Dwivedi Ved P, Bhattacharya Debapriya, Yadav Vinod, Singh Dhiraj K, Kumar Santosh, Singh Mona, Ojha Durbadal, Ranganathan Anand, Van Kaer Luc, Chattopadhyay Debprasad, Das Gobardhan
Immunology Group, International Centre for Genetic Engineering and BiotechnologyNew Delhi, India.
Special Centre for Molecular Medicine, Jawaharlal Nehru UniversityNew Delhi, India.
Front Cell Infect Microbiol. 2017 May 1;7:149. doi: 10.3389/fcimb.2017.00149. eCollection 2017.
Tuberculosis (TB) remains one of the greatest health concerns worldwide, which has hindered socioeconomic development in certain parts of the world for many centuries. Although current TB therapy, "Directly Observed Treatment Short-course," is effective, it is associated with unwanted side effects and the risk for the generation of drug-resistant organisms. The majority of infected individuals successfully confine the mycobacterial organisms and remain asymptotic unless immune responses are perturbed. Thus, host immunity can protect against TB and immunomodulation is therefore an attractive therapeutic option. Previous studies have shown that TNF-α and Nitric Oxide (NO) in conjunction with IFN-γ-producing T helper 1 (Th1) cells play critical roles in host protection against TB. Here, we show that bergenin, a phytochemical isolated from tender leaves of , activates the MAP kinase and ERK pathways and induces TNF-α, NO and IL-12 production in infected macrophages. We further show that bergenin induces Th1 immune responses and potently inhibits bacillary growth in a murine model of infection. These findings identify bergenin as a potential adjunct to TB therapy.
结核病(TB)仍然是全球最重大的健康问题之一,在许多世纪以来一直阻碍着世界某些地区的社会经济发展。尽管当前的结核病治疗方法“直接观察短程治疗”是有效的,但它会带来不良副作用以及产生耐药生物的风险。大多数感染者能够成功限制分枝杆菌的生长,并且除非免疫反应受到干扰,否则他们不会出现症状。因此,宿主免疫可以预防结核病,免疫调节因此成为一种有吸引力的治疗选择。先前的研究表明,肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)与产生干扰素-γ的辅助性T细胞1(Th1)一起,在宿主抵抗结核病的过程中发挥着关键作用。在此,我们表明,从[植物名称]嫩叶中分离出的一种植物化学物质岩白菜素,可激活丝裂原活化蛋白激酶(MAP激酶)和细胞外信号调节激酶(ERK)途径,并在受感染的巨噬细胞中诱导TNF-α、NO和白细胞介素-12(IL-12)的产生。我们进一步表明,岩白菜素在小鼠[感染类型]感染模型中可诱导Th1免疫反应并有效抑制细菌生长。这些发现确定岩白菜素是结核病治疗的一种潜在辅助药物。