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Ran S, Peng R, Guo Q, Cui J, Chen G, Wang Z. Bupleurum in Treatment of Depression Disorder: A Comprehensive Review. Pharmaceuticals (Basel) 2024; 17:512. [PMID: 38675471 PMCID: PMC11054835 DOI: 10.3390/ph17040512] [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: 02/22/2024] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of depression has been steadily rising in recent years, making it one of the most prevalent mental illnesses. As the pursuit of novel antidepressant drugs captivates the pharmaceutical field, the therapeutic efficacy of Traditional Chinese Medicine (TCM) has been widely explored. Chaihu (Bupleurum) has been traditionally used for liver conditions such as hepatitis, liver inflammation, liver fibrosis, and liver cancer. It is believed to have hepatoprotective effects, promoting liver cell regeneration and protecting against liver damage. In addition, Bupleurum has also been used as a Jie Yu (depression-relieving) medicine in China, Japan, Republic of Korea, and other Asian countries for centuries. This review article aims to summarize the research conducted on the antidepressant properties and mechanisms of Bupleurum, as well as discuss the potential of TCM formulas containing Bupleurum. This review highlights various antidepressant ingredients isolated from Bupleurum, including saikosaponin A, saikosaponin D, rutin, puerarin, and quercetin, each with distinct mechanisms of action. Additionally, Chinese herb prescriptions and extracts containing Bupleurum, such as Chaihu Shugansan, Xiaoyaosan, and Sinisan, are also included due to their demonstrated antidepressant effects. This review reveals that these Bupleurum compounds exhibit antidepressant effects through the regulation of neurotransmitter mechanisms (such as 5-HT and DA), the NMDA (N-methyl-D-aspartate) system, brain-derived neurotrophic factor (BDNF), and other intracellular signaling pathways. Collectively, this comprehensive review provides insights into the multiple applications of Bupleurum in the treatment of depression and highlights its potential as an alternative or complementary approach to traditional therapies. However, it is essential to consider the potential adverse effects and clinical restrictions of Bupleurum despite its promising potential. Further research is needed to elucidate its specific mechanisms of action and evaluate its effectiveness in human subjects.
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Affiliation(s)
| | | | | | | | - Gang Chen
- Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; (S.R.); (R.P.); (Q.G.); (J.C.)
| | - Ziying Wang
- Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; (S.R.); (R.P.); (Q.G.); (J.C.)
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2
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Mao Y, Ma S, Liu C, Liu X, Su M, Li D, Li Y, Chen G, Chen J, Chen J, Zhao J, Guo X, Tang J, Zhuge Y, Xie Q, Xie W, Lai R, Cai D, Cai Q, Zhi Y, Li X. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int 2024; 18:384-419. [PMID: 38402364 DOI: 10.1007/s12072-023-10633-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 12/18/2023] [Indexed: 02/26/2024]
Abstract
Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.
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Affiliation(s)
- Yimin Mao
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China.
| | - Shiwu Ma
- Department of Infectious Diseases, The 920th Hospital of Chinese PLA Joint Logistics Support Force, Kunming, 650032, Yunnan, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaoyan Liu
- Department of Pharmacy, Huangpu Branch of the 9th People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China
| | - Minghua Su
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Dongliang Li
- Department of Hepatobiliary Medicine, The 900th Hospital of Chinese PLA Joint Logistics Support Force, Fuzhou, 350025, Fujian, China
| | - Yiling Li
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Gongying Chen
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China
| | - Jun Chen
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Jinjun Chen
- Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xiaoyan Guo
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Jieting Tang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wen Xie
- Center of Liver Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100088, China
| | - Rongtao Lai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Qingxian Cai
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Yang Zhi
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Xiaoyun Li
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
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3
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Zhang Y, Tian J, Ni J, Wei M, Li T, Shi J. Polygala tenuifolia and Acorus tatarinowii in the treatment of Alzheimer's disease: a systematic review and meta-analysis. Front Pharmacol 2024; 14:1268000. [PMID: 38283842 PMCID: PMC10815298 DOI: 10.3389/fphar.2023.1268000] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 12/11/2023] [Indexed: 01/30/2024] Open
Abstract
Background: The complexity of Chinese medicine treatment for Alzheimer's disease (AD) utilizing a multi-herb therapy makes the evidence in current studies insufficient. Herb pairs are the most fundamental form of multi-herb formulae. Among the Chinese herbal formulas for AD treatment, Polygala tenuifolia (PT) and Acorus tatarinowii (AT) appeared as the most commonly used herbal pairs in combination. Objective: The aim of this study is to evaluate the clinical efficacy and safety of the combination of PT and AT in the treatment of AD. Methods: We systematically searched and screened randomized controlled trials of pairing PT and AT for the treatment of AD patients in eight databases with a search deadline of June 26, 2023. Authors, year of publication, title, and basic information such as subject characteristics (age, sex, and race), course of disease, control interventions, dose, and treatment duration were extracted from the screened studies. Primary outcomes assessed included mini-mental state examination (MMSE), activities of daily living (ADL), and AD assessment scale-cognitive subscale (ADAS-cog), while secondary outcomes included efficiency and adverse events. The quality of the included studies was assessed using the Cochrane risk of bias tool. The mean difference with 95% confidence intervals (MD [95% CI]) and risk ratio (RR) was selected as the effect size, and the data were analyzed and evaluated using RevMan 5.4 and Stata 16. Results: A total of sixteen eligible and relevant studies involving 1103 AD participants were included. The combination of PT and AT plus conventional drugs was superior to single conventional drugs in MMSE [MD = 2.57, 95%CI: (1.44, 3.69); p < 0.00001; I 2 = 86%], ADL [MD = -3.19, 95%CI: (-4.29, -2.09); p < 0.00001; I 2 = 0%], and ADAS-cog scores [MD = -2.09, 95%CI: (-3.07, -1.10); p < 0.0001; I 2 = 0%]. The combination of PT and AT plus conventional drugs had a significantly more favorable benefit in clinical effectiveness [RR = 1.27, 95%CI: (1.12, 1.44); p = 0.0002; I 2 = 0%]. Adverse events were not increased with the combination of PT and AT plus conventional drugs compared to conventional drugs [RR = 0.65, 95%CI: (0.35, 1.19); p = 0.16; I 2 = 0%]. The experimental group treated with the combination of PT and AT alone for AD was comparable in MMSE, ADL, and ADAS-cog scores compared with the control group treated with single conventional drugs. Conclusion: Compared to single conventional drugs, the combination of PT and AT may be used as an alternative therapy to improve global cognition and functioning in AD, and the combination of PT and AT as adjunctive therapy appears to produce a better therapeutic response to AD in terms of efficacy without increasing the risk of adverse events. However, the very low to low quality of available evidence limits confidence in the findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023444156.
