Based on Plasma Metabonomics and Network Pharmacology Exploring the Therapeutic Mechanism of Gynura procumbens on Type 2 Diabetes.

Wenjing Guo,Jiahui Wu,Shilin Yang,Mi Liu,Xiao He,Yulin Feng,Mingzhen He,Hui Ouyang

doi:10.3389/fphar.2021.674379

Abstract

Gynura procumbens (GP) is a perennial herbal medicine and food homologous plant, which has been reported to have a good hypoglycemic effect. However, its active components and underlying mechanism of action are not clear. Here, we aimed to confirm the effects of GP on type 2 diabetes (T2DM) from several different aspects. We used UPLC/Q-TOF MS to analyze the metabolic patterns, which included blood samples of clinical subjects and db/db mice to screen for serum metabolic markers and metabolic pathways. We also used network pharmacology to study GP targets in the treatment of T2DM. Data from endogenous metabolites in plasma showed that two common pathways, including glycerol phosphate metabolism and retinol metabolism, were identified in plasma samples of the groups. Finally, Western blot analysis was used to verify the expression of proteins in the PI3K/AKT and AGE–RAGE signaling pathways. The protein expression of AKT, eNOS, iNS, and MAPK was significantly upregulated, and the expression of caspase-8 and caspase-3 was significantly downregulated. Thus, our findings indicated that GP could alleviate insulin resistance by regulating biometabolic markers and key proteins in the PI3K/AKT and AGE–RAGE signaling pathways to treat T2DM.

Highlights

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with clinical symptoms, such as chronic hyperglycemia and insulin resistance
We focused on plasma metabolomics, network pharmacology technology, and Western blot analysis to evaluate the antidiabetic effects of Gynura procumbens (GP) on mice with T2DM
In the negative and positive ion modes of mouse plasma samples, the principal component analysis (PCA) score map (Figures 1-C1 and D1) showed that the control group and the model group were obviously divided into two groups, which proved that there was a significant difference between the two groups

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with clinical symptoms, such as chronic hyperglycemia and insulin resistance. Referred to the latest data from the International Diabetes Federation, a significant number of individuals with diabetes aged 20–79 years have reached 425 million worldwide, of which T2DM accounts for 90–95% (Roden and Shulman, 2019; Zimmet et al, 2014). It has been estimated that by the year 2045, there will be 629 million diabetic patients. Oral hypoglycemic drugs and insulin injections are the main strategies that are used for the treatment of diabetes. Sulfonylureas and biguanides can control the blood glucose level of patients, these drugs have shown adverse side effects in the clinic and basically have no protective effect on islet B cells (Chen et al, 2017). An increased number of individuals prefer to use natural products to prevent and treat T2DM (Cortés-Martín et al, 2021)

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