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1
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Zhao L, Zheng L. A Review on Bioactive Anthraquinone and Derivatives as the Regulators for ROS. Molecules 2023; 28:8139. [PMID: 38138627 PMCID: PMC10745977 DOI: 10.3390/molecules28248139] [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: 11/05/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Anthraquinones are bioactive natural products, which are often found in medicinal herbs. These compounds exert antioxidant-related pharmacological actions including neuroprotective effects, anti-inflammation, anticancer, hepatoprotective effects and anti-aging, etc. Considering the benefits from their pharmacological use, recently, there was an upsurge in the development and utilization of anthraquinones as reactive oxygen species (ROS) regulators. In this review, a deep discussion was carried out on their antioxidant activities and the structure-activity relationships. The antioxidant mechanisms and the chemistry behind the antioxidant activities of both natural and synthesized compounds were furtherly explored and demonstrated. Due to the specific chemical activity of ROS, antioxidants are essential for human health. Therefore, the development of reagents that regulate the imbalance between ROS formation and elimination should be more extensive and rational, and the exploration of antioxidant mechanisms of anthraquinones may provide new therapeutic tools and ideas for various diseases mediated by ROS.
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Affiliation(s)
- Lihua Zhao
- Tianjin Renai College, Tianjin 301636, China;
| | - Lin Zheng
- College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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2
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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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3
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Zhou P, Zhang J, Xu Y, Zhang P, Xiao Y, Liu Y. Simultaneous quantification of anthraquinone glycosides, aglycones, and glucuronic acid metabolites in rat plasma and tissues after oral administration of raw and steamed rhubarb in blood stasis rats by UHPLC-MS/MS. J Sep Sci 2021; 45:529-541. [PMID: 34784448 DOI: 10.1002/jssc.202100623] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/30/2021] [Accepted: 11/10/2021] [Indexed: 12/17/2022]
Abstract
Rhubarb is a widely used herbal medicine. To achieve different effects, rhubarb is usually steamed with rice wine (steamed rhubarb). This steaming treatment increases the blood-activating and stasis-removing effects of rhubarb. A specific and accurate ultra high performance liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of anthraquinone glycosides, aglycones, and glucuronic acid metabolites in plasma and tissues after administration of raw rhubarb and steamed rhubarb in blood stasis rats. Chromatographic separation was performed on ACQUITY UPLC BEH Shield RP 18 column using the mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Satisfactory linearity, precision, accuracy, extraction recovery, and matrix effect have been achieved. From pharmacokinetic study, it showed that glucuronic acid metabolites were found abundantly in plasma as bioactive components. The lower area under concentration-time curve, maximum concentration, and higher apparent volume of distribution (P < 0.01), body clearance (P < 0.01) values in steamed rhubarb showed that most components of steamed rhubarb have lower bioavailability in plasma compared with raw rhubarb. But it found these components were mainly distributed in spleen and liver with large blood flow and perfusion rates. The pharmacokinetics and tissue distribution studies of anthraquinone components will provide helpful information for clinical application of steamed rhubarb and raw rhubarb.
