Antileishmanial Activity Laboratory, Medicinal Plants Research Center, Federal University of Piaui, Teresina, Piauí, Brazil
Department of Veterinary Morphophysiology, Federal University of Piauí, Teresina, Piauí, Brazil.
Antimicrob Agents Chemother. 2020 Nov 17;64(12). doi: 10.1128/AAC.00807-20.
In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the treatment of BALB/c mice infected with After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.
在这项研究中，我们证明了将常规两性霉素 B（Amph B）与没食子酸（GA）和鞣花酸（EA）结合在局部制剂中用于治疗 BALB/c 小鼠皮肤利什曼病的潜在关联效应。对制剂进行了初步稳定性测试，并进行了 Amph B、GA、Amph B+GA、EA 和 Amph B+EA 的药物释放研究，同时评估了感染 BALB/c 小鼠的治疗效果。感染 40 天后，将动物分为 6 组，每天两次用含有 Amph B、GA、Amph B+GA、EA 或 Amph B+EA 的凝胶治疗 21 天，阴性对照组用载体治疗。在接受治疗的动物中，病变大小减小，寄生虫负荷减少。用 GA、EA 以及与 Amph B 组合进行的治疗的组织病理学分析显示，存在成纤维细胞、肉芽组织和胶原沉积的界限分明的病变，以及活化的巨噬细胞。含有 GA 和 EA 的制剂在所有评估参数中均激活了巨噬细胞，导致先天免疫反应细胞的激活，从而产生愈合和保护作用。GA 和 EA 与 Amph B 产生了协同作用，这使得它们有望与常规 Amph B 联合用于治疗皮肤利什曼病。
