Lopes Luciane C, de Carvalho João Ernesto, Kakimore Marise, Vendramini-Costa Débora B, Medeiros Maria A, Spindola Humberto M, Ávila-Román Javier, Lourenço Ana M, Motilva Virginia
Programa de Pós-Graduação strictu senso em Ciências Farmacêuticas, Universidade de Sorocaba, UNISO, Rodovia Raposo Tavares, KM 92.5, Sorocaba, SP, Cep 18023-000, Brazil.
Inflammopharmacology. 2014 Jun;22(3):179-85. doi: 10.1007/s10787-013-0182-8. Epub 2013 Aug 9.
Cycloeucalenone (1) and 24-oxo-31-norcycloartanone (2) obtained from Solanum cernuum Vell. were assayed to explore their pharmacologic roles. Previous studies showed that (2) has selective activity against lung tumor cell line (NCIH460) which expresses high levels of COX-2, suggesting its role in inflammatory process, and also a link between chronic inflammation and cancer-associated process. Dichloromethane crude extract (DCE) significantly reduced writhing and stretching induced by 0.8 % acetic acid at a dose of 100, 300, and 600 mg/kg, po; oral administration of different doses of (1) and (2) also displayed significant analgesic and anti-inflammatory effects in the writhing acetic acid test (p < 0.0001). Selected oral doses of both compounds (100 and 50 mg/kg) were assayed in the carrageenan-induced paw edema model. Compound (2) showed significant activity during the early phase (1.5-6 h) and also in the late phase (48 h) (p < 0.01). The anti-nociceptive activity observed for the compounds (1) and (2) and DCE was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decrease COX-2 protein expression, although only compound (2) reached a significant response (p < 0.05 vs control). However, in vitro Sirtuin 1 activity and TNF-α production in THP-1 macrophages were not affected.
从夜香树中提取的环木菠萝烯酮(1)和24-氧代-31-去甲环阿尔廷酮(2)进行了测定,以探究它们的药理作用。先前的研究表明,(2)对高表达COX-2的肺癌细胞系(NCIH460)具有选择性活性,表明其在炎症过程中的作用,以及慢性炎症与癌症相关过程之间的联系。二氯甲烷粗提物(DCE)在剂量为100、300和600mg/kg口服时,能显著减少0.8%乙酸诱导的扭体和伸展反应;口服不同剂量的(1)和(2)在扭体乙酸试验中也显示出显著的镇痛和抗炎作用(p<0.0001)。在角叉菜胶诱导的爪肿胀模型中测定了两种化合物的选定口服剂量(100和50mg/kg)。化合物(2)在早期阶段(1.5-6小时)和晚期阶段(48小时)均显示出显著活性(p<0.01)。观察到化合物(1)、(2)和DCE的抗伤害感受活性与抑制炎症和伤害感受过程中涉及的不同介质有关。两种化合物均降低COX-2蛋白表达,尽管只有化合物(2)达到显著反应(与对照组相比,p<0.05)。然而,THP-1巨噬细胞中的体外沉默调节蛋白1活性和TNF-α产生未受影响。