Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa

BACKGROUND: The escalating dominance of resistant Pseudomonas aeruginosa strains as infectious pathogen had urged the researchers to look for alternative and complementary drugs. OBJECTIVE: The objective of this study is to address the biological targets and probable mechanisms of action underlying the potent antibacterial effect of the isolated compounds from Euphorbia hirta (L.) against P. aeruginosa. MATERIALS AND METHODS: The action mechanisms of caffeic acid (CA) and epicatechin 3-gallate (ECG) on P. aeruginosa cells were investigated by several bacterial physiological manifestations involving outer membrane permeabilization, intracellular potassium ion efflux, and nucleotide leakage. RESULTS: The findings revealed that ECG and CA targeted both cell wall and cytoplasmic membrane of P. aeruginosa. The cellular membrane destruction and ensuing membrane permeability perturbation of P. aeruginosa had led to the ascending access of hydrophobic antibiotics, release of potassium ions, and leakages of nucleotides. CONCLUSION: The overall study concludes that ECG and CA isolated from E. hirta possess remarkable anti-infective potentials which can be exploited as drug template for the development of new antibacterial agent against resistant P. aeruginosa pathogen. SUMMARY: Epicatechin 3-gallate (ECG) and caffeic acid (CA) exhibited remarkable bactericidal abilities by increasing the outer membrane and plasma membrane permeability of Pseudomonas aeruginosa pathogen. ECG and CA had facilitated the entry of hydrophobic antibiotics into P. aeruginosa by disintegrating the lipopolysaccharides layer of the outer membrane. ECG-induced potassium efflux with efficiency close to that obtained with cefepime suggesting mode of action through membrane disruption. Both ECG and CA had caused consistent leakage of intracellular nucleotide content with the increase in time. Abbreviations used: ECG: Epicatechin 3-gallate; CA: Caffeic acid; E. hirta: Euphoria hirta.