ginsenoside-m1 and Diabetic-Nephropathies

Diabetic kidney disease (DKD) is a common and devastating complication in diabetic patients, which is recognized as a large and growing problem leading to end-stage kidney disease. As dietary-mediated therapies are gradually becoming more acceptable to patients with DKD, we planned to find active compounds on preventing DKD progression from dietary material. The present paper reports the renoprotective properties and underlying mechanisms of ginsenoside compound K (CK), a major metabolite in serum after oral administration of ginseng. CK supplementation for 16 weeks could improve urine microalbumin, the ratio of urinary albumin/creatinine and renal morphological abnormal changes in db/db mice. In addition, CK supplementation reshaped the gut microbiota by decreasing the contents of

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Kidney; Mice; Toll-Like Receptor 4

Though the antidiabetic effect of ginsenoside compound K (CK) has been well studied, the effect of CK on diabetic nephropathy (DN) is not clear. Whether CK would have a protective effect against DN and it could exert the protective effect by inhibiting the oxidative stress, NLRP3 inflammasome and NF-κB/p38 signaling pathway were investigated in this study. Here, the HFD (high fat diet)/STZ (streptozotocin)-induced DN mice model was established to assess the CK effect in vivo. Parallel experiments uncovering the molecular mechanism by which CK prevents from DN was performed in rat glomerular mesangial cell line HBZY-1 exposed to high glucose. CK (10, 20, 40 mg/kg/day) were intragastrically administered for 8 weeks, the general status, biochemical parameters, renal pathological changes and oxidative stress-parameters were observed, and the NLRP3 inflammasome and NF-κB/p38 signaling pathway were evaluated. The results showed that the elevated fasting blood glucose, serum creatinine, blood urea nitrogen and 24-hour urine protein of the DN mice were significantly decreased, and the proliferation of glomerular mesangial matrix was alleviated by CK. In addition, the generation of ROS in the kidney was significantly decreased, and the expression of Nox1 and Nox4 proteins were down-regulated. Further, the expression of NLRP3 inflammasome components (NLRP3, ASC and Caspase-1) and the inflammatory cytokines IL-1β and IL-18 were also significantly down-regulated in vivo and in vitro. The phosphorylation of renal p38 MAPK was also inhibited by CK. MCC950 (an inhibitor of NLRP3 inflammasome) and VX-765 (a Caspase-1 Inhibitor) showed significant interaction with CK on the decrease of IL-1β concentration in HBZY-1 cells. In conclusion, our study provided evidence that the protective effect of CK on diabetes-induced renal injury is associated with down-regulating the expression of NADHP oxidase, and inhibition of ROS-mediated activation of NLRP3 inflammasome and NF-κB/p38 signaling pathway, suggesting its therapeutic implication for renal inflammation.

Topics: Animals; Cell Line; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diet, High-Fat; Inflammasomes; Kidney; Mice, Inbred C57BL; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; p38 Mitogen-Activated Protein Kinases; Protective Agents; Rats; Sapogenins; Signal Transduction

Purpose: Compound K (CK), the metabolic product of protopanaxadiol saponin in vivo, has many pharmacological activities. In this study, we discuss the preparation of CK, and its protective effect on kidneys of diabetic rats. CK was prepared from ginsenoside Rbt after transformation by 3-glucosidase, separation and purification by silica gel column chromatography. In the present study, we established a rat model of diabetes mellitus using high-fat diet and streptozotocin (STZ). After seven weeks of treatment, the levels of fasting blood glucose (FBG), total cholesterol (TC), total glycerin (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), blood urea nitrogen (BUN), uric acid (UA), serum creatinine (Scr), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) were evaluated in normal and diabetic rats. Also, renal pathomorphism changes were observed by HE stain, and TGF-β1 protein expression in the renal tissue was measured by Western blot. The yield of CK was 14.55 mg/mL, which was higher than that of other methods. After seven weeks, CK could decrease FBG, TC, TG, LDL-C, BUN, UA, Scr and MDA of diabetic rats, while CK also enhanced HDL-C and GSH, SOD and GSH-PX. Additionally, CK improved the pathological changes and decreased TGF-β1 protein expression in the renal tissue. CK improved the pathological changes in the renal tissue, enhanced the antioxidant capacity, reduced the damage of TGF-β1 to renal tissue, and protected the diabetic rats.

Topics: Animals; Biomarkers; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Gene Expression Regulation; Ginsenosides; Kidney; Molecular Structure; Panax; Rats; Transforming Growth Factor beta1