Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico.
Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosió Villegas, Secretaría de Salud, Ciudad de México 14080, Mexico.
Molecules. 2021 May 14;26(10):2921. doi: 10.3390/molecules26102921.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug-drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56-320 mg/kg), antiallodynic (100-562 mg/kg), and antihyperalgesic and anti-inflammatory (10-178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.
非甾体抗炎药（NSAIDs）被广泛应用，但它们的不良反应需要寻找新的治疗方法。拉巴烷型二萜多丙酯酸具有胃保护、气管平滑肌松弛、抗肿瘤、抗寄生虫和抗菌活性。本研究旨在评估多丙酯酸对大鼠的镇痛、抗痛觉过敏、抗痛觉超敏和抗炎作用。此外，还分析了多丙酯酸与萘普生联合治疗痛觉过敏的效果，以及涉及的药物相互作用类型。通过向大鼠右后爪注射 1%甲醛来检测痛觉，通过向大鼠左后爪注射 1%角叉菜胶溶液来检测热痛觉过敏和炎症。在 L5/L6 脊神经结扎模型上评估痛觉过敏。多丙酯酸产生了显著的镇痛（56-320mg/kg）、抗痛觉过敏（100-562mg/kg）和抗痛觉超敏和抗炎（10-178mg/kg）作用。通过用纳曲酮、ODQ 和甲硫哒嗪预处理大鼠来探索镇痛机制，发现前两种化合物阻断了这种作用，这表明阿片受体和鸟苷酸环化酶参与了镇痛作用。等辐射分析表明，在联合治疗痛觉过敏时，多丙酯酸和萘普生具有协同作用。
