Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

Kidney structural integrity is critical for bodily excretory mechanism. Diabetes has been considered as one of the major risk factors for chronic kidney disease, but the underlying mechanism remains elusive. The present study investigates the transcriptomic and proteomic profiling of long-term impact of high-fat diet on renal tissue in mice and role of dehydrozingerone (DH) in reinstating the normal kidney function. Animals were divided into four groups- healthy (NCD+Veh), diabetic (HFD-STZ), healthy+DH (NCD+Veh+DH) and treatment (HFD-STZ+DH). 65th days of HFD-fed C57BL/6 mice developed diabetes and kidney dysfunction evident by albuminuria, proteinuria, and glucotoxicity with accumulation of glucose, triglyceride, cholesterol, and total protein in blood serum. The HFD-fed kidney showed renal injuries, including prominent defects in the glomerular filtration system by downregulation of proteins involved in transport, metabolic process, energy production, anti-oxidation, etc. Downregulation of lipid metabolism is most impacted metabolic process under diabetic condition. Downregulation of transport proteins mainly impact the functioning of podocytes, cell adhesion and cytoskeletal rearrangement. HFD feeding also increased oxidative stress and induced mitochondrial dysfunction, and thereby activating the pro-apoptotic pathway. Both transcriptomic and proteomic studies revealed the potential of Dehydrozingerone in attenuating the diabetic condition by positively regulating transport system, mitochondrial function, lipid metabolism, DNA damage and epigenetic alteration, and oxidative stress, which reinstate the kidney function.

肾脏结构的完整性对于机体的排泄机制至关重要。糖尿病已被视为慢性肾脏病的主要风险因素之一，但其潜在机制仍难以捉摸。本研究旨在探究高脂肪饮食对小鼠肾脏组织长期影响的转录组学和蛋白质组学特征，以及脱氢姜酮（DH）在恢复正常肾脏功能中的作用。动物被分为四组：健康组（NCD+Veh）、糖尿病组（HFD-STZ）、健康+DH组（NCD+Veh+DH）和治疗组（HFD-STZ+DH）。在高脂肪饮食喂养的第65天，C57BL/6小鼠出现糖尿病和肾脏功能障碍，表现为蛋白尿、白蛋白尿和葡萄糖毒性，血液血清中葡萄糖、甘油三酯、胆固醇和总蛋白的积累。高脂肪饮食喂养的肾脏表现出肾损伤，包括肾小球过滤系统中蛋白质在运输、代谢过程、能量产生、抗氧化等方面的显著下调。在糖尿病条件下，脂质代谢的下调是最受影响的代谢过程。运输蛋白的下调主要影响足细胞的机能、细胞粘附和细胞骨架的重排。高脂肪饮食喂养还增加了氧化应激并诱导线粒体功能障碍，从而激活促凋亡途径。转录组学和蛋白质组学研究揭示了脱氢姜酮通过正向调节运输系统、线粒体功能、脂质代谢、DNA损伤和表观遗传修饰、氧化应激等途径，减轻糖尿病状况的潜力，从而恢复肾脏功能。