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Affiliation(s)
- Ping Zhou
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China
| | - Jing Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China.,State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China
| | - Yudi Xu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China
| | - Peng Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China
| | - Yongqing Xiao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China
| | - Ying Liu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China
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4
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Wang D, Wang XH, Yu X, Cao F, Cai X, Chen P, Li M, Feng Y, Li H, Wang X. Pharmacokinetics of Anthraquinones from Medicinal Plants. Front Pharmacol 2021; 12:638993. [PMID: 33935728 PMCID: PMC8082241 DOI: 10.3389/fphar.2021.638993] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 02/03/2021] [Indexed: 12/23/2022] Open
Abstract
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
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Affiliation(s)
- Dongpeng Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China
| | - Xian-He Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiongjie Yu
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Fengjun Cao
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiaojun Cai
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Ping Chen
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Minglun Li
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Yibin Feng
- School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Hongliang Li
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China
| | - Xuanbin Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China.,Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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5
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Bai JW, Chen XR, Tang Y, Cui WQ, Li DL, God'spower BO, Yang Y. Study on microwave assisted extraction of chrysophanol and its intervention in biofilm formation of Streptococcus suis. RSC Adv 2019; 9:28996-29004. [PMID: 35528391 PMCID: PMC9071839 DOI: 10.1039/c9ra04662c] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 09/07/2019] [Indexed: 12/03/2022] Open
Abstract
A microwave assisted extraction technology was used to extract chrysophanol from rhubarb. The present study will focus on the optimum extraction conditions of chrysophanol and discuss the inhibitory effect of chrysophanol on the biofilm formation of Streptococcus suis (S. suis). A Box-Behnken design based on single-factor experiments was applied to optimize the microwave assisted extraction process and to study the factors' relationships with each other. The results showed that a microwave temperature of 56 °C, ethanol concentration of 70%, microwave power of 540 W and liquid to raw material ratio of 55 mL g-1 were the optimal conditions for the microwave method. The yield of chrysophanol was 2.54 ± 0.07% under the optimal conditions, which was in agreement with the predicted value (2.64%). Then, the chemical structure of the extracted chrysophanol was identified by LC-MS. In addition, in vitro experiments showed that chrysophanol has an inhibitory effect on S. suis (minimum inhibitory concentration was 1.98 μg mL-1) and was shown to significantly inhibit the capability of S. suis to form a biofilm using crystal violet staining. Finally, scanning electron microscopy analysis showed that the three-dimensional structure of the biofilm deposited by the S. suis community was destroyed by chrysophanol.
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Affiliation(s)
- Jing-Wen Bai
- College of Science, Northeast Agricultural University 600 Changjiang Road, Xiangfang Harbin Heilongjiang 150030 P. R. China +86 451 55191442
| | - Xing-Ru Chen
- College of Veterinary Medicine, Northeast Agricultural University Harbin China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development Harbin China
| | - Yang Tang
- College of Science, Northeast Agricultural University 600 Changjiang Road, Xiangfang Harbin Heilongjiang 150030 P. R. China +86 451 55191442
| | - Wen-Qiang Cui
- College of Veterinary Medicine, Northeast Agricultural University Harbin China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development Harbin China
| | - Da-Long Li
- College of Horticulture, Northeast Agricultural University Harbin China
| | - Bello-Onaghise God'spower
- College of Veterinary Medicine, Northeast Agricultural University Harbin China
- Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development Harbin China
| | - Yu Yang
- College of Science, Northeast Agricultural University 600 Changjiang Road, Xiangfang Harbin Heilongjiang 150030 P. R. China +86 451 55191442
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6
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Ancuceanu R, Dinu M, Dinu-Pirvu C, Anuţa V, Negulescu V. Pharmacokinetics of B-Ring Unsubstituted Flavones. Pharmaceutics 2019; 11:E370. [PMID: 31374885 PMCID: PMC6723510 DOI: 10.3390/pharmaceutics11080370] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 07/23/2019] [Accepted: 07/23/2019] [Indexed: 02/07/2023] Open
Abstract
B-ring unsubstituted flavones (of which the most widely known are chrysin, baicalein, wogonin, and oroxylin A) are 2-phenylchromen-4-one molecules of which the B-ring is devoid of any hydroxy, methoxy, or other substituent. They may be found naturally in a number of herbal products used for therapeutic purposes, and several have been designed by researchers and obtained in the laboratory. They have generated interest in the scientific community for their potential use in a variety of pathologies, and understanding their pharmacokinetics is important for a grasp of their optimal use. Based on a comprehensive survey of the relevant literature, this paper examines their absorption (with deglycosylation as a preliminary step) and their fate in the body, from metabolism to excretion. Differences among species (inter-individual) and within the same species (intra-individual) variability have been examined based on the available data, and finally, knowledge gaps and directions of future research are discussed.
