samples with β-glucuronidase/sulfatase both in beagle dogs and Wistar rats. In vitro and in situ experiment models including in situ rat intestinal perfusion, Caco-2 cell monolayer transport and small intestinal flora incubation system were used to discuss the possible mechanism. RESULTS The results of pharmacokinetic interactions showed that combination significantly reduced the system exposures of total Rh and BG. Compared with Rh or BG alone, the mean area under concentration-time curves (AUC(0-t)) of total Rh and BG reduced by 31% and 77% in beagle dog experiment. In Wistar rat experiment, the AUC(0-t) of total Rh and BG reduced by 22% and 21%. Subsequently, the results of in situ rat intestinal perfusion and small intestinal flora incubation system tests revealed that combination may decrease the absorption and metabolism of BG. However, combination could not affect the transport profile of BG across the Caco-2 cell. Moreover, combination did not affect the absorption or metabolism profile of Rh in all three in situ/in vitro experiments. CONCLUSIONS It was deduced that the possible mechanism of the reduction of the system exposures of total Rh and BG was related to that combination decreased the metabolism of BG to B or the phase II conjugates of Rh/BG excreted from liver/bile duct to their free aglycones in vivo by inhibiting intestinal flora. The potent effects of combination on the phase II conjugates of Rh and B in pharmacokinetics, shown in this paper, indicated that more attention should be paid to the phase II conjugates metabolites of these polyphenols (undergo extensive phase II conjugation reactions in vivo) when applied herbal products composed of these coexist compounds.
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Affiliation(s)
- Zhanguo Wang
- College of Life Science, Sichuan University, No.24 South Section 1, First Ring Road, Chengdu 610064, Sichuan Province, PR China
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Sahebkar A. Baicalin as a potentially promising drug for the management of sulfur mustard induced cutaneous complications: a review of molecular mechanisms. Cutan Ocul Toxicol 2012; 31:226-234. [PMID: 22107027 DOI: 10.3109/15569527.2011.633950] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Sulfur mustard (SM) is a bifunctional alkylating agent with strong blistering, irritant, mutagenic and cytotoxic properties. SM has been widely deployed as a chemical warfare agent for over a century, leading to extensive casualties. Skin is among the first and most heavily damaged organs upon SM exposure. Unfortunately, a considerable fraction of SM-intoxicated patients are still suffering from chronic cutaneous complications. While these complications adversely affect patients' quality of life, there is as yet no ideal treatment for them and therapeutic options are limited and mainly symptomatic. During recent decades, remarkable progress has been made in understanding molecular mechanisms underlying SM-induced dermatotoxicity and several intra- and extracellular targets have been identified. This review argues that baicalin, a bioactive flavonoid from the roots of Scutellaria spp., could counteract different molecular and biochemical abnormalities that mediate SM dermatotoxicity and could therefore be regarded as a promising therapeutic option for the management of SM-induced cutaneous lesions.
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Affiliation(s)
- Amirhossein Sahebkar
- Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.
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Zaidi SF, Muhammad JS, Shahryar S, Usmanghani K, Gilani AH, Jafri W, Sugiyama T. Anti-inflammatory and cytoprotective effects of selected Pakistani medicinal plants in Helicobacter pylori-infected gastric epithelial cells. JOURNAL OF ETHNOPHARMACOLOGY 2012; 141:403-10. [PMID: 22433535 DOI: 10.1016/j.jep.2012.03.001] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 03/01/2012] [Accepted: 03/04/2012] [Indexed: 05/24/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Helicobacter pylori infection is associated with gastritis, peptic ulcer, and gastric cancer. Due to its high global prevalence and uprising resistance to available antibiotics, efforts are now directed to identify alternative source to treat and prevent associated disorders. In the present study, effect of selected indigenous medicinal plants of Pakistan was evaluated on the secretion of interleukin-8 (IL-8) and generation of reactive oxygen species (ROS) in a bid to rationalize their medicinal use and to examine the anti-inflammatory and cytoprotective effects in gastric epithelial cells. MATERIALS AND METHODS AGS cells and clinically isolated Helicobacter pylori strain (193C) were employed for co-culture experiments. Anti-Helicobacter pylori activity and cytotoxic effects of the selected plants were determined by serial dilution method and DNA fragmentation assay respectively. ELISA and flow cytometry were performed to evaluate the effect on IL-8 secretion and ROS generation in Helicobacter pylori-infected cells. RESULTS At 100μg/ml, extracts of Alpinia galangal, Cinnamomum cassia, Cinnamomum tamala, Mentha arvensis, Myrtus communis, Oligochaeta ramose, Polygonum bistorta, Rosa damascena, Ruta graveolens, Syzygium aromaticum, Tamarix dioica, and Terminalia chebula exhibited strong inhibitory activity against IL-8 secretion. Of these, four extracts of Cinnamomum cassia, Myrtus communis, Syzygium aromaticum, and Terminalia chebula markedly inhibited IL-8 secretion at both 50 and 100μg/ml. Cinnamomum cassia was further assessed at different concentrations against Helicobacter pylori and TNF-α stimulated IL-8 secretion, which displayed significant suppression of IL-8 in a concentration-dependent-manner. Among the plants examined against ROS generation, Achillea millefolium, Berberis aristata, Coriandrum sativum, Foeniculum vulgare, Matricaria chamomilla and Prunus domestica demonstrated significant suppression of ROS from Helicobacter pylori-infected cells (p<0.01). CONCLUSION Results of the study revealed anti-inflammatory and cytoprotective effects of selected medicinal plants which could partially validate the traditional use of these plants in GI disorders particularly associated with Helicobacter pylori. Furthermore, results obtained may lead to possible future candidates of chemoprevention against peptic ulcer or gastric cancer.
