Hepatotoxicity of Tripterygium wilfordii after ganoderma solid fermentation and its effect on expression of Nrf2 in rats / 中草药

ABSTRACT

Objective: To investigate the hepatotoxicity of Tripterygium wilfordii after ganoderma solid fermentation product-Ling-Lei fermentation substance. Methods: SD rats were randomly separated into three groups control (C), Ling-lei fermentation substance (LF), and T. wilfordii (TW) groups. SD rats in LF and TW groups were ig administered with 95% ethanol extract of Ling-lei fermentation substance and T. wilfordii at the doses of 2.037 5 and 0.64 g/kg, respectively once a day for consecutive 30 d. After administration, the blood biochemical index and liver histopathological examination were determined. The expression levels of Nrf2 and P38 protein in liver tissue were tested by Western blotting. Results: The liver histopathological examination revealed that rats in LF group showed the central cells necrosis in liver tissue only, the local cytoplasm dissolved in peripheral cells, and the apoptosis appeared. Rats in TW group showed the small necrosis, nuclear apoptosis, obvious collagen fibers in liver cells, and cells dissolved the necrosis. Compared with C group, content of alanine aminotransferase (ALT), expression levels of nucleoprotein Nrf2 and P38 protein of rats in LF and TW groups increased, while these indicators in LF group decreased obviously compared with TW group (P < 0.05). The levels of albumin (ALB) and total protein (TP) in LF and TW groups decreased compared with C group (P < 0.05), while ALB and TP in LF group decreased significantly compared with TW group (P < 0.05). Conclusion: The hepatotoxicity of Ling-lei fermentation substance is lower than that of T. Wilfordii, and its toxic mechanism may be associated with anti-oxidation initiated by activating the P38 MARK and the Nrf2-ARE signaling pathways.