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Affiliation(s)
- Robert Ancuceanu
- Department of Pharmaceutical Botany and Cell Biology, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Mihaela Dinu
- Department of Pharmaceutical Botany and Cell Biology, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
| | - Cristina Dinu-Pirvu
- Department of Physical Chemistry and Colloidal Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest 020956, Romania
| | - Valentina Anuţa
- Department of Physical Chemistry and Colloidal Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest 020956, Romania
| | - Vlad Negulescu
- Department of Toxicology, Clinical Pharmacology and Psychopharmacology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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7
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Xing H, Ren C, Kong Y, Ni Q, Wang Z, Zhao D, Li N, Chen X, Lu Y. Determination of GL-V9, a derivative of wogonin, in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after oral and pulmonary administration. Biomed Chromatogr 2019; 33:e4556. [PMID: 30990904 DOI: 10.1002/bmc.4556] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/18/2019] [Accepted: 04/11/2019] [Indexed: 12/13/2022]
Abstract
GL-V9, a derivative of wogonin, shows much more potent anticancer properties than wogonin. In this study, a selective, sensitive and rapid ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of GL-V9 in rat plasma. Plasma samples were processed using methanol to precipitate protein. Chromatographic separation of analytes was achieved on a C18 column using gradient elution within 4.5 min. The mobile phase consisted of acetonitrile and water including 0.1% (v/v) formic acid and 5 mm ammonium acetate. GL-V9 and caffeine (internal standard) were monitored by positive electrospray triple quadrupole mass spectrometer and quantified using multiple reaction monitoring (MRM) mode with the transitions of m/z 410.20 → 126.10 (GL-V9) and 195.10 → 138.00 (IS: caffeine), respectively. Good linearity was obtained over the range of 2-1000 ng/mL (R2 > 0.99) and the extraction recovery was 101.91 ± 11.34%. The intra- and inter-day precision variations were small (RSD 1.35-6.96%) and the relative error (RE) of accuracy was -7.35-6.27%. The established and validated UPLC-MS/MS method was successfully applied to study the pharmacokinetic behavior of GL-V9 after administration through different delivery routes. The results demonstrated that pulmonary delivery exhibited a greater advantage in terms of improving bioavailability compared with oral administration.
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Affiliation(s)
- Han Xing
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Chang Ren
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Ying Kong
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Qi Ni
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Zeyu Wang
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Di Zhao
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Ning Li
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Xijing Chen
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yang Lu
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
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8
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Prateeksha, Yusuf MA, Singh BN, Sudheer S, Kharwar RN, Siddiqui S, Abdel-Azeem AM, Fernandes Fraceto L, Dashora K, Gupta VK. Chrysophanol: A Natural Anthraquinone with Multifaceted Biotherapeutic Potential. Biomolecules 2019; 9:E68. [PMID: 30781696 PMCID: PMC6406798 DOI: 10.3390/biom9020068] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Revised: 02/05/2019] [Accepted: 02/07/2019] [Indexed: 12/16/2022] Open
Abstract
Chrysophanol is a unique anthraquinone having broad-spectrum therapeutic potential along with ecological importance. It is the first polyketide that has been reported to be biosynthesized in an organism-specific manner. The traditional Chinese and Korean medicinal systems provide evidence of the beneficial effects of chrysophanol on human health. The global distribution of chrysophanol encountered in two domains of life (bacteria and eukaryota) has motivated researchers to critically evaluate the properties of this compound. A plethora of literature is available on the pharmacological properties of chrysophanol, which include anticancer, hepatoprotective, neuroprotective, anti-inflammatory, antiulcer, and antimicrobial activities. However, the pharmacokinetics and toxicity studies on chrysophanol demand further investigations for it to be used as a drug. This is the first comprehensive review on the natural sources, biosynthetic pathways, and pharmacology of chrysophanol. Here we reviewed recent advancements made on the pharmacokinetics of the chrysophanol. Additionally, we have highlighted the knowledge gaps of its mechanism of action against diseases and toxicity aspects.