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Affiliation(s)
- Syed Faisal Zaidi
- Department of Gastroenterology and Hematology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
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Zhou X, Liu D, Zhao T, Yao K, Wang X, Wang L, Yang X. Mechanical and Baicalin Delivery Properties of Adhesive Matrices for Iontophoretic Flexible Electrodes. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 20:529-42. [PMID: 19228452 DOI: 10.1163/156856209x416520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Xueqin Zhou
- a School of Chemical Engineering, Tianjin Unviersity, Tianjin 300072, China; Research Institute of Polymeric Materials, Tianjin University, Tianjin 300072, China
| | - Dongzhi Liu
- b School of Chemical Engineering, Tianjin Unviersity, Tianjin 300072, China
| | - Tian Zhao
- c School of Chemical Engineering, Tianjin Unviersity, Tianjin 300072, China
| | - Kangde Yao
- d Research Institute of Polymeric Materials, Tianjin University, Tianjin 300072, China
| | - Xueyan Wang
- e Tianjin Changzheng Hospital, Tianjin 300021, China
| | - Lei Wang
- f Tianjin Changzheng Hospital, Tianjin 300021, China
| | - Xinjian Yang
- g Tianjin Changzheng Hospital, Tianjin 300021, China
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Neuroprotective Effects of San-Huang-Xie-Xin-Tang in the MPP(+)/MPTP Models of Parkinson's Disease In Vitro and In Vivo. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:501032. [PMID: 22474505 PMCID: PMC3303814 DOI: 10.1155/2012/501032] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Accepted: 12/17/2011] [Indexed: 01/08/2023]
Abstract
San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1–methyl–4–phenylpyridinium (MPP+)/1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP) models of Parkinson's disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP+ in vitro and MPTP in vivo. In MPP+-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP+-induced gp91phox activation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP+-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection.
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Eftang LL, Esbensen Y, Tannæs TM, Bukholm IRK, Bukholm G. Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. pylori exposed gastric epithelial cells. BMC Microbiol 2012; 12:9. [PMID: 22248188 PMCID: PMC3292955 DOI: 10.1186/1471-2180-12-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2011] [Accepted: 01/17/2012] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA⁻ H. pylori variants. RESULTS Interleukin-8 was the most significantly up-regulated gene and appears to play a paramount role in the epithelial cell response to H. pylori infection and in the pathological processes leading to gastric disease. MAPK and NF-kappaB cellular pathways were powerfully activated, but did not seem to explain the impressive IL-8 response. There was marked up-regulation of TP53BP2, whose corresponding protein ASPP2 may interact with H. pylori CagA and cause marked p53 suppression of apoptosis. Other regulators of apoptosis also showed abberant regulation. We also identified up-regulation of several oncogenes and down-regulation of tumor suppressor genes as early as during the first 24 h of infection. H. pylori OMPLA phase variation did not seem to influence the inflammatory epithelial cell gene response in this experiment. CONCLUSION In whole genome analysis of the epithelial response to H. pylori exposure, IL-8 demonstrated the most marked up-regulation, and was involved in many of the most important cellular response processes to the infection. There was dysregulation of apoptosis, tumor suppressor genes and oncogenes as early as in the first 24 h of H. pylori infection, which may represent early signs of gastric tumorigenesis. OMPLA⁺/⁻ did not affect the acute inflammatory response to H. pylori.
