Combination of Ginsenoside Rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-β1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy

Abstract

IntroductionAnti-oxidative stress and inhibition of TGF-β1/Smads signaling cascade are essential therapeutic strategies for diabetic nephropathy (DN). In this study, we aimed to explore the effect of combination of Ginsenoside Rg1 and Astragaloside IV on oxidative stress and TGF-β1/Smads signaling in DN rats.Materials and methodsWistar rats were divided into five groups: N group, M group (streptozotocin [STZ], intraperitoneally), G group (STZ rats with Ginsenoside Rg1, intragastrically [ig]), A group (STZ rats with Astragaloside IV, ig) and C group (STZ rats with Ginsenoside Rg1 and Astragaloside IV, ig). The levels of methane dicarboxylic aldehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-PX), total anti-oxidative capacity (T-AOC), blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (SCr) and urinary creatinine (UCr) were detected in all the groups. The left kidneys of the rats were harvested to detect the expression of TGF-β1, Smad2/3, Smad7 and CTGF by immunohistochemical staining, while the right kidneys were used to detect the mRNA expression of TGF-β1, Smad7 and CTGF by real-time PCR.ResultsRats in G group, A group and C group had lower level of MDA but higher levels of CAT, GSH-PX and T-AOC compared with rats in M group. Rats in C group showed the best anti-oxidative stress level. G group, A group and C group treatments significantly decreased the levels of BUN, SCr, β2-MG and UCr. In addition, C group treatment showed the best kidney protective effect. G group, A group and C group treatments significantly diminish ED both factor and mRNA overexpression of TGF-β1 and CTGF but increase Smad7 expression in kidney tissue.ConclusionThe combination of Ginsenoside Rg1 and Astragaloside IV may potentially protect against DN by reducing oxidative stress and inhibiting TGF-β1/Smads signaling cascade.

Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 β/β‐Catenin Pathway by Restoring Autophagic Activity

“…In addition, studies show that ginsenoside Rg1 can alleviate liver fibrosis, chronic obstructive pulmonary disease, and [20][21][22]. Previous studies show that ginsenoside Rg1 combined with astragaloside IV can protect renal function, which may be related to antioxidant stress and inhibition of TGF-β1/Smads pathway [23]. In this study, we confirmed the protective effect of ginsenoside Rg1 on renal function in diabetic nephropathy rats and further examined the effects of ginsenoside Rg1 on autophagic activity and podocyte EMT.…”

Diverse Role of TGF-β in Kidney Disease

“…A. Mey and Astragaloside IV from Radix astragali have also improved fibrosis and inflammation in STZ-induced diabetic nephropathy by inhibiting TGF-β/Smad2/3 while enhancing Smad7 signaling (Du et al, 2018). Asperulosidic acid, a bioactive iridoid glycoside, can also exert renal protective effects by inactivating both TGF-β/Smad and NF-κB signaling pathways (Xianyuan et al, 2019).…”

Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF‐κB/NLRP3 Axis

“…Furthermore, the inhibitory effects of Rg1 on the activation of NLRP3 were reversed by LEU, which strongly suggested that Rg1 decreased hyperlipidemia-induced pyroptosis in podocytes by inhibiting the mTOR/NF- κ B/NLRP3 axis. A previous study showed that the combination of Rg1 and astragaloside relieved renal fibrosis in DN by inhibiting the TGF- β 1/Smads pathway and oxidative stress [ 33 ]. Consistent with this, Rg1 significantly reduced proteinuria, improved renal function, and alleviated tissue damage in diabetic rats.…”

“…Four weeks after STZ injection, the successfully modelled DN rats were randomly divided into the (untreated) DN and ginsenoside Rg1-treated groups ( n = 8 in each group) and administered with vehicle (aqua distillate) or 50 mg/kg ginsenoside Rg1 once daily by oral gavage for 8 weeks. This dose of ginsenoside Rg1 has been proved to be effective and safe [ 33 ]. At the end of the regimen, the rats were anaesthetized adequately; then, the urine creatinine (UCr), urinary microalbumin (Malb), blood urea nitrogen (BUN), and serum creatinine (Scr) levels were measured.…”