Pandurangan Kamalakannan, Krishnappan Vidyalakshmi, Subramanian Viswanathan, Subramanyan Ramaswamy
Department of Pharmacology, Meenakshi Medical College & Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631 552, Tamilnadu, India.
Department of Pharmacology, Madha Dental College & Hospitals, Chennai 600 069, India.
Eur J Pharmacol. 2014 Mar 15;727:148-57. doi: 10.1016/j.ejphar.2014.01.033. Epub 2014 Jan 31.
The aim of the present study was to evaluate the antinociceptive action of certain dimethoxy flavones (DMF, (7,2׳-dimethoxy flavone, 7,3׳-dimethoxy flavone, 7,4׳-dimethoxy flavone and 7,8,-dimethoxy flavone) and the possible mechanisms involved. The antinociceptive effect of dimethoxy flavones was investigated in mice employing acetic acid-induced abdominal writhings, formalin-induced nociception and hot water tail immersion assay procedures. To identify the possible mechanisms involved in the antinociceptive action of these compounds, acetic acid-induced abdominal constriction assay alone was employed. Mice were pretreated with naloxone, yohimbine, ondansetron, haloperidol, bicuculline or glibenclamide before dimethoxy flavone treatment to identify the role of opioid, adrenergic, 5HT3-serotonergic, dopaminergic, gamma-amino butyric acid (GABA) receptor or potassium channels, respectively. The investigated dimethoxy flavones produced a significant reduction in the number of abdominal constrictions in acetic acid assay. A dose dependent decrease in paw-licking response time was evident in both the early and late phases of formalin induced nociception. A significant increase in reaction time was also evident after treatment with various dimethoxy flavones in hot water tail immersion assay. Pretreatment with naloxone, ondansetron or glibenclamide significantly attenuated the antinociceptive effect of all the four dimethoxy flavones. Yohimbine pretreatment attenuated the antinociceptive response of 7,3׳-dimethoxy flavone, 7,4׳-dimethoxy flavone and 7,8-dimethoxy flavone. Pretreatment with haloperidol potentiated the antinociceptive response of all the tested dimethoxy flavones. The antinociceptive effect of 7,2׳-dimethoxy flavone and 7,3׳-dimethoxy flavone was annulled by bicuculline pretreatment. The results of the present study reveal the antinociceptive effect of dimethoxy flavones involving multiple pathways.
本研究的目的是评估某些二甲氧基黄酮（DMF，即7,2'-二甲氧基黄酮、7,3'-二甲氧基黄酮、7,4'-二甲氧基黄酮和7,8-二甲氧基黄酮）的抗伤害感受作用及其可能涉及的机制。采用醋酸诱导的扭体反应、福尔马林诱导的伤害感受和热水浸尾试验程序，在小鼠中研究了二甲氧基黄酮的抗伤害感受作用。为了确定这些化合物抗伤害感受作用中可能涉及的机制，仅采用了醋酸诱导的腹部收缩试验。在给予二甲氧基黄酮治疗前，分别用纳洛酮、育亨宾、昂丹司琼、氟哌啶醇、荷包牡丹碱或格列本脲对小鼠进行预处理，以确定阿片类、肾上腺素能、5HT3-血清素能、多巴胺能、γ-氨基丁酸（GABA）受体或钾通道的作用。在所研究的醋酸试验中，所研究的二甲氧基黄酮使腹部收缩次数显著减少。在福尔马林诱导的伤害感受的早期和晚期阶段，舔爪反应时间均呈剂量依赖性降低。在热水浸尾试验中，用各种二甲氧基黄酮处理后，反应时间也显著增加。用纳洛酮、昂丹司琼或格列本脲预处理可显著减弱所有四种二甲氧基黄酮的抗伤害感受作用。育亨宾预处理减弱了7,3'-二甲氧基黄酮、7,4'-二甲氧基黄酮和7,8-二甲氧基黄酮的抗伤害感受反应。用氟哌啶醇预处理增强了所有测试的二甲氧基黄酮的抗伤害感受反应。荷包牡丹碱预处理消除了7,2'-二甲氧基黄酮和7,3'-二甲氧基黄酮的抗伤害感受作用。本研究结果揭示了二甲氧基黄酮涉及多种途径的抗伤害感受作用。
