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Hoshi A, Funakoshi H, Otoyama Y, Yoshida H, Momo K. Kampo medicine inducing drug-induced liver injury: A case report and systematic review. Drug Discov Ther 2025; 18:325-335. [PMID: 39756858 DOI: 10.5582/ddt.2024.01087] [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] [Indexed: 01/07/2025]
Abstract
Kampo medicine, comprising various conventional crude drug products, poses challenges in identifying adverse event causality. We present a case of severe liver injury following the administration of Saibokuto and attempted to identify the likely causative crude drug inducing liver injury through a systematic literature review. A 29-year-old woman developed severe liver injury approximately two months after Saibokuto administration, necessitating steroid pulse therapy for recovery. The literature search was conducted on February 15, 2023 in Japan. Using PubMed and the "Igaku Chuo Zasshi (ICHUSHI) database," two individuals independently selected studies published between January 1997 and February 15, 2023. The search focused on studies involving human subjects, published in either English or Japanese, and specifically investigated Kampo medicines categorized as over-the-counter or prescription drugs suspected as causative agents of drug-induced liver injury (DILI). Studies on health supplements, discontinued Kampo medicines, and autoimmune hepatitis, were excluded. As it is ethically impossible to rechallenge drugs that cause liver injury, this review primarily relied on case report literature. Through the review, 37 cases (men/women: 12/25, including present case) were analyzed, including 32 reports (36 cases) from 3,055 studies that met the inclusion criteria. Notably, 65.9% of cases were associated with Scutellariae radix, with onset occurring within 45 (1-730) days and recovery within 35 (7-184) days. Our case study and literature review underscore a prevalent association between liver injury and Kampo medicines containing Scutellariae radix. Vigilant liver function monitoring, particularly within the first 2 months of administration, is recommended, especially for formulations containing Scutellariae radix.
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Affiliation(s)
- Akane Hoshi
- Department of Pharmacy, Showa University Hospital, Tokyo, Japan
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan
| | - Haruki Funakoshi
- Department of Pharmacy, Showa University Hospital, Tokyo, Japan
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan
| | - Yumi Otoyama
- Department of Medicine, Division of Gastroenterology, School of Medicine, Showa University, Tokyo, Japan
| | - Hitoshi Yoshida
- Department of Medicine, Division of Gastroenterology, School of Medicine, Showa University, Tokyo, Japan
| | - Kenji Momo
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan
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Bu Z, Xu Y, Zhou X, Wang X, Liu S, Wang L, Yang B, Zhou X, Lu G, Liu J, Liu Z. Exploring the therapeutic potential of "Xiaochaihu Decoction": a systematic review and meta-analysis on the clinical effectiveness and safety in managing cancer-related fever. Front Pharmacol 2024; 15:1359866. [PMID: 38803432 PMCID: PMC11128760 DOI: 10.3389/fphar.2024.1359866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/15/2024] [Indexed: 05/29/2024] Open
Abstract
Objective: This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related Fever (CRF). Methods: Eight databases were systematically searched in September 2023. The risk of bias (ROB) 2.0 tool recommended by Cochrane Handbook was applied to evaluate the ROB of the included randomized controlled trials (RCTs). Additionally, the quality of evidence was assessed using the Grading of recommendations assessment, development and evaluation (GRADE) tool. Results: We included 18 RCTs involving 1,424 patients. Compared to Western medicine or Xinhuang Tablets, Xiaochaihu Decoction significantly improved clinical effectiveness in CRF patients (risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.17, 1.32) and expedited the normalization of body temperature (mean difference [MD] = -5.29, 95%CI: -5.59, -4.99). It also demonstrated a reduction in tumor necrosis factor-α (TNF-α) levels (MD = -0.63, 95%CI: -0.84, -0.41) and an increase in IL-2 levels (MD = 1.42, 95%CI: -1.09, 1.74). Analysis of Karnofsky Performance Status (KPS) scores showed that the use of Xiaochaihu Decoction improved the quality of life in CRF patients (RR = 1.57, 95%CI: 1.11, 2.22) and reduced the incidence of adverse events. However, it is important to note that the majority of included studies showed "some concerns" in risk of bias based on ROB 2.0, and the evidence quality assessed by GRADE method was rated as "low". Conclusion: While this study suggests the clinical effectiveness and safety of Xiaochaihu Decoction in treating patients with CRF, confirming these findings will necessitate additional high-quality, large-scale RCTs in future research. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023484068.
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Affiliation(s)
- Zhijun Bu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yaoyu Xu
- The First Clinical College, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Xian Zhou
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
| | - Xuefeng Wang
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shuyuan Liu
- School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Linyan Wang
- School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Bei Yang
- Acupuncture and Bone Injury College, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Xiaodie Zhou
- The First Clinical College, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Guanhang Lu
- School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Jianping Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zhaolan Liu
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Tran NKS, Lee JH, Lee MJ, Park JY, Kang KS. Multitargeted Herbal Prescription So Shiho Tang: A Scoping Review on Biomarkers for the Evaluation of Therapeutic Effects. Pharmaceuticals (Basel) 2023; 16:1371. [PMID: 37895842 PMCID: PMC10610176 DOI: 10.3390/ph16101371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/21/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
Alternative medicines, especially herbal remedies, have been employed to treat infections and metabolism-related chronic inflammation because their safety and multidimensional therapeutic potential outweigh those of synthetic drugs. So Shiho Tang (SSHT), a well-known Oriental prescription (Xiao Chai Hu Tang in Chinese) composed of seven herbs, is traditionally prescribed to treat various viral infections and chronic metabolic disorders in Asia with or without the support of other natural medicines. To provide a general background on how SSHT is used as a medicinal alternative, we conducted a scoping review using the PubMed database system. Among the 453 articles, 76 studies used aqueous extracts of SSHT alone. This result included seven clinical studies and 69 basic studies: cell-based, animal-based, and ex vivo studies. The in vitro and clinical reports mainly focus on hepatic infection and hepatocarcinoma, and the documentation of in vivo tests of SSHT presents a wide range of effects on cancer, fibrosis, inflammation, and several metabolic disorder symptoms. Additionally, among the seven clinical records, two reverse-effect case studies were reported in middle-aged patients. In brief, this systematic review provides general knowledge on the natural remedy SSHT and its potential in phytotherapeutic primary health care.
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Affiliation(s)
- Nguyen Khoi Song Tran
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (N.K.S.T.); (J.H.L.); (M.J.L.)
| | - Ji Hwan Lee
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (N.K.S.T.); (J.H.L.); (M.J.L.)
| | - Myong Jin Lee
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (N.K.S.T.); (J.H.L.); (M.J.L.)
| | - Jun Yeon Park
- Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Republic of Korea
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (N.K.S.T.); (J.H.L.); (M.J.L.)
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Chilvery S, Yelne A, Khurana A, Saifi MA, Bansod S, Anchi P, Godugu C. Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 108:154510. [PMID: 36332383 DOI: 10.1016/j.phymed.2022.154510] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 08/06/2022] [Accepted: 10/16/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND The liver plays an important role in regulating the metabolic processes and is the most frequently targeted organ by toxic chemicals. Acetaminophen (APAP) is a well-known anti-allergic, anti-pyretic, non-steroidal anti-inflammatory drug (NSAID), which upon overdose leads to hepatotoxicity, the major adverse event of this over-the-counter drug. PURPOSE APAP overdose induced acute liver injury is the second most common cause that often requires liver transplantation worldwide, for which N-acetyl cysteine is the only synthetic drug clinically approved as an antidote. So, it was felt that there is a need for the novel therapeutic approach for the treatment of liver diseases with less adverse effects. This review provides detailed analysis of the different plant extracts; phytochemicals and herbal formulations for the amelioration of APAP-induced liver injury. METHOD The data was collected using different online resources including PubMed, ScienceDirect, Google Scholar, Springer, and Web of Science using keywords given below. RESULTS Over the past decades various reports have revealed that plant-based approaches may be a better treatment choice for the APAP-induced hepatotoxicity in pre-clinical experimental conditions. Moreover, herbal compounds provide several advantages over the synthetic drugs with fewer side effects, easy availability and less cost for the treatment of life-threatening diseases. CONCLUSION The current review summarizes the hepatoprotective effects and therapeutic mechanisms of various plant extracts, active phytoconstituents and herbal formulations with potential application against APAP induced hepatotoxicity as the numbers of hepatoprotective natural products are more without clinical relativity. Further, pre-clinical pharmacological research will contribute to the designing of natural products as medicines with encouraging prospects for clinical application.