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Affiliation(s)
- Yuchen Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jinzhou Tian
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jingnian Ni
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Mingqing Wei
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ting Li
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jing Shi
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Chen C, Gong W, Tian J, Gao X, Qin X, Du G, Zhou Y. Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase. J Pharm Anal 2023; 13:640-659. [PMID: 37440914 PMCID: PMC10334278 DOI: 10.1016/j.jpha.2023.04.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/07/2023] [Accepted: 04/23/2023] [Indexed: 07/15/2023] Open
Abstract
Radix Bupleuri (RB) is commonly used to treat depression, but it can also lead to hepatotoxicity after long-term use. In many anti-depression prescriptions, RB is often used in combination with Radix Paeoniae Alba (RPA) as an herb pair. However, whether RPA can alleviate RB-induced hepatotoxicity remain unclear. In this work, the results confirmed that RB had a dose-dependent antidepressant effect, but the optimal antidepressant dose caused hepatotoxicity. Notably, RPA effectively reversed RB-induced hepatotoxicity. Afterward, the mechanism of RB-induced hepatotoxicity was confirmed. The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase (GSS) activity in the liver, and further cause liver injury through oxidative stress and nuclear factor kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Furthermore, the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated. The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity, thereby promoting the conversion of saikosaponins to saikogenins in vivo. Different from saikosaponin A and saikosaponin D, which are directly combined with GSS as an inhibitor, their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity. Based on this, RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway. In conclusion, the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
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Affiliation(s)
- Congcong Chen
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
| | - Wenxia Gong
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
| | - Junshen Tian
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
| | - Xiaoxia Gao
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
| | - Guanhua Du
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yuzhi Zhou
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China
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5
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Khuanphram N, Taya S, Kongtawelert P, Wongpoomchai R. Sesame Extract Promotes Chemopreventive Effect of Hesperidin on Early Phase of Diethylnitrosamine-Initiated Hepatocarcinogenesis in Rats. Pharmaceutics 2021; 13:pharmaceutics13101687. [PMID: 34683980 PMCID: PMC8538859 DOI: 10.3390/pharmaceutics13101687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/01/2021] [Accepted: 10/11/2021] [Indexed: 12/28/2022] Open
Abstract
The combination of natural products is an alternative approach to achieving chemopreventive potential. Accordingly, citrus hesperidin exhibits numerous biological activities, including anticarcinogenic activities, while the sesamin in sesame exhibits potent anticancer activities and lipid-lowering effects. We investigated the cancer chemopreventive effects of mixed sesame and orange seed extract (MSO) containing hesperidin and sesamin in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Rats were injected with DEN once a week for 3 weeks to induce hepatocarcinogenesis. Rats were fed with MSO and various compositions that included sesame extract (SE) and hesperidin. The 10-week administration of MSO more effectively inhibited the number and size of hepatic GST-P-positive foci than hesperidin in DEN-initiated rats. MSO and hesperidin decreased the number of PCNA-positive hepatocytes but increased the apoptotic cells in DEN-induced rats. Furthermore, MSO and its constituents suppressed hepatic triglyceride content concurrently along with the expression of fatty acid synthase. Although the 5-week administration of MSO or hesperidin did not alter hepatic, preneoplastic lesion formation in DEN-initiated rats, it alleviated DEN-induced hepatotoxicity. MSO and its applied compositions did not impact upon the cytochrome P450 system. In conclusion, sesame extract promoted the chemopreventive effect of hesperidin on DEN-induced early stage of hepatocarcinogenesis in rats. The inhibitory mechanisms are likely involved with the induction of cell apoptosis, suppression of cell proliferation and modulation of hepatic lipogenesis. This study may provide revelations in the development of alternative treatments against hepatocellular carcinoma.
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Affiliation(s)
- Napaporn Khuanphram
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Sirinya Taya
- Functional Food Research Unit, Science and Technology Research Institute, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Prachya Kongtawelert
- Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Rawiwan Wongpoomchai
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
- Correspondence: ; Tel.: +66-53-935325; Fax: +66-53-894031
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Wang P, Gao X, Liang M, Fang Y, Jia J, Tian J, Li Z, Qin X. Dose-Effect/Toxicity of Bupleuri Radix on Chronic Unpredictable Mild Stress and Normal Rats Based on Liver Metabolomics. Front Pharmacol 2021; 12:627451. [PMID: 34557088 PMCID: PMC8452938 DOI: 10.3389/fphar.2021.627451] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 08/24/2021] [Indexed: 01/23/2023] Open
Abstract
Depression, one of the most prevalent psychiatric diseases, affects the quality of life of millions of people. Studies have shown that the lower polar fraction of Bupleuri Radix (PBR) elicited therapeutic effects in chronic unpredictable mild stress (CUMS) rats. In contrast, comparatively mild liver injury was observed in normal rats administered a high PBR dose. It is essential to clarify the effective and safe dose of PBR and its dose-effect/toxicity relationship. In this study, we used the CUMS model to evaluate the effects and toxicities of PBR and to decipher the dose-effect/toxicity relationship and mechanism using the liver metabonomics combined with multivariate statistical analysis. In CUMS rats, PBR improved the depression-like behaviors including reduced body growth rate, anhedonia, and locomotor activities, and markedly reduced the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In control rats, PBR treatment altered ALT and AST from typical levels. Moreover, the effective dose range for CUMS rats was 12.6–163 g (herb)/kg, the median toxicity dose for CUMS and normal rats were 388 and 207 g (herb)/kg. The toxicological results showed that the cytokeratin-18 fragment level was increased significantly in CUMS rats given with 100 g (herb)/kg PBR. After a comprehensive analysis, the use of PBR dose was determined to be 12.6–50 g (herb)/kg. In CUMS rats, PBR could reverse amino acid metabolism, energy metabolism, sphingolipid metabolism, and β-oxidation of fatty acids to produce an anti-depressant effect in a dose-dependent manner. In control rats, two additional metabolic pathways were significantly perturbed by PBR, including glycerophospholipid metabolism and bile acid metabolism. Moreover, the comprehensive metabolic index including dose-effect index (DEI) and dose toxicity index (DTI) had a remarkable ability (ROC = 0.912, ROC = 0.878) to predict effect and toxicity. The DEI and DTI were used to determine the dose range of effect and toxicity which was shown high concordance with previous results. Furthermore, the CUMS rats possessed a higher toxicity tolerance dose of PBR which was consistent with the theory of “You Gu Wu Yun” in traditional Chinese medicine. The metabonomics techniques combined with correlation analysis could be used to discover indicators for comprehensive evaluations of efficacy and toxicity.
