Bortoleti Bruna Taciane da Silva, Detoni Mariana Barbosa, Gonçalves Manoela Daiele, Tomiotto-Pellissier Fernanda, Silva Taylon Felipe, Concato Virginia Marcia, Rodrigues Ana Carolina Jacob, Carloto Amanda Cristina, de Matos Ricardo Luís Nascimento, Fattori Victor, Arakawa Nilton Syogo, Verri Waldiceu Ap, Costa Idessania Nazareth, Conchon-Costa Ivete, Miranda-Sapla Milena Menegazzo, Wowk Pryscilla Fanini, Pavanelli Wander Rogério
Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute (ICC/Fiocruz-PR), Curitiba, Paraná, Brazil; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
Chem Biol Interact. 2022 Jul 1;361:109969. doi: 10.1016/j.cbi.2022.109969. Epub 2022 May 5.
Leishmaniasis is a group of chronic parasitic diseases in humans caused by species of the Leishmania genus. Current treatments have high toxicity, cost, duration, limited effectiveness, significantly complex administration, and drug-resistant strains. These factors highlight the importance of research into new therapies that use drugs without toxic effects. Solidagenone (SOL), the main labdane diterpene isolated from the plant Solidago chilensis, has anti-inflammatory, gastroprotective, antioxidant, tissue repair-inducing effects, suggesting a role in novel drug development. This study investigates in vivo mechanism action of SOL treatment in L. amazonensis-infected BALB/c mice. SOL was isolated from the roots of S. chilensis, and L. amazonensis-infected mice were treated daily with SOL (10, 50, 100 mg/kg) by gavage for 30 days. Gastric (NAG, MPO), hepatic (AST, ALT), systemic (body weight, NO) toxicity, leishmanicidal activity (lesion size, parasite burden), cell profile (macrophage, neutrophil infiltration), antioxidant (ABTS, NBT, NO), oxidant parameters (FRAP, ABTS), Th1, Th2, Th17 cytokines (CBA), collagen deposition (picrosirius), arginase, iNOS, NF-kB, and NRF2 (immunofluorescence) were evaluated. In vivo results showed SOL-treatment did not induce gastric, hepatic, or systemic toxicity in L. amazonensis-infected mice. SOL was able to reduce the lesion size and parasite load at the site of infection, increasing macrophage infiltration and neutrophil migration, exerting a balance in antioxidant (increased ABTS, NBT reduction, and NO), oxidative (increased FRAP and ABTS), and anti-inflammatory responses (reduced TNF-α, IFN-γ and increased IL-6, IL-17 production), and inducing arginase, iNOS, NF-kB, NRF2 and collagen deposition (type III), favoring wound healing and accelerating tissue repair at the site injury.
利什曼病是由利什曼原虫属的物种引起的一组人类慢性寄生虫病。目前的治疗方法具有高毒性、高成本、疗程长、疗效有限、给药显著复杂以及存在耐药菌株等问题。这些因素凸显了研究使用无毒副作用药物的新疗法的重要性。从智利一枝黄花中分离出的主要半日花烷二萜化合物毛连菜酮（SOL）具有抗炎、胃保护、抗氧化、诱导组织修复的作用，提示其在新型药物开发中具有一定作用。本研究调查了SOL治疗对感染亚马逊利什曼原虫的BALB/c小鼠的体内作用机制。从智利一枝黄花的根部分离出SOL，并对感染亚马逊利什曼原虫的小鼠每天经口灌胃给予SOL（10、50、100mg/kg），持续30天。评估了胃（NAG、MPO）、肝（AST、ALT）、全身（体重、NO）毒性、杀利什曼活性（病变大小、寄生虫负荷）、细胞分布（巨噬细胞、中性粒细胞浸润）、抗氧化（ABTS、NBT、NO）、氧化参数（FRAP、ABTS）、Th1、Th2、Th17细胞因子（CBA）、胶原沉积（天狼星红染色）、精氨酸酶、诱导型一氧化氮合酶、核因子κB和核因子E2相关因子2（免疫荧光）。体内实验结果表明，SOL治疗未在感染亚马逊利什曼原虫的小鼠中诱导胃、肝或全身毒性。SOL能够减小感染部位的病变大小并降低寄生虫负荷，增加巨噬细胞浸润和中性粒细胞迁移，在抗氧化（ABTS增加、NBT还原和NO增加）、氧化（FRAP和ABTS增加）和抗炎反应（TNF-α、IFN-γ减少，IL-6、IL-17产生增加）方面发挥平衡作用，并诱导精氨酸酶、诱导型一氧化氮合酶、核因子κB、核因子E2相关因子2和胶原沉积（III型），有利于伤口愈合并加速损伤部位的组织修复。