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Affiliation(s)
- Shrilekha Chilvery
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Amit Yelne
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Amit Khurana
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Mohd Aslam Saifi
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Sapana Bansod
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Pratibha Anchi
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
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Jiang M, Wang X, Lv B, Lu Y, Ma X, Liu W, Bai G, Gao X. Psoralen induces hepatotoxicity by covalently binding to glutathione-S-transferases and the hepatic cytochrome P450. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154165. [PMID: 35792449 DOI: 10.1016/j.phymed.2022.154165] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/10/2022] [Accepted: 05/10/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Psoraleae Fructus has been widely used in China and its surroundings; however, Psoraleae Fructus and its compound preparation have been reported recently to cause liver injury in clinics. Thus, its safe use has attracted increasing attention. The possible mechanism is related to the metabolism of psoralen, but it still needs further clarification. PURPOSE The present study was designed to evaluate the toxicity of psoralen and investigate the potentially related molecular mechanisms using chemical biology methods combined with animal experiments to provide evidence for the rational clinical use of psoralen. METHODS An in vivo experiment was conducted with a time series of 20-80 mg/kg psoralen to verify its toxic performance. Target capture and click reactions were used to investigate direct targets of psoralen. Selectivity for different glutathione-S-transferase (GST) subtypes in the liver and inhibition of cytochrome P450 (CYP450) were also detected. RESULTS Psoralen build-up in the liver is the primary cause of liver damage. Our study revealed the mechanism by which psoralen induces liver injury. Psoralen can bind directly to CYP2D6, CYP3A4, GST-α, and GST-μ and inhibit their activities, causing the depletion of glutathione (GSH) in vivo, which in turn induces hepatic damage. The special structure of α,β-unsaturated lactones in psoralen facilitates its attachment to its target; therefore, complementing psoralen with GSH can efficiently protect the liver from damage. CONCLUSIONS Psoralen causes a disorder in drug metabolism by inhibiting the activity of CYPs and GSTs, causing exhaustion of GSH, and subsequently leading to liver damage. The co-administration of GSH and psoralen is an effective way to avoid liver injury in clinical settings.
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Affiliation(s)
- Min Jiang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
| | - Xiaoying Wang
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Bin Lv
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yujie Lu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
| | - Xianghui Ma
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Wenjuan Liu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China
| | - Gang Bai
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
| | - Xiumei Gao
- Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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Li Y, Yan D, Jin J, Tan B, Chen X, Zou B, Song G, Weng F, Liu C, Qiu F. Clarify the potential cholestatic hepatotoxicity components from Chinese Herb Medicine and metabolism’s role via hBSEP vesicles and S9/hBSEP vesicles. Toxicol In Vitro 2022; 80:105324. [DOI: 10.1016/j.tiv.2022.105324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 01/24/2022] [Indexed: 12/24/2022]
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Pang Z, Zhu Q. Traditional Chinese Medicine is an Alternative Therapeutic Option for Treatment of Pseudomonas aeruginosa Infections. Front Pharmacol 2021; 12:737252. [PMID: 34512364 PMCID: PMC8429605 DOI: 10.3389/fphar.2021.737252] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/18/2021] [Indexed: 12/17/2022] Open
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen causing life-threatening infections in cystic fibrosis patients and immunocompromised individuals, and it is a leading cause of nosocomial infections associated with significant morbidity and mortality. Treatment of P. aeruginosa infections is challenging due to the antibiotic resistance to most of the conventional antibiotics. Development of alternative therapeutic options is urgently demanded for the patients who have antibiotic-resistant infections. Traditional Chinese medicine (TCM) has a clinical history of thousands of years for prevention and treatment of infectious diseases in China, taking advantages of improving clinical outcomes, producing less side effects, inhibiting pathogen, and modulating host immunity. Recent research has revealed a variety of natural products derived from TCM showing significant antimicrobial effects on antibiotic-resistant strains of P. aeruginosa alone or combined with antibiotics in vitro or in animal models, suggesting that TCM is a promising complementary and alternative therapeutic approach for treatment of chronic P. aeruginosa infections. This review summarizes the recent findings attempting to dissect the mechanisms of TCM combating P. aeruginosa infections and highlights the molecular targets of TCM on P. aeruginosa and host.
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Affiliation(s)
- Zheng Pang
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.,Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China.,Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qingjun Zhu
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.,Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China.,Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
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Koenig G, Callipari C, Smereck JA. Acute Liver Injury After Long-Term Herbal "Liver Cleansing" and "Sleep Aid" Supplement Use. J Emerg Med 2021; 60:610-614. [PMID: 33579656 DOI: 10.1016/j.jemermed.2021.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/23/2020] [Accepted: 01/02/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Acute liver injury is reported in association with toxins, pharmaceuticals, and viral infections. Increasingly prevalent are cases of herbal- and dietary supplement-related hepatotoxicity. Early recognition of this potentially life-threatening complication by emergency care providers leads to more appropriate management and disposition. CASE REPORT A 53-year-old woman presented to the emergency department with a 3-day history of jaundice and increased abdominal girth after a month-long use of a combination herbal "liver-cleansing" compound and a nightly herbal "sleep aid." The "Liver Detoxifier and Regenerator" listed multiple constituents, including concentrated scute root and turmeric root; "Restful Sleep" listed multiple constituents, including valerian. Emergency department evaluation revealed marked hyperbilirubinemia with liver enzyme elevations indicative of cholestatic jaundice. Imaging studies, including ultrasound and abdominal magnetic resonance imaging, revealed hepatomegaly and steatosis without biliary dilatation; a biopsy specimen was obtained, and the results were consistent with drug-induced liver injury. The patient's liver function abnormalities gradually improved with discontinuation of the products as well as a tapered course of corticosteroid therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A significant proportion of the U.S. adult population uses herbal and dietary supplements. Most patients do not discuss nonprescription medication use with their providers and many physicians will not specifically ask about herbal supplements. It is important for emergency physicians to be aware of the potential for herbal supplements to contribute to acute liver injury and be able to investigate the active agents reported in these formulations. The diagnostic criteria for cholestatic jaundice and drug-induced liver injury are discussed.
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Affiliation(s)
- Gavin Koenig
- Georgetown University School of Medicine, Washington, DC
| | - Cameron Callipari
- Department of Emergency Medicine, New York Presbyterian-Columbia/Cornell, New York, NY
| | - Janet A Smereck
- Department of Emergency Medicine, Georgetown University Medical Center, Washington, DC; MedStar Georgetown University Hospital, Washington, DC
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Angela C, Wang W, Lyu H, Zhou Y, Huang X. The effect of dietary supplementation of Astragalus membranaceus and Bupleurum chinense on the growth performance, immune-related enzyme activities and genes expression in white shrimp, Litopenaeus vannamei. FISH & SHELLFISH IMMUNOLOGY 2020; 107:379-384. [PMID: 33059009 DOI: 10.1016/j.fsi.2020.10.014] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/09/2020] [Accepted: 10/12/2020] [Indexed: 06/11/2023]
Abstract
A 56-day feeding trial was conducted to investigate the effects of dietary supplementation of Astragalus membranaceus or/and Bupleurum chinense on the growth performance, immune enzymes, and related gene expression of Pacific white shrimp (Litopenaeus vanammei). Six experimental diets were formulated and supplemented with two levels (0.25% and 0.5%) of each herb and their combination. At the end of the trial, the specific growth rate and feed conversion ratio of shrimp were significantly (P < 0.05) improved by herbal diets. Besides, the activities of immune-related enzymes such as superoxide dismutase (SOD), alkaline phosphatase (AKP), and lysozyme in serum and hepatopancreas were significantly (P < 0.05) elevated in shrimp fed A. membranaceus or/and B. chinense. The high expression levels of immune deficiency (IMD), lysozyme, and Toll-like receptor mRNA directly or indirectly reflected the activation effect of innate immune in shrimp by dietary A. membranaceus or/and B. chinense. However, no significant difference (P > 0.05) among the herbal incorporated treatments was detected on the growth performance and immune response. In conclusion, the results suggest that A. membranaceus and B. chinense could be used as a beneficial feed additives and alternatives to antibiotics for white shrimp aquaculture.
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Affiliation(s)
- Cornel Angela
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, China
| | - Weilong Wang
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, China
| | - Hongyu Lyu
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, China
| | - Yue Zhou
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, China
| | - Xuxiong Huang
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, China.