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Affiliation(s)
- Peng Wang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Xiaoxia Gao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry Education of Shanxi University, Taiyuan, China
| | - Meili Liang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Yuan Fang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Jinping Jia
- Scientific Instrument Center, 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 Education of Shanxi University, Taiyuan, China
| | - Zhenyu Li
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry Education of Shanxi University, Taiyuan, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,Key Laboratory of Chemical Biology and Molecular Engineering of Ministry Education of Shanxi University, Taiyuan, China
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Teschke R, Eickhoff A, Schulze J, Danan G. Herb-induced liver injury (HILI) with 12,068 worldwide cases published with causality assessments by Roussel Uclaf Causality Assessment Method (RUCAM): an overview. Transl Gastroenterol Hepatol 2021; 6:51. [PMID: 34423172 PMCID: PMC8343418 DOI: 10.21037/tgh-20-149] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 04/13/2020] [Indexed: 12/11/2022] Open
Abstract
Herbal products including herbal medicines are worldwide used in large amounts for treating minor ailments and for disease prevention. However, efficacy of most herbal products has rarely been well documented through randomized controlled trials in line with evidence-based medicine concepts, which could be used to estimate the benefit/risk ratio. Instead, much better documented are adverse reactions such as liver injury associated with the consumption of some herbal products, so called herb-induced liver injury (HILI), which represents a clinical challenge. In order to establish HILI as valid diagnosis, the use of a diagnostic algorithms such as Roussel Uclaf Causality Assessment Method (RUCAM) is widely recommended, although physicians in some countries are reluctant to use RUCAM for their HILI cases. This review on worldwide HILI and RUCAM, developed as part of the artificial intelligence ideas, reveals that China is the leading country with 24 publications on HILI cases that were all assessed for causality using RUCAM, followed by Korea with 15 reports, Germany with 9 reports, the US with 7 reports, and Spain with 6 reports, whereas the remaining countries provided less than 4 reports. The total number of assessed HILI cases is 12,068 worldwide derived from 80 publications but in each report HILI case numbers were variable in a range from 1 up to 6,971. This figure compares with 46,266 cases of drug-induced liver injury (DILI) published worldwide from 2014 to early 2019 also assessed for causality by RUCAM. The original version of RUCAM was validated and established in 1993 and updated in 2016 that should be used in future HILI cases. RUCAM is an objective, structured, and validated method, specifically designed for liver injury. It is a scoring system including case data elements to be assessed and scored individually to provide a final score in five causality gradings. Among the 11,404/12,068 HILI (94.5%) cases assessable for evaluation, causality gradings were highly probable in 4.2%, probable in 15.5%, possible in 70.3%, and unlikely or excluded in 10.0%. To improve the future reporting of RUCAM based HILI cases, recommendations include the strict adherence to instructions outlined in the updated RUCAM and, in particular, to follow prospective data collection on the cases to ensure completeness of case data. In conclusion, RUCAM can well be used to assess causality in suspected HILI cases, and additional efforts are now required to increase the quality of the reported cases.
