Abstract
Panax ginseng was employed in the treatment of “Xiao-Ke” symptom, which nowadays known as diabetes mellitus, in traditional Chinese medicine for more than a thousand years. Ginsenoside Re was the major pharmacologic ingredient found abundantly in ginseng. However, the anti-diabetic of Ginsenoside Re and its underlying mechanism in metabolic level are still unclear. Serum and urine metabolomic method was carried out to investigate the anti-diabetic pharmacological effects and the potential mechanism of Ginsenoside Re on high-fat diet combined streptozotocin-induced type 2 diabetes mellitus (T2DM) rats based on ultra-high-performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum and urine samples were collected from the control group (CON), T2DM group, metformin (MET) treatment group, and ginsenoside Re treatment group after intervention. The biochemical parameters of serum were firstly analyzed. The endogenous metabolites in serum and urine were detected by UHPLC-MS. The potential metabolites were screened by multivariate statistical analysis and identified by accurate mass measurement, MS/MS, and metabolite databases. The anti-diabetic-related metabolites were analyzed by KEGG metabolic pathway, and its potential mechanism was discussed. The treatment of ginsenoside Re significantly reduced the blood glucose and serum lipid level improved the oxidative stress caused by T2DM. Biochemical parameters (urea nitrogen, uric acid) showed that ginsenoside Re could improve renal function in T2DM rats. Respective 2 and 6 differential metabolites were found and identified in serum and urine of ginsenoside Re compared with T2DM group and enriched in KEGG pathway. Metabolic pathways analysis indicated that the differential metabolites related to T2DM were mainly involved in arachidonic acid metabolism, Vitamin B6, steroid hormone biosynthesis, and bile secretion metabolic pathways. This study verified the anti-diabetic and anti-oxidation effects of ginsenoside Re, elaborated that ginsenoside Re has a good regulation of the metabolic disorder in T2DM rats, which could promote insulin secretion, stimulated cannabinoid type 1 receptor (CB1), and CaMKK β to activate AMPK signaling pathway, inhibited insulin resistance, and improved blood glucose uptake and diabetic nephropathy, so as to play the role of anti-diabetic.
Highlights
The epidemic of diabetes mellitus (DM) and its complications poses a major threat to global health; about 1 out of 11 adults worldwide have DM, which is the ninth major cause of death globally [1]
DM is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and nearly 90% of cases are T2DM, which is caused by insulin resistance and lack of proper response to hyperglycemia [2]
UHPLC-MS was used to study the anti-diabetic effect of ginsenoside Re on T2DM rats induced by a high-fat diet and streptozotocin
Summary
The epidemic of diabetes mellitus (DM) and its complications poses a major threat to global health; about 1 out of 11 adults worldwide have DM, which is the ninth major cause of death globally [1]. It has been reported that oxidative stress was one of the causes of insulin resistance and impaired insulin secretion, which eventually leads to T2DM [4]. Continuous oxidative stress and dysfunction of various metabolic pathways were the main cause of diabetic complications, such as diabetic nephropathy [5]. The treatment of T2DM is mainly focused on the injection of insulin or its peptide derivatives, oral anti-diabetic drugs, and dietary control. Insulin injection brings inconvenience to patients’ daily life, while long-term oral administration of chemical drugs may cause side effects. Researchers are exploring new alternative medicines for the treatment of T2DM, such as traditional herbal medicines, which were attracting increasing attention because of their less toxicity and side effects [6]
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