Abstract
Hepatotoxicity induced by medicinal herb Polygonum multiflorum Thunb. attracts wide attention in the world recently. 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. This study aims to observe TSG-provided the aggravation on acetaminophen (APAP)-induced hepatotoxicity in mice by inducing hepatic expression of cytochrome P450 (CYP450) enzymes. Serum alanine/aspartate aminotransferase (ALT/AST) analysis and liver histological evaluation showed that TSG (200, 400, 800 mg/kg) exacerbated the hepatotoxicity induced by sub-toxic dose of APAP (200 mg/kg) in mice, but TSG alone had no hepatotoxicity. TSG aggravated hepatic reduced glutathione (GSH) depletion and APAP-cysteine adducts (APAP-CYS) formation induced by APAP in mice. TSG increased the expression of CYP2E1, CYP3A4 and CYP1A2 both in mice and in human normal liver L-02 hepatocytes. TSG also enhanced liver catalytic activity of CYP2E1, CYP3A4 and CYP1A2 in mice. TSG induced the nuclear translocation of aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR), and TSG-provided the aggravation on APAP-induced hepatotoxicity in mice was reversed by PXR or AHR inhibitors. In summary, our results demonstrate that TSG enhances hepatic expression of CYP3A4, CYP2E1 and CYP1A2, and thus exacerbates the hepatotoxicity induced by APAP in mice. PXR and AHR both play some important roles in this process.
Highlights
Medicinal herb Polygonum multiflorum Thunb. is one of the most commonly used traditional Chinese medicines (TCMs) for restoring grey hair and anti-aging, removing toxicity for eliminating carbuncles, nourishing the liver and kidney, and it is widely used as tonic functional foods[5,6]
2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. with high content, and it is a chemical marker used by the Chinese Pharmacopoeia for evaluating the quality of Polygonum multiflorum Thunb.[5]
After mice were pre-treated with different doses of TSG (100, 200, 400, 800 mg/kg) for 12 h, TSG dose-dependently exacerbated APAP-induced liver injury evidenced by markedly increased serum ALT and AST activities (Fig. 1B)
Summary
Medicinal herb Polygonum multiflorum Thunb. is one of the most commonly used traditional Chinese medicines (TCMs) for restoring grey hair and anti-aging, removing toxicity for eliminating carbuncles, nourishing the liver and kidney, and it is widely used as tonic functional foods[5,6]. A growing number of clinical studies have shown the linkage of Polygonum multiflorum Thunb.-containing herbal products with hepatotoxicity, but the toxicological www.nature.com/scientificreports/. It can be seen that the hepatotoxicity induced by Polygonum multiflorum Thunb. A clinical report showed that only 15 cases (accounting for 9.5% of all suspected 158 cases of hepatotoxicity) were caused by the ingestion of Polygonum multiflorum Thunb. Herb-drug interactions may be a breakthrough point to study the hepatotoxicity induced by Polygonum multiflorum Thunb. N-acetyl p-benzoquinoneimine (NAPQI), a hepatotoxic metabolite of APAP, is metabolized by CYP450 enzymes in livers, isoforms such as CYP2E1, CYP3A4 and CYP1A217,18. 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. The aggravation of TSG on APAP-induced liver injury by inducing hepatic expression of CYP2E1, CYP3A4 and CYP1A2 was investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
