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

摘要

BACKGROUND : The Rubiaceae family has played a significant role in drug discovery by providing molecules withpotential use as templates for the development of therapeutic drugs. This study was designed to study the invitro synergistic effect of six Rubiaceae species in combination with a known anti-TB drug. The antioxidant andanti-inflammatory activity of these species were also evaluated to investigate additional benefits in antimycobacterialtreatment.METHODS : The checkerboard method was used to determine the antimycobacterial synergistic activity of plantextracts 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 wasperformed 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 activityof extracts. The crude extract of Cremaspora triflora produced the best synergistic effect with rifampicin, witha fractional inhibitory concentration (FIC) index of 0.08 against Mycobacterium aurum. Extracts of Psychotriazombamontana had the best antioxidant activity with an IC50 value of 1.77 μg/mL, lower than the IC50 oftrolox 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 rifampicinand also good free radical scavenging ability and anti-inflammatory activity. These preliminary results warrant furtherstudy on these plants to determine if compounds isolated from these species could lead to the developmentof bioactive compounds that can potentiate the activity of rifampicin even against resistant mycobacteria.