title: Does Concurrent Use of Some Botanicals Interfere with Treatment of Tuberculosis?
abstract: Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of TB, as suggested by results of a recent clinical trial of the South African botanical Sutherlandia frutescens (L.) R. Br. (Sutherlandia). Here we provide a brief summary of Sutherlandia's effects upon rodent microglia and neurons relevant to tuberculosis of the central nervous system (CNS-TB). We have observed that ethanolic extracts of Sutherlandia suppress production of reactive oxygen species (ROS) in rat primary cortical neurons stimulated by NMDA and also suppress LPS- and interferon γ (IFNγ)-induced ROS and nitric oxide (NO) production by microglial cells. Sutherlandia consumption mitigates microglial activation in the hippocampus and striatum of ischemic brains of mice. RNAseq analysis indicates that Sutherlandia suppresses gene expression of oxidative stress, inflammatory signaling and toll-like receptor pathways that can reduce the host's immune response to infection and reactivation of latent Mycobacterium tuberculosis. As a precautionary measure, we recommend that individuals receiving isoniazid for pulmonary or cerebral TB, be advised not to concurrently use botanicals or dietary supplements having antioxidant activity.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA. folkw@missouri.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Folk
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Smith
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA.|Center for Translational Neurosciences, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA.|Center for Translational Neurosciences, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Chuang
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA.|Center for Translational Neurosciences, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Zezong
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.|Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA.|Center for Translational Neurosciences, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D007887:Fabaceae / Q000737:chemistry*; D017628:Microglia / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014376:Tuberculosis / Q000628:therapy*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species
keywords: Antioxidant; Botanicals; Isoniazid; Nitric oxide; ROS; Sutherlandia; Tuberculosis