Regulation Of Gut-Brain Axis: Therapeutic Studies And In Vitro And In Vivo Evaluation Of Celastrus Paniculata Seed Extract In Ulcerative Colitis

Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with rising global incidence; current therapies (5-aminosalicylates, corticosteroids, immunosuppressants, biologics) are limited by incomplete response and adverse effects. Emerging evidence indicates that intestinal inflammation in UC is bi-directionally linked to the central nervous system through the gut brain axis, with neuroinflammation, altered neurotrophin signalling, and behavioural disturbance accompanying colonic disease activity. Celastrus paniculatus Willd. (Celastraceae) seeds, a traditional Ayurvedic "Medhya Rasayana," possess documented antioxidant, anti-inflammatory, nervine, and gut motility modulating properties, making them a rational candidate for a dual gut brain therapeutic strategy in UC. Objective: To evaluate the antioxidant and anti-inflammatory activity of an ethanolic Celastrus paniculatus seed extract (CPSE) in vitro, and it’s ameliorative and gut brain axis modulatory effects in a dextran sulfate sodium (DSS) induced murine model of UC in vivo. Methods: CPSE was screened phytochemically and evaluated in vitro using DPPH radical scavenging, protein denaturation inhibition, and LPS-stimulated RAW 264.7 macrophage cytokine assays. Colitis was induced in Wistar rats using 3% DSS in drinking water for 7 days; animals were allocated to normal control, DSS control, DSS + sulfasalazine (100 mg/kg), DSS + CPSE (200 mg/kg), and DSS + CPSE (400 mg/kg) groups (n = 6/group) and treated orally for 14 days. Disease Activity Index (DAI), colon length, colonic histopathology, tissue cytokines/oxidative stress markers, and gut brain axis biomarkers (serum serotonin, hippocampal BDNF, serum corticosterone) with anxiety like behaviour (elevated plus maze, forced swim test) were assessed. Results: CPSE exhibited dose dependent free radical scavenging and anti-inflammatory activity in vitro. In vivo, CPSE (400 mg/kg) attenuated body weight loss, reduced DAI and colon shortening, normalized colonic TNF-α/IL-6/IL-10 balance, and improved gut brain axis parameters (elevated hippocampal BDNF, normalized serotonin and corticosterone, improved anxiety like behaviour) relative to DSS controls, approaching the reference drug sulfasalazine. Conclusion: These findings support the hypothesis that CPSE ameliorates experimental colitis while concurrently modulating gut brain axis mediators, warranting further mechanistic and translational investigation of Celastrus paniculatus as an adjunct or complementary therapeutic in UC associated neurobehavioral comorbidity