[Tanshinone IIA protects against triptolide-induced liver injury via Nrf2/ARE activation]
Cui-wen Guan1, Jing Jin1, Jia Li1
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Abstract:
The aim of this study is to investigate the protection effect of tanshinone IIA (Tan) against triptolide (TP)-induced liver injury and the mechanisms involved. Acute liver injury was induced by intraperitoneal injection of TP (1 mg x kg(-1)) in mice. The activities of AST, ALT and LDH in serum and the levels of GSH, GST, GSH-PX, SOD, CAT and MDA in liver tissue were detected. The histopathological changes of liver tissues were observed after HE staining. Nrf2 translocation in liver tissue was detected by Western blotting, and real-time PCR was used to measure the expression levels of GCLC, NQO1 and HO-1 mRNA. The results showed that pretreatment with Tan significantly prevented the TP induced liver injury as indicated by reducing the activities of AST, ALT and LDH (P < 0.01). Tan pretreatment also prevented TP-induced oxidative stress in the mice liver by inhibiting MDA and restoring the levels of GSH, GST, SOD and CAT (P < 0.05). Parallel to these changes, pretreatment with Tan could attenuate histopathologic changes induced by TP. Furthermore, the results indicated that Tan pretreatment caused nuclear accumulation of Nrf2 as well as induction of mRNA expression of antioxidant response element (ARE)-driven genes such as GCLC, NQO1 and HO-1. These results indicated that Tan could protect against TP-induced acute liver injury via the activation of Nrf2/ARE pathway.
Insights
Tanshinone IIA protects against triptolide-induced liver injury by reducing oxidative stress and inflammation. This protection is mediated through the activation of the Nrf2/ARE pathway, highlighting a potential therapeutic strategy for liver damage.
Area of Science:
- Hepatology
- Toxicology
- Pharmacology
Background:
- Triptolide (TP) is a compound known to induce acute liver injury.
- Oxidative stress and inflammation are key mechanisms in TP-induced hepatotoxicity.
- Tanshinone IIA (Tan) is a potential therapeutic agent with antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of Tanshinone IIA against triptolide-induced liver injury in mice.
- To elucidate the underlying mechanisms, particularly the role of the Nrf2/ARE pathway.
Main Methods:
- Acute liver injury was induced in mice using triptolide.
- Biochemical markers (AST, ALT, LDH, GSH, MDA) and antioxidant enzyme activities (GSH-PX, SOD, CAT) were measured.
- Histopathological analysis, Western blotting for Nrf2 translocation, and real-time PCR for ARE-driven genes (GCLC, NQO1, HO-1) were performed.
Main Results:
- Tanshinone IIA pretreatment significantly reduced liver injury markers (AST, ALT, LDH) and inhibited oxidative stress (decreased MDA, restored GSH and antioxidant enzymes).
- Histopathological examination showed attenuated liver damage in Tan-pretreated mice.
- Tan treatment led to nuclear accumulation of Nrf2 and increased expression of Nrf2/ARE target genes (GCLC, NQO1, HO-1).
Conclusions:
- Tanshinone IIA demonstrates significant hepatoprotective effects against triptolide-induced acute liver injury.
- The protective mechanism involves the activation of the Nrf2/ARE signaling pathway, enhancing the cellular antioxidant defense system.
- Tanshinone IIA represents a promising therapeutic candidate for managing drug-induced liver injury.
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