Carballo-Villalobos A I, González-Trujano M E, López-Muñoz F J
Laboratorio No.7 'Dolor y Analgesia' del Departamento de Farmacobiología, Cinvestav-Sede Sur, México, D.F., México; Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México, D.F., México.
Eur J Pain. 2014 Mar;18(3):396-405. doi: 10.1002/j.1532-2149.2013.00378.x. Epub 2013 Aug 5.
Acacetin is a bioflavonoid with pharmacological properties such as antinociceptive/anti-inflammatory activities. However, scientific evidence of its spectrum activity and mechanisms of action is unknown.
Acacetin administered via i.p. was assessed using several nociceptive experimental models such as the writhing test, the formalin test and carrageenan paw oedema in the thermal plantar tests (Hargreaves method) in mice, as well as the pain-induced functional impairment model in rat (PIFIR model).
Acacetin produced a significant and dose-dependent inhibition of the writhes with an ED50 = 20 mg/kg. Furthermore, acacetin inhibited licking and shaking associated with nociceptive behaviour mainly in the inflammatory phase of the formalin test. No significant differences were observed in the plantar test in mice, but a minor response was obtained in the PIFIR model. Animals receiving pre-treatment of WAY100635 (0.1 mg/kg, s.c.), flumazenil (3 mg/kg, i.p.) or naloxone (1 mg/kg, i.p.) partially reduced the antinociceptive response of acacetin in the writhing test. Presence of the inhibitors in the NO-cGMP-K(+) channel pathway did not modify the antinociceptive effect of acacetin in the writhing or the formalin test.
Our data showed that systemic administration of acacetin decreased visceral and inflammatory nociception and prevented the formalin-induced oedema. In the mechanism of the acacetin antinociceptive effect, 5-HT1A, GABA/BDZs and opioid receptors but not the NO-cGMP-K(+) channel pathway seem to be involved. The data presented prove acacetin to be potentially useful in the therapy of pain-related diseases.
刺槐素是一种具有抗伤害性/抗炎活性等药理特性的生物类黄酮。然而，其光谱活性和作用机制的科学证据尚不清楚。
通过腹腔注射给予刺槐素，使用多种伤害性实验模型进行评估，如扭体试验、福尔马林试验、小鼠热足底试验（哈格里夫斯法）中的角叉菜胶足肿胀试验，以及大鼠疼痛诱导功能障碍模型（PIFIR模型）。
刺槐素对扭体产生显著且剂量依赖性的抑制作用，半数有效剂量（ED50）=20毫克/千克。此外，刺槐素主要在福尔马林试验的炎症期抑制与伤害性行为相关的舔舐和颤抖。在小鼠足底试验中未观察到显著差异，但在PIFIR模型中获得了轻微反应。预先接受WAY100635（0.1毫克/千克，皮下注射）、氟马西尼（3毫克/千克，腹腔注射）或纳洛酮（1毫克/千克，腹腔注射）预处理的动物，在扭体试验中部分降低了刺槐素的抗伤害性反应。一氧化氮-环鸟苷酸-K⁺通道途径中的抑制剂存在，并未改变刺槐素在扭体试验或福尔马林试验中的抗伤害性作用。
我们的数据表明，刺槐素全身给药可减轻内脏和炎症性伤害感受，并预防福尔马林诱导的水肿。在刺槐素抗伤害性作用机制中，似乎涉及5-羟色胺1A、γ-氨基丁酸/苯二氮䓬类和阿片受体，但不涉及一氧化氮-环鸟苷酸-K⁺通道途径。所呈现的数据证明刺槐素在疼痛相关疾病的治疗中可能具有潜在用途。