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Affiliation(s)
- Prateeksha
- Department of Biosciences, Integral University, Lucknow-226026, Uttar Pradesh, India;
- Herbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow-226001, Uttar Pradesh, India
| | - Mohd Aslam Yusuf
- Department of Bioengineering, Integral University, Lucknow-226016, Uttar Pradesh, India;
| | - Brahma N. Singh
- Herbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow-226001, Uttar Pradesh, India
| | - Surya Sudheer
- Department of Chemistry and Biotechnology, ERA Chair of Green Chemistry, Tallinn University of Technology, 12618 Tallinn, Estonia;
| | - Ravindra N. Kharwar
- Centre of Advanced Study in Botany, Institute of Science, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India;
| | - Saba Siddiqui
- Integral Institute of Agricultural Science and Technology (IIAST), Integral University, Lucknow-226026, Uttar Pradesh, India;
| | - Ahmed M. Abdel-Azeem
- Botany Department, Faculty of Science, University of Suez Canal, Ismailia 41522, Egypt;
| | - Leonardo Fernandes Fraceto
- Institute of Science and Technology of Sorocaba, São Paulo State University–Unesp, Sorocaba–São Paulo 18087-180, Brazil;
| | - Kavya Dashora
- Centre for Rural Development and Technology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India;
| | - Vijai K. Gupta
- Department of Chemistry and Biotechnology, ERA Chair of Green Chemistry, Tallinn University of Technology, 12618 Tallinn, Estonia;
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9
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Wang WT, Hao CH, Zhang SX, Zhang XH, Guo F, Sun SY, Zhang R, Zhao ZY, Tang LD. Neuroprotective effect of Sanqi Tongshuan Tablets on sequelae post-stroke in rats. CHINESE HERBAL MEDICINES 2019. [DOI: 10.1016/j.chmed.2018.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
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10
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Zhang Y, Zhang Z, Song R. The Influence of Compatibility of Rhubarb and Radix Scutellariae on the Pharmacokinetics of Anthraquinones and Flavonoids in Rat Plasma. Eur J Drug Metab Pharmacokinet 2018; 43:291-300. [PMID: 29134502 DOI: 10.1007/s13318-017-0444-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND AND OBJECTIVES Rhubarb-Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma. METHODS Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC-MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma. The concentrations of phase II conjugates of flavonoid aglycones and anthraquinone aglycones were also determined after hydrolyzing the plasma with sulfatase. RESULTS Compared with administration of Radix scutellariae alone, co-administration of Rhubarb significantly decreased the first maximum plasma concentration (C max1) of baicalin, wogonside, and the phase II conjugates of baicalein, wogonin to 46.40, 61.27, 41.49, and 20.50%, respectively. The area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was significantly decreased from 82.60 ± 20.22 to 51.91 ± 7.46 μM·h for rhein and 276.83 ± 98.02 to 175.42 ± 86.82 μM·h for the phase II conjugates of wogonin after compatibility. The time to reach the first maximum plasma concentration (T max1) of anthraquinones was shortened and the second peak of anthraquinones disappeared after compatibility. CONCLUSIONS Compatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids.
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Affiliation(s)
- Yaqing Zhang
- Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, 24 Tongjia lane, Nanjing, 210009, China.,State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China
| | - Zunjian Zhang
- Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, 24 Tongjia lane, Nanjing, 210009, China.,State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China
| | - Rui Song
- Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, 24 Tongjia lane, Nanjing, 210009, China. .,State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.
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11
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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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12
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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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13
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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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Li YX, Gong XH, Li Y, Zhang RQ, Yuan A, Zhao MJ, Zeng DW, Peng C. The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic Characteristics of Main Components in Rheum palmatum L. Phytother Res 2015; 29:1259-64. [PMID: 25963314 DOI: 10.1002/ptr.5369] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/20/2015] [Accepted: 04/16/2015] [Indexed: 11/05/2022]
Abstract
Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe-emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug-drug interaction medicated by chemical reaction and cytochromes P450.
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Affiliation(s)
- Yun-xia Li
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Xiao-hong Gong
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Yan Li
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Ruo-qi Zhang
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - An Yuan
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Meng-jie Zhao
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Dai-wen Zeng
- Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, China
| | - Cheng Peng
- Pharmacy College, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, 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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Hou ML, Chang LW, Lin CH, Lin LC, Tsai TH. Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes. JOURNAL OF ETHNOPHARMACOLOGY 2014; 155:1291-1299. [PMID: 25046826 DOI: 10.1016/j.jep.2014.07.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 06/26/2014] [Accepted: 07/10/2014] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have investigated the comparative pharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment. MATERIALS AND METHODS The comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats was studied by liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug-metabolizing genes after SHXXT treatment was investigated by microarray analysis and real-time polymerase chain reaction (RT-PCR). RESULTS A validated LC-MS/MS method was applied to investigate the comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats. The pharmacokinetic results demonstrate that the loperamide-induced constipation reduced the absorption of rhein. Cmax significantly reduced by 2.5-fold, the AUC decreased by 27.8%; however, the elimination half-life (t1/2) was prolonged by 1.6-fold. Tmax and mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold, respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of microarray analysis on gene expression indicate that five drug-metabolizing genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the SHXXT (0.5 g/kg) treatment. CONCLUSION The loperamide-induced constipation reduced the absorption of rhein. Since among the 25,338 genes analyzed, there were five genes significantly altered by SHXXT treatment. Thus, information on minor drug-metabolizing genes altered by SHXXT treatment indicates that SHXXT is relatively safe for clinical application.
