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吗啡烷型异喹啉生物碱密隆宁具有抑制 TNF-α 和 IL-1β 产生的抗炎和镇痛作用。

Milonine, a Morphinandienone Alkaloid, Has Anti-Inflammatory and Analgesic Effects by Inhibiting TNF-α and IL-1β Production.

机构信息

Laboratory of Immunopharmacology, Department of Physiology and Pathology, Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.

Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270-901, Brazil.

出版信息

Inflammation. 2017 Dec;40(6):2074-2085. doi: 10.1007/s10753-017-0647-9.

DOI:10.1007/s10753-017-0647-9
PMID:28801761
Abstract

Milonine is a morphinandienone alkaloid from Cissampelos sympodialis Eichl (Menispermaceae), a plant used in Brazil to treat inflammatory disorders. In this study, we evaluated the anti-inflammatory and analgesic activity of milonine (MIL) by using classical experimental models of inflammation and nociception. The results showed that MIL reduced the paw edema formation induced by lipopolysaccharide, prostaglandin E, and bradykinin, without interfering with the serotonin-induced edema. With respect to the nociception experiments, MIL decreased the exudate into the peritoneum induced by acetic acid, maintaining the tissue morphology. The alkaloid was able to inhibit the peritonitis induced by carrageenan, decreasing mainly the migration of polymorphonuclear cells, without altering the mononuclear cell number, and reduced the levels of TNF-α and IL-1β in the peritoneum. In addition, MIL was able to decrease the frequency of abdominal writhing induced by acetic acid but did not increase the latency time of the animals in the hot plate test. MIL significantly reduced the nociceptive behavior of paw licking induced by formalin only at the second phase of the test. In conclusion, we demonstrate that milonine has anti-inflammatory and anti-nociceptive activities by inhibiting mediators essential for the inflammatory process.

摘要

米隆宁是一种来自天仙藤(防己科)的吗啡烷二酮生物碱,该植物在巴西被用于治疗炎症性疾病。在这项研究中,我们使用炎症和疼痛的经典实验模型来评估米隆宁(MIL)的抗炎和镇痛活性。结果表明,MIL 减少了脂多糖、前列腺素 E 和缓激肽诱导的足肿胀,而不干扰 5-羟色胺诱导的水肿。关于疼痛实验,MIL 减少了由乙酸引起的腹膜渗出,保持了组织形态。该生物碱能够抑制角叉菜胶诱导的腹膜炎,主要减少多形核细胞的迁移,而不改变单核细胞数量,并降低腹膜中 TNF-α 和 IL-1β 的水平。此外,MIL 能够减少由乙酸引起的腹部扭曲的频率,但不会增加动物在热板试验中的潜伏期。MIL 仅在测试的第二阶段显著减少了由福马林引起的足部舔舐的疼痛行为。总之,我们证明米隆宁通过抑制炎症过程中必需的介质具有抗炎和镇痛作用。

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