Effects of ethanol extract from senna leaf (EESL) on inflammation and oxidative stress in mice: A non-targeted metabolomic study

Background Senna leaf is a commonly used medication for treating constipation, and long-term use can cause damage to the intestinal mucosa and lead to drug dependence. But the exact mechanism remains unclear.Objective Using non-targeted metabolomics technology to study the mechanism of senna leaf ethanol extract (EESL) inducing inflammation and oxidative stress in mice and causing side effects.Methods EESL was administered to mice by gavage to detect inflammation and oxidative stress-related factors in mice, and the EESL components and differential metabolites in mouse plasma were analyzed using non-targeted metabolome techniques.Results 23 anthraquinone compounds were identified in the EESL, including sennoside and their derivatives. Administration of EESL to mice resulted in a significant increase in pro-inflammatory factors, IL-1 beta, and IL-6 in the plasma, while the levels of IgA significantly decreased. The levels of oxidative stress significantly increased, and the intestinal mucosal integrity was impaired. 21 endogenous in plasma metabolites were identified as differential metabolites related with taurine and taurine metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and sphingolipid metabolism. These metabolic pathways are related to oxidative stress and inflammation.Conclusion Senna leaf can inhibit the expression of tight junction proteins in the intestinal mucosa and disrupt intestinal mucosal barrier integrity, exacerbating oxidative stress and inflammation induced by bacterial LPS entering the bloodstream. In addition, the impact of Senna leaf on tryptophan metabolism may be linked to the occurrence of drug dependence.