Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, 60430-270 Fortaleza, Ceará, Brazil; National Institute of Science and Technology, Institute of Biomedicine of Brazilian Semi-arid, Faculty of Medicine, Federal University of Ceará, 60430-270 Fortaleza, Ceará, Brazil.
Pharmacol Biochem Behav. 2013 Sep;110:19-26. doi: 10.1016/j.pbb.2013.05.016. Epub 2013 Jun 5.
This study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100 mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30 mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with L-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of K(ATP) channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10-100 mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, K(ATP)-channels and adenosine receptors.
本研究旨在评估芒果苷可能具有的全身性抗伤害感受活性，并使用小鼠的急性化学（乙酸、甲醛和辣椒素）和热（热板和尾部闪烁）伤害感受模型来阐明其潜在机制。芒果苷在 10 至 100mg/kg 的口服剂量下，对乙酸引起的内脏痛觉模型和甲醛及辣椒素引起的神经炎症性疼痛模型中的化学致痛具有显著的镇痛作用，且呈纳洛酮敏感性，提示内源性阿片类物质参与了其作用机制。在辣椒素试验中，芒果苷（30mg/kg）的镇痛作用不受各自竞争性和非竞争性瞬时受体电位香草酸 1（TRPV1）拮抗剂，辣椒素和钌红，或预先给予非选择性一氧化氮合酶抑制剂 L-NAME 或可溶性鸟苷酸环化酶抑制剂 ODQ 的影响。然而，芒果苷的作用被 K(ATP)通道阻断剂格列本脲和腺苷受体拮抗剂 8-苯茶碱预处理的动物显著逆转。芒果苷未能改变热板和尾部闪烁试验模型中的热伤害感受，表明其镇痛作用仅为外周而不是中枢。口服给予的芒果苷（10-100mg/kg）耐受性良好，且在各自的旷场和转棒试验中不会损害小鼠的活动能力或运动协调能力，表明观察到的镇痛作用与镇静或运动异常无关。本研究的结果表明，芒果苷具有外周镇痛作用，其作用机制涉及内源性阿片类物质、K(ATP)通道和腺苷受体。
