AUTHOR=Aro Abimbola O. , Dzoyem Jean Paul , Goddard Amelia , Fonteh Pascaline , Kayoka-Kabongo Prudence N. , McGaw Lyndy J. 

TITLE=In vitro Antimycobacterial, Apoptosis-Inducing Potential, and Immunomodulatory Activity of Some Rubiaceae Species

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00185

DOI=10.3389/fphar.2019.00185

ISSN=1663-9812

ABSTRACT=<p>Tuberculosis (TB), a disease caused by microorganisms of the <italic>Mycobacterium tuberculosis</italic> complex, infects almost one-third of the world’s population. The TB epidemic has been further exacerbated by the emergence of multi, extensively, and totally-drug-resistant (MDR, XDR, and TDRTB) strains. An effective immune response plays a crucial role in determining the establishment of TB infection. Therefore, the modulation of the immune system has been considered as a vital approach for the treatment or control of various immune-related diseases such as TB. In this study, the antimycobacterial, immunomodulatory, and apoptosis-inducing effects of six Rubiaceae species were evaluated. A twofold serial dilution method was used to determine the minimum inhibitory concentration values of the plant extracts. The effect of the extracts on the activity of 15-lipoxygenase was investigated. The levels of six different cytokines, IL-2, IL-4, IL-5, IL-10, IFN-γ, and TNF-α, were measured in LPS-activated U937 cell line while the apoptosis-inducing effect of the extracts was evaluated using an annexin V/PI assay using a flow cytometer. The results obtained revealed that all the six extracts tested had antimycobacterial activity against <italic>M. tuberculosis</italic> H37Rv, <italic>M. tuberculosis</italic> ATCC 25177, and <italic>Mycobacterium bovis</italic> ATCC 27299 strains, with MIC values ranging from 39 to 312 μg/mL. The extracts of <italic>Cremaspora triflora</italic> and <italic>Cephalanthus natalensis</italic> were the most active against <italic>M. tuberculosis</italic> (MIC = 39 μg/mL), followed by <italic>Pavetta lanceolata</italic> and <italic>Psychotria zombamontana</italic> against <italic>M. bovis</italic> (MIC = 78 μg/mL). The extracts of <italic>P. zombamontana</italic> and <italic>Psychotria capensis</italic> had remarkable IC<sub>50</sub> values of 4.32 and 5.8 μg/mL, respectively, better than that of quercetin. The selected extracts promoted Th1/Th2 balances in an <italic>in vitro</italic> model at the tested concentration which may suggest the therapeutic value of the plant in diseases where inflammation is a significant factor such as TB. The addition of the crude extracts of <italic>C. triflora</italic>, <italic>P. capensis</italic>, and <italic>P. zombamontana</italic> at the tested concentrations to the cell culture medium induced apoptosis in a time- and dose-dependent manner. This interesting preliminary result generated from this study encourages further investigations of these extracts owing to the LOX-inhibitory effect, immunomodulatory, and apoptotic-inducing properties in addition to their antimycobacterial properties.</p>