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Affiliation(s)
- Rolf Teschke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/ Main, Frankfurt/Main, Germany
| | - Axel Eickhoff
- Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/ Main, Frankfurt/Main, Germany
| | - Johannes Schulze
- Institute of Occupational, Social and Environmental Medicine, Goethe-University Frankfurt/Main, Frankfurt/Main, Germany
| | - Gaby Danan
- Pharmacovigilance consultancy, Paris, France
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8
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Lam RPK, Lau EHY, Yip WL, Leung JKS, Tsui MSH. Traditional Chinese medicine poisoning in the emergency departments in Hong Kong: Trend, clinical presentation and predictors for poor outcome. World J Emerg Med 2021; 12:143-150. [PMID: 33728008 PMCID: PMC7947561 DOI: 10.5847/wjem.j.1920-8642.2021.02.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 07/08/2020] [Indexed: 11/19/2022] Open
Affiliation(s)
- Rex Pui Kin Lam
- Emergency Medicine Unit, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China
- Accident and Emergency Department, Queen Mary Hospital, Hong Kong, China
- Accident and Emergency Department, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
| | - Eric Ho Yin Lau
- School of Public Health, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China
| | - Wai Lam Yip
- Accident and Emergency Department, Queen Mary Hospital, Hong Kong, China
| | - Joe Kai Shing Leung
- Accident and Emergency Department, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
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9
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Ng JY, Lau SKC. Complementary and alternative medicine status in ovarian cancer guidelines: A systematic review. Eur J Integr Med 2020. [DOI: 10.1016/j.eujim.2020.101227] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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10
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Lee FY, Wong HS, Chan HK, Mohamed Ali N, Abu Hassan MR, Omar H, Abdul Mutalib NA. Hepatic adverse drug reactions in Malaysia: An 18-year review of the national centralized reporting system. Pharmacoepidemiol Drug Saf 2020; 29:1669-1679. [PMID: 33064335 DOI: 10.1002/pds.5153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 10/08/2020] [Accepted: 10/12/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE To determine the incidence, demographic profile, background of reporters, causative agents, severity and clinical outcomes of hepatic adverse drug reaction (ADR) reports in Malaysia using the national ADR reporting database. METHODS The ADR reports recorded between 2000 and 2017 were retrospectively analysed to identify hepatic ADR reports. The trend and characteristics of hepatic ADR cases were described. Multivariate disproportionality analysis of the causative agents was performed to generate signals of hepatic ADRs. RESULTS A total of 2090 hepatic ADRs (1.77% of all ADRs) were reported with mortality rate of 12.7% among cases with known clinical outcomes. The incidence of hepatic ADR reporting in Malaysia increased significantly over 18 years from 0.26 to 9.45 per million population (P < .001). Antituberculosis drugs (n = 268, 12.82%) was the most common suspected class of causative agents with a reporting odds ratio (ROR) and 95% CI of 8.39 (7.26-9.70), followed by traditional/complementary medicines or herbal/dietary supplements (TCM/HDS) (n = 235, 11.24%, ROR 3.26 [2.84-3.75]), systemic antibacterials (n = 159, 7.61%, ROR 2.65 [2.25-3.13]), lipid modifying agents (n = 142, 6.79%, ROR 2.21 [1.86-2.63]) and amiodarone (n = 137, 6.56%, ROR 35.25 [28.40-43.75]). Most (72.9%) of the TCM/HDS were not registered with the authorities. CONCLUSIONS Hepatic ADR cases have increased significantly in Malaysia, with antituberculosis drugs, systemic antibacterials, and TCM/HDS being the most common causative agents reported. Most TCM/HDS reported to be associated with hepatic ADR were not registered with the authorities.
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Affiliation(s)
- Fei Yee Lee
- Clinical Research Centre, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Hin-Seng Wong
- Clinical Research Centre, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Huan-Keat Chan
- Clinical Research Centre, Sultanah Bahiyah Hospital, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Norleen Mohamed Ali
- Pharmacovigilance Section, Center For Post-Registration and Cosmetic Control, National Pharmaceutical Regulatory Agency (NPRA), Petaling Jaya, Selangor, Malaysia
| | - Muhammad Radzi Abu Hassan
- Clinical Research Centre, Sultanah Bahiyah Hospital, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia.,Gastroenterology Unit, Department of Medicine, Sultanah Bahiyah Hospital, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Haniza Omar
- Hepatology Department, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Noor Aliza Abdul Mutalib
- Hepatology Department, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
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11
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Zhang C, Wu Y, Yuan S, Dou X, Sheng Q, Wang J, Tian W, Yao L, Ding Y. Characteristics of Drug-Induced Liver Injury in Northeast China: Disease Spectrum and Drug Types. Dig Dis Sci 2020; 65:3360-3368. [PMID: 31907771 DOI: 10.1007/s10620-019-06030-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 12/22/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The aim of this study was to determine the disease spectrum and drug types causing drug-induced liver injury (DILI) in northeast China, so that the affected population can be reminded of the need to increase their post-medication monitoring. METHODS A total of 470 DILI patients hospitalized at Shengjing Hospital between 2013 and 2016 were involved in this retrospective study. RESULTS There were significant differences in the disease spectrum of the different age groups (P < 0.001) and genders (P = 0.009). Drugs used to treat osteopathies, dermatitis and infections, as well as health care supplements, each accounted for > 10% of all drugs that caused DILI. The percentage of DILIs related to Chinese herbal medicines (CHMs) gradually increased with patient age (P = 0.002). The percentage of males taking health supplements or CHMs was significantly lower compared with females. Total bilirubin (β = 0.01, OR = 1.01, P < 0.001) and INR (β = 0.74, OR = 2.11, P < 0.001) were found to be independent predictors of liver damage. CONCLUSIONS The main type of drug that causes DILI in northeast China is a CHM. There are differences in the disease spectrum found in DILI patients of different ages and gender. Making appropriate changes in the drug-taking habits of high-risk groups and the drugs used to treat high-risk underlying diseases, as well as increasing patient monitoring, may help to reduce the incidence of DILIs.
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Affiliation(s)
- Chong Zhang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Yuyu Wu
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Suyu Yuan
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Qiuju Sheng
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Jingyan Wang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Wenyue Tian
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Lan Yao
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China.
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12
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Teschke R, Danan G. Worldwide Use of RUCAM for Causality Assessment in 81,856 Idiosyncratic DILI and 14,029 HILI Cases Published 1993-Mid 2020: A Comprehensive Analysis. MEDICINES (BASEL, SWITZERLAND) 2020; 7:E62. [PMID: 33003400 PMCID: PMC7600114 DOI: 10.3390/medicines7100062] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/23/2020] [Accepted: 09/25/2020] [Indexed: 04/12/2023]
Abstract
Background: A large number of idiosyncratic drug induced liver injury (iDILI) and herb induced liver injury(HILI) cases of variable quality has been published but some are a matter of concern if the cases were not evaluated for causality using a robust causality assessment method (CAM) such as RUCAM (Roussel Uclaf Causality Assessment Method) as diagnostiinjuryc algorithm. The purpose of this analysis was to evaluate the worldwide use of RUCAM in iDILI and HILI cases. Methods: The PubMed database (1993-30 June 2020) was searched for articles by using the following key terms: Roussel Uclaf Causality Assessment Method; RUCAM; Idiosyncratic drug induced liver injury; iDILI; Herb induced liver injury; HILI. Results: Considering reports published worldwide since 1993, our analysis showed the use of RUCAM for causality assessment in 95,885 cases of liver injury including 81,856 cases of idiosyncratic DILI and 14,029 cases of HILI. Among the top countries providing RUCAM based DILI cases were, in decreasing order, China, the US, Germany, Korea, and Italy, with China, Korea, Germany, India, and the US as the top countries for HILI. Conclusion: Since 1993 RUCAM is certainly the most widely used method to assess causality in IDILI and HILI. This should encourage practitioner, experts, and regulatory agencies to use it in order to reinforce their diagnosis and to take sound decisions.
