Ginsenoside Rg1 ameliorates cardiac oxidative stress and inflammation in streptozotocin-induced diabetic rats

Abstract

Background and purpose: Ginsenoside Rg1 (GS Rg1), as an important active substance of Panax ginseng, has been proven to have elaborate cardioprotective effects. The purpose of this study was to detect that GS Rg1 attenuates cardiac oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats (DM). Methods: Cardiac function was assessed by heart rate and blood pressure. Markers relevant to myocardial oxidative stress and antioxidant capacity, and inflammatory reaction factors were detected. The mRNA and protein expression were detected by RT-qPCR and Western blot, respectively. Results: GS Rg1 treatment significantly reduced the symptoms of cardiac hypertrophy and hypertension, and also decreased oxidative stress, inflammation response, NF-κB expression and NLRP3 inflammasome expression. GS Rg1 enhanced mitochondrial biogenesis by increasing PGC-1α, complex III and complex Ⅳ expression. GS Rg1 treatment significantly increased the expression of AMPK, Nrf2 and HO-1 in cardiac tissues. Conclusion: GS Rg1 exhibited protective effect against STZ-induced cardiac dysfunction, which is potentially associated with AMPK/Nrf2/HO-1 signal pathway.

Keywords: AMPK; Ginsenoside Rg1; HO-1; Nrf; inflammation; oxidative stress.

Figure 1

Effects of GS Rg1 on the indicators in the control and diabetic rats. (A) The MAP levels. (B) The heart rate. (C) The body weight. (D) The hypertrophy index. (E) The blood glucose levels. (F) The LDH levels. (G) The CK-MB levels. (H) The AST levels. P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D. Abbreviations: MAP, mean arterial pressure; LDH, lactate dehydrogenase; CK-MB, creatine kinase-MB; AST, aspartate aminotransferase; C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng Rg1 20mg/kg/day.

Figure 2

Effects of GS Rg1 on the cardiac oxidative stress and antioxidant defense system in control and diabetic rats. (A) Cardiac TBARS levels. (B) Cardiac ROS levels. (C) Cardiac hydrogen peroxide levels. (D) Cardiac peroxynitrite levels. (E) Myocardial SOD levels. (F) Myocardial catalase levels. (G) Myocardial GSH levels. (H) Myocardial GPx levels. P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D. Abbreviations: C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng 20mg/kg/day; TBARS, thiobarbituric acid reactive substances; ROS, reactive oxygen species; SOD, total superoxide dismutase; GSH, reduced glutathione; GPx, glutathione peroxidase.

Figure 3

Effects of GS Rg1 supplementation on cardiac and plasma inflammatory cytokines of control and diabetic rats. (A) Cardiac IL-1β levels. (B) Cardiac IL-6 levels. (C) Cardiac TNF-α levels. (D) Plasma IL-1β levels. (E) Plasma IL-6 levels. (F) Plasma TNF-α levels. The significance was set at P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D. Abbreviations: C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng Rg1 20mg/kg/day; IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumour necrosis factor-α.

Figure 4

Effects of GS Rg1 treatment on inflammatory response in cardiac tissues of control and diabetic rats. (A) NF-κB mRNA expression. (B) TLR4 mRNA expression. (C) NLRP3 mRNA expression. (D) ASC mRNA expression. (E) NF-B protein expression. Values are represented as mean±SD. P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D; ($) vs D+GS Rg1 20. Abbreviations: C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng 20mg/kg/day; CC, compound C; NF-κB, nuclear factor κB; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 5

Effects of GS Rg1 administration on the expression of the mitochondrial biogenesis proteins, Nrf2, HO-1 in the hearts of control and diabetic rats. (A) mRNA expression of PGC-1α. (B) mRNA expression of Nrf2. (C) mRNA expression of HO-1. (E) protein expression of PGC-1α. (F) protein expression of complex III. (G) protein expression of complex V. P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D; ($) vs D+GS Rg1 20. Abbreviations: C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng 20mg/kg/day; CC, compound C; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, hemeoxygenase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 6

Effects of GS Rg1 administration on the protein expression levels of AMPK/Nrf2/HO-1 signaling components in the hearts of control and diabetic rats. Myocardial expression of (A) AMPK, p-AMPK; (B) Nrf2 and (C) HO-1. Values are represented as mean±SD. P<0.05. (*) vs C; (#) vs C+GS Rg1 20; (&) vs D; ($) vs D+GS Rg1 20. Abbreviations: C, control; D, STZ-induced diabetic; GS Rg1 20, ginseng 20mg/kg/day; CC, compound C; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, hemeoxygenase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.