Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway. (March 2020)

• Record Type: Journal Article
• Authors: Yang, Shu; Ma, Chuanrui; Wu, Han; zhang, Hao; Yuan, Fengyi; Yang, Guangyan; Yang, Qi; Jia, Lijing; Liang, Zhen; Kang, Lin
• Is Part Of: Pharmacological research. Volume 153(2020)
• Publication Date: 2020-03
• Subjects: ACC acetyl-CoA carboxylase 1 -- ACOX1 acyl-CoA oxidase 1 -- AdipoR adiponectin receptor -- Arg1 arginase 1 -- AUC area under the curve -- BAX BCL2 associated X protein -- Ccr creatine clearance ratio -- Chi3l3 chitinase-like 3 -- Col4α1 collagen type IV alpha 1 Chain -- CPT1α carnitine palmitoyl transferase 1 alpha -- Cr creatine -- CXCL1 C-X-C motif chemokine ligand 1 -- FBS fasting blood sugar -- FOXO1 forkhead box O1 -- GLUT4 glucose transporter type 4 -- HOMA-IR homeostasis model assessment-insulin resistance -- IFN-γ Interferon gamma -- NF-Kappa-B Inhibitor alpha -- IL-4/6/10 interleukin-4/6/10 -- IRS1 insulin receptor substrate 1 -- LCAD long-chain acyl-CoA dehydrogenase -- LKB1 liver kinase B1 -- MCAD medium-chain acyl-CoA dehydrogenase -- Mgl2 macrophage lectin 2 -- Mrc1 mannose receptor C-type 1 -- NEFA non-esterified fatty acid -- NOS2 nitric oxide synthase 2 -- PA palmitate acid -- PAS periodic acid-Schiff stain -- PPARα peroxisome proliferator activated receptor alpha -- SREBP1c sterol regulatory element-binding protein 1 -- T−CHO total cholesterol -- TG triglycerides -- TGF-β1 transforming growth factor beta 1 -- TNFα tumor necrosis factor alpha; Hematoxylin (PubChem CID: 442514) -- Eosin (PubChem CID: 11048) -- Tectorigenin (PubChem CID: 5281811) -- Oil red O (PubChem CID: 62330); Tectorigenin -- Diabetic nephropathy -- Adiponectin receptor1/2 -- Endothelium function -- Macrophage polarization; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104678
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage renal disease worldwide. However, therapeutic drugs for DN treatment are still in lack. The glomerular endothelium is essential to maintain selective permeability of glomerular filtration barrier and glomerular vasculature function. Growing evidences show that endothelial dysfunction or injury is the initial stage of vascular damage in DN, which can be induced by hyperglycemia, lipotoxicity, and inflammation. Therefore, to improve the function of vascular endothelium in kidney is a key point for treatment of DN. As a plant isoflavone, tectorigenin (TEC) has attracted considerable attention due to its anti-proliferative and anti-inflammatory functions. However, whether TEC could inhibit the DN development remains unknown. In this study, we examined the effects of TEC on DN development in db/db mice, a type of genetic defect diabetic mice that can spontaneously develop into severe renal dysfunction. Intriguingly, TEC treatment restored diabetes-induced glucose and lipid metabolic disorder; and improved the deterioration of renal function, particularly the renal endothelium function in db/db mice. Additionally, TEC inhibited the renal inflammation via reducing macrophages infiltration and M1 polarization. Moreover, TEC inhibited lipopolysaccharide (LPS)-induced endothelial injury and M1 polarization in vitro . Mechanistically, TEC partially restored the reduction in expression of adiponectin receptor 1/2 (AdipoR1/2), pi-LKB1, pi-AMPKα, and PPARα in vitro and in vivo . Noteworthy, these beneficial pharmacological activities mediated by TEC were significantly attenuated after AdipoR1/2 knockdown by siRNA, indicating that AdipoR1/2 plays a critical role in protection against DN. Collectively, these results suggested that TEC have a potently effect for retarding type 2 diabetes–associated DN.