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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, D-60590 Frankfurt/Main, Germany
| | - Gaby Danan
- Pharmacovigilance Consultancy, F-75020 Paris, France;
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13
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Teschke R, Zhu Y, Jing J. Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases. J Clin Transl Hepatol 2020; 8:200-214. [PMID: 32832401 PMCID: PMC7438347 DOI: 10.14218/jcth.2020.00009] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/05/2020] [Accepted: 03/31/2020] [Indexed: 12/13/2022] Open
Abstract
Herb-induced liver injuries (HILI) by traditional herbal medicines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in worldwide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from mainland China, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, however, the following recommendations are given: (1) preference of prospective study design with use of the updated RUCAM version; (2) clear separation of HILI cohorts from those of other herbal products or DILI; (3) case series for epidemiology studies should contain many essential data, possibly also as supplementary material; (4) otherwise, preference of single case reports providing individual case data and RUCAM-based causality gradings, and applying liver test threshold values; and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.
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Affiliation(s)
- Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/ Main, Frankfurt/Main, Germany
- Correspondence to: Rolf Teschke, Department of Internal Medicine II, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Leimenstrasse 20, D-63450 Hanau, Germany. Tel: +49-6181-21859, Fax: +49-6181-2964211, E-mail:
| | - Yun Zhu
- The Fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Jing Jing
- The Fifth Medical Center, General Hospital of PLA, Beijing, China
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14
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Zhang Y, Gu L, Xia Q, Tian L, Qi J, Cao M. Radix Astragali and Radix Angelicae Sinensis in the Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-analysis. Front Pharmacol 2020; 11:415. [PMID: 32425767 PMCID: PMC7203419 DOI: 10.3389/fphar.2020.00415] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 03/18/2020] [Indexed: 02/02/2023] Open
Abstract
Introduction There are many clinical studies in the treatment of idiopathic pulmonary fibrosis (IPF) with herbal medicine including Astragalus mongholicus Bunge, Radix Astragali (RA) and Angelica sinensis (Oliv.) Diels, Radix Angelicae Sinensis (RAS). These have obtained good curative effect. There is no systematic evaluation on the clinical efficacy of RA and RAS in patients with IPF. The aim of this systematic review and meta-analysis was to critically evaluate the current evidence of efficacy and safety of RA and RAS in IPF. Methods We searched the primary database for randomized controlled trial (RCT) of RA and RAS treating IPF. We assessed the quality of included studies using the Jadad rating scale and referred to the Cochrane Reviewer's Handbook for guidelines to assess the risk of bias. We extracted the main outcomes of included RCTs and a meta-analysis was conducted using the Cochrane Collaboration's RevMan5.3 software. Results Seventeen eligible RCTs were identified and made a systematic review and meta-analysis. Risk of bias and quality of included RCTs were carried out. The results of meta-analysis showed that total effective rate and traditional Chinese medicine syndrome effective rate were statistically significantly higher in the experimental group than the control group, main pulmonary function index, six minute walking distance and Borg scale questionnaire score were statistically significantly better in the experimental group than the control group and incidence of adverse reactions was statistically significantly lower in the experimental group than the control group. Conclusion RA and RAS are effective and safe in the treatment of IPF, which is beneficial to pulmonary function and exercise tolerance of these patients.
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Affiliation(s)
- Yufeng Zhang
- Department of Respiratory Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, China.,Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Lina Gu
- Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Qingqing Xia
- Department of Respiratory Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, China
| | - Lijun Tian
- Department of Critical Care Medicine, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Jia Qi
- Department of Pharmacy, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengshu Cao
- Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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15
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Shin NR, Gu N, Choi HS, Kim H. Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation. Am J Physiol Endocrinol Metab 2020; 318:E52-E61. [PMID: 31770016 DOI: 10.1152/ajpendo.00221.2019] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.
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Affiliation(s)
- Na Rae Shin
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Siksa, Goyang, Gyeonggi-do, Republic of Korea
| | - Namyi Gu
- Department of Clinical Pharmacology and Therapeutics, Clinical Trial Center, Dongguk University College of Medicine and Ilsan Hospital, Siksa, Goyang, Gyeonggi-do, Republic of Korea
| | - Han Seok Choi
- Department of Endocrinology, Dongguk University, Dongguk-ro, Goyang, Gyeonggi-do, Republic of Korea
| | - Hojun Kim
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Siksa, Goyang, Gyeonggi-do, Republic of Korea
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16
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Philips CA, Augustine P, Rajesh S, Y PK, Madhu D. Complementary and Alternative Medicine-related Drug-induced Liver Injury in Asia. J Clin Transl Hepatol 2019; 7:263-274. [PMID: 31608219 PMCID: PMC6783675 DOI: 10.14218/jcth.2019.00024] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/12/2019] [Accepted: 08/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of complementary and alternative medicines (CAMs) for treatment of acute and chronic diseases is on the rise world over, especially in Asian countries, and mostly in China and India. Drug-induced liver injury (DILI) due to CAM is increasingly reported in the literature from multiple centers all around the world and with large-number patient series published from the West, mostly based on nation-wide DILI networks and multicenter collaboration. Comprehensive DILI networks are lacking among major Asian countries with high incidence of CAM practices. Chinese medical societies dealing with drug toxicity, CAM practice and hepatobiliary disease have adopted an integrated approach to establishing identification, diagnosis and treatment of CAM-related DILI, representing a systematic approach that could be iterated by other countries for improving patient outcomes. In this exhaustive review, we provide published data on CAM-related DILI in Asia, with detail on incidences along with analysis of patient population and their clinical outcomes. Concise and clear discussion on commonly implicated CAM agents in major Asian countries and associated chemical and toxicology analyses as well as descriptions of liver biopsy findings are discussed with future directions.
