Hesperidin inhibits NOX4 mediated oxidative stress and inflammation by upregulating SIRT1 in experimental diabetic neuropathy

Hesperidin possesses myriads of pharmacological benefits, including anti-inflammatory and antioxidant prop-erties. Herein, we speculated that the described pharmacological benefits of hesperidin might be due to its potentiating action on SIRT1; thereby, inhibition of NOX4. We developed diabetic neuropathy in Sprague-Dawley rats by feeding them a high-fat diet (HFD) for 12 weeks. We checked the effect of hesperidin on the level of oxidative stress, inflammatory markers, NOX4, and SIRT1 by biochemical analysis, histopathology, immunoblotting, immunocytochemistry, and real-time qPCR in HFD-fed rats and Palmitate encountered rat glial C6 cells. Hesperidin administration improved mechanical, thermal allodynia, and glucose homeostasis. There was a decrease in oxidative stress and inflammation and an enhanced level of antioxidant enzymes. Besides, the expression of NOX4 was down-regulated, while SIRT1 was upregulated. Interestingly, hesperidin treatment protected them from oxidative and inflammatory damage by upregulating SIRT1 and inhibiting NOX4 expression.

Automated summary

Hesperidin, a flavonoid, exerts its pharmacological benefits by enhancing SIRT1 and inhibiting NOX4, leading to the improvement of diabetic neuropathy. This study confirmed the effects of hesperidin on oxidative stress, inflammation, NOX4, and SIRT1 through various experimental analyses in HFD-fed rats and rat glial C6 cells stimulated with Palmitate.