Nascimento Olívia Azevêdo, Espírito-Santo Renan Fernandes do, Opretzka Luíza Carolina França, Barbosa-Filho José Maria, Gutierrez Stanley Juan Chavez, Villarreal Cristiane Flora, Soares Milena Botelho Pereira
Faculdade de Farmácia, Universidade Federal da Bahia, 40170-290 Salvador, BA, Brazil.
Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, 40296-710 Salvador, BA, Brazil.
Molecules. 2016 Dec 21;21(12):1757. doi: 10.3390/molecules21121757.
Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56-100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56-25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund's adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production.
瑞帕林是链烷酰胺类天然生物碱，可通过简单方法合成，这增强了它们在药物开发中的潜在应用价值。在此，研究了瑞帕林在瑞士小鼠疼痛和炎症的体外及体内试验中的药理特性。通过放射免疫分析和实时聚合酶链反应测定炎症介质。瑞帕林I、II、III和IV（1.56 - 100毫克/千克；腹腔注射）在福尔马林试验中产生剂量相关的镇痛作用，其半数有效剂量（ED）值分别为22.93、114.2、31.05和6.63毫克/千克。以更强的效力作为指导参数，对瑞帕林IV进行了进一步研究。瑞帕林IV对甩尾试验未产生镇痛作用，表明其镇痛作用不是中枢介导的作用。事实上，瑞帕林IV（1.56 - 25毫克/千克）对完全弗氏佐剂（CFA）诱导的小鼠爪部炎症产生剂量相关的镇痛和抗水肿作用。在CFA诱导的炎症过程中，瑞帕林IV既不调节细胞因子TNF-α和IL - 10的产生，也不调节COX - 2信使核糖核酸的表达。另一方面，瑞帕林IV降低了炎症爪部的前列腺素E₂水平。在体外试验中，瑞帕林IV在活化巨噬细胞中未表现出抑制活性。这些结果首次表明，瑞帕林IV可能通过抑制前列腺素的产生诱导镇痛和抗炎作用。
