Cinnamaldehyde ameliorates obesity-induced nephropathy in C۵۷BL/۶ mice via modulation of AMPK/ACC and NF-kB pathways

Objective(s): 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.Materials and Methods: The molecular docking analysis on AMPK & NF-kB was carried out to identify possible targets of Cinnamaldehyde. In preclinical study, ۴-week-old C۵۷BL/۶ mice (۱۸–۲۰ gm) were fed a conventional diet or HFD for ۱۲ weeks After the fifth week of HFD intervention, mice were divided into six groups (n=۱۰): vehicle group; HFD group; HFD+CA (۲۰ mg/kg); HFD+CA (۴۰ mg/kg); HFD+Orlistat (۱۰ mg/kg); and CA Perse (۴۰ mg/kg) treated orally for ۴۹ days. On day ۸۴, 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.Results: In silico studies showed strong binding of Cinnamaldehyde with AMPK and NF-kB. Cinnamaldehyde showed a significant (P<۰.۰۰۱) decrease in BW, BMI, blood glucose, leptin, insulin, HOMA-IR, total cholesterol, triglycerides, creatinine, albumin, TNF-α, IL-۶, and IL-β in serum and urinary albumin. It also produced a significant (P<۰.۰۰۱) reduction in KIM-۱, type-IV collagen, IL-۱۸, and NGAL urinary levels. Further, it produced a significant (P<۰.۰۰۱) 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. Conclusion: Cinnamaldehyde significantly protects against obesity-associated nephropathy in C۵۷BL/۶ mice by HFD via modulating the AMPK/ACC and NF-kB pathways.

کلیدواژه ها:

AMPK pathway ، Cinnamaldehyde ، Inflammation ، NF-kB pathway ، Obesity-associated - nephropathy ، Oxidative stress