Regulating Neuroinflammatory Biomarkers in Nitroglycerine induced Migraine in Rats: A Therapeutic role of Chrysanthemum indicum extract

Abstract Objective Chronic migraine (CM) is characterised by unilateral/bilateral pulsatile headaches at least 15 days per month. Central sensitization can be demonstrated by a prolonged increase in trigeminal nucleus caudalis (TNC) neuron activity in response to painful stimuli. Scientists are continually researching migraine treatments, hoping herbal remedies may work better. Network pharmacological approach was used to assess Chrysanthemum indicum (CIHE) leaf hydroalcoholic extract to evaluate antimigraine activity. Methods We investigated specific genes involved in the migraine, extracted gene ontology, biological pathways, and protein-protein interaction analysis were determined with the screened 61 common genes by network pharmacological approach added with docking analysis. In vivo studies have been carried out with CD1 Mice (25-30g) randomly made into five groups. CIHE is prepared to evaluate antimigraine activity. MMP9, TNF-α, NFkB, IL-1β, CGRP, and iNOS were evaluated after administration of Nitroglycerine (10mg/kg; i.p). Results The elevated protein levels were significantly reduced with the treatment of CIHE (200mg/kg and 400mg/kg; p.o). Additionally histological and western blot analysis confirmed the reduction of specified proteins in the brain as well as blood. Docking analysis revealed that 1,5-Bis(4-dimethylaminophenyl)-1,4-pentadien-3-one (-10.3 KJ/mol), Naphthalene-1-carboxylic acid 4-formyl-phenyl ester (-9.7KJ/mol), and 3-(3-Nitrophenyl)-2'-acrylonaphthone (-9.7KJ/mol) are shown highest binding affinity. Interpretation: CIHE may attain antimigraine activity through suppression of neuroinflammatory cytokines by the natural extract of Chrysanthemum indicum in a dose dependent manner and isolation of hit molecules from the CIHE is required for further investigation.