Mechanistic insights into Cistanche deserticola aqueous extract in alleviating functional constipation: Integration of gut microbiota remodeling and focal adhesion-associated mucosal repair.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola Ma (Orobanchaceae), a widely used botanical drug in Traditional Chinese Medicine, is traditionally utilized to moisten the intestines and relieve constipation, particularly for senile and deficiency-induced constipation.

AIM OF THE STUDY: To evaluate the restorative effects of C. deserticola (CD) aqueous extract on functional constipation (FC) and elucidate its multi-omic mechanisms mediated by the gut microbiota-short-chain fatty acid (SCFA)-host axis.

MATERIALS AND

METHODS

The CD extract was phytochemically characterized via UPLC-Q-TOF-MS/MS. Loperamide induced FC mice were treated with physiologically relevant doses of CD extract (369 and 615 mg/kg/day). Efficacy was assessed via phenotypic, biochemical, and histopathological evaluations. Mechanisms were explored integrating 16S rRNA sequencing, targeted SCFA metabolomics, and colonic transcriptomics. Fecal microbiota transplantation (FMT) was conducted to verify microbiota dependency. Key signaling networks were validated using Western blotting and immunofluorescence.

RESULTS

CD administration significantly accelerated intestinal transit, repaired mucosal barriers, restored gastrointestinal hormones, and mitigated oxidative and inflammatory stress. Microbiome profiling demonstrated CD reversed dysbiosis by enriching beneficial SCFA-producers (e.g., Lachnospiraceae NK4A136 group), correspondingly elevating colonic propionate and butyrate. FMT confirmed these therapeutic effects were microbiota-driven. Transcriptomic and molecular validations revealed that CD-mediated microecological restoration reactivated the Integrin αL/p-FAK/Filamin C mechanotransduction cascade and PDGFC/SGK1 signaling pathways, thereby promoting focal adhesion and structural mucosal repair.

CONCLUSIONS

CD alleviates FC by concurrently remodeling the gut microbiota, enhancing SCFA production, and reactivating colonic mechanotransductive tissue repair networks. This provides a robust scientific rationale for its traditional ethnopharmacological use in constipation management.