Gupta Himani, Bhandari Uma
Department of Pharmacology, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi-110062, India.
Iran J Basic Med Sci. 2025;28(7):60-872. doi: 10.22038/ijbms.2025.83913.18157.
Chronic kidney disease (CKD) is a life-threatening condition often resulting from obesity and other pathologies. The present study assesses the nephroprotective effect of Cinnamaldehyde against high-fat diet (HFD) obesity-associated nephropathy in rodents.
The molecular docking analysis on AMPK & NF-kB was carried out to identify possible targets of Cinnamaldehyde. In preclinical study, 4-week-old C57BL/6 mice (18-20 gm) were fed a conventional diet or HFD for 12 weeks After the fifth week of HFD intervention, mice were divided into six groups (n=10): vehicle group; HFD group; HFD+CA (20 mg/kg); HFD+CA (40 mg/kg); HFD+Orlistat (10 mg/kg); and CA Perse (40 mg/kg) treated orally for 49 days. On day 84, mice were fasted overnight, and urine and blood were collected for various biochemical analyses. Animals were sacrificed, and kidneys were removed for histopathology and immunohistochemistry.
studies showed strong binding of Cinnamaldehyde with AMPK and NF-kB. Cinnamaldehyde showed a significant (<0.001) decrease in BW, BMI, blood glucose, leptin, insulin, HOMA-IR, total cholesterol, triglycerides, creatinine, albumin, TNF-α, IL-6, and IL-β in serum and urinary albumin. It also produced a significant (<0.001) reduction in KIM-1, type-IV collagen, IL-18, and NGAL urinary levels. Further, it produced a significant (P<0.001) increase in urine creatinine, serum adiponectin, and kidney SOD, GSH, GST, and GPx. Immunohistology indicated suppressed NF-kB and activated AMPK/ACC pathways. Histopathology showed improvement in glomerular inflammation, tubular injury, and degeneration in kidney tissue.
Cinnamaldehyde significantly protects against obesity-associated nephropathy in C57BL/6 mice by HFD via modulating the AMPK/ACC and NF-kB pathways.
慢性肾脏病（CKD）是一种常由肥胖和其他病理状况导致的危及生命的疾病。本研究评估肉桂醛对啮齿动物高脂饮食（HFD）肥胖相关肾病的肾保护作用。
对AMPK和NF-κB进行分子对接分析，以确定肉桂醛的可能靶点。在临床前研究中，将4周龄的C57BL/6小鼠（18 - 20克）喂食常规饮食或高脂饮食12周。在高脂饮食干预的第五周后，将小鼠分为六组（n = 10）：溶剂对照组；高脂饮食组；高脂饮食 + 肉桂醛（20毫克/千克）组；高脂饮食 + 肉桂醛（40毫克/千克）组；高脂饮食 + 奥利司他（10毫克/千克）组；以及肉桂醛单独（40毫克/千克）口服给药49天组。在第84天，小鼠禁食过夜，收集尿液和血液用于各种生化分析。处死动物，取出肾脏进行组织病理学和免疫组织化学检查。
研究表明肉桂醛与AMPK和NF-κB有强烈结合。肉桂醛使体重、体重指数、血糖、瘦素、胰岛素、HOMA-IR、总胆固醇、甘油三酯、肌酐、白蛋白、血清和尿白蛋白中的TNF-α、IL-6和IL-β显著（<0.001）降低。它还使尿KIM-1、IV型胶原、IL-18和NGAL水平显著（<0.001）降低。此外，它使尿肌酐、血清脂联素以及肾脏中的超氧化物歧化酶、谷胱甘肽、谷胱甘肽S-转移酶和谷胱甘肽过氧化物酶显著（P<0.001）升高。免疫组织学显示NF-κB受到抑制，AMPK/ACC途径被激活。组织病理学显示肾脏组织中的肾小球炎症、肾小管损伤和变性有所改善。
肉桂醛通过调节AMPK/ACC和NF-κB途径，显著保护C57BL/6小鼠免受高脂饮食引起的肥胖相关肾病的侵害。
