Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.

Objectives: Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology.

Methods: This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein.

Key findings: In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats.

Conclusion: Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.