Folk WR1,
Smith A2,
Song H3,4,
Chuang D3,4,
Cheng J5,
Gu Z3,4,
Sun G2,3,4.
- 1Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA. folkw@missouri.edu.
- 2Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
- 3Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, 65211, USA.
- 4Center for Translational Neurosciences, University of Missouri, Columbia, MO, 65211, USA.
- 5Department of Computer Science, University of Missouri, Columbia, MO, 65211, USA.
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.
KEYWORDS:
Antioxidant; Botanicals; Isoniazid; Nitric oxide; ROS; Sutherlandia; Tuberculosis