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Kong DZ, Liang N, Yang GL, Zhang Z, Liu Y, Li J, Liu X, Liang S, Nikolova D, Jakobsen JC, Gluud C, Liu JP. Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B. Cochrane Database Syst Rev 2019; 2019:CD013090. [PMID: 31697415 PMCID: PMC6953322 DOI: 10.1002/14651858.cd013090.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Chronic hepatitis B is associated with high morbidity and mortality. Chronic hepatitis B requires long-term management aiming at reduction of the risks of hepatocellular inflammatory necrosis, liver fibrosis, decompensated liver cirrhosis, liver failure, and liver cancer, and improving health-related quality of life. The Chinese herbal medicine formula Xiao Chai Hu Tang has been used to decrease discomfort and replication of the virus in people with chronic hepatitis B. However, the benefits and harms of Xiao Chai Hu Tang formula have never been established with rigorous review methodology. OBJECTIVES To assess the benefits and harms of Xiao Chai Hu Tang formula versus placebo or no intervention in people with chronic hepatitis B. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and seven other databases to 1 March 2019. We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp), ClinicalTrials.gov (www.clinicaltrials.gov/), and the Chinese Clinical Trial Registry for ongoing or unpublished trials to 1 March 2019. SELECTION CRITERIA We included randomised clinical trials, irrespective of publication status, language, and blinding, comparing Xiao Chai Hu Tang formula versus no intervention or placebo in people with chronic hepatitis B. We included participants of any sex and age, diagnosed with chronic hepatitis B according to guidelines or as defined by the trialists. We allowed co-interventions when the co-interventions were administered equally to all the intervention groups. DATA COLLECTION AND ANALYSIS Review authors independently retrieved data from reports and after correspondence with investigators. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our secondary outcomes were hepatitis B-related mortality, hepatitis B-related morbidity, and adverse events considered 'not to be serious'. We presented the meta-analysed results as risk ratios (RR) with 95% confidence intervals (CI). We assessed the risks of bias using risk of bias domains with predefined definitions. We used GRADE methodology to evaluate our certainty in the evidence. MAIN RESULTS We included 10 randomised clinical trials with 934 participants, but only five trials with 490 participants provided data for analysis. All the trials compared Xiao Chai Hu Tang formula with no intervention. All trials appeared to have been conducted and published only in China. The included trials assessed heterogeneous forms of Xiao Chai Hu Tang formula, administered for three to eight months. One trial included participants with hepatitis B and comorbid tuberculosis, and one trial included participants with hepatitis B and liver cirrhosis. The remaining trials included participants with hepatitis B only. All the trials were at high risk of bias, and the certainty of evidence for all outcomes that provided data for analyses was very low. We downgraded the evidence by one or two levels because of outcome risk of bias, inconsistency or heterogeneity of results (opposite direction of effect), indirectness of evidence (use of surrogate outcomes instead of clinically relevant outcomes), imprecision of results (the CIs were wide), and publication bias (small sample size of the trials). Additionally, 47 trials lacked the necessary methodological information needed to ensure the inclusion of these trials in our review. None of the included trials aimed to assess clinically relevant outcomes such as all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, or hepatitis B-related morbidity. The effects of Xiao Chai Hu Tang formula on the proportion of participants with adverse events considered 'not to be serious' is uncertain (RR 0.43, 95% CI 0.02 to 11.98; I2 = 69%; very low-certainty evidence). Only three trials with 222 participants reported the proportion of people with detectable hepatitis B virus DNA (HBV-DNA), but the evidence that Xiao Chai Hu Tang formula reduces the presence of HBV-DNA in the blood (a surrogate outcome) is uncertain (RR 0.62, 95% CI 0.45 to 0.85; I2 = 0%; very low-certainty evidence). Only two trials with 160 participants reported the proportion of people with detectable hepatitis B virus e-antigen (HBeAg; a surrogate outcome) (RR 0.72, 95% CI 0.50 to 1.02; I2 = 38%; very low-certainty evidence) and the evidence is uncertain. The evidence is also uncertain for separately reported adverse events considered 'not to be serious'. FUNDING two of the 10 included trials received academic funding from government or hospital. None of the remaining eight trials reported information on funding. AUTHORS' CONCLUSIONS The clinical effects of Xiao Chai Hu Tang formula for chronic hepatitis B remain unclear. The included trials were small and of low methodological quality. Despite the wide use of Xiao Chai Hu Tang formula, we lack data on all-cause mortality, serious adverse events, health-related quality of life, hepatitis B-related mortality, and hepatitis B-related morbidity. The evidence in this systematic review comes from data obtained from a maximum three trials. We graded the certainty of evidence as very low for adverse events considered not to be serious and the surrogate outcomes HBeAg and HBV-DNA. We found a large number of trials which lacked clear description of their design and conduct, and hence, these trials are not included in the present review. As all identified trials were conducted in China, there might be a concern about the applicability of this review outside China. Large-sized, high-quality randomised sham-controlled trials with homogeneous groups of participants and transparent funding are lacking.
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Affiliation(s)
- De Zhao Kong
- Liaoning University of Traditional Chinese MedicineChong Shan East Road 79ShenyangLiaoning ProvinceChina110032
- The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineDepartment of CardiologyBeiling Street 33ShenyangLiaoning ProvinceChina110032
- Liaoning University of Traditional Chinese MedicineCo‐construct Key Laboratory of Theory of Visceral Manifestations and ApplicationsChong Shan East Road 79ShenyangLiaoning ProvinceChina110032
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupCopenhagenDenmark
| | - Ning Liang
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupCopenhagenDenmark
- Beijing University of Chinese MedicineCentre for Evidence‐Based Chinese MedicineBei San Huan Dong Lu 11, Chaoyang DistrictBeijingChina100029
| | - Guan Lin Yang
- Liaoning University of Traditional Chinese MedicineChong Shan East Road 79ShenyangLiaoning ProvinceChina110032
| | - Zhe Zhang
- The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineChong Shan East Street 79ShenyangLiaoning ProvinceChina110032
| | - Yue Liu
- Liaoning University of Traditional Chinese MedicineCo‐construct Key Laboratory of Theory of Visceral Manifestations and ApplicationsChong Shan East Road 79ShenyangLiaoning ProvinceChina110032
| | - Jing Li
- Beijing University of Chinese MedicineCentre for Evidence‐Based Chinese MedicineBei San Huan Dong Lu 11, Chaoyang DistrictBeijingChina100029
| | - Xuehan Liu
- Beijing University of Chinese MedicineCentre for Evidence‐Based Chinese MedicineBei San Huan Dong Lu 11, Chaoyang DistrictBeijingChina100029
| | - Shibing Liang
- Shanxi University of Traditional Chinese MedicineSchool of Basic MedicineJinci road, Wan Bailin districtTaiyuanShanxi ProvinceChina030000
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupCopenhagenDenmark
| | - Janus C Jakobsen
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupCopenhagenDenmark
- Holbaek HospitalDepartment of CardiologyHolbaekDenmark4300
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupCopenhagenDenmark
| | - Jian Ping Liu
- Beijing University of Chinese MedicineCentre for Evidence‐Based Chinese MedicineBei San Huan Dong Lu 11, Chaoyang DistrictBeijingChina100029
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Jing J, Wang RL, Zhao XY, Zhu Y, Niu M, Wang LF, Song XA, He TT, Sun YQ, Xu WT, Yu SM, Wang LP, Guo YM, Bai ZF, Xiao XH, Wang JB. Association between the concurrence of pre-existing chronic liver disease and worse prognosis in patients with an herb- Polygonum multiflorum thunb. induced liver injury: a case-control study from a specialised liver disease center in China. BMJ Open 2019; 9:e023567. [PMID: 30782709 PMCID: PMC6340630 DOI: 10.1136/bmjopen-2018-023567] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/17/2018] [Accepted: 11/26/2018] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES The present study aimed to evaluate the association between the concurrence of pre-existing chronic liver diseases (CLD) and worse prognosis in patients with HILI. DESIGN A case-control study. SETTING Tertiary hospital specialising in liver diseases in China. PARTICIPANTS 145 hospitalised HILI patients were assessed with respect to prognosis by comparing HILI with or without pre-existing CLD from February 2007 to January 2017. Twenty-five HILI cases with pre-existing alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) and 200 ALD or NAFLD controls matched 1:8 for sex, age (±4 years old), body mass index (±2 kg/m2), the type of CLD, alcohol intake (±5 g/d) and the presence or absence of cirrhosis. PRIMARY OUTCOME MEASURES Mortality and chronicity in HILI patients with or without pre-existing CLD, and matched CLD patients. RESULTS Of the 193 714 hospitalised patients with liver diseases, 5703 patients met the diagnostic criteria for drug-induced liver injury (DILI), which was attributed to Polygonum multiflorum Thunb. (PMT) in 145 patients. Among these HILI patients, 22.8% (33 of 145) had pre-existing CLD, including 17 (51.5%) with ALD, 8 (24.2%) with NAFLD, 5 (15.2%) with chronic viral hepatitis and 3 (9.1%) with autoimmune liver disease. Compared with HILI patients without CLD, HILI patients with pre-existing CLD showed higher mortality (0.9% vs 9.1%, p=0.037) and higher chronicity (12.5% vs 30.3%, p=0.016). Compared with matched ALD (136 patients) or NAFLD (64 patients) patients, HILI patients with pre-existing ALD showed higher chronicity (35.3% vs 11.8%, p=0.019). Multivariate logistic regression analysis found that concurrence of pre-existing CLD was an independent risk factor for both of chronicity and mortality (OR 3.966, 95% CI 1.501 to 10.477, p=0.005), especially the chronicity (OR 3.035, 95% CI 1.115 to 8.259, p=0.030). CONCLUSIONS Concurrence of pre-existing CLD could be an independent risk factor for worse prognosis, especially chronicity, in PMT-related HILI.
