Magalhães Bettina Quintanilha, Machado Francisco P, Sanches Paola S, Lima Bárbara, Falcão Deborah Quintanilha, von Ranke Natalia, Bello Murilo Lamim, Rodrigues Carlos Rangel, Santos Marcelo Guerra, Rocha Leandro, Faria Robson X
Laboratório de Biotecnologia, Alimentação e Saúde, Universidade Federal Fluminense, R. Alexandre Moura, 8-São Domingos, Niterói 24210-200, Brazil.
Laboratório de Tecnologia de Produtos Naturais, Faculdade de Farmácia, Universidade Federal Fluminense, Rua Doutor Mário Viana 523, Santa Rosa, Niterói 24241-000, Brazil.
Pharmaceutics. 2022 Apr 21;14(5):911. doi: 10.3390/pharmaceutics14050911.
P2X7R is a purinergic receptor with broad expression throughout the body, especially in immune system cells. P2X7R activation causes inflammatory mediators to release, including interleukin-1β (IL-1β), the processing and release of which are critically dependent on this ion channel activation. P2X7R's therapeutic potential augments the discovery of new antagonistic compounds. Thus, we investigated whether the essential oil could block P2X7R activity. The essential oil (ESO) dose-dependently inhibited ATP-promoted PI uptake and IL-1β release with an IC of 113.3 ± 3.7 ng/mL and 274 ± 91 ng/mL, respectively, and the essential oil nanoemulsion (ESON) improved the ESO inhibitory effect with an IC of 81.4 ± 7.2 ng/mL and 62 ± 2 ng/mL, respectively. ESO and ESON reversed the carrageenan-activated peritonitis in mice, and ESON exhibited an efficacy higher than ESO. The majority substance from essential oil, β-caryophyllene, impaired the ATP-evoked PI uptake and IL-1β release with an IC value of 26 ± 0.007 ng/mL and 97 ± 0.012 ng/mL, respectively. Additionally, β-caryophyllene reduced carrageenan-induced peritonitis, and the molecular modeling and computational simulation predicted the intermolecular interactions in the P2X7R situs. In silico, results indicated β-caryophyllene as a potent allosteric P2X7R antagonist, although this substance may present toxic effects for humans. These data confirm the nanoemulsion of essential oil from as a promisor biotechnology strategy for impaired P2X7R functions and the inflammatory response.
P2X7R是一种嘌呤能受体，在全身广泛表达，尤其是在免疫系统细胞中。P2X7R的激活会导致炎症介质的释放，包括白细胞介素-1β（IL-1β），其加工和释放严重依赖于该离子通道的激活。P2X7R的治疗潜力推动了新型拮抗化合物的发现。因此，我们研究了该精油是否能阻断P2X7R的活性。该精油（ESO）呈剂量依赖性地抑制ATP促进的PI摄取和IL-1β释放，其IC50分别为113.3±3.7 ng/mL和274±91 ng/mL，而精油纳米乳剂（ESON）提高了ESO的抑制作用，其IC50分别为81.4±7.2 ng/mL和62±2 ng/mL。ESO和ESON均可逆转角叉菜胶诱导的小鼠腹膜炎，且ESON的疗效高于ESO。该精油的主要成分β-石竹烯可损害ATP诱发的PI摄取和IL-1β释放，其IC值分别为26±0.007 ng/mL和97±0.012 ng/mL。此外，β-石竹烯可减轻角叉菜胶诱导的腹膜炎，分子建模和计算模拟预测了P2X7R位点的分子间相互作用。计算机模拟结果表明，β-石竹烯是一种有效的P2X7R变构拮抗剂，尽管该物质可能对人类有潜在毒性。这些数据证实了该精油纳米乳剂作为一种有前景的生物技术策略，可用于改善P2X7R功能和炎症反应。
