Extracts of six Rubiaceae species combined with rifampicin have good in vitro synergistic antimycobacterial activity and good anti-inflammatory and antioxidant activities

BACKGROUND : The Rubiaceae family has played a significant role in drug discovery by providing molecules with potential use as templates for the development of therapeutic drugs. This study was designed to study the in vitro synergistic effect of six Rubiaceae species in combination with a known anti-TB drug. The antioxidant and anti-inflammatory activity of these species were also evaluated to investigate additional benefits in antimycobacterial treatment. METHODS : The checkerboard method was used to determine the antimycobacterial synergistic activity of plant extracts combined with rifampicin. The antioxidant activity of extracts was determined by the 2,2-diphenyl- 1-picrylhydrazyl (DPPH) method. Anti-inflammatory activity via inhibition of nitric oxide (NO) production was performed in LPS-activated RAW 264.7 macrophages using the Griess assay. RESULTS : Combination of rifampicin with the crude extracts resulted in a 4 to 256-fold increase of activity of extracts. The crude extract of Cremaspora triflora produced the best synergistic effect with rifampicin, with a fractional inhibitory concentration (FIC) index of 0.08 against Mycobacterium aurum. Extracts of Psychotria zombamontana had the best antioxidant activity with an IC50 value of 1.77 μg/mL, lower than the IC50 of trolox and ascorbic acid (5.67 μg/mL and 4.66 μg/mL respectively). All the extracts tested inhibited nitric oxide (NO) production in a concentration dependent manner with the percentage of inhibition varying from 6.73 to 86.27 %. CONCLUSION : Some of the Rubiaceae species investigated have substantial in vitro synergistic effects with rifampicin and also good free radical scavenging ability and anti-inflammatory activity. These preliminary results warrant further study on these plants to determine if compounds isolated from these species could lead to the development of bioactive compounds that can potentiate the activity of rifampicin even against resistant mycobacteria.The University of Pretoria Institutional Research Theme for Animal and Zoonotic Diseases (IRT-AZD), National Research Foundation (NRF, Grant No 81010) and Medical Research Council (MRC) of South Africa provided funding to support this study. The National Research Foundation (NRF) provided a doctoral fellowship to AOA. The University of Pretoria provided a postdoctoral fellowship to JPD.http://www.biomedcentral.com/bmccom/plementalternmedam2017Paraclinical Science