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Affiliation(s)
- Jing Jing
- Department of Integrative Medicine, Medical School of Chinese PLA, Beijing, China
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Rui-lin Wang
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Xin-yan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Yun Zhu
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Ming Niu
- Institute of Chinese Herbal Medicine, Beijing 302 Hospital, Beijing, China
| | - Li-fu Wang
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Xue-ai Song
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Ting-ting He
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Yong-qiang Sun
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Wen-tao Xu
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Si-miao Yu
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Li-ping Wang
- Division of Integrative Medicine, Beijing 302 Hospital, Beijing, China
| | - Yu-ming Guo
- Institute of Chinese Herbal Medicine, Beijing 302 Hospital, Beijing, China
| | - Zhao-fang Bai
- Institute of Chinese Herbal Medicine, Beijing 302 Hospital, Beijing, China
| | - Xiao-he Xiao
- Department of Integrative Medicine, Medical School of Chinese PLA, Beijing, China
- Institute of Chinese Herbal Medicine, Beijing 302 Hospital, Beijing, China
| | - Jia-bo Wang
- Institute of Chinese Herbal Medicine, Beijing 302 Hospital, Beijing, China
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Kong DZ, Liang N, Liu JP, Nikolova D, Jakobsen JC, Gluud C. Xiao Chai Hu Tang, a Chinese herbal medicine formula, for chronic hepatitis B. Hippokratia 2018. [DOI: 10.1002/14651858.cd013090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- De Zhao Kong
- Liaoning University of Traditional Chinese Medicine; Chong Shan East Road 79 Shenyang Liaoning Province China 110032
- The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine; Department of Cardiology; Beiling Street 33 Shenyang Liaoning Province China 110032
- Liaoning University of Traditional Chinese Medicine; Co-construct Key Laboratory of Theory of Visceral Manifestations and Applications; Chong Shan East Road 79 Shenyang Liaoning Province China 110032
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Copenhagen Denmark
| | - Ning Liang
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Copenhagen Denmark
- Beijing University of Chinese Medicine; Centre for Evidence-Based Chinese Medicine; Bei San Huan Dong Lu 11, Chaoyang District Beijing China 100029
| | - Jian Ping Liu
- Beijing University of Chinese Medicine; Centre for Evidence-Based Chinese Medicine; Bei San Huan Dong Lu 11, Chaoyang District Beijing China 100029
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Copenhagen Denmark
| | - Janus C Jakobsen
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Copenhagen Denmark
- Holbaek Hospital; Department of Cardiology; Holbaek Denmark 4300
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Copenhagen Denmark
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Lou JW, Cao LL, Zhang Q, Jiang DJ, Yao WF, Bao BH, Cao YD, Tang YP, Zhang L, Wang K, Dai GC. The toxicity and efficacy evaluation of different fractions of Kansui fry-baked with vinegar on Walker-256 tumor-bearing malignant ascites effusion rats and normal rats. JOURNAL OF ETHNOPHARMACOLOGY 2018; 219:257-268. [PMID: 29559373 DOI: 10.1016/j.jep.2018.03.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 03/08/2018] [Accepted: 03/08/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Kansui, the root of Euphorbia kansui S.L.Liou ex S.B.Ho (E.kansui), is a classical traditional Chinese medicine (TCM) with certain toxicity. According to the theory of TCM, kansui fry-baked wtith vinegar (VEK) possesses low toxicity and mild diuretic and purgative efficacy. In clinical practice, it is commonly used for the treatmtablent of ascites and oliguria. The present study aimed to evaluate the toxicity and efficacy of different fractions of VEK and reveal the underlying material basis by employing an animal model of malignant ascites effusion (MAE) in rats. MATERIALS AND METHODSTA The MAE rats as the model were constructed in SPF male wistar rats by intraperitoneal injection of Walker-256 tumor cells. The MAE rats were used and randomly divided into the control group (normal rats), control groups with different fractions (VEKA, VEKB, VEKC and VEKD), model group (MAE rats), positive control group (model group with furosemide), model groups with different fractions (VEKA, VEKB, VEKC and VEKD). Histopathological observation was used to confirm Walker-256 tumor-bearing organ injuries in rats. For the efficacy evaluation, the ascites and urine volumes, the urinary electrolyte concentrations (Na+, K+ and Cl-) and pH, the ascites levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, IFN-γ and VEGF), PRA, the serum levels of Ang II, ALD and ADH, as well as AQP8 protein expression in the gastrointestinal tract were detected. Furthermore, different levels of indicators were measured in the toxicity evaluation of different fractions both on normal and model rats, including serum liver enzymes (AST and ALT), serum oxidative damage parameters (GSH, MDA, LDH and SOD), expressions of inflammatory parameters (NF-κB, ICAM-1 and E-cadherin) and apoptosis signals (caspase-3, -8, -9, Bcl-2 and Bax) in the liver and gastrointestinal tract. RESULTS Walker-256 tumor-bearing malignant ascites effusion rats showed obvious hepatic and gastrointestinal injuries by histopathological observation. In the efficacy evaluation, model rats treated with VEKB and VEKC showed significant urine increase (VEKB, P < 0.01; VEKC, P < 0.01) and ascites reduction (VEKB, P < 0.01; VEKC, P < 0.01). These two fractions also balanced the concentrations of Na+, K+ and Cl- in urine (VEKB, all P < 0.05; VEKC, all P < 0.05), remarkably decreased urinary pH (VEKB, P < 0.01; VEKC, P < 0.01), and reduced the ascites levels of IL-2, IL-6, TNF-α, IFN-γ and VEGF (VEKB, all P < 0.01; VEKC, all P < 0.01) in the model rats. Moreover, levels of PRA, the serum Ang II, ALD and ADH of model rats were decreased after treated by VEKB and VEKC (VEKB, all P < 0.05; VEKC, all P < 0.05). Meanwhile, the expression of gastrointestinal AQP8 of the model rats was also enhanced after treated by VEKB and VEKC (VEKB, P < 0.01; VEKC, P < 0.01). In the toxicity evaluation, although VEKB and VEKC caused toxic indexes moved to the worse aspects in normal rats, nearly all of these indicators notably improved in the model rats. Additionally, VEKA showed no effect on the indicators, either in the efficacy evaluation or in the toxicity evaluation. And VEKD could significantly improve some indicators (urine volume, concentration of K+ in urine, serum MDA, AI and caspase-9) in MAE rats. CONCLUSIONS VEKB and VEKC were demonstrated a significant efficacy in treating malignant ascites effusion, which could reduce hepatic and gastrointestinal damage on the model rats but cause the same damage to the normal. These data embody the traditional Chinese medicine application principle: You Gu Wu Yun. And these results will provide reference for the safer and better clinical utilization of kansui.
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Affiliation(s)
- Jian-Wei Lou
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Liang-Liang Cao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Pharmacy, Nanjing Hospital of Traditional Chinese Medicine, Nanjing 210001, China
| | - Qiao Zhang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Dong-Jing Jiang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Wei-Feng Yao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Bei-Hua Bao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu-Dan Cao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu-Ping Tang
- College of Pharmacy and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China
| | - Li Zhang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Kun Wang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Guan-Cheng Dai
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
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14
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Gao X, Liang M, Fang Y, Zhao F, Tian J, Zhang X, Qin X. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles. Front Pharmacol 2018; 8:995. [PMID: 29379441 PMCID: PMC5775221 DOI: 10.3389/fphar.2017.00995] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 12/26/2017] [Indexed: 12/11/2022] Open
Abstract
The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS) may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS) (with depression) and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR) produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.
