| Summary: | 博士 === 長庚大學 === 臨床醫學研究所 === 105 === Drug-induced liver injury can cause severe hepatotoxicity. Acetaminophen (APAP) is one of the most commonly used antipyretic and analgesic drug in many countries. However, its overdose has become a prevalent cause of acute liver failure. Scutellariae radix is an important herb used in traditional medicine. The flavonoid extracts of scutellariae radix showed anti-allergic, antioxidant, anti-inflammatory, and anti-cancer characteristics. Therefore, the aim of this study was to investigate the hepatoprotective properties and action mechanisms of baicalin (BA), a major flavonoid of scutellariae radix, in a mouse model exhibiting APAP-induced liver injury.
In the present study, our data showed that APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose-dependent manner (15–60 mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30 mg/kg. BA treatment at 30mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-α and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. These results collectively suggested that the protective effects of BA on APAP-induced hepatotoxicity in mice seem to be associated with anti-inflammatory mechanisms and may be mediated through ERK pathways.
Our results also demonstrated that APAP overdose significantly increased the malondialdehyde (MDA) activity when compared with the control animals. BA treatment after APAP administration significantly attenuated the elevation of this parameter in APAP-induced liver injury mice. In addition, BA treatment could decrease hepatic IL-17 expression and IL-17-producing γδT cells recruitment, which was induced after APAP overdose. These findings collectively implied that IL-17 contributes to the hepatoprotective effects of BA.
In conclusion, our study demonstrated that BA administration could effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and reducing its downstream effectors of inflammatory responses. In addition, BA treatment could suppress accumulation of γδT cells and exert hepatoprotective effects via attenuation of IL-17-mediated inflammation. It could effectively decrease APAP-induced liver injury in part by inhibition of hepatic IL-17 expression and its effectors, including inflammatory markers and neutrophils infiltration. Taken together, these findings indicated that BA may potentially develop as a hepatoprotective drug and can be considered as a promising therapeutic agent for APAP-induced liver injury in humans.
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