Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.
Departamento de Analises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil.
Parasitol Res. 2021 Apr;120(4):1511-1517. doi: 10.1007/s00436-020-06944-5. Epub 2020 Nov 24.
Chagas disease (CD) is endemic in Latin America. Drugs available for its treatment are benznidazole (BZ)/nifurtimox (NF), both with low efficacy in the late infection and responsible for several side effects. Studies of new drugs for CD among natural products, and using drug combinations with BZ/NF are recommended. Silibinin (SLB) is a natural compound that inhibits the efflux pump (Pgp) of drugs in host cell membranes, causes death of trypanosomatids, has anti-inflammatory activity, and was never assayed against T. cruzi. Here, in vitro and in vivo activities of SLB, SLB+BZ, and BZ against T. cruzi Y strain were evaluated. Cytotoxicity of SLB in VERO cells by the MTT method revealed IC50 of 250.22 μM. The trypanocidal activity evaluated by resazurin method in epimastigotes showed that SLB 25 μM inhibited parasite growth. SLB IC50 and selectivity index (SI) for amastigote were 79.81 μM and 3.13, respectively. SLB100+BZ10 showed higher parasite inhibition (91.44%) than SLB or BZ. Swiss mice infected with Y strain were treated with SLB, SLB+BZ, and BZ. Parasitemia was evaluated daily and 90, 180, and 240 days after treatment in surviving animals by hemoculture, blood qPCR, and after euthanasia, by qPCR in heart tissue. SLB monotherapy was not able to control the parasitemia/mortality of the animals. Parasitological negativation of 85.7-100% was observed in the experimental groups treated with SLB+BZ. Although SLB had shown activity against T. cruzi in vitro, it was not active in mice. Thus, the results of the therapeutic effect observed with SLB+BZ may be interpreted as a result from BZ action.
恰加斯病（CD）在拉丁美洲流行。现有的治疗药物有苯并咪唑（BZ）/硝呋莫司（NF），但在晚期感染时疗效较低，且具有多种副作用。建议针对天然产物中的 CD 进行新药研究，并采用 BZ/NF 联合用药。水飞蓟素（SLB）是一种天然化合物，可抑制宿主细胞膜上的药物外排泵（Pgp），导致寄生虫死亡，具有抗炎活性，从未针对 T. cruzi 进行过检测。在此，评估了 SLB、SLB+BZ 和 BZ 对 T. cruzi Y 株的体外和体内活性。通过 MTT 法评估 SLB 在 VERO 细胞中的细胞毒性，发现其 IC50 为 250.22 μM。用 Resazurin 法评估的滋养体杀活性表明，25 μM 的 SLB 可抑制寄生虫生长。SLB 对滋养体的 IC50 和选择性指数（SI）分别为 79.81 μM 和 3.13。SLB100+BZ10 对寄生虫的抑制率（91.44%）高于 SLB 或 BZ。用 Y 株感染的瑞士小鼠用 SLB、SLB+BZ 和 BZ 进行治疗。通过血培养、血液 qPCR 和安乐死后 qPCR 在心组织中评估感染后 90、180 和 240 天存活动物的寄生虫血症。SLB 单药治疗不能控制动物的寄生虫血症/死亡率。用 SLB+BZ 治疗的实验组观察到 85.7-100%的寄生虫学阴性。尽管 SLB 已显示出对 T. cruzi 的体外活性，但在小鼠中无活性。因此，观察到的 SLB+BZ 治疗效果可能被解释为 BZ 作用的结果。