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Affiliation(s)
- Xiaoxia Gao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Meili Liang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, China
| | - Yuan Fang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Fang Zhao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Junsheng Tian
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Xiang Zhang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Department of Chemistry, University of Louisville, Louisville, KY, United States
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China
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15
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Wang S, Zhang Y, Zhang Q, Peng S, Shen C, Yu Y, Zhang M, Yang W, Wu Q, Zhang Y, Li S, Qiao Y. Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2017; 52:129-137. [PMID: 28412648 DOI: 10.1016/j.etap.2017.04.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 03/29/2017] [Accepted: 04/02/2017] [Indexed: 05/27/2023]
Abstract
Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations. Further, SSa and SSd induced LC3 puncta formation in U2OS-mCherry-EGFP-LC3 cells. Blockage of autophagy by 3-methyladenine did not abrogate the cytotoxicities induced by SSa and SSd. In parallel, none of SSc, SSb1, or SSb2 caused cell injury. Our study reveals how changes in chemical ingredients are connected to the toxicity of Chaihu during vinegar baking process and also provides a guidance for structure optimization to reduce drug induced toxicity.
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Affiliation(s)
- Shifeng Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Yuxin Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Qiao Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Sha Peng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Chen Shen
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Yangyang Yu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Minyu Zhang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Wei Yang
- ACEA Biosciences Inc., Hangzhou 310030, China
| | - Qinghua Wu
- HD Biosciences Co., Ltd, Shanghai 201201, China
| | - Yanling Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
| | - Shiyou Li
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
| | - Yanjiang Qiao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
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16
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Xiong F, Guan YS. Cautiously using natural medicine to treat liver problems. World J Gastroenterol 2017; 23:3388-3395. [PMID: 28596675 PMCID: PMC5442075 DOI: 10.3748/wjg.v23.i19.3388] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Revised: 03/12/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds of human diseases for thousands of years. The treatment protocols of natural medicine are integrative in nature, and are required to utilize the most appropriate therapies to address the needs of the individual patient. Because of the relative convenience, safety and efficacy, natural medicine is now increasing worldwide. Naturopathic doctors are licensed in many areas of the world and regulated partly by law in these areas, which is quite different from various other forms of complementary and alternative medicine. Liver diseases, such as hepatitis, liver cirrhosis and liver carcinoma, are serious health problems worldwide. Nearly half of the natural agents used in treatment of liver diseases today are natural products and their derivatives. Although natural medicine is beneficial and safe, physicians should pay close attention to the potential side-effects of the naturopathic agents, which lead to liver injury, interstitial pneumonia and acute respiratory failure. Therefore, when administrating naturopathic protocols to patients for the treatment of liver diseases, we should try our best to prevent and avoid as much as possible the negative impact of these medicines. This article highlights the current practice and recommended improvement of natural medicines in the treatment of liver diseases and gives some specific examples to emphasize the prevention and management of adverse reactions of the natural agents and suggests that natural medicine should be cautiously used to treat liver problems.
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Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology. BIOMED RESEARCH INTERNATIONAL 2017; 2017:7597596. [PMID: 28593176 PMCID: PMC5448051 DOI: 10.1155/2017/7597596] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 04/20/2017] [Indexed: 12/13/2022]
Abstract
Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b2, c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri. This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.
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Li X, Li X, Lu J, Huang Y, Lv L, Luan Y, Liu R, Sun R. Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study. Altern Ther Health Med 2017; 17:219. [PMID: 28420359 PMCID: PMC5395759 DOI: 10.1186/s12906-017-1733-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/07/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. METHODS Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro. RESULTS SS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro. CONCLUSION Our results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury.
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A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines. Molecules 2017; 22:molecules22040632. [PMID: 28420096 PMCID: PMC6154655 DOI: 10.3390/molecules22040632] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 04/06/2017] [Accepted: 04/12/2017] [Indexed: 12/15/2022] Open
Abstract
Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one—Xiao-Chai-Hu-Tang (XCHT)—a composite formula, and the other—Radix Polygoni Multiflori (Heshouwu)—a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu. According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future.
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Pharmacokinetic interactions of herbal medicines for the treatment of chronic hepatitis. J Food Drug Anal 2016; 25:209-218. [PMID: 28911662 PMCID: PMC9332521 DOI: 10.1016/j.jfda.2016.11.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 07/05/2016] [Accepted: 11/07/2016] [Indexed: 12/26/2022] Open
Abstract
Chronic liver disease is a serious global health problem, and an increasing number of patients are seeking alternative medicines or complementary treatment. Herbal medicines account for 16.8% of patients with chronic liver disease who use complementary and alternative therapies. A survey of the National Health Insurance Research Database in Taiwan reported that Long-Dan-Xie-Gan-Tang, Jia-Wei-Xia-Yao-San, and Xiao-Chai-Hu-Tang (Sho-saiko-to) were the most frequent formula prescriptions for chronic hepatitis used by traditional Chinese medicine physicians. Bioanalytical methods of herbal medicines for the treatment of chronic hepatitis were developed to investigate pharmacokinetics properties, but multicomponent herbal formulas have been seldom discussed. The pharmacokinetics of herbal formulas is closely related to efficacy, efficiency, and patient safety of traditional herbal medicines. Potential herbal formula–drug interactions are another essential issue during herbal formula administration in chronic hepatitis patients. In a survey with the PubMed database, this review article evaluates the existing evidence-based data associated with the documented pharmacokinetics profiles and potential herbal–drug interactions of herbal formulas for the treatment of chronic hepatitis. In addition, the existing pharmacokinetic profiles were further linked with clinical practice to provide insight for the safety and specific use of traditional herbal medicines.
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Teschke R, Larrey D, Melchart D, Danan G. Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs. MEDICINES (BASEL, SWITZERLAND) 2016; 3:E18. [PMID: 28930128 PMCID: PMC5456249 DOI: 10.3390/medicines3030018] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 07/04/2016] [Accepted: 07/06/2016] [Indexed: 02/08/2023]
Abstract
Background: Traditional Chinese Medicine (TCM) with its focus on herbal use is popular and appreciated worldwide with increased tendency, although its therapeutic efficacy is poorly established for most herbal TCM products. Treatment was perceived as fairly safe but discussions emerged more recently as to whether herb induced liver injury (HILI) from herbal TCM is a major issue; Methods: To analyze clinical and case characteristics of HILI caused by herbal TCM, we undertook a selective literature search in the PubMed database with the search items Traditional Chinese Medicine, TCM, alone and combined with the terms herbal hepatotoxicity or herb induced liver injury; Results: HILI caused by herbal TCM is rare and similarly to drugs can be caused by an unpredictable idiosyncratic or a predictable intrinsic reaction. Clinical features of liver injury from herbal TCM products are variable, and specific diagnostic biomarkers such as microsomal epoxide hydrolase, pyrrole-protein adducts, metabolomics, and microRNAs are available for only a few TCM herbs. The diagnosis is ascertained if alternative causes are validly excluded and causality levels of probable or highly probable are achieved applying the liver specific RUCAM (Roussel Uclaf Causality Assessment Method) as the most commonly used diagnostic tool worldwide. Case evaluation may be confounded by inappropriate or lacking causality assessment, poor herbal product quality, insufficiently documented cases, and failing to exclude alternative causes such as infections by hepatotropic viruses including hepatitis E virus infections; Conclusion: Suspected cases of liver injury from herbal TCM represent major challenges that deserve special clinical and regulatory attention to improve the quality of case evaluations and ascertain patients' safety and benefit.
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Affiliation(s)
- Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Teaching Hospital of the Medical Faculty of the Goethe University, Frankfurt/Main D-63450, Germany.
| | - Dominique Larrey
- Department of Liver and Transplantation-IRB-INSERM (Institut de Recherche Biologique-INstitut de la Santé Et de la Recherche Médicale) 1183, Saint Eloi Hospital, Montpellier University, 34295 Montpellier, France.
| | - Dieter Melchart
- Competence Centre for Complementary Medicine and Naturopathy (CoCoNat), Klinikum rechts der Isar, Technische Universität München, Munich D-80801, Germany.
- Institute for Complementary and Integrative Medicine, University Hospital Zurich and University of Zurich, Zurich CH-8091, Switzerland.
| | - Gaby Danan
- Pharmacovigilance Consultancy, Paris 75020, France.
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Teo DCH, Ng PSL, Tan SH, Lim AT, Toh DSL, Chan SY, Cheong HH. Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:192. [PMID: 27389194 PMCID: PMC4937524 DOI: 10.1186/s12906-016-1168-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 06/14/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients. METHODS AERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details. RESULTS Fifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1-8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia. CONCLUSIONS Drug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM.
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Affiliation(s)
- Desmond Chun Hwee Teo
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
| | - Patricia Suet Leng Ng
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Siew Har Tan
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Adena Theen Lim
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Dorothy Su Lin Toh
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Sui Yung Chan
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
| | - Han Hui Cheong
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
- />Department of Pharmacy, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899 Singapore
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Frenzel C, Teschke R. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation. Int J Mol Sci 2016; 17:E588. [PMID: 27128912 PMCID: PMC4881436 DOI: 10.3390/ijms17050588] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 03/31/2016] [Accepted: 04/11/2016] [Indexed: 12/13/2022] Open
Abstract
Herb induced liver injury (HILI) and drug induced liver injury (DILI) share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM) rarely causes elevated liver tests (LT). However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method) is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.
