Bidirectional effects of geniposide in liver injury: Preclinical evidence construction based on meta-analysis

Gardenia jasminoides J.Ellis is widely used to treat liver diseases in traditional Chinese medicine. Geniposide, a major active constituent of Gardenia jasminoides J.Ellis, exerts therapeutic effects against liver injury, however, it also induces hepatotoxicity.This meta-analysis was designed to determine the mechanisms of both the hepatoprotective and hepatotoxic effects of geniposide.The articles analysed in this meta-analysis were primarily obtained from five databases. The 10-item SYRCLE risk-of-bias tool was used to evaluate the quality of the included articles. STATA (version 15.1) was used to evaluate the total effect or toxicity sizes. In addition, three-dimensional (3D) dose/time-effect and mechanistic analyses were performed to assess the therapeutic and toxic effects of geniposide.A total of 25 studies involving 479 animals were included. Meta-analysis revealed that geniposide not only significantly (P < 0.001) increased liver injury indices including ALT and AST levels but also improved liver function by decreasing the levels of ALT, AST and inflammatory factors in animal models of liver injury. The 3D dose/time-effect analysis revealed that geniposide administered at a dose of 20-150 mg/kg for 5-28 days effectively protected the liver without inducing toxicity. Mechanistically, geniposide exerts protective or toxic effects by regulating the TNF-α/NF-κB pathway to control oxidative stress and inflammatory responses.Geniposide exhibits dual pharmacological activity in liver injury. It exerts potent hepatoprotective effects when administered at a dose of 20-150 mg/kg for 5-28 days.