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Affiliation(s)
- Lars L Eftang
- Department of Clinical Molecular Biology (Epigen), Institute of Clinical Medicine, University of Oslo, Akershus University Hospital, Lørenskog, Norway
- Department of Gastroenterological Surgery, Akershus University Hospital, Lørenskog, Norway
| | - Ying Esbensen
- Department of Clinical Molecular Biology (Epigen), Institute of Clinical Medicine, University of Oslo, Akershus University Hospital, Lørenskog, Norway
| | - Tone M Tannæs
- Department of Clinical Molecular Biology (Epigen), Akershus University Hospital, Lørenskog, Norway
| | - Ida RK Bukholm
- Department of Gastroenterological Surgery, Akershus University Hospital, Lørenskog, Norway
- Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway
| | - Geir Bukholm
- Institute of Health and Society, University of Oslo, Oslo, Norway
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San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis. J Nat Med 2011; 66:311-20. [PMID: 21979292 DOI: 10.1007/s11418-011-0592-0] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Accepted: 09/13/2011] [Indexed: 12/31/2022]
Abstract
Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R-induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways.
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Lee J, Tseng C, Wu S, Chang F, Chiu C, Wu Y. San-Huang-Xie-Xin-Tang extract suppresses hepatitis C virus replication and virus-induced cyclooxygenase-2 expression. J Viral Hepat 2011; 18:e315-24. [PMID: 21692943 PMCID: PMC7185454 DOI: 10.1111/j.1365-2893.2010.01424.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side effects and only a 50-70% cure rate in genotype 1 HCV-infected patients upon current standard treatment with pegylated interferon-α plus ribavirin, new therapeutic regimens are still needed. San-Huang-Xie-Xin-Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti-inflammatory effect. Here, we describe a (+)-catechin-containing fraction extracted from SHXT, referred as SHXT-frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC50 /EC50) of 84, and displayed synergistic anti-HCV effects when combined with interferon-α, HCV protease inhibitor telaprevir or polymerase inhibitor 2'-C-methylcytidine. The activation of factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) signalling pathway has particular relevance to HCV-associated HCC. SHXT-frC treatment also caused a concentration-dependent decrease in the induction of COX-2 and NF-κB expression caused by either HCV replication or HCV NS5A protein. Collectively, SHXT-frC could be an adjuvant treatment for patients with HCV-induced liver diseases.
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Affiliation(s)
- J.‐C. Lee
- Department of Biotechnology, College of Life Science,Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung
| | - C.‐k. Tseng
- Department of Biotechnology, College of Life Science
| | - S.‐F. Wu
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung
| | - F.‐R. Chang
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung
| | - C.‐C. Chiu
- Department of Biotechnology, College of Life Science
| | - Y.‐C. Wu
- Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung,Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University,Natural Medicinal Products Research Center, China Medical University Hospital, Taichung, Taiwan, China
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Huang S, Chang SJ, Yang M, Chen JJC, Chang WH. Nanoscale hepatoprotective herbal decoction attenuates hepatic stellate cell activity and chloroform-induced liver damage in mice. Int J Nanomedicine 2011; 6:1365-71. [PMID: 21760731 PMCID: PMC3133527 DOI: 10.2147/ijn.s19503] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND San-Huang-Xie-Xin-Tang (SHXXT) decoction, a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, preparation of the decoction requires addition of boiling water that causes loss of numerous effective components. METHODS To improve the bioavailability of the decoction, nanoscale SHXXT was developed. Chloroform-induced liver injury and hepatic stellate cell activity in mice were used to demonstrate the hepatoprotective characteristics of nanoscale SHXXT decoction. RESULTS Liver/body weight ratio and serum aspartate and alanine aminotranferase levels were recovered by the nanoscale SHXXT. TIMP-1 gene expression was inhibited and MMP-2 gene expression was accelerated in activated hepatic stellate cells. CONCLUSION Nanoscale SHXXT decoction prepared in room temperature water could have preserved hepatoprotective ability. The results of this study indicate that nanoscale SHXXT could be extracted easily. The simple preparation of this herbal decoction is more convenient and energy-efficient.
