Ultra-performance liquid chromatography-mass spectrometry-based metabolomics reveals Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes.

Background: As a typical chronic metabolic disease, type 2 diabetes mellitus causes a heavy health-care burden to society. In this study, we applied the metabolomics strategy to explore the potential molecular mechanism of the Huangqiliuyi decoction (HQLYD) for type-2 diabetes (T2D). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) combined with pattern recognition methods was utilized to select specific metabolites closely associated with HQLYD. Biomarker pathway analysis and biological network were utilized to uncover the therapeutic effect and action mechanism related to HQLYD. A total of twenty-five biomarkers were identified in the animal model, in which sixteen biomarkers are associated with HQLYD treatment for T2D. They attenuated the abnormalities of metabolic pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and the citrate cycle. HQLYD also significantly elevated the serum FINS and SOD, GSP-x level in the liver and kidney, and reduced the serum TC, TG, HDL, LDL, urea, Scr, AST, ALT, FBG, IRS, MDA, and CAT level. We found that the therapeutic mechanism of HQLYD against T2D affected amino acid metabolism, glucose metabolism and lipid metabolism. Metabolomics revealed that the Huangqiliuyi decoction attenuates abnormal metabolism as a novel therapeutic opportunity for type 2 diabetes.

Toll-like receptor 4 is involved in myocardial damage following paraquat poisoning in mice.

The ingestion of the herbicide paraquat (PQ) can cause multiple organ injury including cardiac lesions. However, the underlying mechanism of myocardial damage is not known. Toll-like receptor 4 (TRL4) is a pattern-recognition receptor in the innate immune response to microbial pathogens. TLR4 is involved in heart dysfunction such as septic shock or myocardial ischemia. We investigated whether TLR4 would be linked to the pathogenesis of heart disease due to PQ exposure. Wild type mice (WT) and TLR4-deficient mice were injected intraperitoneally with 75mg/kg of PQ to induce myocardial damage and tested for echocardiographic assessment, histopathology, pro-inflammatory cytokine and TLR4 expression. WT mice after PQ exposure displayed deteriorate cardiac function, pathological damages, increased TLR4 mRNA and protein levels as well as myocardial TNF-α and IL-1ß levels. Compared with WT mice, TLR4-deficient mice were significantly resistant to the PQ-induced injury. We concluded that the TLR4 was required as a mediator and played an important role in myocardial damage due to PQ.