Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages

For the discovery of new pentacyclic triterpenes as a potential anti-inflammatory agent, microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 was investigated. Stereo-selective hydroxylation and epoxidation reactions were observed in the biotransformation. Moreover, six new metabolites were isolated and structurally elucidated by HR-ESI-MS and NMR spectrum. All the compounds were evaluated upon the inhibitory effects of nitric oxide (NO) release in RAW 264.7 cells induced by lipopolysac-charide (LPS) and high-mobility group box 1 (HMGB1). Among them, compound 3 (13, 28-epoxy-3 beta, 7 beta, 21 beta-trihydroxy-urs-11-ene) with the unique epoxy structure and compound 5 (3 beta, 21 beta, 24, 28-tetrahydroxy-urs-12-en-30-oic acid), exhibited a considerable inhibitory effect on both models while compound 2 (urs-12-ene-3 beta, 7 beta, 21 beta, 28-tetraol) showed a significant bias in the LPS-induced inflammatory response with IC(50 )value of 2.22 mu M. Therefore, this study could provide some insights on the discovery of the pentacyclic triterpene leads for the treatment of either DAMPs or PAMPs triggered inflammation.

Automated summary

This study investigates the microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 for the discovery of new pentacyclic triterpenes as potential anti-inflammatory agents. Six new metabolites were isolated and their structures were determined. The compounds were evaluated for their inhibitory effects on nitric oxide release in RAW 264.7 cells induced by lipopolysac-charide and high-mobility group box 1. Compound 3 and compound 5 exhibited significant inhibitory effects on both models, indicating their potential for treating inflammation triggered by DAMPs or PAMPs.