title: Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.
abstract: Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Ping-Han
authors.initials: PH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Li-Xue
authors.initials: LX
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Wan
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Xiao-Na
authors.initials: XN
authors.lastname: Mao
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Fang-Yi
authors.initials: FY
authors.lastname: Long
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Sichuan Academy of Chinese Medicine Sciences, Chengdu, China. Electronic address: 934534055@qq.com.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China. Electronic address: dujr_1@163.com.
authors.forename: Jun-Rong
authors.initials: JR
authors.lastname: Du
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001592:Benzyl Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D005260:Female; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000097:blood; D005996:Nitroglycerin / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests; D014278:Trigeminal Nuclei / Q000187:drug effects*
chemical_list: D000700:Analgesics; D001592:Benzyl Alcohols; D005960:Glucosides; D016760:Proto-Oncogene Proteins c-fos; D009569:Nitric Oxide; C045345:gastrodin; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide
keywords: Anti-migraine drug; CGRP; Gastrodin derivative; Nitric oxide; Nitroglycerin; Trigeminovascular system