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

Tao Wang,Jiayi Xu,Xiaolei Wang,Yanbin Gao,Rongchuan Yue,Bingjie Wu,Yimin Shi,Yimeng Li

doi:10.1155/2020/2735714

Abstract

Background Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. Methods In vitro and in vivo models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry. Results Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats. Conclusion Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/NLRP3 axis, indicating a potential therapeutic function in DN.

Highlights

Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), and the primary cause of end-stage renal diseases (ESRD) [1]
E pyroptotic cascade is triggered by the nucleotide oligomerization domain- (NOD-) like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex consisting of NLRP3, apoptosis-associated speck-like protein (ASC) with caspase recruitment domain (CARD) domain and procaspase-1 [8, 9], and the downstream inflammatory pathway is driven by caspase-1 [10, 11]
Recent studies show that high glucose and fat levels can activate NLRP3 inflammasomes and caspase-1 triggered pyroptosis [15, 16]. e inflammatory mammalian target of rapamycin (mTOR)-NLRP3-IL-1β axis is activated during lung injury, and its inhibition can reduce the immunopathological damage in lung tissues [17]

Summary

Introduction

Diabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), and the primary cause of end-stage renal diseases (ESRD) [1]. Recent studies show that high glucose and fat levels can activate NLRP3 inflammasomes and caspase-1 triggered pyroptosis [15, 16]. E inflammatory mTOR-NLRP3-IL-1β axis is activated during lung injury, and its inhibition can reduce the immunopathological damage in lung tissues [17]. E aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. Rg1 inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/ NLRP3 axis, indicating a potential therapeutic function in DN

Methods

Results

Conclusion