Cucurbitacin IIb mitigates concanavalin A-induced acute liver injury by suppressing M1 macrophage polarization.

Cucurbitacins are a class of triterpenoid compounds extracted from plants and possess various pharmacological applications. Cucurbitacin IIb (CuIIb), extracted from the medicinal plant Hemsleya amabilis (Cucurbitaceae), has served as a traditional Chinese medicine for the treatment of bacterial dysentery and intestinal inflammation. CuIIb has been shown to exhibit anti-inflammatory activity; however, the protective effect of CuIIb against concanavalin A (Con A)-induced acute liver injury (ALI) and the fundamental mechanism remain unelucidated. In this study, we established an acute liver injury mouse model using Con A to investigate the effects of CuIIb on ALI. The results revealed that CuIIb significantly reduced serum aminotransferase levels and increased the survival rate of mice. Additionally, CuIIb effectively attenuated hepatocyte apoptosis, hepatic histopathological damage, and oxidative stress. Notably, CuIIb inhibited the polarization of M1 macrophages in vivo and in vitro. Moreover, the expression levels of pro-inflammatory cytokines related to M1 macrophages, such as interleukin (IL)-12, IL-1β, IL-6 and tumor necrosis factor-α (TNF-α), were reduced. CuIIb regulated M1 macrophage activation by modulating the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Conclusively, these results demonstrated that CuIIb significantly prevented Con A-induced ALI by suppressing M1 macrophage polarization via the MAPK and NF-κB signaling pathways, demonstrating the potential use of CuIIb for ALI treatment.