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Objectives: Wulingsan has been used to cure disease about disorders related to fluid balance for thousands of years. The clinical practice of modern Chinese medicine has found that Wulingsan has the effect on reducing weight and fat, but its mechanism is not clear. This study investigated its effects on obesity rats and explored the underlying mechanisms by analyzing the plasma metabolic profiling. Methods: The effects of Wulingsan on obesity were evaluated with obesity rats induced by high‐fat diet. Ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC‐Q‐TOF/MS) was performed to discover potential biomarkers and evaluate whether Wulingsan could regulate these biomarkers. The levels of triglyceride (TG), total cholesterol (TC), high‐density lipoprotein (HDL‐C), and low‐density lipoprotein (LDL‐C) in serum were assessed by ELISA kits. Results: Remarkably, TG, TC, HDL‐C and LDL‐C in obesity rats were ameliorated after oral administration of Wulingsan. Further investigation indicated that the plasma metabolic profiles were clearly improved. Twelve potential biomarkers were identified. After intervention, these biomarkers turned back to normal level at some extent. Conclusion: The results showed that Wulingsan extract groups were normalized. Additionally, this study also showed that the metabonomics method was a promising tool to unravel how traditional Chinese medicines worked and these data can provide scientific basis for clinical application of Wulingsan. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the β but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90β would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms.Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90β. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms.The selective pharmacological inhibitor (HSP90βi) and shHSP90β significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically‐transformed Th17 cells by HSP90βi or shHSP90β were able to inhibit lymphocyte proliferation and colitis in mice. HSP90βi and shHSP90β selectively weakened glycolysis by stopping the direct association of HSP90β and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the “lactate‐STAT5‐TET2” cascade.HSP90β shapes the fate of Th17 cells via glycolysis‐controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC. [ABSTRACT FROM AUTHOR]