Hydroalcoholic extract of Benincasa hispida reinstates renal functional dynamics compromised under diabetic nephropathy.

Diabetic nephropathy is a common complication of type 2 diabetes. Over time, poorly controlled diabetes can lead to permanent kidney failure. Hyperglycemic condition develops with consistent consumption of high fat diet (HFD). The present study focuses on impact of hyperglycemia on overall kidney development and functioning through whole renal tissue transcriptomics and proteomics profiling. We used C57BL/6 mice for developing HFD-fed hyperglycemic mice to develop type 2 diabetes with renal complications. In the initial observation of blood serum from HFD-fed mice, elevated levels of plasma glucose, triglyceride, urea, cholesterol, and decreased level of creatinine, confirmed the diabetic condition. Benincasa hispida (BH) hydroalcoholic extract was used as treatment option in this study. Our phytochemical analysis showed the presence of wide range of bioactive phytochemical belonging to classes of flavonoid, alkaloid, phenolic, triterpenoid, xanthones, Cucurbitacin E, etc. makes it the perfect herb for various pharmacological uses against kidney diseases. In proteomics and transcriptomics studies, renal structural damage under hyperglycemia was identified through significant downregulation of cytoskeletal organization, microtubules, vesicle transport system, extracellular matrix, and cell-cell adhesion. Downregulation of lipid metabolism and mitochondrial transport system compromised the energy production potential of the renal cellular system, and subsequently the compromised system under hyperglycemia triggered the oxidative stress and various other complications. The present study showcasing the potential of Benincasa hispida as a promising treatment strategy against diabetic nephropathy by reversing the negative impact of hyperglycemia.

糖尿病肾病（Diabetic nephropathy）是2型糖尿病的常见并发症。长期血糖控制不佳的糖尿病可引发永久性肾功能衰竭。长期持续摄入高脂饮食（HFD）会诱发高血糖状态。本研究通过全肾组织转录组学（transcriptomics）与蛋白质组学（proteomics）表征分析，探究高血糖对肾脏整体发育与功能的影响。我们选用C57BL/6小鼠构建高脂饮食诱导的高血糖小鼠模型，以制备伴肾脏并发症的2型糖尿病模型。对高脂饮食小鼠的血清初始检测结果显示，血浆葡萄糖、甘油三酯、尿素、胆固醇水平升高，而肌酐水平降低，证实该糖尿病模型构建成功。本研究选用毛冬瓜（Benincasa hispida, BH）水醇提取物作为治疗制剂。植物化学分析表明，该提取物含有黄酮类、生物碱类、酚类、三萜类、口山酮类、葫芦素E等多种生物活性植物化学成分，使其成为治疗肾脏疾病的优质药用草本。在蛋白质组学与转录组学分析中，我们发现高血糖状态下，肾脏结构损伤相关的细胞骨架组织、微管、囊泡运输系统、细胞外基质及细胞间黏附相关通路均显著下调。脂代谢与线粒体运输系统的下调损害了肾细胞的能量产生能力，进而在高血糖胁迫下触发氧化应激及多种其他并发症。本研究证实，毛冬瓜提取物可逆转高血糖带来的负面影响，有望成为治疗糖尿病肾病的潜在干预策略。