Ginsenoside Rg1 ameliorates aging-induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice

Aging is often accompanied by liver injury and fibrosis, eventually leading to the decline in liver function. However, the mechanism of aging-induced liver injury and fibrosis is still not fully understood, to the best of our knowledge, and there are currently no effective treatment options available for liver aging. Ginsenoside Rg1 (Rg1) has been reported to exert potent anti-aging effects due to its potential antioxidant and anti-inflammatory activity. The present study aimed to investigate the protective effect and underlying mechanism of action of Rg1 in aging-induced liver injury and fibrosis in senescence-accelerated mouse prone 8 (SAMP8) mice treated for 9 weeks. The histopathological results showed that the arrangement of hepatocytes was disordered, vacuole-like degeneration occurred in the majority of cells, and collagen IV and TGF-beta 1 expression levels, that were detected via immunohistochemistry, were also significantly upregulated in the SAMP8 group. Rg1 treatment markedly improved aging-induced liver injury and fibrosis, and significantly downregulated the expression levels of collagen IV and TGF-beta 1. In addition, the dihydroethylene staining and western blotting results showed that Rg1 treatment significantly reduced the levels of reactive oxygen species (ROS) and IL-1 beta, and downregulated the expression levels of NADPH oxidase 4 (NOX4), p47phox, p22phox, phosphorylated-NF-kappa B, caspase-1, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain and the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which were significantly upregulated in the liver tissues of elderly SAMP8 mice. In conclusion, the findings of the present study suggested that Rg1 may attenuate aging-induced liver injury and fibrosis by reducing NOX4-mediated ROS oxidative stress and inhibiting NLRP3 inflammasome activation.

Automated summary

The study demonstrated that Ginsenoside Rg1 (Rg1) can significantly improve aging-induced liver injury and fibrosis, reduce the expression levels of collagen IV and TGF-beta 1, and potentially alleviate liver damage by reducing NOX4-mediated ROS oxidative stress and inhibiting NLRP3 inflammasome activation.