Gardenia jasminoides fruit extract ameliorates non-alcoholic steatohepatitis with fibrosis by modulating inflammatory and fibrogenic pathways

Despite advances in drug development, treatment for non-alcoholic steatohepatitis (NASH)-related liver fibrosis remains limited, underscoring the need for more effective therapeutic strategies. Gardenia jasminoides exhibits promising anti-inflammatory and anti-fibrotic properties, suggesting its potential as a therapeutic candidate for NASH-related liver fibrosis. Accordingly, this study aimed to investigate the therapeutic potential of Gardenia jasminoides fruit extract (GJE) in a rat model of NASH with fibrosis induced by a high-fat, high-fructose (HFHF) diet, and to elucidate the underlying molecular mechanisms. Male Sprague-Dawley rats were randomly assigned to four groups (n = 6/group): 1) Control group, fed a standard diet; 2) NASH with fibrosis group (NF), fed a HFHF diet for 20 weeks; 3) Low-dose GJE group (NF + Low dose GJE), treated with 0.119 g/kg BW of GJE; and 4) High-dose GJE group (NF+High dose GJE), treated with 0.239 g/kg BW of GJE. GJE was administered via intragastric gavage once daily from weeks 13-20. Serum markers of liver injury (ALT and AST) were assessed. Liver histology was examined to evaluate NASH and fibrosis severity. Immunohistochemistry was performed to detect NF-kB p65 and Col1a1 expression and protein levels of MMP-12, α-SMA, IL-13 and TGF-β1 were quantified. Serum ALT and AST levels were significantly increased in the NF group, which also showed the highest NASH histopathology scores and collagen deposition. GJE treatment significantly reduced ALT and AST levels in both low- and high- dose groups. The low-dose GJE group showed marked improvement in NASH histopathology, while both treatment groups exhibited reduced hepatic collagen deposition. GJE treatment significantly suppressed NF-kB p65 and Col1a1 expression, along with downregulation of MMP-12, α-SMA, IL-13 and TGF-β1 protein levels. In conclusion, GJE effectively ameliorated HFHF diet-induced NASH with fibrosis by modulating inflammatory and fibrogenic pathways.