Akebia saponin D attenuates ulcerative colitis via targeting EGFR and remodeling gut microbiota homeostasis.

ASD demonstrated significant therapeutic efficacy in DSS-induced UC mice, attenuating body weight loss, restoring colonic length, and improving mucosal barrier integrity.

• A dextran sulfate sodium (DSS)-induced UC mouse model was established and ASD treatment was administered to observe effects on colitis and organ toxicity.
• ASD treatment resulted in attenuated body weight loss compared to untreated DSS mice.
• Colonic length was restored following ASD treatment.
• Mucosal barrier integrity was improved with ASD treatment.
• Organ toxicity was assessed alongside therapeutic efficacy measurements.

ASD substantially remodeled gut microbiota composition and metabolic profiles, notably elevating the abundance of Akkermansia muciniphila and levels of indole-3-carbinol.

• 16S rRNA sequencing and untargeted metabolomics were conducted to assess gut microbiota and metabolite landscape changes.
• Fecal microbiota transplantation (FMT) was performed to assess the involvement of gut microbiota in ASD's therapeutic effects.
• Akkermansia muciniphila (A. muciniphila) abundance was notably elevated following ASD treatment.
• Levels of the metabolite indole-3-carbinol (I3C) were notably elevated following ASD treatment.
• ASD is described as a 'microbiota-modulating therapeutic agent' in the context of its mechanism.

Single-cell RNA sequencing revealed that ASD promoted the expansion of Hmgb2+ transit-amplifying cells and Muc2+ goblet cells in colonic tissues.

• scRNA-seq was performed using the MGISEQ-2000 platform to characterize the ASD-induced cellular landscape of the colon.
• Hmgb2+ transit-amplifying cells (TACs) showed expanded populations following ASD treatment.
• Muc2+ goblet cells (GCs) showed expanded populations following ASD treatment.
• These cellular changes were identified at single-cell resolution in colonic tissues.

EGFR was identified as a key molecular target of ASD, functioning upstream of the MEK/ERK/AP-1 signaling cascade.

• Network pharmacology approaches were employed to predict and validate potential molecular targets of ASD.
• ASD was demonstrated to target EGFR as a key molecular target.
• EGFR functions upstream of the MEK/ERK/AP-1 signaling cascade in ASD's mechanism of action.
• ASD alleviates intestinal inflammation by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.
• Inflammation was induced in NCM460 and HT29 cells using lipopolysaccharide (LPS), and ASD treatment was applied to evaluate anti-inflammatory effects in vitro.

ASD, a bioactive triterpenoid saponin extracted from Dipsacus asper, has demonstrated potent multimodal bioactivity and was systematically evaluated for therapeutic potential in UC.

• ASD is described as a bioactive triterpenoid saponin extracted from the traditional medicinal herb Dipsacus asper.
• UC is characterized clinically by chronic abdominal pain and bloody hematochezia.
• UC is described as a refractory subtype of inflammatory bowel disease (IBD).
• Both in vivo (DSS mouse model) and in vitro (NCM460 and HT29 cell lines) models were used to evaluate ASD.