Sorghum bicolor polyphenol-rich extract improves insulin sensitivity and protect against chronic stress exacerbated diabetic nephropathy through modulation of Nrf2/NF-κB

Introduction

Sorghum bicolor leaf sheath is known for its rich phytoconstituents 3-in deoxyanthocyanidins with protective and health benefits in targeting oxidative stress, inflammation and apoptosis. This study aimed to investigate Sorghum bicolor polyphenol-rich extract (SBPE) and its combination with metformin on insulin resistance and diabetic nephropathy in high-fat/streptozotocin-induced diabetic rats exposed to chronic stress.

Methods

Antidiabetic and nephroprotective effects of SBPE was investigated in male Wistar rats fed with high-fat diet and injected streptozotocin (35 mg/kg) intraperitoneally. Diabetic rats were exposed to chronic unpredictable mild stress and orally treated with SBPE (200 mg/kg), metformin (250 mg/kg) and SBPE + metformin for 28 days. Kidney function parameters, FBS, insulin, adiponectin, kidney injury marker (KIM-1), triglycerides were determined. Renal tissues inflammatory (TNF-α, IL-1β, IL-10), oxidative stress, apoptotic (caspase-3,-9) and transcriptional factors (Nrf2 and NF-κB) were determined as well as histology.

Results

SBPE significantly reduced FBS, triglycerides insulin and parameters for insulin resistance in diabetic rats exposed to stress. Dysregulated electrolytes, urea, creatinine, adiponectin and KIM-1 were significantly reversed in SBPE and SBPE + metformin groups. SBPE treatment significantly reduced MDA, nitrites, TNF-α, and IL-1β levels, while GSH, catalase, SOD, GST and IL-10 were increased in renal tissues. Increased apoptotic markers (caspase-3, caspase-9) and NF-κB, along with reduced Nrf2 levels, were significantly reversed by SBPE and SBPE + metformin. Distorted kidney histomorphoarchitecture was reversed in SBPE-treated groups.

Conclusion

Sorghum bicolor polyphenol-rich extract and its combination with metformin showed promising antidiabetic effects in stress-exacerbated diabetes in rats through improving insulin sensitivity and nephroprotective mechanisms.