Enzymatic Deglycosylation of Hederacoside C Yields Potent Anti-inflammatory Metabolites for Inflammatory Bowel Disease
Abstract
Hederacoside C (HDC), a pentasaccharide triterpenoid saponin isolated from Pulsatilla chinensis (Bunge) Regel, has documented anti-inflammatory activity but limited oral bioavailability because of its high hydrophilicity. This study investigated whether enzymatic deglycosylation could generate HDC metabolites with enhanced anti-inflammatory activity. Using α-L-rhamnosidase (RhaK), three principal deglycosylated metabolites, designated HDC-1–HDC-3, were generated and characterized. In lipopolysaccharide-stimulated RAW 264.7 macrophages, HDC-1 and HDC-3 exhibited greater anti-inflammatory activity than the parent compound, as demonstrated by stronger suppression of the pro-inflammatory cytokines IL-1β and IL-6. Although HDC-3 showed the highest in vitro activity, HDC-1 was selected for in vivo evaluation because it combined substantial biological activity with a higher preparative yield and greater scalability. In a dextran sulfate sodium-induced murine colitis model, intraperitoneal administration of HDC-1 at 1.25, 2.5, and 5 mg/kg dose-dependently reduced body-weight loss and disease activity, preserved colon length, decreased colonic IL-1β and IL-6 levels, and improved histopathological injury. Under the tested dosing regimens, HDC-1 produced greater therapeutic effects than oral HDC at 100 mg/kg and mesalazine at 200 mg/kg. These findings identify HDC-1 as a promising deglycosylated lead compound and support enzymatic biotransformation as a scalable strategy for developing potent saponin-derived candidates for the treatment of inflammatory bowel disease.
Keywords: Hederacoside C; enzymatic deglycosylation; α-L-rhamnosidase; triterpenoid saponin; DSS-induced colitis; anti-inflammatory activity; inflammatory bowel disease.
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