Spleen and thymus metabolomics strategy to explore the immunoregulatory mechanism of total withanolides from the leaves of Datura metel L. on imiquimod-induced psoriatic skin dermatitis in mice.

Our previous work demonstrated that total withanolides of Datura metel L. leaves (TWD) exhibited excellent therapeutic effects on psoriasis. However, current knowledge of its mechanisms is not deep enough. In this study, integrated spleen and thymus untargeted metabolomics were used to analyze the changes of endogenous metabolites underlying the immunosuppressive activity of TWD on psoriasis animal models induced by imiquimod (IMQ). Results suggested that TWD treatment markedly attenuated IMQ-induced psoriasis and showed significant immunosuppressive activity as evidenced by decreasing the elevation index of spleen and thymus. Meanwhile, TWD significantly reversed the elevation of immunoregulatory factors, including IL-10, IL-17, IL-22 and IL-23. Multivariate trajectory analysis revealed that TWD treatment could restore the psoriasis-disturbed spleen and thymus metabolite profiles towards the normal metabolic status. A total of 25 and 27 metabolites associated with the immunomodulatory effects for which levels changed markedly upon treatment have been identified in spleen and thymus, respectively. These differential metabolites mainly involved in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and lipid metabolism. Our investigation provided a holistic view of TWD for intervention psoriasis through immunoregulation and provided the more scientific information in vivo about a clinical value of TWD for psoriasis.