Machado Janaina Carla Barbosa, da Silva Joyce Cristina, Costa Wêndeo Kennedy, da Silva Márcia Vanusa, de Oliveria Alisson Macário, Daniele-Silva Alessandra, Parente Adriana Marina E Silva, de Sousa Ferreira Sarah, da Silva Diana Pontes, Torres-Rêgo Manoela, Cavalcanti Felipe França, de Freitas Fernandes-Pedrosa Matheus, Ferreira Magda Rhayanny Assunção, Soares Luiz Alberto Lira
Graduate Program in Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil.
Natural Products Laboratory, Department of Biochemistry, Federal University of Pernambuco, Recife, PE, Brazil.
Inflammopharmacology. 2025 Sep 23. doi: 10.1007/s10787-025-01934-4.
Punica granatum (Punicaceae) is a shrub with a worldwide distribution that has been used in folk medicine for the treatment of inflammatory disorders. The study investigated the therapeutic potential of spray-dried hydroethanolic extract (SDE) and spray-dried ethyl acetate fraction (EAF) from Punica granatum leaves in models of pain, inflammation, and snakebite envenomation. Phytochemical analysis highlighted the presence of polyphenols, particularly luteolin and hydrolysable tannins in SDE, and a significant concentration of flavonoids in EAF. Both samples demonstrated safety in murine fibroblast cultures, exhibiting no toxicity at concentrations up to 250 µg/mL. In vivo, EAF (25 mg/kg) showed remarkable peripheral antinociceptive activity, reducing abdominal writhings by 88.0%, comparable to morphine (87.0%), and superior to indomethacin (72.0%). In the formalin test, EAF reduced neurogenic and inflammatory pain by 80.9% and 87.3%, respectively, while SDE (200 mg/kg) reduced writhings by 76.7% and inflammatory pain by 57.1%. In the tail immersion test, both extracts increased latency time, confirming central antinociceptive effects. SDE and EAF also reduced carrageenan-induced edema and leukocyte migration by over 70%. In vitro, both samples completely inhibited the proteolytic and hyaluronidase activities of Bothrops brazili and Bothrops leucurus venoms and strongly inhibited PLA₂ activity. Notably, in vivo administration of SDE and EAF significantly reduced B. leucurus-induced paw edema and myeloperoxidase activity by up to 85.5%. These findings reinforce the traditional use of P. granatum leaves and provide the first report of their in vivo analgesic and antiophidic potential, supporting the role of their rich phenolic composition in modulating inflammatory and venom-induced responses.
石榴（石榴科）是一种分布于世界各地的灌木，在民间医学中被用于治疗炎症性疾病。本研究调查了石榴叶喷雾干燥水乙醇提取物（SDE）和喷雾干燥乙酸乙酯馏分（EAF）在疼痛、炎症和蛇咬伤中毒模型中的治疗潜力。植物化学分析表明，SDE中存在多酚，特别是木犀草素和可水解单宁，EAF中含有大量黄酮类化合物。两个样品在鼠成纤维细胞培养中均显示出安全性，在浓度高达250μg/mL时无毒性。在体内，EAF（25mg/kg）表现出显著的外周抗伤害感受活性，使腹部扭体反应减少88.0%，与吗啡（87.0%）相当，优于吲哚美辛（72.0%）。在福尔马林试验中，EAF分别使神经源性疼痛和炎症性疼痛降低80.9%和87.3%，而SDE（200mg/kg）使扭体反应减少76.7%，炎症性疼痛减少57.1%。在尾部浸入试验中，两种提取物均延长了潜伏期，证实了中枢抗伤害感受作用。SDE和EAF还使角叉菜胶诱导的水肿和白细胞迁移减少了70%以上。在体外，两个样品完全抑制了巴西矛头蝮和白唇矛头蝮毒液的蛋白水解和透明质酸酶活性，并强烈抑制磷脂酶A₂活性。值得注意的是，SDE和EAF的体内给药使白唇矛头蝮诱导的爪部水肿和髓过氧化物酶活性显著降低，最高可达85.5%。这些发现强化了石榴叶的传统用途，并首次报道了其体内镇痛和抗蛇毒潜力，支持了其丰富的酚类成分在调节炎症和毒液诱导反应中的作用。
