Ulcerative colitis therapeutic effects and pharmacokinetics of flexible quercetin nanocrystals prepared with geniposide assistance.

OBJECTIVE

This study aimed to improve the oral bioavailability and therapeutic efficacy of quercetin (QUE) against ulcerative colitis (UC) by formulating flexible quercetin nanocrystals (QUE-NCs) with the assistance of geniposide (Gen).

METHODS

QUE-NCs were prepared via an antisolvent precipitation method leveraging the interaction between QUE and Gen. Therapeutic efficacy was evaluated in a dextran sulfate sodium (DSS)-induced UC mouse model using disease activity index (DAI), colon histopathology (H&E), and ELISA-based biochemical assays. Biosafety was assessed through serum biochemistry, organ indices, and histopathological examination. An HPLC method was developed and validated for quantifying QUE in rat plasma, followed by a pharmacokinetic study in Wistar rats.

RESULTS

QUE-NCs exhibited a flexible rod-like morphology and significantly alleviated UC symptoms, including weight loss, fecal occult blood, and colonic damage. Treatment with QUE-NCs reduced pro-inflammatory cytokines (TNF-α: 173.51 pg·mL-1; IL-6: 32.55 pg·mL-1), restored anti-inflammatory IL-10 levels (126.37 pg·mL-1), and suppressed oxidative stress markers (MPO: 579.95 pg·mL-1; MDA: 62.44 nmol·g-1; iNOS: 6.78 ng·mL-1). The nanocrystal formulation demonstrated excellent biosafety at the tested dose and significantly enhanced QUE's oral bioavailability (294.42% relative to raw QUE).

CONCLUSION

Gen-assisted formulation of QUE-NCs improves both the oral absorption and anti-UC efficacy of QUE, offering a promising nanostrategy for flavonoid-based therapeutic development.