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Affiliation(s)
- Sherry Huang
- Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan
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Shia CS, Hou YC, Juang SH, Tsai SY, Hsieh PH, Ho LC, Chao PDL. Metabolism and pharmacokinetics of san-huang-xie-xin-tang, a polyphenol-rich chinese medicine formula, in rats and ex-vivo antioxidant activity. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:721293. [PMID: 19737807 PMCID: PMC3137274 DOI: 10.1093/ecam/nep124] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/20/2009] [Accepted: 06/25/2009] [Indexed: 01/12/2023]
Abstract
San-Huang-Xie-Xin-Tang (SHXXT), a widely used Chinese herbal formula, consists of rhizomes of Rheum officinale, roots of Scutellaria baicalensis and rhizomes of Coptis chinesis. This study investigated the metabolism and pharmacokinetics of polyphenols in SHXXT, including baicalin, baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol. The quantitation methods of SHXXT decoction and rat serum using high performance liquid chromatography were developed and validated in this study. After oral administration of SHXXT decoction to rats, the parent forms of various constituents and their conjugated metabolites in serum were determined before and after hydrolysis with β-glucuronidase and sulfatase. The results showed that only free form of rhein can be quantitated, whereas the parent forms of coptisine, palmatine, berberine, baicalein, wogonin, emodin, aloe-emodin and chrysophanol were not detected in serum. The glucuronides of baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol were the predominant forms in bloodstream. In order to evaluate the in vivo antioxidant activity of SHXXT, the serum metabolite of SHXXT was prepared, characterized and followed by evaluation of the effect on AAPH-induced hemolysis. The results indicated that metabolites of SHXXT exhibited significant free radical scavenging activity. We suggest that biologists redirect their focus to the bioactivity of the conjugated metabolites of these polyphenols.
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Liou SF, Ke HJ, Hsu JH, Liang JC, Lin HH, Chen IJ, Yeh JL. San-Huang-Xie-Xin-Tang Prevents Rat Hearts from Ischemia/Reperfusion-Induced Apoptosis through eNOS and MAPK Pathways. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:915051. [PMID: 21785641 PMCID: PMC3137793 DOI: 10.1093/ecam/neq061] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 04/20/2010] [Indexed: 12/21/2022]
Abstract
San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg(-1): 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg(-1): 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.
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Affiliation(s)
- Shu-Fen Liou
- Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
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Yang JK, Yeo HD, Baik SC, Jung JY, Kim BM, Jeong MJ, Lee CH, Karigar CS, Park HM, Choi MS. Antibacterial and immuno-modulatory activity of ethanol extracts from Lespedeza sp. during Helicobacter pylori infections. BIOTECHNOL BIOPROC E 2011. [DOI: 10.1007/s12257-009-3115-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Wang YS, Lin RT, Cheng HY, Yang SF, Chou WW, Juo SHH. Anti-atherogenic effect of San-Huang-Xie-Xin-Tang, a traditional Chinese medicine, in cultured human aortic smooth muscle cells. JOURNAL OF ETHNOPHARMACOLOGY 2011; 133:442-7. [PMID: 20974241 DOI: 10.1016/j.jep.2010.10.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2010] [Revised: 10/04/2010] [Accepted: 10/07/2010] [Indexed: 05/12/2023]
Abstract
AIM OF THE STUDY San-huang-xie-xin-tang (SHXXT) is a traditional Chinese medicine and it has been shown to have an anti-inflammatory effect. Since inflammation is one of the major mechanisms of atherosclerosis, we aimed to investigate anti-atherosclerotic effect of SHXXT in human aortic smooth muscle cells (HASMCs). MATERIALS AND METHODS Human aortic smooth muscle cells (HASMCs) were used in the present study, and rendered atherosclerosis by adding lipopolysaccharides. We first tested the effects of SHXXT on HASMC migration and proliferation as they present the major morphological change of atherosclerosis. We also examined whether SHXXT can influence the production of several biomarkers of inflammation and atherosclerosis including reactive oxygen species (ROS), COX-2, ERK1/2, IL-1β, IL-6, IL-8 and MCP-1. RESULTS Using the dimethyl-thiazol-diphenyltetrazoliumbromide (MTT) and wound repair assay, SHXXT was shown to significantly reduce HASMC proliferation and migration, respectively. From the fluorometric assay, SHXXT significantly reduced ROS production. SHXXT down regulated mRNA and protein levels for the COX-2 gene. In addition, phosphorylated ERK1/2 levels were suppressed by SHXXT suggesting HASMC division can be inhibited under pro-inflammatory condition. SHXXT significantly inhibited the production of IL-1β, IL-6, IL-8 and MCP-1 after LPS stimulation. CONCLUSIONS Our results indicated that SHXXT can influence several mechanisms involved in atherosclerosis, which suggests that SHXXT may have a therapeutic potential for cardiovascular disease associated with atherosclerosis.
