The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury

Rao, Tai; Liu, Yating; Zeng, Xiangchang; Li, Chaopeng; Ouyang, Dongsheng

doi:10.1038/s41401-020-0360-3

Cited by 38 publications

(26 citation statements)

References 112 publications

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“…Given that most people taking PM products at the recommended therapeutic dose do not develop liver injury, the intake of direct toxic components may not be sufficient to damage the liver but instead only initiates very mild hepatic cell stress, which can be resisted by the tissue regeneration, repair or antistress systems that maintain the normal structure and functions of hepatocytes exposed to low concentrations of toxic components [ 18 ]. In this study, direct administration of PME, different elution fractions of PME and TSG did not induce any significant pathological changes, which is consistent with the previous study [ 18 ]. Cotreatment with LPS at a nontoxic dose and PM at the clinically equivalent dose causes obvious liver injury in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

Lin

Xiao

Xia

et al. 2021

BMC Complement Med Ther

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Background The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury. Methods Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites. Results The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism. Conclusions These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

Lin

Xiao

Xia

et al. 2021

BMC Complement Med Ther

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“…Growing evidences have revealed that individuals carrying certain class I and II HLA alleles are at increased risk of DILI (Kindmark et al, 2008;Daly et al, 2009;Singer et al, 2010;Lucena et al, 2011;Spraggs et al, 2011;Nicoletti et al, 2016;Parham et al, 2016;Nicoletti et al, 2017;Urban et al, 2017;Kaliyaperumal et al, 2018;Nicoletti et al, 2019). Despite the strong association with HLA, the positive predictive value of HLA allele polymorphisms in drug-induced adverse reactions is limited (Rao et al, 2020). These results suggest that there are other factors, other than the HLA allele, that contribute to the progression of IDILI.…”

Section: Human Leukocyte Antigen Polymorphismsmentioning

confidence: 99%

The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury

et al. 2021

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Drug-induced liver injury (DILI) has become one of the major challenges of drug safety all over the word. So far, about 1,100 commonly used drugs including the medications used regularly, herbal and/or dietary supplements, have been reported to induce liver injury. Moreover, DILI is the main cause of the interruption of new drugs development and drugs withdrawn from the pharmaceutical market. Acute DILI may evolve into chronic DILI or even worse, commonly lead to life-threatening acute liver failure in Western countries. It is generally considered to have a close relationship to genetic factors, environmental risk factors, and host immunity, through the drug itself or its metabolites, leading to a series of cellular events, such as haptenization and immune response activation. Despite many researches on DILI, the specific biomarkers about it are not applicable to clinical diagnosis, which still relies on the exclusion of other causes of liver disease in clinical practice as before. Additionally, circumstantial evidence has suggested that DILI is mediated by the immune system. Here, we review the underlying mechanisms of the immune response to DILI and provide guidance for the future development of biomarkers for the early detection, prediction, and diagnosis of DILI.

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“…Several cases of liver injury associated with Polygonum multiflorum Thumb. have been reported, and it seems that both immunity and HLA-B*35:01 gene polymorphisms are involved (Rao, Liu, Zeng, Li, & Ou-Yang, 2020).…”

Section: Hepatic Reactionsmentioning

confidence: 99%

Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system

Ippoliti

Menniti‐Ippolito

Mazzanti

et al. 2021

Phytotherapy Research

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Herbal tonic and adaptogens are often used to improve overall well-being. However, few clinical evidence supports their use and their safety is not known before marketing. In this context, the aim of our study was to analyze the spontaneous reports of suspected adverse reactions (ARs) to performance enhancing herbal dietary supplements collected by the Italian Phytovigilance System. Between March 2002 and September 2020, 110 spontaneous reports were collected, 58 of which related to products containing botanicals, alone or in association. Twenty-three serious reactions were reported, 21 of which required hospitalization, one was life-threatening and another caused disability. Dermatological and cardiovascular reactions were the most frequent. Hepatic ARs were the most serious (9 out of 10). A positive dechallenge was indicated in 69% of cases, while a positive rechallenge occurred in 15%. Concomitant use of other products was present in 18 reports (31%), while predisposing conditions were indicated in 17 (29%). Present data highlight safety concerns on herbal dietary supplements used as cognitive and physical performance enhancers, mainly due to their quality and use without expert supervision. Considering that postmarketing surveillance is not required for these products, spontaneous reports represent the only tool to point out risks related to food supplements.

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The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury

Cited by 38 publications

References 112 publications

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury

Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system

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