Bidirectional Effect of Geniposide on Liver Injury:A Preclinical Evidence Construction Based on Meta-Analysis

Abstract

Ethnopharmacological relevance: Gardenia jasminoides J.Ellis, as a traditional Chinese medicine, is widely used to treat liver diseases. As one of the major active constituents of Gardenia jasminoides J.Ellis, geniposide is able to exert the effect of treating liver injury, but it also exhibits certain hepatotoxicity while exerting therapeutic efficacy.Aim of the studyThis meta-analysis aimed to address under what circumstances geniposide exerts therapeutic effects or potential toxicity, and its major mechanisms.

Materials and methods: The articles in this study were primarily derived in five databases with the 10-item SYRCLE list for quality evaluation. STATA 15.1 was used to pool total effect or toxicity sizes. Then, three-dimensional dose/time-effect and mechanistic analyses were performed to discern the further detail in toxicity and effect.

Results: After screening, 25 studies with 479 animals were included. Geniposide could significantly raise liver injury indexes such as ALT, AST. However, it was also able to rescue liver function by decreasing ALT, AST and inflammatory indexes in models of liver injury. 3D analysis of the dosage showed that geniposide, at the dosage of 20-150 mg/kg and 5-28 days, can effectively protect the liver without toxicity. Geniposide mainly exhibited toxicity or efficacy by regulating the TNF-α/NF-κB pathway to control oxidative stress and inflammatory response.

Conclusion: Geniposide demonstrates dual bioactivity on liver injury. It is suitable for geniposide to apply at the dosage of 20-150 mg/kg and 5-28 days with significant hepatoprotective effect.

Note:
Funding Declaration: This work was supported by Xinglin Scholar Research Project of Chengdu University of TCM (grant no. QJRC2022028 and QJJJ2022010), Major scientific research problems and key topics of medical technology problems of China Medical Education Association (2022KTZ016) and “The Hundred Talents Program” of the Hospital of Chengdu University of Traditional Chinese Medicine (grant no. 22-B09).

Conflicts of Interest: None

Keywords: Geniposide, Liver injury, Hepatoprotective, Hepatotoxicity, Meta-analysis