Bio-Guided Fractionation of Oil Palm (Elaeis guineensis) Fruit and Interactions of Compounds with First-Line Antituberculosis Drugs against Mycobacterium tuberculosis H37Ra

Abstract

Natural products with antimycobacterial adjuvant potential may be utilized to address the rise of multidrug-resistant tuberculosis (TB). The antioxidant-rich oil palm (Elaeis guineensis) fruit (OPF) was investigated for antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Ra using bio-guided fractionation techniques, followed by determination of fractional inhibition index (FIC) with first-line anti-TB drugs. In vitro screening using microplate Alamar blue assay showed n-hexane and chloroform partitions of OPF mesocarp had a minimum inhibitory concentration (MIC) of 400–800 µg/mL. The n-hexane fraction contained nonanoic acid (C9H18O2), decanoic acid (C10H20O2), and dodecanoic acid (C12H24O2), identified by gas chromatography-mass spectrometry, which all had an MIC of 50 µg/mL. Nonanoic and decanoic acids had additive effects when combined with streptomycin (FIC index: 0.625) and rifampicin (FIC index: 0.75), respectively. Isoniazid had a 16-fold increase in activity when combined with nonanoic acid and decanoic acid. The combination of nonanoic acid with streptomycin was bactericidal to 99.9% of MTB H37Ra by Day 7 of the time-kill assay, with structural damage of the cell wall observed using electron microscopy. Cytotoxicity assessment using Vero cells confirmed nonanoic acid had low toxicity with LC50 of > 200 µg/mL. The bio-guided fractionation of OPF shows the presence of fatty acids with anti-TB adjuvant potential.