Wenxuan Liu,Xiangka Hu,Xiaorui Han,Kexin Zeng,Xuedong Ren,Yining Chang,Chunmei Dai
Ethnopharmacology relevance Tangningtongluo Tablets (TNTL), a novel Miao ethnic medicine for treating type 2 diabetes mellitus (T2DM) and its complications. However, its potential bioactive components and the pharmacological mechanisms underlying its therapeutic effects remain unclear. Aim of the study This study aims to preliminarily explore the protective effects of TNTL and its active components on pancreatic cells via the PI3K/Akt/FoxO1 pathway and further investigate the underlying mechanisms. Materials and methods LC-MS was employed to identify components in serum, and network pharmacology was used to forecast active components and their mechanisms. The protective effects and mechanisms of TNTL and its active components on pancreatic β-cells in diabetic mice were investigated using HE staining, MTT assay, EdU assay, TUNEL staining, Western blot analysis, and qPCR analysis. Results A total of 29 active components of TNTL were detected in rat serum. Network pharmacology results indicated that luteolin, catechin, and chlorogenic acid are key compounds of TNTL in regulating the PI3K/Akt/FoxO1 pathway. Compared with the model group, TNTL and its active components reduced ROS and MDA levels, increased SOD levels, and reduced pro-apoptotic factor expression to alleviate pancreatic β-cells damage. They also activated PI3K/Akt/FoxO1 signaling and decreased apoptotic proteins. Conclusion This study demonstrates that TNTL mitigates oxidative stress and reduces pancreatic β-cell apoptosis in diabetic mice through modulation of the PI3K/Akt/FoxO1 pathway.
Feier Cheng,Xinhui Ge,Yao Zhang,Jia Li,Shaoqing Yan,Yunlong Li,Min Wang
The hypoglycemic effects and underlying molecular mechanisms of combining two dietary compounds, quercetin (Que) and d-chiro-inositol (DCI) on hepatic insulin resistance in C57BL/6J mice that were fed a high fat diet and saturated palmitic acid (PA)-treated hepatocytes were studied. Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) are important antioxidant enzymes . Insufficient secretion of these enzymes will inhibit the normal phosphorylation of insulin receptors in the liver, thereby limiting the transmission of insulin signals and producing insulin resistance. The results showed that QD (both Que and DCI) led to the recovery of the activity of CAT, SOD, GPx, suggesting that QD was helpful in preventing mice hepatic insulin resistance. In PA-induced human hepatoma cells (HepG2), QD improved the antioxidant level in cells. The fluoro-immunoassay showed that QD effectively reduced the translocation of protein kinase Cε to cell membranes in the HepG2. Western blotting results suggested that QD increased the signal transduction in the IRS-2/PI3K/Akt/FoxO1 pathway. Overall, these results showed that the combination of 5 μmol Que and 5 μmol DCI ameliorated high fat diet-induced hepatic insulin resistance.
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