The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms

Abstract

Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine’s neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 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 gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. Methods: 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, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. Results: The results of the present trial showed that 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. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). Conclusion: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

Herbal treatments for migraine: A systematic review of randomised‐controlled studies

“…However, the largest overall prophylactic effect occurred in participants taking the combination of omega-3 fatty acids and curcumin. There was similar treatment efficacy in participants taking either curcumin or omega-3 alone (Abdolahi et al, 2017;Abdolahi et al, 2019). In a similarly-designed study, in addition to prophylactic medications (topiramate and amitriptyline), the effects of either a placebo, curcumin (80 mg daily), coenzyme Q10 CoQ10 are the most widely used components of the coriander plant with the most important constituents being the essential oil and fats (Sahib et al, 2013).…”

Clinical use of omega-3 fatty acids in migraine

“…These experiments also confirmed that the combination of omega-3/nano-curcumin significantly reduced the frequency, severity, and duration of headache attacks. [ 39 ]…”

“…[ 37 , 38 ] Human and experimental pre-clinical research also highlighted the role of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), confirming that they contribute to sustaining inflammation and neurogenic pain in migraine. [ 39 ]…”

The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders

“…It is worth noting that magnetic NPs also show 70% chemotherapy (temozolomide)delivering capability and distribution in intracranial tumor region in pet dogs (Young et al, 2018). Moreover, recent studies reveal that treatment with omega-3 fatty acids and curcumin NPs significantly reduces inflammation in migraine patients by suppressing the expressions of TNF-α, intercellular adhesive molecule 1, and cooxygenase-2/inducible nitric oxide synthase (Abdolahi et al, 2017(Abdolahi et al, , 2019Soveyd et al, 2018; Table 1). Together, the above evidences indicate that NPs have enormous potential in brain diseases by facilitating drug delivery, inducing synergistic effects, and reducing drug toxicity.…”