Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway. (5th December 2016)

• Record Type: Journal Article
• Authors: Ji, Xiaoqian; Li, Changzheng; Ou, Yitao; Li, Ning; Yuan, Kai; Yang, Guizhi; Chen, Xiaoyan; Yang, Zhicheng; Liu, Bing; Cheung, Wai W.; Wang, Lijing; Huang, Ren; Lan, Tian
• Is Part Of: Molecular and cellular endocrinology. Volume 437(2016)
• Page Start: 268
• Page End: 279
• Publication Date: 2016-12-05
• Subjects: Andrographolide -- Diabetic nephropathy -- Oxidative stress -- Inflammation -- Akt -- NF-κB; ROS reactive oxygen species -- NADPH nicotinamide adenine dinucleotide phosphate -- 4-HNE 4-hydroxynonenal -- NAC N-acetyl-L-cysteine -- PDTC ammonium pyrrolidinedithiocarbamate -- PAS Periodic Acid-Schiff -- FN fibronectin -- TGF-β1 transforming growth factor-β1 -- TNF-α tumor necrosis factor alpha -- PCNA proliferating cell nuclear antigen -- STZ streptozotocin -- ND normal diet -- HFD high-fat diet -- HG high glucose -- ECM extracellular matrix -- MCs mesangial cells -- DN diabetic nephropathy; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.06.029
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-κB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. Highlights: Andrographolide improved metabolic parameters and renal function of diabetic mice with nephropathy. Andrographolide suppressed the overdeposition of extracellular matrix in diabetic kidney and mesangial cells. Andrographolide suppressed NOX1 expression, ROS production in diabetic nephropathy. Andrographolide suppressed mesangial proliferation and inflammation in diabetic nephropathy. Andrographolide attenuated Akt/NF-κB signaling pathway in diabetic nephropathy.