Abstract
Panax ginseng and Panax notoginseng, two well-known medical plants with economic value, have a long history of use for managing various diseases in Asian countries. Accumulating clinical and experimental evidence suggests that notoginsenosides and ginsenosides, which are the major bioactive components of the plants, have a variety of beneficial effects on several types of disease, including metabolic, vascular, and central nervous system disease. Considerable attention has been focused on ginsenoside Rb1 derived from their common ownership as an anti-diabetic agent that can attenuate insulin resistance and various complications. Particularly, in vitro and in vivo models have suggested that ginsenoside Rb1 exerts various pharmacological effects on metabolic disorders, including attenuation of glycemia, hypertension, and hyperlipidemia, which depend on the modulation of oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Regulation of these pathophysiological mechanisms can improve blood glucose and insulin resistance and protect against macrovascular/microvascular related complications. This review summarizes the pharmacological effects and mechanisms of action of ginsenoside Rb1 in the management of diabetes or diabetic complications. Moreover, a multi-target effect and mechanism analysis of its antidiabetic actions were performed to provide a theoretical basis for further pharmacological studies and new drug development for clinical treatment of type 2 diabetes. In conclusion, ginsenoside Rb1 exerts significant anti-obesity, anti-hyperglycemic, and anti-diabetic effects by regulating the effects of glycolipid metabolism and improving insulin and leptin sensitivities. All of these findings suggest ginsenoside Rb1 exerts protective effects on diabetes and diabetic complications by the regulation of mitochondrial energy metabolism, improving insulin resistance and alleviating the occurrence complications, which should be further explored. Hence, ginsenoside Rb1 may be developed as a potential anti-obesity, anti-hyperglycemic, and anti-diabetic agent with multi-target effects.
Highlights
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia caused by insufficient insulin secretion and/or insulin action
C/EBPα, recombinant human CCAAT/enhancer binding protein alpha; DM, diabetes mellitus; DC, diabetic cardiomyopathy; DN, diabetic nephropathy; FBG, fasting blood glucose; FINS, fasting insulin; HOMA-IR, homeostasis model assessment-insulin resistance; HG, high glucose; HFD, high-fat diet; GLUT, glucose transporter; HOCl, hypochlorous acid; GLP-1, glucagon-like peptide-1; IL-6 and/or IL-1β, pro-inflammatory cytokines; IRS1, insulin receptor substrate-1; iNOS, inducible nitric oxide synthase; MAPK, mitogen activated protein kinase; MI/R, myocardial ischemia/reperfusion; NO, nitric oxide; PPARγ, peroxisome proliferator-activated receptor γ; PKB/Akt, protein kinase B; PI3K, phosphatidylinositol 3-kinase; Rin-m5F, Rattus pancreatic β-cell line; RF stands for references; STZ, streptozotocin; SD, Sprague–Dawley rat; T2DM, type 2 diabetes; TNF-α, tumor necrosis factor-α; 11β-HSD1, 11β-Hydroxysteroid dehydrogenase type I
Protopanaxadiol and its main representative ingredient, ginsenoside Rb1, prevented the HG-induced increase in fibronectin expression in mesangial cells cultivated under diabetic conditions and this effect was associated with regulating the p44/42, p38, Jun amino-terminal kinases (JNKs)/SAPK of the mitogen activated protein kinase (MAPK) signal pathways, and Akt phosphorylation levels [60], indicating that Rb1 may be used as a remedy for DN, a major complication of diabetes mellitus
Summary
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia caused by insufficient insulin secretion and/or insulin action. The increased prevalence of DM, especially type 2 diabetes (T2DM) [1,2,3], is a multi-factor disease resulting from both genetic factors, such as obesity, impaired postprandial insulin secretion, and partial pancreatic ß-cell damage, and environmental factors, including obesity, unhealthy dietary patterns, lack of exercise, and aging [4]. These factors lead to persistent hyperglycemia and a subsequent decrease in insulin sensitivity, which in turn causes a series of metabolic disorders [5]. Systematic review and analysis of preclinical studies of ginsenoside Rb1 against diabetes and its complications were to be carried out, all evidence available from animal experiments or preceding
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