Departamento de Saúde, Curso de Farmácia, Universidade Federal de Sergipe, SE, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
J Ethnopharmacol. 2013 Oct 7;149(3):685-93. doi: 10.1016/j.jep.2013.07.027. Epub 2013 Jul 29.
The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases. Thus, the present study was designed to investigate whether the leaf ethyl acetate (Eta) fraction from Mirabilis jalapa exhibits antinociceptive effect in clinically relevant pain models in mice. Furthermore, we have investigated the role of cholinergic system in the antinociceptive action produced by Eta in mice.
The effect of Eta administered orally (10mg/kg, p.o.) in mice was verified on the painful hypersensitivity (mechanical allodynia) in models of chronic inflammation (subcutaneous injection of complete Freund's Adjuvant-CFA in the plantar surface of the right hind paw), postoperative (paw surgical incision) and neuropathic (partial sciatic nerve ligation) pain. In the chronic inflammation model, we further verified the effect of Eta treatment on paw edema and interleukin-1β (IL-1β) levels. We also investigated the role of muscarinic and nicotinic receptors in the antiallodynic action produced by Eta as well as the possible action of Eta on in vitro and ex vivo acetylcholinesterase activity in CFA treated animals. Furthermore, we verified the effect of Eta treatment on the parameters of liver and kidney lesion (level of urea, and activity of aspartate aminotransferase and alanine aminotransferase).
Eta produced marked reduction in the allodynia caused by CFA, surgical incision and partial sciatic nerve ligation. However, Eta did not alter the paw edema or the increase of IL-1β levels produced by CFA. The antinociceptive effect of Eta was reversed by the pre-treatment of animals with the antagonists of muscarinic (atropine, 5mg/kg, s.c) or nicotinic (mecamylamine, 0.001mg/kg, s.c.) receptors. Eta did not alter in vitro acetylcholinesterase activity in blood or spinal cord samples, but it reversed the increase in the acetylcholinesterase activity observed in the spinal cord samples from mice injected with CFA. Moreover, Eta did not alter the indicators of liver or kidney lesion.
Based on its use in traditional medicine, the results of the present study confirmed the antinociceptive properties of Eta in clinically relevant pain models. Also its effect on the CFA-induced chronic inflammation seems to be related to acetylcholinesterase inhibition and cholinergic system.
在巴西，将紫茉莉的叶子煎剂或浸剂用于传统医学，以治疗炎症和疼痛性疾病。因此，本研究旨在探究紫茉莉叶的乙酸乙酯（Eta）馏分是否具有在临床上相关的疼痛模型中发挥镇痛作用。此外，我们还研究了胆碱能系统在 Eta 产生的镇痛作用中的作用。
通过口服给予 Eta（10mg/kg，p.o.），在慢性炎症（右后爪足底皮下注射完全弗氏佐剂-CFA）、术后（爪手术切口）和神经病理性（部分坐骨神经结扎）疼痛模型中验证 Eta 的作用。在慢性炎症模型中，我们进一步验证了 Eta 治疗对爪肿胀和白细胞介素-1β（IL-1β）水平的影响。我们还研究了毒蕈碱和烟碱受体在 Eta 产生的抗痛觉过敏作用中的作用以及 Eta 对 CFA 处理动物的体外和离体乙酰胆碱酯酶活性的可能作用。此外，我们验证了 Eta 治疗对肝和肾损伤参数（尿素水平以及天冬氨酸转氨酶和丙氨酸转氨酶的活性）的影响。
Eta 显著减少了 CFA、手术切口和部分坐骨神经结扎引起的痛觉过敏。然而，Eta 并未改变 CFA 引起的爪肿胀或白细胞介素-1β水平的升高。用毒蕈碱（阿托品，5mg/kg，s.c）或烟碱（美加明，0.001mg/kg，s.c）受体拮抗剂预处理动物可逆转 Eta 的镇痛作用。Eta 未改变血液或脊髓样本中的体外乙酰胆碱酯酶活性，但可逆转 CFA 注射小鼠脊髓样本中观察到的乙酰胆碱酯酶活性增加。此外，Eta 并未改变肝或肾损伤的指标。
基于其在传统医学中的应用，本研究结果证实了 Eta 在临床上相关的疼痛模型中的镇痛特性。此外，其对 CFA 诱导的慢性炎症的作用似乎与乙酰胆碱酯酶抑制和胆碱能系统有关。
