Microbial transformation of isorhodeasapogenin (1), the major steroidal sapogenin of Tupistra chinensis, was performed with the fungus Syncephalastrum racemosum (AS 3.264). As a result, nine new biotransformation metabolites (2-10) were isolated and their structures were elucidated by spectroscopic analysis. Hydroxylation, oxidation and glycosylation reactions were observed on the B, C, D and F rings of steroidal skeleton. Substrate (1) and its biotransformed metabolites 2-6, 8-10 were evaluated for their anti-neuroinflammatory effect on the NO accumulation induced by LPS in BV-2 cells. All the tested metabolites were found to have more potential anti-neuroinflammatory activity than the substrate. Especially, metabolites 2, 5 and 6 exhibited significant inhibition on NO production after hydroxylation at C-12 or C-15. Moreover, metabolite 2 dose-dependently reduced the LPS-induced protein expression of iNOS and COX-2.
microbial transformation, Syncephalastrum racemosum, anti-neuroinflammatory activity, isorhodeasapogenin
NCBI PubMed ID: 32512266Publication DOI: 10.1016/j.bioorg.2020.103870Journal NLM ID: 1303703Publisher: Orlando, FL: Academic Press
Correspondence: He X
Institutions: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China, Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Methods: 13C NMR, 1H NMR, NMR-2D, IR, HPLC, immunoblotting, extraction, optical rotation measurement, CC, cell growth, HR-ESI-MS, determination of NO production, filtration
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