Microbial transformation of Soyasapogenol C and potential of its metabolites against HMGB1 and LPS-triggered inflammation.

Soyasapogenol C, a oleanane-type pentacyclic triterpenoid, is mainly derived from soybean and its residual cake after oil extraction. Herein, microbial transformation of soyasapogenol C by Bacillus megaterium CGMCC 1.1741 and Streptomyces griseus ATCC 13273 was performed, and 8 new metabolites were obtained. Their structures were elucidated on the basis of HR-ESI-MS, 1D and 2D NMR and X-Ray analysis. As a result, stereoselective and site-specific hydroxylation, carbonylation, rare double bond transfer, and methoxylation occur on the triterpenoid skeleton. Next, all compounds were evaluated against nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) and high mobility group box-1 protein (HMGB1). Compound 3 exhibited potent inhibitory activity in inflammatory models induced by LPS and HMGB1, with IC50 values of 3.92 ± 1.89 and 14.97 ± 1.33 μM, respectively. Molecular docking further revealed hydroxyl groups on C-24/C-3 of 3 may interact with residues N46, E43, and A38 in HMGB1 through multiple hydrogen bonds. These findings demonstrated the potential of soyasapogenol derivatives as food additives or drug candidates for the prevention and treatment of chronic inflammatory diseases.