20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

Abstract

Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis

“…Ginsenoside Rg3 suppresses tumour growth by enhancing apoptosis, decelerating proliferation, metastasis, and angiogenesis, increasing the chemosensitivity of tumour cells, and promoting host immunity [ 11 ]. As a multifunctional factor, Rg3 can also exert a protective effect on diabetic kidney disease by repressing the inflammatory response [ 30 ]. Additionally, Rg3 effectively ameliorated LPS-induced acute lung injury through certain specific pathways [ 14 , 31 , 32 ].…”

Pharmacological properties, molecular mechanisms and therapeutic potential of ginsenoside Rg3 as an antioxidant and anti-inflammatory agent

“…The NF-κB signaling cascade is the initial event in response to oxidative stress in diabetes ( Archuleta et al, 2009 ). A study showed that Rg3 decreased urine protein associated with DN in a rat model via inhibition of NF-κB p65 ( Zhou et al, 2020 ). Another study found that 20(S)-Rg3 ameliorated renal histopathological injury and dyslipidemia through the MAPK and NF-κB pathways in C57BL/6 mice with an intraperitoneal injection of STZ and a high-fat diet (HFD).…”

“…For diabetic complications, inhibition of the apoptotic signaling pathway can protect renal tissue in DN. Rg3 protected renal tubular epithelial cells from apoptosis in vitro ( Zhou et al, 2020 ). Li et al suggested that Rg3 reduced Bax and cleaved caspase3 and enhanced the expression of Bcl-2 and Bcl-XL to inhibit apoptosis in the kidneys of DN mice ( Li et al, 2021 ).…”

“…In metabolic diseases, Rg3 reduces FBG, glycosylated protein and blood lipids in diabetic rats ( Kang et al, 2008 ; Li et al, 2021 ). Rg3 improves CRE and urine protein elevation in DN mice by increasing antioxidant activity and reducing renal inflammation ( Zhou et al, 2020 ; Li et al, 2021 ). Rg3 inhibited the proliferation and metastasis of various cancer cells, such as liver cancer cells, intestinal cancer cells, osteosarcoma cells, etc.…”

Efficacy of Tripterygium Glycosides for Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials

“…pathological changes of clinical DN patients are characterized by glomerular mesangial matrix expansion, glomerular basement membrane (GBM) thickening, and formation of glomerular nodular sclerosis [2][3] . The clinical manifestations of DN include hypertension, massive proteinuria, edema, and progressive decrease in renal function [4] . The precise mechanisms of DN pathogenesis are yet to be fully elucidated.…”