Gambogenic acid protects against high glucose-induced damage of renal tubular epithelial cells by inhibiting pyroptosis through regulating the AMPK–TXNIP pathway

Ningxu Li; Xiuying Wen; Mingjuan Tang; Xiangmei  Peng; Qizhi Sheng; Ping Liu

doi:10.15586/qas.v14i2.990

Ningxu Li

Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Xiuying Wen

Department of Traditional Chinese Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Mingjuan Tang

Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Xiangmei Peng

Department of Nephrology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Qizhi Sheng

Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Ping Liu

Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Keywords

AMPK–TXNIP, gambogenic acid, high glucose, inflammation, pyroptosis, renal tubular epithelial cells

Abstract

Diabetic nephropathy, a chronic inflammatory disease, is characterized by hyperglycemia-stimulated pyroptosis of renal tubular epithelial cells. Gambogic acid, a primary component of gamboge resin, exerts detoxification, antioxidant, anticancer, anti-angiogenesis and anti-inflammatory capacities. However, the nephroprotective effect of gambogic acid on diabetic nephropathy remains unknown. Human kidney (renal) epithelial cell line HK-2 was treated with dextrorotatory-glucose (D-glucose) to establish an in vitro cell model of diabetic nephropathy, followed by incubation with gambogic acid. CCK-8 was designed to detect cell viability. Enzyme-linked-immunosorbent serologic assay (ELISA) was used to detect the levels of inflammation-related factors. Pyroptosis and underlying mechanism were investigated by Western blot assay. High glucose treatment decreased the viability of HK-2 cell line, while gambogic acid incubation restored the reduced cell viability. High glucose-induced increase in the levels of tumor necrosis factor-α (TNF-α), Interleukin (IL)-6, Monocyte chemoattractant protein-1 (MCP-1) and IL-1β were reduced by gambogic acid. The protein expressions of NLR family pyrin domain containing 3 (NLRP3), N-terminal domain of gasdermin D (GSDMD-N), caspase-1, IL-1β and IL-18 were up-regulated in HK-2 cells after high glucose condition, while down-regulated by incubation of gambogic acid. Gambogic acid attenuated high glucose-induced increase of thioredoxin-interacting protein (TXNIP) and phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) in HK-2 cell line. Gambogenic acid protected renal tubular epithelial cells against high glucose-induced inflammation and pyroptosis through suppression of AMPK–TXNIP pathway, providing a potential strategy for the prevention of diabetic nephropathy.

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