stilbenes and Chemical-and-Drug-Induced-Liver-Injury--Chronic

Traditional Chinese medicine Heshouwu, named Polygoni Multiflori Radix in Pharmacopoeia of the People's Republic of China (PPRC, 2020), is derived from the root tuber of Polygonum multiflorum Thunb., Heshouwu or processed Heshouwu is well known for its function in reducing lipids and nourishing the liver. However, increasing cases of Heshouwu-induced hepatotoxicity were reported in recent years. Researchers have begun to study the paradoxical effects of Heshouwu on the liver. 2,3,5,4'-tetrahydroxystilbene-2-

Topics: Animals; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Medicine, Chinese Traditional; Rats; Stilbenes

Herb-induced liver injury results from the interplay between the herb and host with the herbal components serving as the major origin for hepatotoxicity. Although Polygoni Multiflori Radix (PMR) has been frequently reported to induce liver injury, contributions of its major components such as emodin, emodin-8-O-β-D-glucopyranoside, physcion and 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) towards its hepatotoxicity have not been clearly identified. Our initial cytotoxicity screenings of the major PMR components using rat hepatocytes identified emodin as the most toxic. Subsequently, the bile acid homeostasis-related mechanisms of emodin and its combination treatment with TSG in PMR-associated liver injury were explored in sandwich-cultured rat hepatocytes (SCRH) and verified in rats. In SCRH, emodin was found to be able to induce total bile acid accumulation in a dose-dependent manner. In both SCRH and rats, the presence of TSG significantly enhanced the hepatotoxicity of emodin via i) increasing its hepatic exposure by inhibiting its glucuronidation mediated metabolism; ii) enhancing its disruption on bile acid homeostasis through amplifying its inhibition on bile acid efflux transporters and its up-regulation on bile acids synthesis enzymes; iii) enhancing its apoptosis. Our study for the first time demonstrated the critical role of the combination treatment with emodin and TSG in PMR-induced liver injury.

Topics: Animals; Bile Acids and Salts; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Drug-Related Side Effects and Adverse Reactions; Emodin; Glucosides; Rats; Stilbenes

A novel pro-phytomicelle formulation with small molecule phytochemicals as nanomaterials was developed for the oral delivery of pterostilbene (PTE) in our previous work. The present report was designed to preclinically evaluate the

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury, Chronic; Cytokines; HMGB1 Protein; Liver; Mice; Rats; Stilbenes; Treatment Outcome

Resveratrol, a phytoalexin found in grapes and red wines, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of resveratrol on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Oral administration of resveratrol (20 mg/kg daily for 4 weeks) remarkably prevented the DMN-induced loss in body and liver weight, and inhibited the elevation of serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Resveratrol also increased serum albumin and hepatic glutathione levels and reduced the hepatic level of malondialdehyde due to its antioxidant effect. Furthermore, DMN-induced elevation of hydroxyproline content was reduced in the resveratrol treated rats, the result of which was consistent with the reduction in type I collagen mRNA expression and the histological analysis of liver tissue stained with Sirius red. The reduction in hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining, and the reduction in transforming growth factor-beta1 mRNA expression were associated with resveratrol treatment. In conclusion, resveratrol exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that resveratrol may be useful in the prevention of the development of hepatic fibrosis.

Topics: Alkylating Agents; Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury, Chronic; Dimethylnitrosamine; Down-Regulation; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Male; Organ Size; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Resveratrol; RNA, Messenger; Stilbenes; Transforming Growth Factor beta1; Weight Loss