Laboratório de Neuroinflamação, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil.
Laboratório Central de Extração, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará, Brazil.
PLoS One. 2020 Sep 17;15(9):e0238834. doi: 10.1371/journal.pone.0238834. eCollection 2020.
Peperomia pellucida (PP) belongs to the Peperomia genus, which has a pantropic distribution. PP is used to treat a wide range of symptoms and diseases, such as pain, inflammation, and hypertension. Intriguingly, PP extract is used by different tropical countries for its anti-inflammatory and antinociceptive effects. In fact, these outcomes have been shown in animal models, though the exact bioactive products of PP that exert such results are yet to be discovered. To determine and elucidate the mechanism of action of one of these compounds, we evaluated the antinociceptive effect of the novel dimeric ArC2 compound, Pellucidin A by using in vivo and in silico models. Animals were then subjected to chemical, biphasic and thermal models of pain. Pellucidin A induced an antinociceptive effect against chemical-induced pain in mice, demonstrated by the decrease of the number of writhes, reaching a reduction of 43% and 65% in animals treated with 1 and 5 mg/kg of Pellucidin A, respectively. In the biphasic response (central and peripheral), animals treated with Pellucidin A showed a significant reduction of the licking time exclusively during the second phase (inflammatory phase). In the hot-plate test, Pellucidin A did not have any impact on the latency time of the treated animals. Moreover, in vivo and in silico results show that Pellucidin A's mechanism of action in the inflammatory pain occurs most likely through interaction with the nitric oxide (NO) pathway. Our results demonstrate that the antinociceptive activities of Pellucidin A operate under mechanism(s) of peripheral action, involving inflammatory mediators. This work provides insightful novel evidence of the biological properties of Pellucidin A, and leads to a better understanding of its mechanism of action, pointing to potential pharmacological use.
胡椒科佩珀米娅属（Peperomia pellucida，PP）植物广泛分布于热带地区，具有清热利湿、活血化瘀等功效，可用于治疗疼痛、炎症、高血压等多种症状和疾病。有趣的是，不同热带国家的人们使用 PP 提取物来发挥其抗炎和镇痛作用。事实上，这些结果已在动物模型中得到证实，尽管 PP 发挥这些作用的确切生物活性产物尚未被发现。为了确定和阐明其中一种化合物的作用机制，我们使用体内和体外模型评估了新型二聚体 ArC2 化合物 Pellucidin A 的镇痛作用。然后，动物被置于化学、双相和热痛模型中。Pellucidin A 诱导化学诱导的疼痛的镇痛作用在小鼠中，通过扭体次数的减少来证明，用 1 和 5 mg/kg 的 Pellucidin A 治疗的动物分别减少了 43%和 65%。在双相反应（中枢和外周）中，用 Pellucidin A 治疗的动物在第二相（炎症相）中舔舐时间明显减少。在热板试验中，Pellucidin A 对治疗动物的潜伏期没有影响。此外，体内和体外结果表明，Pellucidin A 在炎症性疼痛中的作用机制很可能是通过与一氧化氮（NO）途径相互作用。我们的结果表明，Pellucidin A 的镇痛活性通过外周作用机制发挥作用，涉及炎症介质。这项工作为 Pellucidin A 的生物学特性提供了有价值的新证据，并对其作用机制有了更好的理解，为其潜在的药理学应用指明了方向。
