# Hepato-renal protection by ferulic acid in a type 2 diabetic rat model: in vivo and in silico insights into carbohydrate metabolism, REDOX balance, and inflammation modulation

## TL;DR

Ferulic acid protects the liver and kidneys in diabetic rats by improving metabolism, reducing oxidative stress, and lowering inflammation.

## Contribution

This study demonstrates ferulic acid's hepato-renal protective effects in T2D through in vivo and in silico mechanisms.

## Key findings

- FA improved pancreatic β-cell function, insulin levels, and reduced glucose and glycosylated hemoglobin.
- FA enhanced antioxidant status and reduced inflammatory markers in liver and kidney tissues.
- Molecular docking showed FA has stronger binding affinity to diabetes-related proteins than metformin.

## Abstract

Type 2 diabetes (T2D) is a global health concern characterized by pancreatic β-cell dysfunction, which disrupts multiple biochemical pathways. Consequently, treatments that target various pathways are essential. This study evaluates the hepato-renal protective effects of ferulic acid (FA) in T2D, focusing on carbohydrate metabolism, oxidative stress, and inflammation using in vivo and in silico approaches.

T2D was induced in male Wistar rats using fructose and streptozotocin. After 28 days of FA treatment, biochemical analyses were performed to measure glucose, glycosylated hemoglobin, insulin, liver enzymes (ALT, AST, ALP), renal markers (creatinine, uric acid, BUN), and antioxidant status (SOD, CAT, GSH, MDA) in the liver and kidney. Pro-inflammatory markers (NF-κB-p65, IL-1β, IL-6) were evaluated in the liver and kidney. Molecular docking studies were also conducted to assess FA’s interaction with key T2D-related proteins.

FA treatment improved pancreatic β-cell function, increased insulin levels, and reduced serum glucose and glycosylated hemoglobin. Liver function, renal markers, and hepatic glycogen content improved significantly, and diabetes-induced weight loss was reversed. FA inhibited pancreatic α-amylase, intestinal α-glucosidase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, while enhancing hexokinase activity. Notably, FA improved antioxidant status and reduced inflammatory mediators in diabetic rats. Molecular docking revealed that FA exhibits stronger binding affinity and greater inhibitory potential against key diabetes-related proteins compared to metformin.

FA offers hepato-renal protection in T2D by modulating carbohydrate metabolism, oxidative stress, and inflammation, highlighting its potential as a therapeutic agent against T2D.