Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Trindade, Florianópolis, SC 88040-900, Brazil; Graduate Program in Neuroscience, Center of Biological Sciences, Federal University of Santa Catarina, SC 88040-900, Florianópolis, Brazil.
Department of Chemistry, Center of Physical and Mathematical Sciences, Federal University of Santa Catarina, Trindade, Florianópolis, SC 88040-900, Brazil.
Phytomedicine. 2016 May 15;23(5):429-40. doi: 10.1016/j.phymed.2016.02.002. Epub 2016 Mar 2.
The plants of the genus Polygala (Polygalaceae) have been used for a long time in folk medicine to treat pain and inflammation. The species Polygala molluginifolia is native to southern Brazil and is popularly known as "cânfora". The presented study analyzes the antinociceptive effect of hydroalcoholic extract from Polygala molluginifolia (HEPm) and an isoflavone (ISO) isolated from the extract, in behavioral models of pain in mice, as well as the mechanism underlying this effect.
The phytochemical analysis of HEPm was performed through a capillary electrophoresis analysis and colorimetric test. The antinociceptive effects of HEPm and ISO (10-1000 mg/kg, i.g.) were evaluated by applying the formalin test; mechanical and thermal hyperalgesia to postoperative pain in mice. The possible involvement of opioid receptors, TRPV1 and TRPA1 channels in the antinociceptive effect of HEPm and ISO were also evaluated. Finally, the nonspecific effects of HEPm and ISO were evaluated by measuring locomotor activity (Open-field Test) and corporal temperature.
The 5,3',4'-trihydroxy-6″,6″-dimethylpyrano[2″,3″:7,6] isoflavone (ISO) was identified in HEPm by capillary electrophoresis analysis and selected for the experimental tests. The oral administration of HEPm or of ISO significantly inhibited the neurogenic and inflammatory phases of formalin-induced pain, edema formation and local hyperemia, without causing any change to locomotor activity. Acute and repeated treatment of animals with HEPm reduced mechanical and thermal (heat and cold) hyperalgesia in the postoperative pain. In addition, administering HEPm or ISO markedly reduced nociceptive behavior induced by the peripheral and central injection of TRPV1 and TRPA1 channels activators. Finally, the antinociception provided by the administration of HEPm or ISO was reversed by the preadministration of naloxone.
Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of HEPm and ISO in animal models of acute pain without causing sedation or locomotor dysfunction. This effect appears to be mediated, at least in part, by the activation of opioid receptors and/or by the inhibition of TRPV1 and TRPA1 channels. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant Polygala molluginifolia in the development of phytomedicines with analgesic properties.
大戟属（大戟科）的植物长期以来一直被民间医学用于治疗疼痛和炎症。原产于巴西南部的 Polygala molluginifolia 俗称“坎福拉”。本研究分析了大戟属 molluginifolia 的水醇提取物（HEPm）和从提取物中分离出的一种异黄酮（ISO）在小鼠疼痛行为模型中的镇痛作用及其作用机制。
通过毛细管电泳分析和比色试验对 HEPm 的植物化学分析。通过应用福尔马林试验评估 HEPm 和 ISO（10-1000mg/kg，ig）的镇痛作用；机械和热痛觉过敏术后疼痛的小鼠。还评估了 HEPm 和 ISO 的阿片受体、TRPV1 和 TRPA1 通道参与镇痛作用的可能性。最后，通过测量运动活动（旷场试验）和体温来评估 HEPm 和 ISO 的非特异性作用。
通过毛细管电泳分析鉴定 HEPm 中含有 5,3',4'-三羟基-6″,6″-二甲氧基吡喃[2″,3″:7,6]异黄酮（ISO），并选择其进行实验测试。HEPm 或 ISO 的口服给药显著抑制了福尔马林诱导的疼痛的神经源性和炎症性阶段、水肿形成和局部充血，而不会引起运动活动的任何变化。急性和重复治疗动物可减轻术后疼痛的机械性和热（热和冷）痛觉过敏。此外，HEPm 或 ISO 的给药可显著减少外周和中枢注射 TRPV1 和 TRPA1 通道激活剂引起的疼痛行为。最后，给予纳洛酮可逆转 HEPm 或 ISO 给药引起的镇痛作用。
综上所述，这些结果为 HEPm 和 ISO 在急性疼痛动物模型中具有显著镇痛作用提供了首个实验证据，而不会引起镇静或运动功能障碍。这种作用似乎至少部分通过激活阿片受体和/或抑制 TRPV1 和 TRPA1 通道来介导。此外，这项研究提供了新的科学证据，并强调了药用植物 Polygala molluginifolia 在开发具有镇痛特性的植物药方面的治疗潜力。
