ArticleJournal of ginseng research2026
Integrated LC-HRMS and in silico prediction discovery a hydroxylated protopanaxatriol metabolite in vivo with enhanced anti-inflammatory activity.
Article in Journal of ginseng research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Protopanaxatriol (PPT), a key aglycone of ginsenosides, exhibits significant anti-inflammatory potential but suffers from poor oral bioavailability. After oral administration, PPT is transformed by gastric acid, gut microbiota, and liver enzymes into metabolites with enhanced bioactivity. Methods: We employed an integrated metabolomics strategy combining LC-HRMS, in silico prediction, and molecular networking to systematically characterize PPT metabolism in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Metabolites were identified across serum, urine, and feces samples. Results: A total of 20 metabolites were identified, including the novel 25-hydroxy-PPT (25OH-PPT), discovered for the first time. Mechanistic in vitro assays demonstrated that 25OH-PPT was exclusively generated under simulated gastric conditions via an acid-catalyzed, non-enzymatic hydroxylation pathway. Functional evaluation showed that 25OH-PPT exhibited significantly stronger anti-inflammatory activity than PPT (IC Conclusions: These findings uncover a new metabolic activation pathway of PPT, providing mechanistic insights into its pharmacological effects and offering new perspectives for designing PPT-based therapeutics.
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