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Affiliation(s)
- Mei-Ling Hou
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Li-Wen Chang
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chi-Hung Lin
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
| | - Lie-Chwen Lin
- National Research Institute of Chinese Medicine, Taipei, Taiwan
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
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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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Hou ML, Chang LW, Lin CH, Lin LC, Tsai TH. Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS/MS. Molecules 2014; 19:4058-75. [PMID: 24699148 PMCID: PMC6271780 DOI: 10.3390/molecules19044058] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 03/22/2014] [Accepted: 03/27/2014] [Indexed: 12/12/2022] Open
Abstract
Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the comparative pharmacokinetics of rhein in rats. A sensitive and specific method combining liquid chromatography with electrospray ionization tandem mass spectrometry has been developed and validated to simultaneously quantify six active compounds in the pharmaceutical herbal product SHXXT to further study their pharmacokinetics in rats. Multiple reaction monitoring (MRM) was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. There were no significant matrix effects in the quantitative analysis and the mean recovery for rhein in rat plasma was 91.6%±3.4%. The pharmacokinetic data of rhein demonstrate that the herbal formulae or the single herbal extract provide significantly higher absorption rate than the pure compound. This phenomenon suggests that the other herbal ingredients of SHXXT and rhubarb extract significantly enhance the absorption of rhein in rats. In conclusion, the herbal formulae (SHXXT) are more efficient than the single herb (rhubarb) or the pure compound (rhein) in rhein absorption.
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Affiliation(s)
- Mei-Ling Hou
- Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan.
| | - Li-Wen Chang
- Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan.
| | - Chi-Hung Lin
- Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan.
| | - Lie-Chwen Lin
- National Research Institute of Chinese Medicine, No. 155-1, Sec. 2, Li-Nong St., Beitou District, Taipei 11221, Taiwan.
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei 11221, Taiwan.
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Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:137631. [PMID: 24348687 PMCID: PMC3856151 DOI: 10.1155/2013/137631] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Revised: 07/24/2013] [Accepted: 07/30/2013] [Indexed: 11/21/2022]
Abstract
Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic) modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD) rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO) model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP-43) fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20) acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.
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Ding Y, Peng M, Zhang T, Tao JS, Cai ZZ, Zhang Y. Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis withβ-glucuronidase and sufatase: a review of bio-analytical methods. Biomed Chromatogr 2013; 27:1280-95. [DOI: 10.1002/bmc.2912] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Revised: 03/03/2013] [Accepted: 03/04/2013] [Indexed: 11/08/2022]
Affiliation(s)
- Yue Ding
- Experiment Center for Teaching and Learning; Shanghai University of Traditional Chinese Medicine; Shanghai; 201203; People's Republic of China
| | | | - Tong Zhang
- Experiment Center for Teaching and Learning; Shanghai University of Traditional Chinese Medicine; Shanghai; 201203; People's Republic of China
| | - Jian-Sheng Tao
- School of Pharmacy; Shanghai University of Traditional Chinese Medicine; Shanghai; 201203; People's Republic of China
| | - Zhen-Zhen Cai
- Experiment Center for Teaching and Learning; Shanghai University of Traditional Chinese Medicine; Shanghai; 201203; People's Republic of China
| | - Yong Zhang
- Experiment Center for Teaching and Learning; Shanghai University of Traditional Chinese Medicine; Shanghai; 201203; People's Republic of China
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Li H, Guo H, Wu L, Zhang Y, Chen J, Liu X, Cai H, Zhang K, Cai B. Comparative pharmacokinetics study of three anthraquinones in rat plasma after oral administration of Radix et Rhei Rhizoma extract and Dahuang Fuzi Tang by high performance liquid chromatography–mass spectrometry. J Pharm Biomed Anal 2013; 76:215-8. [DOI: 10.1016/j.jpba.2012.12.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 12/04/2012] [Accepted: 12/05/2012] [Indexed: 12/01/2022]
