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两种天然萜类化合物对 的驱虫活性研究

Antiparasitic Activity of Two Natural Terpenes from against .

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Medicina y Biología Experimental de Cuyo, Mendoza, 5500, Argentina.

Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, M5502, Argentina.

出版信息

J Nat Prod. 2023 Apr 28;86(4):797-803. doi: 10.1021/acs.jnatprod.2c00976. Epub 2023 Mar 1.

Abstract

Leishmaniasis is a neglected disease caused by flagellated parasites of the genus affecting more than 10 million people worldwide. Current treatments for leishmaniasis involve the administration of poorly tolerated drugs with toxic side effects in patients. There is an imperative necessity for novel compounds to treat this disease. One of the most used strategies in the search for different antiparasitic compounds is the screening of purified plant molecules. The diterpenes 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide (HABTO) and 5-epi-icetexone (ICTX) isolated from were shown to be effective against and . They displayed an antiproliferative effect against promastigotes. They also induce an increase in ROS levels and affect the mitochondrial activity of parasites. HABTO and ICTX in an model of cutaneous leishmaniasis decrease footpad swelling, parasite load, and splenic index. Moreover, they induce significant reduction in the O.D. of total anti-Leishmania IgG and IgG1 subtype antibody responses against compared to the PBS group but maintain high levels of IgG2a. This suggests that in HABTO- or ICTX-treated mice, there is a slowdown in the progression of the disease. These terpenes could be considered as possible novel antileishmanial agents against and thus treat cutaneous leishmaniasis.

摘要

利什曼病是一种由鞭毛寄生虫引起的被忽视的疾病,影响全球超过 1000 万人。目前治疗利什曼病的方法涉及使用耐受性差且对患者有有毒副作用的药物。因此,迫切需要新型化合物来治疗这种疾病。在寻找不同抗寄生虫化合物的过程中,最常用的策略之一是筛选纯化的植物分子。从 中分离出的二萜 12-羟基-11,14-二酮-6,8,12-枞酸三烯-19,20-内酯 (HABTO) 和 5-表-icetexone (ICTX) 被证明对 和 有效。它们对 和 的 有抗增殖作用。它们还会导致 ROS 水平升高,并影响寄生虫的线粒体活性。在 导致的皮肤利什曼病模型中,HABTO 和 ICTX 可减少足垫肿胀、寄生虫负荷和脾脏指数。此外,与 PBS 组相比,它们可显著降低针对 的总抗利什曼原虫 IgG 和 IgG1 亚型抗体反应的 OD 值,但保持 IgG2a 水平较高。这表明在 HABTO 或 ICTX 治疗的小鼠中,疾病的进展放缓。这些萜类化合物可被视为针对 和 的新型潜在抗利什曼原虫药物,从而治疗皮肤利什曼病。

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