Study on Structure-Function Relationship of the Anti-inflammatory and Anti-cancer Effects of Catechins Using Cell Models andNetwork Pharmacology

Objective: To explore the relationship between the structure of tea catechins and their anti-inflammatory and anti-cancer activities and to preliminarily elucidate the underlining mechanism behind the structure-function relationship. Methods: The lipopolysaccharide-induced murine macrophage cells RAW 264.7 and human colorectal cancer cells HCT116 were used as in vitro models for inflammation and cancer. The in vitro anti-inflammatory and anti-cancer activities of catechins were analyzed by Griess reagent colorimetric method and tetramethyl azothiazole blue colorimetric method. The key targets and pathways of the anti-inflammatory and anti-cancer of each catechin monomer were predicted by network pharmacology. The interactions between catechins and key target proteins were simulated by molecular docking technique, and the binding ability of each component to key targets was compared. Results: The significant in vitro anti-inflammatory and anti-cancer potentials of eight catechins were confirmed. Additionally, the galloyl group in gallated catechins, the pyrogallol moiety of B-ring in pyrogallol-type catechins, and the trans-type structure of C₂-C₃ in trans catechins were found to be beneficial for their anti-inflammatory and anti-cancer activities, however, an antagonistic effect was also observed between the pyrogallol moiety in B-ring and the galloyl group of pyrogallol-type gallated catechins. Furthermore, multiple targets and pathways were predicted to be involved in the anti-inflammatory and anti-cancer effects of eight catechin monomers. The galloyl group in catechins was found to be beneficial for their regulatory effects on multiple targets and their interaction with key target proteins including IL6, TNF, and AKT1 through hydrogen bonding. The present study preliminarily reveals the structure-function relationship behind the anti-inflammatory and anti-cancer functions of catechins. It provides theoretical and technical instruction for further elucidation of the relationship between the functional effects and the molecular structures of catechins.