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Affiliation(s)
- Christian Frenzel
- Department of Medicine I, University Medical Center Hamburg Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, 63450 Hanau, Germany.
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Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain. Case Reports Hepatol 2016; 2016:4356749. [PMID: 27144042 PMCID: PMC4842037 DOI: 10.1155/2016/4356749] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 03/21/2016] [Indexed: 12/13/2022] Open
Abstract
Many herbal preparations are routinely used and have been occasionally associated with a wide range of side effects, from mild to severe. Chinese skullcap and black catechu are herbal medications commonly used for their hepatoprotective and other properties. We report a case of acute toxic hepatitis associated with ingestion of Chinese skullcap and black catechu in one preparation for the alleviation of joint pain.
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Hong M, Li S, Tan HY, Wang N, Tsao SW, Feng Y. Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects. Int J Mol Sci 2015; 16:28705-45. [PMID: 26633388 PMCID: PMC4691073 DOI: 10.3390/ijms161226126] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 11/25/2015] [Accepted: 11/25/2015] [Indexed: 02/07/2023] Open
Abstract
Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.
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Affiliation(s)
- Ming Hong
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Hor Yue Tan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Sai-Wah Tsao
- Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Sun R, Zeng M, Du T, Li L, Yang G, Hu M, Gao S. Simultaneous determinations of 17 marker compounds in Xiao-Chai-Hu-Tang by LC-MS/MS: Application to its pharmacokinetic studies in mice. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 1003:12-21. [PMID: 26397748 DOI: 10.1016/j.jchromb.2015.09.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/04/2015] [Accepted: 09/05/2015] [Indexed: 01/29/2023]
Abstract
The purpose of this study is to develop and validate an UPLC-MS/MS method to quantify different marker compounds from Xiao-Chai-Hu-Tang (XCHT, a Chinese traditional herbal) in biological samples and apply the method to pharmacokinetic study. A Waters BEH C18 UPLC column was used with acetonitrile/0.1% formic acid mobile phases. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode. A one-step protein precipitation by methanol was used to extract the analytes from blood. Seventeen commercially available compounds from the different compositing herbals were selected as markers. The results revealed that all of the calibration curves showed good linear regression (r(2)>0.9918). The intra-day and inter-day precisions (RSD) of all of these markers at three different levels were less than 15.0% and the bias of the accuracies ranged from -13.5% to 16.6%.The extraction recoveries of all of these 17 markers were from 70.8% to 113.7% and the matrix effects ranged from 71.8% to 114.8%. The stabilities of these compounds in blood were evaluated by analyzing three replicates of QC samples at three different concentrations following storage at 25°C for 6h, 4°C for 24h, and -80°C for 30 days. All the samples displayed 85-115% precision and accuracy after various stability tests. The validated method was successfully applied to pharmacokinetic study in A/J mouse with oral administration of XCHT. All of these markers were detected and the pharmacokinetic parameters of 8 compounds were able to be calculated. This method is sensitive and reproducible that can be used for XCHT's in vivo study.
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Affiliation(s)
- Rongjin Sun
- College of Pharmacy, Hubei University of Medicine, 30 South Renmin Road, Shiyan, Hubei, China; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA
| | - Min Zeng
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, Hubei, China
| | - Ting Du
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, Hubei, China
| | - Li Li
- College of Pharmacy, Hubei University of Medicine, 30 South Renmin Road, Shiyan, Hubei, China; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA
| | - Guangyi Yang
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan, Hubei, China
| | - Ming Hu
- College of Pharmacy, Hubei University of Medicine, 30 South Renmin Road, Shiyan, Hubei, China; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA
| | - Song Gao
- College of Pharmacy, Hubei University of Medicine, 30 South Renmin Road, Shiyan, Hubei, China; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
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Teschke R, Eickhoff A. Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps. Front Pharmacol 2015; 6:72. [PMID: 25954198 PMCID: PMC4407580 DOI: 10.3389/fphar.2015.00072] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 03/18/2015] [Indexed: 12/19/2022] Open
Abstract
Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.
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Affiliation(s)
- Rolf Teschke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt MainFrankfurt, Germany
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Teschke R. Traditional Chinese Medicine Induced Liver Injury. J Clin Transl Hepatol 2014; 2:80-94. [PMID: 26357619 PMCID: PMC4521264 DOI: 10.14218/jcth.2014.00003] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 02/27/2014] [Accepted: 03/02/2014] [Indexed: 12/12/2022] Open
Abstract
Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with particular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials.
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Affiliation(s)
- Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt/ Main, Germany
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Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. Clin Liver Dis 2013; 17:715-35, x. [PMID: 24099027 DOI: 10.1016/j.cld.2013.07.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Herbal and dietary supplement use is common. Most marketed products consist of complex mixtures. Although they are perceived as safe, instances of hepatotoxicity attributable to these products underscore their potential for injury, but the exact component that is responsible for injury is difficult to discern. The lenient regulatory environment in the United States, which opens the possibility of adulteration and contamination, adds to the challenge of disease attribution. Although many different herbal and dietary supplements have been reported to cause liver injury, in the United States, products used for bodybuilding and weight loss are the most commonly implicated.
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Affiliation(s)
- Victor J Navarro
- Division of Hepatology, Einstein Healthcare Network, 5401 Old York Road, Klein Building, Suite 505, Philadelphia, PA 19141, USA.
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31
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Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH. Ginseng in traditional herbal prescriptions. J Ginseng Res 2013; 36:225-41. [PMID: 23717123 PMCID: PMC3659587 DOI: 10.5142/jgr.2012.36.3.225] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Revised: 03/20/2012] [Accepted: 03/20/2012] [Indexed: 01/30/2023] Open
Abstract
Panax ginseng Meyer has been widely used as a tonic in traditional Korean, Chinese, and Japanese herbal medicines and in Western herbal preparations for thousands of years. In the past, ginseng was very rare and was considered to have mysterious powers. Today, the efficacy of drugs must be tested through well-designed clinical trials or meta-analyses, and ginseng is no exception. In the present review, we discuss the functions of ginseng described in historical documents and describe how these functions are taken into account in herbal prescriptions. We also discuss the findings of experimental pharmacological research on the functions of ginseng in ginseng-containing prescriptions and how these prescriptions have been applied in modern therapeutic interventions. The present review on the functions of ginseng in traditional prescriptions helps to demystify ginseng and, as a result, may contribute to expanding the use of ginseng or ginseng-containing prescriptions.
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Affiliation(s)
- Ho Jae Park
- Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 130-701, Korea
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32
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Mullin GE. The Use of Complementary and Alternative Medicine for Liver Disease. Nutr Clin Pract 2013; 28:277-9. [DOI: 10.1177/0884533612475133] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther 2013; 37:3-17. [PMID: 23121117 DOI: 10.1111/apt.12109] [Citation(s) in RCA: 199] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Revised: 09/18/2012] [Accepted: 10/06/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Herbal and dietary supplements are commonly used throughout the World. There is a tendency for underreporting their ingestion by patients and the magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is not uncommonly encountered, but the precise incidence and manifestations have not been well characterised. AIMS To review the epidemiology, presentation and diagnosis of herbal hepatotoxicity. This review will mainly discuss single ingredients and complex mixtures of herbs marketed under a single label. METHODS A Medline search was undertaken to identify relevant literature using search terms including 'herbal', 'herbs', 'dietary supplement', 'liver injury', 'hepatitis' and 'hepatotoxicity'. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. RESULTS The incidence rates of herbal hepatotoxicity are largely unknown. The clinical presentation and severity can be highly variable, ranging from mild hepatitis to acute hepatic failure requiring transplantation. Scoring systems for the causality assessment of drug-induced liver injury may be helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity features of commonly used herbal products, such as Ayurvedic and Chinese herbs, black cohosh, chaparral, germander, greater celandine, green tea, Herbalife, Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid, have been individually reviewed. Furthermore, clinically significant herb-drug interactions are also discussed. CONCLUSIONS A number of herbal medicinal products are associated with a spectrum of hepatotoxicity events. Advances in the understanding of the pathogenesis and the risks involved are needed to improve herbal medicine safety.
