title: Nordihydroguaiaretic acid (NDGA) and α-mangostin inhibit the growth of Mycobacterium tuberculosis by inducing autophagy.
abstract: Tuberculosis (TB) remains as a global health problem. The prevalence of this infection is related to the association with other diseases, such as HIV, neglect treatment and misuse of antibiotics. Hence, the identification of new drugs is required to eradicate TB. Possible alternatives to existing antibiotics include pure compounds extracted from medicinal plants, which are an important source of antimicrobial agents. The aim of this study was to evaluate the effect of nordihydroguaiaretic acid (NDGA) and α-mangostin on Mycobacterium tuberculosis growth and bacterial survival in infected macrophages derived from the human THP-1 cell line and monocytes. Our results show that both compounds directly inhibit M. tuberculosis growth in liquid medium with Minimal Inhibitory Concentrations (MIC) of 250 and 62 μg/mL respectively, likely through preventing bacterial replication. In addition, NDGA and α-mangostin were able to induce autophagy in human cells at lower concentrations (7 and 6 μg/mL, respectively) and contributed to the elimination of intracellular bacteria. NDGA and α-mangostin could be candidates for coadjuvant therapy in cases of drug-resistant TB, and their ability to enhance the immune response by promoting autophagy might contribute to TB treatment.
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guzmán-Beltrán
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Rubio-Badillo
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Juárez
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Hernández-Sánchez
authors.affiliation: Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, México City, Mexico. Electronic address: marthatorres98@yahoo.com.
authors.forename: Martha
authors.initials: M
authors.lastname: Torres
mesh_terms: D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology; D009637:Masoprocol / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D044004:Xanthones; D009637:Masoprocol; C021053:mangostin
keywords: Autophagy; Mycobacterium tuberculosis; Nordihydroguaiaretic acid; α-Mangostin