Robledo Sara M, Murillo Javier, Arbeláez Natalia, Montoya Andrés, Ospina Victoria, Jürgens Franziska M, Vélez Iván D, Schmidt Thomas J
PECET-School of Medicine, University of Antioquia, Calle 70 # 52-21, Medellin 0500100, Colombia.
University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, PharmaCampus, Corrensstrasse 48, D-48149 Münster, Germany.
Pharmaceuticals (Basel). 2022 Jun 22;15(7):776. doi: 10.3390/ph15070776.
Leishmaniasis may occur in three different clinical forms, namely, visceral, mucocutaneous and cutaneous, which are caused by different species of trypanosomatid protozoans of the genus . Pentavalent antimonials are the leading treatment for cutaneous leishmaniasis despite the hepatic, renal, and cardiac toxicity. In addition, the response of some species to pentavalent antimonials is increasingly poorer, and therefore new and more potent therapeutic alternatives are needed. L., Asteraceae, is a traditional medicinal plant of Europe and preparations of its flowers are commonly used externally to treat disorders of the musculoskeletal system as well as superficial inflammatory conditions. Previous studies have shown that Arnica tincture (AT), an ethanolic extract prepared from the flowerheads of as well as isolated Arnica sesquiterpene lactones (STLs) have antileishmanial activity in vitro against and , as well as in vivo against . In this work, we studied the in vitro cytotoxicity and antileishmanial activity of AT and STLs against both and . The in vivo therapeutic effect of AT was studied in hamsters with cutaneous Leishmaniasis (CL) caused by experimental infection with and . Furthermore, various semisolid Arnica preparations were also evaluated against . The STLs and the AT possess a very high in vitro activity against both species with median effective concentrations (EC) ranging from 1.9 to 5.9 μg/mL. The AT was not cytotoxic for human tissue macrophages, skin fibroblasts, and hepatic cells. The therapeutic response of hamsters infected with to the topical treatment with AT was 87.5% at a dose of 19.2 μg STL/2× day/60 d, 72.7% at doses of 19.2 μg STL/1× d/60 d and 67% at a dose of 38.4 μg STL/2× d/60 d. In turn, the therapeutic response in hamsters infected with was 100% when treated at a dose of 19.2 μg STL/2× day/60 d and 71% at a dose of 38.4 μg STL/2× d/60 d. On the other hand, the effectiveness of treatment with glucantime administered intralesionally at a dose of 200 mg/every three days for 30 days was 62.5% for and 37.5% for infection. These results are promising and encourage the implementation of clinical trials with AT in CL patients as a first step to using AT as a drug against CL.
利什曼病可能以三种不同的临床形式出现,即内脏型、黏膜皮肤型和皮肤型,它们由利什曼原虫属不同种类的锥虫原生动物引起。尽管五价锑剂存在肝毒性、肾毒性和心脏毒性,但仍是皮肤利什曼病的主要治疗药物。此外,一些利什曼原虫种类对五价锑剂的反应越来越差,因此需要新的、更有效的治疗替代方案。土木香属菊科植物,是欧洲的一种传统药用植物,其花的制剂通常外用治疗肌肉骨骼系统疾病以及浅表炎症。先前的研究表明,土木香酊剂(AT),一种从土木香头状花序制备的乙醇提取物以及分离出的土木香倍半萜内酯(STLs)在体外对杜氏利什曼原虫和墨西哥利什曼原虫具有抗利什曼活性,在体内对硕大利什曼原虫也有抗利什曼活性。在这项研究中,我们研究了AT和STLs对杜氏利什曼原虫和墨西哥利什曼原虫的体外细胞毒性和抗利什曼活性。在由硕大利什曼原虫和墨西哥利什曼原虫实验感染引起皮肤利什曼病(CL)的仓鼠中研究了AT的体内治疗效果。此外,还评估了各种半固体土木香制剂对硕大利什曼原虫的作用。STLs和AT对两种利什曼原虫均具有非常高的体外活性,半数有效浓度(EC)范围为1.9至5.9μg/mL。AT对人体组织巨噬细胞、皮肤成纤维细胞和肝细胞无细胞毒性。感染硕大利什曼原虫的仓鼠以19.2μg STL/2次/天/60天的剂量进行局部治疗时,治疗反应率为87.5%,以19.2μg STL/1次/天/60天的剂量治疗时为72.7%,以38.4μg STL/2次/天/60天的剂量治疗时为67%。相应地,感染墨西哥利什曼原虫的仓鼠以19.2μg STL/2次/天/60天的剂量治疗时,治疗反应率为100%,以38.4μg STL/2次/天/60天的剂量治疗时为71%。另一方面,以200mg/每三天一次、共30天的剂量病灶内注射葡糖胺锑钠进行治疗,对硕大利什曼原虫感染的有效性为62.5%,对墨西哥利什曼原虫感染为37.5%。这些结果很有前景,并鼓励在CL患者中开展使用AT的临床试验,作为将AT用作抗CL药物的第一步。