Liver injury induced by a Japanese herbal medicine, sairei‐to (TJ‐114, Bupleurum and Hoelen Combination, Chai‐Ling‐Tang) R1

Aiba, Tsuneo; Takahashi, Toru; Suzuki, Kenji; Okoshi, Shogo; Nomoto, Minoru; Uno, Katsuji; Aoyagi, Yoshinobu

doi:10.1111/j.1440-1746.2006.03373.x

Cited by 22 publications

(10 citation statements)

References 5 publications

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“…Chai Ling Tang), which is included in a blend of two TCM products, Xiao Chai Hu Tang and Wu Ling San Wan, and experienced liver injury [166,167]. Among the Sairei To ingredients are Alisma , Atractylis , Bupleurum , Cinnamomum , Ginseng , Glycyrrhiza , Pinellia , Polyporus , Poria , Scutellaria , Zingiber and Zizyphus .…”

Section: Narratives Of Tcm Hili Casesmentioning

confidence: 99%

“…Among the Sairei To ingredients are Alisma , Atractylis , Bupleurum , Cinnamomum , Ginseng , Glycyrrhiza , Pinellia , Polyporus , Poria , Scutellaria , Zingiber and Zizyphus . Several possible offending agents are considered, including Pinellia ternate [166] and other components of Sairei To [167]. …”

Section: Narratives Of Tcm Hili Casesmentioning

confidence: 99%

“…Among these are incorrect reporting [163], comedication [162], preexisting infections by viral hepatitis [162], water or acetone based products [162,163,219], and the use of raw or processed Polygonum multiflorum , whereby processing is achieved by boiling of the reddish roots with black beans [162,163,218]. Consensus exists that both raw and processed Polygonum multiflorum can cause liver injury in humans [165,166]. For raw Polygonum multiflorum applied to mice, the liver injury of water decocta was considerably more pronounced than that of the acetone extract; meanwhile, the hepatotoxicity of the acetone extract of raw Polygonum multiflorum was much higher as compared to the acetone extract of the processed Polygonum multiflorum [218].…”

Section: Pathogenetic Aspects Of Liver Injury From Herbal Tcmmentioning

confidence: 99%

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Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs

et al. 2016

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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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Section: Narratives Of Tcm Hili Casesmentioning

confidence: 99%

Section: Narratives Of Tcm Hili Casesmentioning

confidence: 99%

Section: Pathogenetic Aspects Of Liver Injury From Herbal Tcmmentioning

confidence: 99%

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Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs

et al. 2016

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“…It has also been reported that Saireito occasionally causes side effects such as immunodeficiency, gastro-duodenal ulcer and osteoporosis that are often associated with long-term administration of corticosteroids 55 . Drug-induced pneumonitis and drug-induced acute hepatitis have been also reported with Saireito treatment 56,57 . However, the side effects of these TCHM are usually underreported in clinical trials.…”

Section: Introductionmentioning

confidence: 92%

Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases

Zhong

Deng

Chen

et al. 2013

Kidney International

148

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Traditional Chinese herbal medications (TCHM) are frequently used in conjunction with western pharmacotherapy for treatment of chronic kidney diseases (CKD) in China and many other Asian countries. The practice of traditional Chinese medicine is guided by cumulative empiric experience. Recent in vitro and animal studies have confirmed the biological activity and therapeutic effects of several TCHM in CKD. However, the level of evidence supporting TCHM is limited to small, non-randomized trials. Due to variations in the prescription pattern of TCHM and the need for frequent dosage adjustment, which are inherent to the practice of traditional Chinese medicine, it has been challenging to design and implement large randomized clinical trials of TCHM. Several TCHM are associated with significant adverse effects, including nephrotoxicity. However, reporting of adverse effects associated with TCHM has been inadequate. To fully realize the therapeutic use of TCHM in CKD we need molecular studies to identify active ingredients of TCHM and their mechanism of action, rigorous pharmacologic studies to determine the safety and meet regulatory standards required for clinical therapeutic agents, and well-designed clinical trials to provide evidence-based support of their safety and efficacy.

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“…According to the Chinese pharmacopoeia, the clinical safe dosage of RB prescriptions ranged from 3 g/day to 10 g/day, based on 70 kg body weight. However, based on accumulating evidence, RB probably contributes to hepatotoxicity, particularly overdose-induced acute liver injury and accumulation-related hepatotoxicity [8–11]. Patients using Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang or Chinese herbal products containing more than 19 g of RB might were recently shown to have an increased risks of liver injury [3].…”

Section: Introductionmentioning

confidence: 99%

Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study

et al. 2017

BMC Complement Altern Med

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BackgroundRadix 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.MethodsSerum 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.ResultsSS 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.ConclusionOur 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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Liver injury induced by a Japanese herbal medicine, sairei‐to (TJ‐114, Bupleurum and Hoelen Combination, Chai‐Ling‐Tang) R1

Cited by 22 publications

References 5 publications

Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs

Traditional Chinese Medicine (TCM) and Herbal Hepatotoxicity: RUCAM and the Role of Novel Diagnostic Biomarkers Such as MicroRNAs

Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases

Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study

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