THE NEUROMODULATORY IMPACTS OF Ω-3 FATTY ACIDS AND NANO-CURCUMIN IN MIGRAINES: A CLINICAL TRIAL STUDY FROM GENE EXPRESSION TO CLINICAL SYMPTOMS

Background and Aim: The present study designed to evaluate the nutrigenomic modulatory effects of ω-3, nano-curcumin, and their combination, on neuroinflammation and clinical symptoms in migraine patients. Methods: Migraine is a neuroinflammatory disorder characterized by recurrent attacks of pain. The observations have demonstrated the role played by COX-2/ iNOS in migraine’s neuroinflammatory pathogenesis and pain. ω -3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS. Based on recent evidences, both of poly unsaturated fatty acids and curcumin in a synergistic manner can enhance the effects of drugs use in migraine treatment such as valproate sodium and NSAIDS respectively. Recently, several in vitro and in vivo evidences have been suggested a synergistic relation between ω-3 fatty acids and curcumin in neuroinflammatory condition. In this context, we hypotheses that the combination of ω-3 fatty acids and nano-curcumin could enhance their neuroprotective/ neuromedulatory effects in migraine patients resulted in reduction of headache attacks and severity of pain. Thus, in an attempt to find how ω-3 fatty acids and curcumin can exert neuromodulatory properties, present study was designed to examine COX-2/ iNOS network gene expression, their gene products, i.e. serum levels of COX-2 and iNOS and clinical manifestation of disease in migraine patients.This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, COX-2/iNOS mRNA and serum levels were measured, using real-time PCR and ELISA respectively. The clinical symptom were also recorded. According to results, ω-3 fatty acids and nano-curcumin can reinforce each other’s effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. The combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). Therefore, the combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention. Conclusion: To our knowledge, the current clinical trial is the first study of the effects of ω-3 fatty acids and nano-curcumin supplementation on COX-2/iNOS gene expression and their product (COX-2 and iNOS enzymes) or clinical manifestations in migraine patients. The use of COX-2 inhibitor agents and new researches on iNOS inhibitors in migraine treatment demonstrated that the COX-2/iNOS network may play pivotal role in the neuroinflammatory pathogenesis of migraine. In this study, we found that the combination of ω-3 fatty acids and nano-curcumin have additive effects in down regulation of COX-2/iNOS gene expression and serum concentrations as well as headache attacks, the severity of pain and duration of headaches. Therefore, targeting these compounds can be a promising approach to help migraine prevention. However, further clinical studies are needed to confirm these results

کلیدواژه ها:

Migraine ، Curcumin ، ω-3 Fatty Acids ، COX-2 ، iNOS