<p>Mogroside IIIE Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Podocytes by the Activation of AMPK/SIRT1 Signaling Pathway</p>

Abstract

Background: Diabetic nephropathy (DN) is the leading cause of impaired renal function. The purpose of this study was to investigate the effects of Mogroside IIIE (MG IIIE), a cucurbitane-type compound isolated from Siraitia grosvenorii, in high glucose (HG)induced podocytes and the possible mechanisms. Methods: MPC-5 cells were cultured under normal glucose or HG conditions. After treatment with MG IIIE, cell viability was examined using a cell counting kit-8 assay. The contents of inflammatory factors and oxidative stress-related markers were determined using the corresponding kits. Additionally, apoptosis of MPC-5 cells was determined using flow cytometry assay and the levels of apoptosis-associated proteins were evaluated by Western blot analysis. Moreover, the expression of proteins in AMPK/SIRT1 signaling was tested and the compound C, an AMPK inhibitor, was used to study whether the effects of MG IIIE on HG-induced MPC-5 cells were mediated by activation of the AMPK/SIRT1 signaling pathway. Results: MG IIIE elevated the cell viability of HG-induced MPC-5 cells, reduced the concentrations of inflammatory cytokines and decreased the levels of oxidative stressrelated markers. What's more, the apoptosis of podocytes induced by HG was inhibited after MG IIIE intervention, accompanied by the upregulated expression of Bcl-2 and downregulated expression of Bax, cleaved caspase-3 and cleaved caspase-9. It was also found that MG IIIE could activate the AMPK/SIRT1 signaling, but compound C inhibited this pathway and reversed the inhibitory effects of MG IIIE on inflammation, oxidative stress and apoptosis in HG-stimulated podocytes. Conclusion: MG IIIE can alleviate HG-induced inflammation and oxidative stress of podocytes by the activation of AMPK-SIRT1 signaling.

AMPK-SIRT1 Pathway Modulates The Apoptosis, Proliferation and Migration of AR42J Cells By Regulating p53 and NF-κB

“…SIRT1 is a downstream effector of AMPK, and shares common characteristics with AMPK in metabolism and cell survival [9] . A large number of studies have indicated that AMPK-SIRT1 pathway is involved in a variety of diseases, including cerebral ischemic stroke, liver cancer, diabetic nephropathy, rheumatoid arthritis, sepsis, and Alzheimer's disease [14,15,23,24,25] . However, the role of AMPK-SIRT1 pathway in AP has not been determined, which remains to be investigated.…”

“…The deletion of AMPK promoted the growth of HCC cells [14] . In a recent study, it was found that Mogroside IIIE alleviated the in ammation, oxidative stress and apoptosis of mercury-induced podocyte by activating the AMPK-SIRT1 pathway, while Compound C signi cantly reversed the inhibitory effects of Mogroside IIIE by inhibiting AMPK-SIRT1 pathway [15] . Similarly, in oxygen glucosedeprivation (OGD)-induced myocardial cell injury model, activated AMPK/SIRT1 pathway by Arctigenin down-regulated NF-κB phosphorylation, while inhibited AMPK by the Compound C signi cantly attenuated Arctigenin-exerted protective effects on cardiomyocytes [16] .…”

The Multiple Roles of Fibroblast Growth Factor in Diabetic Nephropathy

“…154 SIRT1 regulates inflammatory responses by deacetylating target molecule, which downregulates transcription of inflammation-related genes by inhibiting the activity of transcription factor NF-κB. 155 Therefore, over-whelming evidence shows that AMPK/ SIRT1 activation reduces renal inflammation, oxidative stress and podocyte apoptosis in DN patients, thus protecting against kidney damages. 156,157 AMPK and SIRT1 are downstream kinases for FGF21.…”

Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model

“…Among them, MGE Ⅱe is primarily present in the unripe fruit of Siraitia grosvenorii (Swingle) C. Jeffrey ( Xiao et al, 2020 ). Studies have shown that MGE reduces blood glucose and lipid levels in diabetic mice, eliminates reactive oxygen species in vitro ( Zhang et al, 2018 ; Liu et al, 2019 ; Zhang et al, 2020 ), and alleviates high glucose-induced inflammation and oxidative stress in podocytes in vitro ( Xue et al, 2020 ). However, whether MGE IIe can improve T2D cardiomyopathy by inhibiting cardiomyocyte apoptosis is unclear.…”