Abstract

 
 
 
 Purpose: To elucidate the bioactive constituents of Asari radix et rhizoma (ARR) in treating migraine based on network pharmacology and nitroglycerin-induced migraine rat model.
 Methods: The potential bioactive constituents of ARR were identified with the aid of literature retrieval and virtual screening, and the migraine-related hub genes were identified using protein-protein interaction and topology analyses. Then, the interaction between the potential bioactive constituents and hub genes was determined with molecular docking and topology, leading to the prediction of the anti-migraine constituents of ARR. Moreover, a rat model of nitroglycerin-induced migraine was used to confirm the prediction by measuring the frequency of head-scratching and head-shaking behavior (FHHB) in the rats. In addition, levels of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) in blood, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in brain were measured using appropriate commercial kits.
 Results: Network pharmacology revealed that naringenin-7-O-β-D-glucopyranoside and higenamine might be the key anti-migraine bioactive constituents of ARR. On addition of naringenin-7-O-β-D- glucopyranoside or higenamine to ARR, there was marked enhancement of the mitigating effect of ARR on nitroglycerin-induced abnormalities in levels of NO, CGRP, 5-HT and NE, as well as FHHB in rats (p < 0.05 or 0.01).
 Conclusion: These findings indicate that naringenin-7-O-β-D-glucopyranoside and higenamine might be the key bioactive and anti-migraine constituents of ARR. However, in addition to naringenin-7-O-β-D- glucopyranoside and higenamine, there were many other anti-migraine constituents in ARR. Therefore, there is need for further investigations on the actual contributions of these two constituents of ARR in treating migraine.
 
 
 
Highlights
Migraine is a primary intermittent headache featured by varying combinations of symptoms related to gastrointestinal, neurological and autonomic changes [1]
Results from STRING showed that the Protein-protein interaction (PPI) network of 278 migraine-related target genes consisted of 257 nodes and 2305 edges
The protein constructions of 13 hub genes were obtained from the PDB website
Summary
Migraine is a primary intermittent headache featured by varying combinations of symptoms related to gastrointestinal, neurological and autonomic changes [1]. Migraine patients often show some characteristic symptoms such as cutaneous allodynia, phonophobia, photophobia, and gastrointestinal symptoms (nausea and emesis) [2]. It is necessary to develop anti-migraine drugs with safety and efficiency. Some significant progress has been made in the development of anti-migraine drugs. Traditional Chinese Medicines (TCMs) are extensively used for the treatment of migraine in China. Studies have indicated that TCMs had good effect and tolerance in the preventive treatment of migraine [4]. Asari Radix et Rhizoma (ARR) is frequently used in TCM clinics for the treatment of migraine. The bioactive anti-migraine constituents of ARR have not been elucidated
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