# Cinnamaldehyde ameliorates obesity-induced nephropathy in C57BL/6 mice via modulation of AMPK/ACC and NF-kB pathways

## TL;DR

Cinnamaldehyde helps protect the kidneys in obese mice by targeting specific biological pathways linked to obesity-related kidney damage.

## Contribution

This study demonstrates that cinnamaldehyde ameliorates obesity-induced nephropathy via AMPK/ACC and NF-kB pathways in mice.

## Key findings

- Cinnamaldehyde significantly reduced body weight, blood glucose, and inflammatory markers in obese mice.
- Cinnamaldehyde improved kidney function and reduced histopathological damage in HFD-fed mice.
- Molecular docking and immunohistochemistry confirmed AMPK/ACC and NF-kB pathway modulation by cinnamaldehyde.

## Abstract

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.

In silico studies showed strong binding of Cinnamaldehyde with AMPK and NF-kB. Cinnamaldehyde showed a significant (P<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 (P<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.