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Affiliation(s)
- C Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
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Fallatah HI, Akbar HO. Autoimmune hepatitis as a unique form of an autoimmune liver disease: immunological aspects and clinical overview. Autoimmune Dis 2012; 2012:312817. [PMID: 23304455 PMCID: PMC3530748 DOI: 10.1155/2012/312817] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Revised: 09/09/2012] [Accepted: 10/12/2012] [Indexed: 12/11/2022] Open
Abstract
Autoimmune hepatitis (AIH) is a unique form of immune-mediated disease that attacks the liver through a variety of immune mechanisms. The outcomes of AIH are either acute liver disease, which can be fatal, or, more commonly, chronic progressive liver disease, which can lead to decompensated liver cirrhosis if left untreated. AIH has characteristic immunological, and pathological, features that are important for the establishment of the diagnosis. More importantly, most patients with AIH have a favorable response to treatment with prednisolone and azathioprine, although some patients with refractory AIH or more aggressive disease require more potent immune-suppressant agents, such as cyclosporine or Mycophenolate Mofetil. In this paper, we discuss the immunological, pathological and clinical features of AIH, as well as the standard and alternative treatments for AIH.
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Affiliation(s)
- Hind I. Fallatah
- Medical Department, Arab Board and Saudi Board of Internal Medicine, MACP, King Abdul Aziz University Hospital, P.O. Box 9714, Jeddah 21423, Saudi Arabia
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Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int 2012; 32:1543-56. [PMID: 22928722 DOI: 10.1111/j.1478-3231.2012.02864.x] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 07/23/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Herbal hepatotoxicity is a field that has rapidly grown over the last few years along with increased use of herbal products worldwide. AIMS To summarize the various facets of this disease, we undertook a literature search for herbs, herbal drugs and herbal supplements with reported cases of herbal hepatotoxicity. METHODS A selective literature search was performed to identify published case reports, spontaneous case reports, case series and review articles regarding herbal hepatotoxicity. RESULTS A total of 185 publications were identified and the results compiled. They show 60 different herbs, herbal drugs and herbal supplements with reported potential hepatotoxicity, additional information including synonyms of individual herbs, botanical names and cross references are provided. If known, details are presented for specific ingredients and chemicals in herbal products, and for references with authors that can be matched to each herbal product and to its effect on the liver. Based on stringent causality assessment methods and/or positive re-exposure tests, causality was highly probable or probable for Ayurvedic herbs, Chaparral, Chinese herbal mixture, Germander, Greater Celandine, green tea, few Herbalife products, Jin Bu Huan, Kava, Ma Huang, Mistletoe, Senna, Syo Saiko To and Venencapsan(®). In many other publications, however, causality was not properly evaluated by a liver-specific and for hepatotoxicity-validated causality assessment method such as the scale of CIOMS (Council for International Organizations of Medical Sciences). CONCLUSIONS This compilation presents details of herbal hepatotoxicity, assisting thereby clinical assessment of involved physicians in the future.
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Affiliation(s)
- Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University, Frankfurt/Main, Germany.
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Zhao W, Li JJ, Yue SQ, Zhang LY, Dou KF. Antioxidant activity and hepatoprotective effect of a polysaccharide from Bei Chaihu (Bupleurum chinense DC). Carbohydr Polym 2012; 89:448-52. [PMID: 24750742 DOI: 10.1016/j.carbpol.2012.03.027] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Revised: 03/08/2012] [Accepted: 03/08/2012] [Indexed: 12/24/2022]
Abstract
Chinese medicine plays a pivotal role in hepatoprotective treatment. In the present study, a water-soluble polysaccharide fraction (WBCP) was fractioned from the roots of Bupleurum chinense and purified by DEAE-cellulose and Surperdex 200 HR chromatography. The physicochemical properties, antioxidative and hepatoprotective activities of WBCP were evaluated in a rat model of hepatic injury caused by d-galactosamine (GalN). Hepatoprotective effect was evaluated by measuring aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities in the plasma of mice. Antioxidant activity was evaluated by measuring biochemical parameters in the mouse liver homogenate, such as glutathione reductase (GR), γ-glutamylcysteine synthetase (GCS), glutathione S-transferase (GST) and superoxide dismutase (SOD) activities, as well as glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) levels. The results showed the oral administration of WBCP could significantly reduce the activity of AST, ALT, ALP and LDH, indicating that WBCP possesses hepatoprotective activity. Furthermore, there was general a statistically significant increase in the activities of GSH, GR, GCS, GST and SOD, and a loss in TBARS in the liver of WBCP-treated group compared with the control group. In addition, the elevated levels of pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-α) in the serum of the experimental animals was significantly returned by WBCP treatment at the dose of 400 mg/kg. These results clearly demonstrated that WBCP possess promising hepatoprotective effects against GalN-induced liver damage, which may be mediated through augmentation of antioxidant defenses.
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Affiliation(s)
- Wei Zhao
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, 15 Changlexi Road, Xi'an, Shaanxi Province 710032, China
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Lee JK, Kim JH, Shin HK. Therapeutic effects of the oriental herbal medicine Sho-saiko-to on liver cirrhosis and carcinoma. Hepatol Res 2011; 41:825-37. [PMID: 21682829 DOI: 10.1111/j.1872-034x.2011.00829.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The traditional Chinese herbal medicine Sho-saiko-to is a mixture of seven herbal preparations that has long been used in the treatment of chronic liver disease. Various clinical trials have shown that Sho-saiko-to protects against the development of hepatocellular carcinoma in cirrhotic patients. However, the mechanism by which Sho-saiko-to protects hepatocytes against hepatic fibrosis and carcinoma is not yet known. Basic science studies have demonstrated that Sho-saiko-to reduces hepatocyte necrosis and enhances liver function. Sho-saiko-to significantly inhibits hepatic fibrosis by inhibiting the activation of stellate cells, the major producers of collagen in the liver, as well as by inhibiting hepatic lipid peroxidation, promoting matrix degradation, and suppressing extracellular matrix (ECM) accumulation. Furthermore, clinical trials have shown that Sho-saiko-to lowers the rate of hepatocellular carcinoma (HCC) development in patients with cirrhosis and increases the survival of patients with HCC. Unfortunately, some case reports have shown the side effects of Sho-saiko-to. Most of the side effects were interstitial pneumonia and acute respiratory failure induced by Sho-saiko-to in Japan. As a result of analyzing these case reports, the incidence and risk are increased by co-administration of interferon, duration of medication, and, high in an elderly population. This review discusses the properties of Sho-saiko-to with regards to the treatment of chronic liver diseases and suggests the side effects of Sho-saiko-to.
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Affiliation(s)
- Jun-Kyoung Lee
- Herbal Medicine, Evidence-Based Medicine Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
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Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011. [PMID: 21264326 DOI: (select(0)from(select(sleep(0)))v)/*'+(select(0)from(select(sleep(0)))v)+'"+(select(0)from(select(sleep(0)))v)+"*] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan. METHODS From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship. FINDINGS In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar. CONCLUSIONS Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
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Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011. [PMID: 21264326 DOI: (select(0)from(select(sleep(7)))v)/*'+(select(0)from(select(sleep(7)))v)+'"+(select(0)from(select(sleep(7)))v)+"*] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan. METHODS From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship. FINDINGS In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar. CONCLUSIONS Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
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40
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Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011. [PMID: 21264326 DOI: 10.1371/journal.pone.0016064'||dbms_pipe.receive_message(chr(98)||chr(98)||chr(98),15)||'] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan. METHODS From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship. FINDINGS In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar. CONCLUSIONS Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
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41
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Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011; 6:e16064. [PMID: 21264326 PMCID: PMC3020221 DOI: 10.1371/journal.pone.0016064] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Accepted: 12/07/2010] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan. METHODS From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship. FINDINGS In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar. CONCLUSIONS Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine
and Industrial Hygiene, National Taiwan University College of Public Health,
Taipei, Taiwan
- Department of Occupational Medicine,
Ton Yen General Hospital, Hsin-Chu, Taiwan
| | - Jung-Der Wang
- Institute of Occupational Medicine
and Industrial Hygiene, National Taiwan University College of Public Health,
Taipei, Taiwan
- Department of Public Health, National
Cheng Kung University College of Medicine, Tainan, Taiwan
- Department of Environmental and
Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pau-Chung Chen
- Institute of Occupational Medicine
and Industrial Hygiene, National Taiwan University College of Public Health,
Taipei, Taiwan
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Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One 2011. [PMID: 36539429 DOI: (select(0)from(select(sleep(3)))v)/*'+(select(0)from(select(sleep(3)))v)+'"+(select(0)from(select(sleep(3)))v)+"*] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan. METHODS From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship. FINDINGS In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar. CONCLUSIONS Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
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Tsuda T, Yashiro S, Gamo Y, Watanabe K, Hoshino T, Oikawa T, Hanawa T. Discrepancy between clinical course and drug-induced lymphocyte stimulation tests in a case of saireito-induced liver injury accompanied by Sjögren syndrome. J Altern Complement Med 2010; 16:501-5. [PMID: 20423219 DOI: 10.1089/acm.2009.0183] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Saireito consists of components of shosaikoto and goreisan. There are several reports of liver injury caused by shosaikoto and saireito, whereas cases caused by goreisan are rarely seen. PATIENT A 70-year-old woman suffered from sicca of the eyes and oral cavity that arose in 2003. In June 2004, we diagnosed her as having Sjögren syndrome on the basis of Schirmer's test, salivary scintigraphy, presence of anti-SS-A/Ro antibody, and subjective symptoms. Although a muscarinic agonist was commenced, her sicca symptoms did not improve. INTERVENTIONS In February 2008, 7.5 g/day of shosaikoto extract granules (for ethical use, Tsumura & Co., Tokyo, Japan) was introduced. Her symptoms and laboratory data did not change. The next month, the treatment was replaced by 9.0 g/day of saireito extract granules (for ethical use, Tsumura & Co., Tokyo, Japan). RESULTS After 10 weeks, elevation of liver enzymes was observed. On suspicion of drug-induced liver injury (DILI), saireito was withdrawn, and the patient's liver enzymes returned to normal the next month. Drug-induced lymphocyte stimulation tests (DLSTs) for saireito, shosaikoto, and goreisan were all positive. CONCLUSIONS The clinical course suggested allergy to the goreisan component of saireito. It is important to be aware of the limitation of DLST as a diagnostic tool for DILI, especially for herbal medicines.