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Affiliation(s)
- Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, Kerala, India
| | - Philip Augustine
- Gastroenterology, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, Kerala, India
| | - Sasidharan Rajesh
- Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, Kerala, India
| | - Praveen Kumar Y
- Gastroenterology, Government Medical College, Thrissur, Kerala, India
| | - Deepak Madhu
- Gastroenterology, Aster MIMS, Calicut, Kerala, India
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17
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He S, Ye T, Wang R, Zhang C, Zhang X, Sun G, Sun X. An In Silico Model for Predicting Drug-Induced Hepatotoxicity. Int J Mol Sci 2019; 20:E1897. [PMID: 30999595 PMCID: PMC6515336 DOI: 10.3390/ijms20081897] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/09/2019] [Accepted: 04/15/2019] [Indexed: 01/10/2023] Open
Abstract
As one of the leading causes of drug failure in clinical trials, drug-induced liver injury (DILI) seriously impeded the development of new drugs. Assessing the DILI risk of drug candidates in advance has been considered as an effective strategy to decrease the rate of attrition in drug discovery. Recently, there have been continuous attempts in the prediction of DILI. However, it indeed remains a huge challenge to predict DILI successfully. There is an urgent need to develop a quantitative structure-activity relationship (QSAR) model for predicting DILI with satisfactory performance. In this work, we reported a high-quality QSAR model for predicting the DILI risk of xenobiotics by incorporating the use of eight effective classifiers and molecular descriptors provided by Marvin. In model development, a large-scale and diverse dataset consisting of 1254 compounds for DILI was built through a comprehensive literature retrieval. The optimal model was attained by an ensemble method, averaging the probabilities from eight classifiers, with accuracy (ACC) of 0.783, sensitivity (SE) of 0.818, specificity (SP) of 0.748, and area under the receiver operating characteristic curve (AUC) of 0.859. For further validation, three external test sets and a large negative dataset were utilized. Consequently, both the internal and external validation indicated that our model outperformed prior studies significantly. Data provided by the current study will also be a valuable source for modeling/data mining in the future.
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Affiliation(s)
- Shuaibing He
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Tianyuan Ye
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Ruiying Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Chenyang Zhang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Xuelian Zhang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Guibo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
| | - Xiaobo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
- Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
- Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China.
- Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China.
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18
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Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway. Acta Pharmacol Sin 2019; 40:75-85. [PMID: 29921882 DOI: 10.1038/s41401-018-0024-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 03/28/2018] [Indexed: 12/23/2022]
Abstract
Toosendanin (TSN) is the main active compound in Toosendan Fructus and Meliae Cortex, two commonly used traditional Chinese medicines. TSN has been reported to induce hepatotoxicity, but its mechanism remains unclear. In this study, we demonstrated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against TSN-induced hepatotoxicity in mice and human normal liver L-02 cells. In mice, administration of TSN (10 mg/kg)-induced acute liver injury evidenced by increased serum alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP) activities, and total bilirubin (TBiL) content as well as the histological changes. Furthermore, TSN markedly increased liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased liver glutathione (GSH) content and Nrf2 expression. In L-02 cells, TSN (2 μM) time-dependently reduced glutamate-cysteine ligase (GCL) activity and cellular expression of the catalytic/modify subunit of GCL (GCLC/GCLM). Moreover, TSN reduced cellular GSH content and the increased ROS formation, and time-dependently decreased Nrf2 expression and increased the expression of the Nrf2 inhibitor protein kelch-like ECH-associated protein-1 (Keap1). Pre-administration of quercetin (40, 80 mg/kg) effectively inhibited TSN-induced liver oxidative injury and reversed the decreased expression of Nrf2 and GCLC/GCLM in vivo and in vitro. In addition, the quercetin-provided protection against TSN-induced hepatotoxicity was diminished in Nrf2 knock-out mice. In conclusion, TSN decreases cellular GSH content by reducing Nrf2-mediated GCLC/GCLM expression via decreasing Nrf2 expression. Quercetin attenuates TSN-induced hepatotoxicity by inducing the Nrf2/GCL/GSH antioxidant signaling pathway. This study implies that inducing Nrf2 activation may be an effective strategy to prevent TSN-induced hepatotoxicity.
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19
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Wang X, Han L, Bi Y, Li C, Gao X, Fan G, Zhang Y. Paradoxical Effects of Emodin on ANIT-Induced Intrahepatic Cholestasis and Herb-Induced Hepatotoxicity in Mice. Toxicol Sci 2018; 168:264-278. [DOI: 10.1093/toxsci/kfy295] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Xue Wang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Lifeng Han
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yajuan Bi
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Caiyu Li
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Xiumei Gao
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Guanwei Fan
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Youcai Zhang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
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Lee H, Lee S, Kang JW, Lee JD. Liver enzyme abnormalities of inpatients with rheumatic diseases: A 10-year retrospective study in a Korean medicine hospital. Phytother Res 2018; 32:1784-1794. [DOI: 10.1002/ptr.6111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 04/11/2018] [Accepted: 04/14/2018] [Indexed: 02/05/2023]
Affiliation(s)
- Hyeonhoon Lee
- Department of Acupuncture and Moxibustion Medicine; Kyung Hee University Korean Medicine Hospital; 23 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
- Department of Clinical Korean Medicine, Graduate School; Kyung Hee University; 26 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
| | - Seunghoon Lee
- Department of Acupuncture and Moxibustion Medicine; Kyung Hee University Korean Medicine Hospital; 23 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
| | - Jung Won Kang
- Department of Acupuncture and Moxibustion Medicine; Kyung Hee University Korean Medicine Hospital; 23 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
- Department of Clinical Korean Medicine, Graduate School; Kyung Hee University; 26 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
| | - Jae-Dong Lee
- Department of Acupuncture and Moxibustion Medicine; Kyung Hee University Korean Medicine Hospital; 23 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
- Department of Clinical Korean Medicine, Graduate School; Kyung Hee University; 26 Kyungheedae-ro, Dongdaemun-gu Seoul 02447 Republic of Korea
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21
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Xu Y, Patel DN, Ng SLP, Tan SH, Toh D, Poh J, Lim AT, Chan CL, Low MY, Koh HL. Retrospective Study of Reported Adverse Events Due to Complementary Health Products in Singapore From 2010 to 2016. Front Med (Lausanne) 2018; 5:167. [PMID: 29946545 PMCID: PMC6006675 DOI: 10.3389/fmed.2018.00167] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 05/14/2018] [Indexed: 01/16/2023] Open
Abstract
