Dietary supplement containing plant sterols exerts a positive effect on inflammatory markers in a chronic colitis murine model

Plant sterols (PS) have reported benefits in alleviating colitis in mice, but the mechanisms involved require further investigation¹. The study aimed to evaluate the effect of a dietary supplement containing PS (PS-DS, 87% of PS and maltodextrin and sucrose ester as excipients) on inflammation biomarkers in a mice model of chronic ulcerative colitis (UC) as a step prior to a study involving UC patients in remission phase. C57BL/6J mice (n = 34) were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for three 5-day periods, with 10-day rest intervals in between. The mice received PS-DS (35 mg PS/kg) daily or placebo by oral gavage, either simultaneously with the DSS exposure (treatment) or 30 days before the first DSS exposure (pre-treatment). After euthanasia, myeloperoxidase (MPO) activity and the levels of pro- (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10) in the colonic tissue were analyzed. The treatment with PS-DS reduced MPO activity (by 19%) compared to control group. This agrees with prior studies that used colitis model induced by DSS (28-43%)² or TNBS (28-43%)³. In addition, the production of TNF-α and IL-6 was attenuated by PS-DS (by 56 and 42%, respectively), as observed in other studies (TNF-α, 45-56%; IL-6, 56-60%)^2-4, while colon levels of IL-10 were increased (1.8-fold). On the other hand, pre-treatment with PS-DS provided additional benefits in UC, since the inhibition of MPO (by 19 vs. 40%) and TNF-α (by 56 vs. 63%) and the increase of IL-10 (1.8 vs. 2.5-fold) were greater compared to PS-DS treatment. These findings suggest that PS-DS has the potential to alleviate UC in mice by modulating the inflammatory response and reducing oxidative stress. However, studies in humans are required to validate and fully understand its anti-inflammatory effect and its safety in the treatment of inflammatory bowel diseases.

This study is part of the project PID2019-104167RB-I00 funded by MCIN/AEI/10.13039/501100011033. Mussa Makran holds an FPU19/00156 grant from the Ministry of Universities (Spain). The experiment complied with European and Spanish regulations (2010/63/EU and RD 53/2013) and was approved by the Generalitat Valenciana, Spain (2022/VSC/PEA/0256).

References: ¹Salehi et al. Front Pharmacol. 2021; 11:599959. ²Kim et al. 2014. Mol Nutr Food Res. 2014, 58, 963-972. ³Lee et al. Planta Med. 2012, 78, 896-898. ⁴Awaad et al. Phytother Res. 2013, 27, 1729-1734.