Protective Effect and Possible Mechanisms of Geniposide for Ischemia-Reperfusion Injury: A Systematic Review with Meta-Analysis and Network Pharmacology of Preclinical Evidence

Background:Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Gardenia jasminoides Ellis. Geniposide has been shown to be effective for treating I/R injury in recent studies. Current effectively pharmaceutical treatments are scarce, and treatment based on geniposide may become a novel option. As far as we know, this research is the initial systematic evaluation of the protective effects of geniposide in I/R injury.Aim of the study:This study is engrossed in evaluating the mechanism of action of geniposide in I/R injury through a preclinical systematic review with meta-analysis and network pharmacology.Materials and methods:We built a systematic review which provided a view of effect and mechanism of geniposide for I/R injury. Based on seven databases, an open-ended search from their inception to August 31st, 2022, was conducted. Animal studies on the effects of geniposide in I/R injury were considered. The data was analyzed using Review Manager 5.3, and bias was assessed using the CAMARADES 10-item scale. 13 articles including 279 animals were selected finally. And network pharmacology was joined to elucidate the mechanism.Results:According to the meta-analysis, in I/R injury, geniposide can attenuate cardiomyocytes viability and the size of MI, decrease the volume of cerebral infraction and neurological score, decrease serum ALT and AST activity, and downregulated serum Cr and BUN. The review found that geniposide protects against I/R injury by inhibiting apoptosis, oxidation, inflammation and improvement of autophagy and mitochondrial respiration, which is consistent with the results of the network pharmacology screening.Conclusion:This preclinical systematic review including meta-analysis and network pharmacology, which was the first one summarizing the relationship between geniposide and ischemia diseases, shows a novel therapy for I/R injury and appears an enticing implication of geniposide in I/R injury, and further research is looked forward. Given the restricted quantity of included researches and the unclear risk of bias of the studies, we should interpret the results with caution.