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Affiliation(s)
- Tokutaro Tsuda
- Department of Oriental Medicine, Doctoral Program of Medical Science, Kitasato University Graduate School, Sagamihara, Kanagawa, Japan.
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Zhu Z, Zhao L, Liu X, Chen J, Zhang H, Zhang G, Chai Y. Comparative pharmacokinetics of baicalin and wogonoside by liquid chromatography–mass spectrometry after oral administration of Xiaochaihu Tang and Radix scutellariae extract to rats. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878:2184-90. [DOI: 10.1016/j.jchromb.2010.06.021] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2009] [Revised: 06/18/2010] [Accepted: 06/18/2010] [Indexed: 11/16/2022]
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Shin JW, Park HJ, Kwon M, Son CG. Scientific evaluation of the chronic toxicity of the herbal medicine CGX in beagle dogs. Food Chem Toxicol 2010; 48:743-9. [PMID: 20034534 DOI: 10.1016/j.fct.2009.12.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2009] [Revised: 12/14/2009] [Accepted: 12/16/2009] [Indexed: 02/07/2023]
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Li HY, Cui L, Cui M. Hot topics in Chinese herbal drugs research documented in PubMed/MEDLINE by authors inside China and outside of China in the past 10 years: based on co-word cluster analysis. J Altern Complement Med 2009; 15:779-85. [PMID: 19534611 DOI: 10.1089/acm.2008.0594] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE This study aims to gain an overview of hot topics related to research focused on Chinese herbal drugs by authors inside China and outside of China in the past 10 years. METHODS PubMed/MEDLINE was utilized in order to investigate and select research that was published on "Chinese herbal drugs" from 1998 to 2007, by authors located both inside and outside of China (MeSH terms were downloaded and ranked). MeSH terms that frequently appeared were identified and co-word analysis was carried out for two groups: (1) authors located in China, and (2) authors based outside of China, respectively. The hot topics concerning research into Chinese herbal drugs were concluded after cluster analysis and related document analysis. RESULTS For authors in the China group versus those outside the China group, the search results were 4790 versus 2609 citations and approximately 40,000 versus 20,000 MeSH terms, respectively. The threshold value of highly frequent terms was set at 30 versus 20, and the cumulative frequency percentage of these terms was 40.92% versus 36.67%, respectively. Thus, 43 highly frequent MeSH terms were identified and 43 x 43 co-word matrices were acquired for each group. The appearance frequency of MeSH showed that most research focused on pharmacology, therapeutic application, phytotherapy, side-effects of Chinese herbal drugs, and identification of active chemical components in herbs. CONCLUSION The hot topics are as follows: (1) anti-inflammatory activity, antioxidant activities, anticancer activity of phytogenic antineoplastic agents, and neuroprotective effects of Chinese herbal drugs; (2) common diseases treated with Chinese herbal drugs include hepatocirrhosis, diabetes, angina, chronic hepatitis B in China, and diabetes, asthma, prostate cancer, and hepatocirrhosis outside of China; (3) Chinese herbal nephropathy and acute hepatitis induced by Chinese herbal drugs; (4) PC-SPES (PDQ) for the treatment of prostate cancer, which was a hot topic for researchers located outside of China; (5) research on extraction of active components from medicinal plants; and finally (6) research related to the identification of the Chinese herbal drugs component with state-of-the-art technologies in China.
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Affiliation(s)
- Hai-Yan Li
- Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Science, Beijing, China
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47
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Lee CH, Wang JD, Chen PC. Case-crossover study of hospitalization for acute hepatitis in Chinese herb users. J Gastroenterol Hepatol 2008; 23:1549-55. [PMID: 18717756 DOI: 10.1111/j.1440-1746.2008.05511.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Despite the increase in popularity of herbal products, there is growing concern over potential health hazards caused by the Chinese herbal medicines (CHMs) that are regularly reimbursed under the National Health Insurance system in Taiwan. This study attempts to determine the association between CHM prescriptions and acute hepatitis-related hospitalizations. METHODS A case-crossover study was designed on 200,000 randomly selected individuals from the National Health Insurance Research Database who were then followed from 1997 to 2002. All medications taken in the 30- and 60-day periods prior to hospitalization were explored and compared with four control periods (the 180- and 360-day periods prior to and after the hospitalization). A conditional logistic regression model was then constructed to determine the odds of CHM being prescribed during these risk periods. RESULTS There were a total of 12 cases with nonviral, nonalcoholic hepatitis patients who took CHM prescriptions during the 30-day risk or control periods. After adjustment for conventional hepatotoxic drugs, the odds ratio during the 30-day risk period was 3.4 (95% confidence interval [CI]: 1.1, 9.8) for nonviral, nonalcoholic acute hepatitis. A detailed historical review of CHMs for each patient revealed that the odds ratio increased to 4.2 for those prescribed formulae containing Radix Paeoniae (95% CI: 1.1, 15.7) and Radix Glycyrrhizae (95% CI: 1.2, 15.2). CONCLUSIONS Chinese herbal users revealed a slightly increased risk of acute hepatitis. We therefore recommend pharmacovigilance and active surveillance for CHMs suspected with hepatotoxicity.
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Affiliation(s)
- Chang-Hsing Lee
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
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48
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Hussain H, Ahmad VU, Anwar S, Miana GA, Krohn K. Chemical constituents of Scutellaria linearis. BIOCHEM SYST ECOL 2008. [DOI: 10.1016/j.bse.2007.12.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Abstract
Perceptions of safety and/or cultural mores prompt individuals to seek herbal slimming aids in preference to conventional dietary, physical activity and medication-based protocols. In recent years, terpenoid-containing dietary supplements have been implicated in causing severe and sometimes fatal hepatotoxicity. Teucrium polium (germander) was the first of these herbal products to be clearly linked to cases of acute liver failure. Subsequently, similar hepatotoxicity has been observed with other members of the Teucrium genus. While diterpenoid-derived reactive metabolites are central to germander hepatotoxicity, it may also be that the hepatic effects of compounds such as Sho-saiko-to, Centella asiatica and Black cohosh are linked to their triterpenoid content. Other non-terpenoid-containing herbal remedies marketed for weight reduction have been causally associated with significant liver injury. Important among these are preparations containing N-nitrosofenfluramine, usnic acid and ephedra alkaloids. Finally, we review recent data on known and emerging hepatotoxins such as Boh-Gol-Zhee, Kava, pyrrolizidine alkaloids and Shou-Wu-Pian. Better public and physician awareness through health education, early recognition and management of herbal toxicity and tighter regulation of complementary/alternative medicine systems are required to minimize the dangers of herbal product use.
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Affiliation(s)
- Shivakumar Chitturi
- Gastroenterology and Hepatology Unit, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.
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50
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Abstract
There is appropriate concern about the potential risk for hepatotoxicity from herbal products because they are unregulated and therefore not standardized with regard to their contents. This is particularly the case for the crude herbals that are commonly formulated as a mixture, so that their ingredients may be ambiguous and even contain harmful contaminants. Presented here is an overview of the more commonly recognized herbal products that have been reported to be associated with liver injury. Although many of them are clearly implicated, there are some, particularly those identified solely through an occasional case report, for which the relationship is uncertain.
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Affiliation(s)
- Leonard B Seeff
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 31 Center Drive, Room 9A27, Bethesda, MD 20892, USA.
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