Identifying Candidate Polyphenols Beneficial for Oxidative Liver Injury through Multiscale Network Analysis

Abstract

Oxidative stress, a driver of liver pathology, remains a challenge in clinical management, necessitating innovative approaches. In this research, we delved into the therapeutic potential of polyphenols for oxidative liver injury using a multiscale network analysis framework. From the Phenol-Explorer database, we curated a list of polyphenols along with their corresponding PubChem IDs. Verified target information was then collated from multiple databases. We subsequently measured the propagative effects of these compounds and prioritized a ranking based on their correlation scores for oxidative liver injury. This result underwent evaluation to discern its effectiveness in differentiating between known and unknown polyphenols, demonstrating superior performance over chance level in distinguishing these compounds. We found that lariciresinol and isopimpinellin yielded high correlation scores in relation to oxidative liver injury without reported evidence. By analyzing the impact on a multiscale network, we found that lariciresinol and isopimpinellin were predicted to offer beneficial effects on the disease by directly acting on targets such as CASP3, NR1I2, and CYP3A4 or by modulating biological functions related to the apoptotic process and oxidative stress. This study not only corroborates the efficacy of identified polyphenols in liver health but also opens avenues for future investigations into their mechanistic actions.