Investigating the mechanism of enhanced medicinal effects of Terminalia chebula fruit after processing based on intestinal flora and metabolomics

Abstract

Background and objectiveTerminalia chebula is a classical medicine for the treatment of lingering dysentery, and both raw and processed T. chebula can alleviate ulcerative colitis (UC). The therapeutic efficacy of T. chebula is enhanced after processing, but the mechanism that processing improves this efficacy is still unknown. We investigated the medicinal effects of raw and processed T. chebula on dextran sulfate sodium (DSS)-induced UC model rats using intestinal flora and metabolomics analyses, in order to elucidate the mechanism by which processing enhances the therapeutic effect. MethodsThe major constituents of raw and processed T. chebula were detected by high-performance liquid chromatography (HPLC). UC model was replicated using the DSS method, and then UC rats were administered raw and processed T. chebula. The general physical signs, disease activity index (DAI) scores, colon histopathological morphology, and the expressions of inflammatory cytokines were used to evaluate the therapeutic effect of T. chebula. In addition, 16 s rRNA sequencing and gas chromatography-mass spectrometry (GC–MS) were used to characterize the intestinal flora and contents of short-chain fatty acids (SCFAs). Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to identify the nontargeted fecal metabolites. ResultsRaw and processed T. chebula significantly improved the general physical signs and colon inflammatory symptoms and decreased DAI scores of UC rats. Both raw and processed T. chebula mitigated intestinal flora disorders in UC rats, increasing probiotic bacteria, including Lactobacillus and Romboutsia. However, the effect of processed T. chebula was more pronounced. Moreover, the levels of SCFAs of DSS-induced UC rats were restored after drug administration, and the processed T. chebula had a better regulatory effect than raw T. chebula. In the fecal nontargeted metabolomics analysis, differential metabolites such as lipids and amino acids were identified. The processed T. chebula can regulate purine metabolism and other pathways to improve UC, and the levels of the disordered metabolites gradually approached those of the control group. ConclusionRaw and processed T. chebula had the capacity to mitigate DSS-induced UC by rebalancing the intestinal flora, restoring the contents of SCFAs, and regulating fecal metabolites, while processed T. chebula showed preferable effects.