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Buddlejasaponin IVb (BJP-IVb), a triterpenoid saponin derived from Pleurotus ostreatus, is abundant in bioactive constituents. However, its potential therapeutic benefits and underlying mechanism of action against ulcerative colitis (UC) remain elusive. Studies performed using a mouse model of colitis caused by dextran sulfate sodium showed that BJP-IVb helped reduce symptoms of UC, such as weight loss, a higher disease activity index, shorter colon length, and colon damage. It also repaired the intestinal barrier function and suppressed inflammation. BJP-IVb activated the Nrf2/HO-1 antioxidant pathway, inhibited ferroptosis, and affected protein expression and oxidative indicators. The combined use of BJP-IVb and Nrf2 inhibitor ML385 negated the effects of BJP-IVb. In Nrf2-KO mice, the protective effects of BJP-IVb were reversed. BJP-IVb inhibited ferroptosis via the Nrf2/GPX4 axis and alleviated gut microbiota dysbiosis. In conclusion, our research validates the therapeutic and protective efficacy of BJP-IVb on ulcerative colits. Additionally, it offers new perspectives on preventing colitis by focusing on the metabolism of gut microbiota using natural substances.

Costunolide (COS) and dehydrocostus lactone (DEH), as natural phytochemical components, mainly originated from Aucklandiae radix (AR) and Vladimiriae radix (VR) used in the treatment of gastric diseases in traditional Chinese medicine. The α-methylene-γ-butyrolactone ring structure is the same active part of COS and DEH, and shows good curative effects, such as breast cancer, leukemia and gastric related diseases. Furthermore, the previous research of the lab team found that the combination of COS and DEH promoted the repair of gastric ulcer and effectively alleviated intestinal metaplasia of gastric mucosa. Nevertheless, the rapid gastric emptying process and inefficient gastrointestinal absorption resulted in low oral bioavailability of COS and DEH. Based on floating and swelling technology, this study developed a gastric floating drug delivery system for prolonging gastric residence time to delay the drug release in the stomach and enhance the bioavailability of COS and DEH. The gastric floating tablets of COS and DEH were prepared by the direct powder compression method, and the optimized formulation contained 30% HPMC K15 M and 10% NaHCO3. The results of response variable showed that the floating lag time was 13.50 ± 1.87 s, total floating time was 11.83 ± 0.41 h, 2 h and 12 h cumulative drug release was 29.87 ± 2.22%, 70.89 ± 4.27%, respectively. Additionally, the physicochemical properties of the floating tablets were characterized by friability, hardness, weight variation, Fourier transform infrared spectrum (FT-IR), differential scanning calorimeter (DSC) and X-ray diffraction (X-RD). The study on release kinetics showed that the drug release mechanism of gastric floating tablets of COS and DEH was both diffusion and matrix erosion. Moreover, scanning electron microscope (SEM), swelling and erosion indexes studies further explained the release mechanism. Furthermore, in vivoX-ray imaging of male New Zealand rabbits proved the gastric retention effect of the gastric floating tablets in the stomach (10 ± 3.46 h). The results of these experiments demonstrated that the gastric floating tablets of COS and DEH had the potential for a good gastric residence time and sustained release effect.