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水飞蓟素单独或联合化疗对实验性耐多药或敏感肺结核的显著治疗作用:体外和体内研究。

A significant therapeutic effect of silymarin administered alone, or in combination with chemotherapy, in experimental pulmonary tuberculosis caused by drug-sensitive or drug-resistant strains: In vitro and in vivo studies.

机构信息

Department of Pathology, Experimental Pathology Section, National Institute of Medical Sciences and Nutrition ''Salvador Zubiran", Mexico City, Mexico.

Genomic Sciences Program, Autonomous University of México City, Mexico City, México.

出版信息

PLoS One. 2019 May 30;14(5):e0217457. doi: 10.1371/journal.pone.0217457. eCollection 2019.

Abstract

For many years, tuberculosis (TB) has been a major public health problem worldwide. Advances for treatment and eradication have been very limited. Silymarin (Sm) is a natural product with antioxidant and hepatoprotective activities that has been proposed as a complementary medicine to reduce the liver injury produced by the conventional anti-TB chemotherapy. Sm also has immunoregulatory and microbicide properties. In this study, we determined the effect of Sm on the growth control of mycobacteria. In vitro studies showed that Sm and Silibinin (the principal active compound of Sm) have microbicidal activity against drug-sensitive and multidrug-resistant (MDR) mycobacteria, induce the production of protective cytokines from infected macrophages, and improve the growth control of mycobacteria (p ≤ 0.0001). Studies in vivo using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria have shown that Sm induces significant expression of Th-1 cytokines such as IFN-γ and IL-12 as well as TNFα, which produce significant therapeutic activity when administered alone and apparently have a synergistic effect with chemotherapy. These results suggest that Sm has a bactericidal effect and can contribute to the control and establishment of a TH1 protective immune response against mycobacterial infection. Thus, it seems that this flavonoid has a promising potential as adjuvant therapy in the treatment of TB.

摘要

多年来,结核病(TB)一直是全球主要的公共卫生问题。在治疗和根除方面的进展非常有限。水飞蓟素(Sm)是一种具有抗氧化和保肝作用的天然产物,已被提议作为一种辅助药物,以减少常规抗结核化疗引起的肝损伤。Sm 还具有免疫调节和杀微生物特性。在这项研究中,我们确定了 Sm 对分枝杆菌生长控制的影响。体外研究表明,Sm 和水飞蓟宾(Sm 的主要活性化合物)对敏感和耐多药(MDR)分枝杆菌具有杀菌活性,诱导感染巨噬细胞产生保护性细胞因子,并改善分枝杆菌的生长控制(p≤0.0001)。使用 BALB/c 小鼠进行的进展性肺结核模型体内研究表明,Sm 诱导 Th1 细胞因子(如 IFN-γ 和 IL-12)以及 TNFα 的显著表达,单独给药时具有显著的治疗活性,并且显然与化疗具有协同作用。这些结果表明,Sm 具有杀菌作用,并有助于控制和建立针对分枝杆菌感染的 TH1 保护性免疫反应。因此,这种类黄酮似乎具有作为结核病治疗辅助治疗的潜在前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f96/6542514/dab7f75553cf/pone.0217457.g001.jpg

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