Marcon Rodrigo, Luiz Ana Paula, Werner Maria Fernanda de Paula, Freitas Cristina Setim, Baggio Cristiane Hatsuko, Nascimento Francisney Pinto do, Soldi Cristian, Pizzolatti Moacir Geraldo, Santos Adair Roberto Soares
Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.
Brain Res. 2009 Oct 27;1295:76-88. doi: 10.1016/j.brainres.2009.07.073. Epub 2009 Jul 30.
Previous studies from our group investigated the antinociceptive property of amyrin octanoate, a synthetic compound derivative from natural precursor alpha, beta-amyrin, against nociceptive response induced by acetic acid and formalin. Here, we investigated some of the mechanisms of action underlying the antinociceptive effects of amyrin octanoate. Amyrin octanoate given intraperitoneally (0.001-1 mg /kg) or intrathecally (10-1000 ng /site) caused dose-dependent and long-lasting inhibition of acetic acid-induced visceral nociception, with mean ID(50) values of 0.003 (0.001-0.005) mg/kg and 122.4 (60.8-246.6) ng/site, respectively. In the capsaicin- and glutamate-induced paw licking, amyrin octanoate caused significant and dose-dependent inhibition of both nociceptive responses, with ID(50) values of 1.36 and 0.04 mg/kg, respectively. Furthermore, amyrin octanoate also reduced significantly the nociception caused by intrathecal injection of glutamate, substance P and capsaicin, with inhibitions of 36+/-11%, 67+/-10% and 78+/-5%, respectively. The antinociception caused by amyrin octanoate in the acetic acid test was significantly attenuated by neonatal pretreatment of mice with capsaicin, but seems to involve mechanisms independent of G(i/o) protein, opioidergic, serotonergic, noradrenergic and cholinergic system, since it was not affected by pertussis toxin, naloxone, yohimbine, mecamylamine or atropine. In addition, amyrin octanoate reduced thermal and mechanical hyperalgesia induced by bradykinin and phorbol myristate acetate in rats, without affecting similar responses caused by prostaglandin E(2). Taken together, the present results shown that octanoate amyrin produces antinociceptive and antihyperalgesic effects, through an interaction with capsaicin-sensitive fibers and the inhibition of the PKC signaling pathway.
我们团队之前的研究调查了辛酸羽扇豆醇酯（一种由天然前体α，β-羽扇豆醇衍生而来的合成化合物）对乙酸和福尔马林诱导的伤害性反应的抗伤害感受特性。在此，我们研究了辛酸羽扇豆醇酯抗伤害感受作用的一些潜在作用机制。腹腔注射（0.001 - 1毫克/千克）或鞘内注射（10 - 1000纳克/部位）辛酸羽扇豆醇酯可引起剂量依赖性且持久的对乙酸诱导的内脏伤害感受的抑制，平均半数有效剂量（ID50）值分别为0.003（0.001 - 0.005）毫克/千克和122.4（60.8 - 246.6）纳克/部位。在辣椒素和谷氨酸诱导的舔足反应中，辛酸羽扇豆醇酯对两种伤害性反应均产生显著且剂量依赖性的抑制，ID50值分别为1.36和0.04毫克/千克。此外，辛酸羽扇豆醇酯还显著降低了鞘内注射谷氨酸、P物质和辣椒素所引起的伤害感受，抑制率分别为36±11%、67±10%和78±5%。在乙酸试验中，辣椒素对新生小鼠进行预处理可显著减弱辛酸羽扇豆醇酯引起的抗伤害感受，但似乎涉及独立于G(i/o)蛋白、阿片能、5-羟色胺能、去甲肾上腺素能和胆碱能系统的机制，因为它不受百日咳毒素、纳洛酮、育亨宾、美加明或阿托品的影响。此外，辛酸羽扇豆醇酯可减轻缓激肽和佛波酯诱导的大鼠热痛觉过敏和机械性痛觉过敏，而不影响前列腺素E2引起的类似反应。综上所述，目前的结果表明，辛酸羽扇豆醇酯通过与辣椒素敏感纤维相互作用并抑制蛋白激酶C信号通路产生抗伤害感受和抗痛觉过敏作用。
