title: Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway.
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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Endocrine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Endocrine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Wai W
authors.initials: WW
authors.lastname: Cheung
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China. Electronic address: 1649405216@qq.com.
authors.forename: Ren
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: lantian012345@163.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000633:toxicity; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D006984:Hypertrophy; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D009249:NADP / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin
chemical_list: D004224:Diterpenes; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C030419:andrographolide; D009249:NADP; D013311:Streptozocin; D004247:DNA; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Akt; Andrographolide; Diabetic nephropathy; Inflammation; NF-κB; Oxidative stress