The objective of this study is to collate and analyse adverse event reports associated with the use of complementary health products (CHP) submitted to the Health Sciences Authority (HSA) of Singapore for the period 2010-2016 to identify various trends and signals for pharmacovigilance purposes. A total of 147,215 adverse event reports suspected to be associated with pharmaceutical products and CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3%) were associated with chemical drugs, 1,807 (1.2%) with vaccines, 1,324 (0.9%) with biological drugs (biologics), and 893 (0.6%) with CHP. The number of adverse event reports associated with Chinese Proprietary Medicine, other complementary medicine and health supplements are presented. Eight hundred and ninety three adverse event reports associated with CHP in the 7-year period have been successfully collated and analyzed. In agreement with other studies, adverse events related to the "skin and appendages disorders" were the most commonly reported. Most of the cases involved dermal allergies (e.g., rashes) associated with the use of glucosamine products and most of the adulterated products were associated with the illegal addition of undeclared drugs for pain relief. Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants detected. Reporting suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The findings from this study help to create greater awareness on the health risks, albeit low, when consuming CHP and dispelling the common misconception that "natural" means "safe." In particular, healthcare professionals and the general public should be aware of potential adulteration of CHP. The analysis of spontaneously reported adverse events is an important surveillance system in monitoring the safety of CHP and helps in the understanding of the risk associated with the use of such products. Greater collaboration and communication between healthcare professionals, regulators, patients, manufacturers, researchers, and the general public are important to ensure the quality and safety of CHP.
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Affiliation(s)
- Yimin Xu
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
- Applied Sciences Group, Pharmaceutical Division, Health Sciences Authority, Singapore, Singapore
| | - Dhavalkumar N. Patel
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
| | - Suet-Leng P. Ng
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Siew-Har Tan
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Dorothy Toh
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Jalene Poh
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Adena Theen Lim
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Cheng-Leng Chan
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Min-Yong Low
- Applied Sciences Group, Pharmaceutical Division, Health Sciences Authority, Singapore, Singapore
| | - Hwee-Ling Koh
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
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Abuelgasim KA, Alsharhan Y, Alenzi T, Alhazzani A, Ali YZ, Jazieh AR. The use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in Saudi Arabia. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 18:88. [PMID: 29530034 PMCID: PMC5848536 DOI: 10.1186/s12906-018-2150-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 03/01/2018] [Indexed: 01/25/2023]
Abstract
BACKGROUND A significant proportion of cancer patients use complementary and alternative medicine (CAM) along with conventional therapies (CT), whereas a smaller proportion delay or defer CT in favor of CAM. Previous studies exploring CAM use among cancer patients in the Middle East region have shown discrepant results. This study investigates the prevalence and pattern of CAM use by Saudi cancer patients. It also discusses the possible benefits and harm related to CAM use by cancer patients, and it explores the beliefs patients hold and their transparency with health care providers regarding their CAM use. METHODS A cross-sectional study was conducted in oncology wards and outpatient clinics by using face-to-face interviews with the participants. RESULTS A total of 156 patients with a median age of 50 years (18-84) participated in the study. The prevalence of CAM use was 69.9%; the most prominent types of CAM were those of a religious nature, such as supplication (95.4%), Quran recitation (88.1%), consuming Zamzam water (84.4%), and water upon which the Quran has been read (63.3%). Drinking camel milk was reported by 24.1% of CAM users, whereas camel urine was consumed by 15.7%. A variety of reasons were given for CAM use: 75% reported that they were using CAM to treat cancer, enhance mood (18.3%),control pain (11.9%), enhance the immune system (11%),increase physical fitness (6.4%), and improve appetite (4.6%). Thirty percent of CAM users had discussed the issue with their doctors; only 7.7% had done so with their nurses. CONCLUSIONS The use of CAM, including camel products, is highly prevalent among cancer patients in the Middle East, but these patients do not necessarily divulge their CAM use to their treating physicians and nurses. Although CAM use can be beneficial, some can be very harmful, especially for cancer patients. Association is known between camel products and brucellosis and Middle East respiratory syndrome coronavirus (MERS-CoV). Both can lead to tremendous morbidity in immune-compromised patients. Doctor-patient communication regarding CAM use is of paramount importance in cancer care.
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Affiliation(s)
- Khadega A. Abuelgasim
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Oncology, Ministry of National Guards, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Yousef Alsharhan
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Tariq Alenzi
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdulaziz Alhazzani
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Yosra Z. Ali
- Department of Oncology, Ministry of National Guards, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Abdul Rahman Jazieh
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Oncology, Ministry of National Guards, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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Chan CL, Ang PS, Li SC. A Survey on Pharmacovigilance Activities in ASEAN and Selected Non-ASEAN Countries, and the Use of Quantitative Signal Detection Algorithms. Drug Saf 2018; 40:517-530. [PMID: 28247278 DOI: 10.1007/s40264-017-0510-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Most Countries have pharmacovigilance (PV) systems in place to monitor the safe use of health products. The process involves the detection and assessment of safety issues from various sources of information, communicating the risk to stakeholders and taking other relevant risk minimization measures. OBJECTIVES This study aimed to assess the PV status in Association of Southeast Asian Nation (ASEAN) countries, sources for postmarket safety monitoring, methods used for signal detection and the need for a quantitative signal detection algorithm (QSDA). Comparisons were conducted with centres outside ASEAN. METHODS A questionnaire was sent to all PV centres in ASEAN countries, as well as seven other countries, from November 2015 to June 2016. The questionnaire was designed to collect information on the status of PV, with a focus on the use of a QSDA. RESULTS Data were collected from nine ASEAN countries and seven other countries. PV activities were conducted in all these countries, which were at different stages of development. In terms of adverse drug reaction (ADR) reports, the average number received per year ranged from 3 to 50,000 reports for ASEAN countries and from 7000 to 1,103,200 for non-ASEAN countries. Thirty-three percent of ASEAN countries utilized statistical methods to help detect signals from ADR reports compared with 100% in the other non-ASEAN countries. Eighty percent agreed that the development of a QSDA would help in drug signal detection. The main limitation identified was the lack of knowledge and/or lack of resources. CONCLUSION Spontaneous ADR reports from healthcare professionals remains the most frequently used source for safety monitoring. The traditional method of case-by-case review of ADR reports prevailed for signal detection in ASEAN countries. As the reports continue to grow, the development of a QSDA would be useful in helping detect safety signals.