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Jiang JY, Yang MW, Qian W, Lin H, Geng Y, Zhou ZQ, Xiao DW. Quantitative determination of rhein in human plasma by liquid chromatography–negative electrospray ionization tandem mass/mass spectrometry and the application in a pharmacokinetic study. J Pharm Biomed Anal 2012; 57:19-25. [DOI: 10.1016/j.jpba.2011.09.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Revised: 08/31/2011] [Accepted: 09/02/2011] [Indexed: 10/17/2022]
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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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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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Ikarashi N, Takeda R, Ito K, Ochiai W, Sugiyama K. The inhibition of lipase and glucosidase activities by acacia polyphenol. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:272075. [PMID: 21660093 PMCID: PMC3096474 DOI: 10.1093/ecam/neq043] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2010] [Accepted: 04/09/2010] [Indexed: 12/31/2022]
Abstract
Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia mearnsii) is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. In an in vitro study, we measured the inhibitory activity of AP on lipase and glucosidase. In addition, we evaluated the effects of AP on absorption of orally administered olive oil, glucose, maltose, sucrose and starch solution in mice. We found that AP concentration-dependently inhibited the activity of lipase, maltase and sucrase with an IC50 of 0.95, 0.22 and 0.60 mg ml−1, respectively. In ICR mice, olive oil was administered orally immediately after oral administration of AP solution, and plasma triglyceride concentration was measured. We found that AP significantly inhibited the rise in plasma triglyceride concentration after olive oil loading. AP also significantly inhibited the rise in plasma glucose concentration after maltose and sucrose loading, and this effect was more potent against maltose. AP also inhibited the rise in plasma glucose concentration after glucose loading and slightly inhibited it after starch loading. Our results suggest that AP inhibits lipase and glucosidase activities, which leads to a reduction in the intestinal absorption of lipids and carbohydrates.
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Affiliation(s)
- Nobutomo Ikarashi
- Department of Clinical Pharmacokinetics, Hoshi University, Tokyo 142-8501, Japan
| | - Rumi Takeda
- Department of Clinical Pharmacokinetics, Hoshi University, Tokyo 142-8501, Japan
| | - Kiyomi Ito
- Department of Clinical Pharmacokinetics, Hoshi University, Tokyo 142-8501, Japan
| | - Wataru Ochiai
- Department of Clinical Pharmacokinetics, Hoshi University, Tokyo 142-8501, Japan
| | - Kiyoshi Sugiyama
- Department of Clinical Pharmacokinetics, Hoshi University, Tokyo 142-8501, Japan
- *Kiyoshi Sugiyama:
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Neuroprotection by the Traditional Chinese Medicine, Tao-Hong-Si-Wu-Tang, against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2010; 2011:803015. [PMID: 21076527 PMCID: PMC2975073 DOI: 10.1155/2011/803015] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2010] [Revised: 08/24/2010] [Accepted: 10/07/2010] [Indexed: 12/29/2022]
Abstract
Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese medicine (TMC). In the present study, oral administration of THSWT (0.7 and 1.4 g kg−1day−1) for 14 days before MCAO dose-dependently attenuated focal cerebral ischemia in rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and active caspase-3 expressions in ischemic regions. These expressions were obviously inhibited by 0.7 g kg−1day−1 THSWT treatment. In addition, THSWT inhibited platelet aggregation stimulated by collagen in washed platelets. In an in vivo study, THSWT (16 g kg−1) significantly prolonged platelet plug formation in mice. However, THSWT (20 and 40 μg mL−1) did not significantly reduce the electron spin resonance (ESR) signal intensity of hydroxyl radical (OH•) formation. In conclusion, the most important findings of this study demonstrate for the first time that THSWT possesses potent neuroprotective activity against MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and platelet activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
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