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Affiliation(s)
- Yung-Song Wang
- Department of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan
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Shih YT, Chen IJ, Wu YC, Lo YC. San-Huang-Xie-Xin-Tang Protects against Activated Microglia- and 6-OHDA-Induced Toxicity in Neuronal SH-SY5Y Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:429384. [PMID: 19339484 PMCID: PMC3135633 DOI: 10.1093/ecam/nep025] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2008] [Accepted: 03/03/2009] [Indexed: 12/30/2022]
Abstract
San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix and Rhei rhizoma, is a traditional Chinese herbal medicine used to treat gastritis, gastric bleeding and peptic ulcers. This study investigated the neuroprotective effects of SHXT on microglia-mediated neurotoxicity using co-cultured lipopolysaccharide (LPS)-activated microglia-like BV-2 cells with neuroblastoma SH-SY5Y cells. Effects of SHXT on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were also examined in SH-SY5Y cells. Results indicated SHXT inhibited LPS-induced inflammation of BV-2 cells by downregulation of iNOS, NO, COX-2, PGE2, gp91phox, iROS, TNF-α, IL-1β, inhibition of IκBα degradation and upregulation of HO-1. In addition, SHXT increased cell viability and down regulated nNOS, COX-2 and gp91phox of SH-SY5Y cells co-cultured with LPS activated BV-2 cells. SHXT treatment increased cell viability and mitochondria membrane potential (MMP), decreased expression of nNOS, COX-2, gp91phox and iROS, and inhibited IκBα degradation in 6-OHDA-treated SH-SY5Y cells. SHXT also attenuated LPS activated BV-2 cells- and 6-OHDA-induced cell death in differentiated SH-SY5Y cells with db-cAMP. Furthermore, SHXT-inhibited nuclear translocation of p65 subunit of NF-κB in LPS treated BV-2 cells and 6-OHDA treated SH-SY5Y cells. In conclusion, SHXT showed protection from activated microglia- and 6-OHDA-induced neurotoxicity by attenuating inflammation and oxidative stress.
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Affiliation(s)
- Yu-Tzu Shih
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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Synthesis, selective anti-Helicobacter pylori activity, and cytotoxicity of novel N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides. Bioorg Med Chem Lett 2010; 20:4922-6. [DOI: 10.1016/j.bmcl.2010.06.048] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Revised: 06/07/2010] [Accepted: 06/08/2010] [Indexed: 11/20/2022]
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Combinative method using HPLC fingerprint and quantitative analyses for quality consistency evaluation of an herbal medicinal preparation produced by different manufacturers. J Pharm Biomed Anal 2010; 52:597-602. [DOI: 10.1016/j.jpba.2010.01.018] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2009] [Revised: 01/07/2010] [Accepted: 01/09/2010] [Indexed: 11/23/2022]
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Li CY, Hou YC, Lee Chao PD, Shia CS, Hsu IC, Fang SH. Potential ex vivo immunomodulatory effects of San-Huang-Xie-Xin-Tang and its component herbs on mice and humans. JOURNAL OF ETHNOPHARMACOLOGY 2010; 127:292-8. [PMID: 19903515 DOI: 10.1016/j.jep.2009.11.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2009] [Revised: 11/02/2009] [Accepted: 11/03/2009] [Indexed: 05/12/2023]
Abstract
AIM OF THE STUDY San-Huang-Xie-Xin-Tang (SHXXT), an important Chinese medicine formula, contains Rhei Rhizoma (RR), Scutellariae Radix (SR) and Coptidis Rhizoma (CR). RR and SR are abundant in anthraquinone and flavonoid polyphenols. Pharmacokinetic study of SHXXT indicated that glucuronides were the predominant forms of polyphenols in rats. MATERIALS AND METHODS As an extension of pharmacokinetic study, the serum metabolites of SHXXT, RR, SR and CR were prepared from rats and quantitated, then the immunomodulation effects were examined by culturing these serum metabolites with murine and human immune cells. RESULTS The results indicated that the inhibitions on nitric oxide (NO) and cytokine production from mitogen-activated peritoneal macrophages by the serum metabolites of SHXXT, RR, SR and CR were through reducing the protein expression of inducible NO synthase (iNOS) and the IC(50) were 0.8%, 1.5%, 3.0% and 0.8% of their blood concentrations, respectively. In addition, the serum metabolites of SHXXT, RR, SR and CR significantly decreased the ratios of interferon-gamma (IFN-gamma) to interleukin (IL)-4 in mitogen-stimulated mice spleen cells and human peripheral blood mononuclear cells (PBMCs). Moreover, the serum metabolites of SHXXT and SR significantly arrested the mitogen-stimulated mice spleen cells at G2/M stage. CONCLUSIONS In conclusion, the serum metabolites of SHXXT and the component herbs exerted promising modulation activities on the immune functions and the cell cycle distribution of mice and human immune cells. We suggest that SHXXT is a promising remedy for immunomodulation through Th1/Th2 regulation.
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Affiliation(s)
- Chia-Yang Li
- Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
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