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Affiliation(s)
- Cheng Leng Chan
- Health Products Regulation Group, Health Sciences Authority, 11 Biopolis Way #11-01 Helios, Singapore, 138667, Singapore. .,School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
| | - Pei San Ang
- Health Products Regulation Group, Health Sciences Authority, 11 Biopolis Way #11-01 Helios, Singapore, 138667, Singapore
| | - Shu Chuen Li
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
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Liver Injury from Herbs and “Dietary Supplements”: Highlights of a Literature Review from 2015 to 2017. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/s40495-018-0124-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Zhao P, Liu B, Wang C. Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model. Clin Toxicol (Phila) 2017; 55:996-1000. [PMID: 28594241 DOI: 10.1080/15563650.2017.1333123] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 05/17/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. OBJECTIVE This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. METHODS A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB). RESULTS Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins. CONCLUSIONS Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established.
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Affiliation(s)
- Pan Zhao
- a Clinical Trial Center , Beijing 302 Hospital , Beijing , China
- b Liver Failure Therapy and Research Center, Beijing 302 Hospital , Beijing , China
| | - Bin Liu
- c Computer Technology Center, Beijing 302 Hospital , Beijing , China
| | - Chunya Wang
- d Emergency & Critical Care Center , Beijing Anzhen Hospital, Capital Medical University , Beijing , China
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26
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Melchart D, Hager S, Albrecht S, Dai J, Weidenhammer W, Teschke R. Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study. World J Hepatol 2017; 9:1141-1157. [PMID: 29085558 PMCID: PMC5648988 DOI: 10.4254/wjh.v9.i29.1141] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Revised: 07/21/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine (TCM) in order to evaluate the frequency of newly detected liver injury.
METHODS Patients with normal values of alanine aminotransferase (ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method (RUCAM) was used.
RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and large-scale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal (ULN) in 844 patients (3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients (0.12%) experienced higher ALT values of ≥ 5 × ULN (300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated.
CONCLUSION In 26 (0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.
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Affiliation(s)
- Dieter Melchart
- Institute for Complementary and Integrative Medicine, University Hospital Zurich and University of Zurich, CH-8091 Zurich, Switzerland
- Competence Centre for Complementary Medicine and Naturopathy (CoCoNat), University Hospital Munich rechts der Isar, Technical University of Munich, D-80801 Munich, Germany
| | - Stefan Hager
- Hospital for Traditional Chinese Medicine, D-93444 Bad Kötzting, Germany
| | - Sabine Albrecht
- Hospital for Traditional Chinese Medicine, D-93444 Bad Kötzting, Germany
| | - Jingzhang Dai
- Hospital for Traditional Chinese Medicine, D-93444 Bad Kötzting, Germany
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Wolfgang Weidenhammer
- Competence Centre for Complementary Medicine and Naturopathy (CoCoNat), University Hospital Munich rechts der Isar, Technical University of Munich, D-80801 Munich, Germany
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty of the Goethe University, D-63450 Hanau, Frankfurt/Main, Germany
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Serum microRNA-122-3p, microRNA-194-5p and microRNA-5099 are potential toxicological biomarkers for the hepatotoxicity induced by Airpotato yam. Toxicol Lett 2017; 280:125-132. [DOI: 10.1016/j.toxlet.2017.08.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/15/2017] [Accepted: 08/20/2017] [Indexed: 12/12/2022]
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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: 96] [Impact Index Per Article: 12.0] [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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Wang Z, Wang X, Zhu J, Cheng F, Yao H, Yang Z, Zhang Z, Wang Q. Qingre Lishi Tuihuang therapy for acute icteric hepatitis B: A systematic review. JOURNAL OF TRADITIONAL CHINESE MEDICAL SCIENCES 2017. [DOI: 10.1016/j.jtcms.2017.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Zhang Y, Han L, He Q, Chen W, Sun C, Wang X, Chen X, Wang R, Hsiao CD, Liu K. A rapid assessment for predicting drug-induced hepatotoxicity using zebrafish. J Pharmacol Toxicol Methods 2017; 84:102-110. [DOI: 10.1016/j.vascn.2016.12.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 11/09/2016] [Accepted: 12/06/2016] [Indexed: 12/12/2022]
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Takahashi K, Kanda T, Yasui S, Haga Y, Kumagai J, Sasaki R, Wu S, Nakamoto S, Nakamura M, Arai M, Yokosuka O. Drug-Induced Liver Injury Associated with Complementary and Alternative Medicines. Case Rep Gastroenterol 2016; 10:706-713. [PMID: 28100990 PMCID: PMC5216216 DOI: 10.1159/000452209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 10/03/2016] [Indexed: 11/19/2022] Open
Abstract
A 24-year-old man was admitted due to acute hepatitis with unknown etiology. After his condition and laboratory data gradually improved with conservative therapy, he was discharged 1 month later. Two months after his discharge, however, liver dysfunction reappeared. After his mother accidentally revealed that he took complementary and alternative medicine, discontinuation of the therapy caused his condition to improve. Finally, he was diagnosed with a recurrent drug-induced liver injury associated with Japanese complementary and alternative medicine. It is important to take the medical history in detail and consider complementary and alternative medicine as a cause of liver disease.
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Affiliation(s)
- Koji Takahashi
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Yuki Haga
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Junichiro Kumagai
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Reina Sasaki
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
- Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
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