A AKTIVITAS ANTIBAKTERI KOMBINASI EKSTRAK DAUN SIRIH HIJAU (Piper betle L.) DAN ANTIBIOTIK TERHADAP Staphylococcus aureus DAN Escherichia coli
AKTIVITAS ANTIBAKTERI KOMBINASI EKSTRAK DAUN SIRIH HIJAU (Piper betle L.) DAN ANTIBIOTIK TERHADAP Staphylococcus aureus DAN Escherichia coli: SYSTEMATIC LITERATURE REVIEW
DOI:
https://doi.org/10.36656/gx6nrp44Keywords:
Piper betle L.; green betel leaf; antibacterial; antibiotics; Staphylococcus aureus; Escherichia coli; synergism; FICI.Abstract
Antibiotic resistance is a major global health problem that reduces the effectiveness of antibacterial therapy and encourages the development of new strategies to improve antibiotic activity. One promising strategy is combining conventional antibiotics with natural products possessing antibacterial properties. Green betel leaf (Piper betle L.) contains phenolic compounds, hydroxychavicol, eugenol, flavonoids, tannins, and other secondary metabolites with potential antibacterial activity. This systematic literature review aimed to evaluate the antibacterial activity of green betel leaf extracts and their interactions with antibiotics against Staphylococcus aureus and Escherichia coli. The literature search was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines using PubMed, Google Scholar, ScienceDirect, Crossref, and Indonesian scientific journal databases. Search terms included “Piper betle”, “green betel leaf”, “antibacterial”, “Staphylococcus aureus”, “Escherichia coli”, “antibiotic combination”, “synergistic”, “MIC”, “checkerboard”, and “FICI”. The reviewed studies demonstrated that P. betle leaf extracts exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria; however, the magnitude of activity was strongly influenced by extraction method, solvent polarity, extract concentration, phytochemical composition, and bacterial characteristics. Ethyl acetate and acetone extracts showed relatively strong antibacterial activity and produced synergistic or additive interactions with selected antibiotics. Conversely, combinations involving methanolic P. betle extract with amoxicillin, chloramphenicol, and cotrimoxazole showed additive or antagonistic effects under certain experimental conditions. Potential mechanisms of synergy include membrane disruption, increased bacterial membrane permeability, modulation of efflux systems, and complementary multi-target actions between phytochemicals and antibiotics. In conclusion, P. betle has potential as an antibiotic adjuvant; nevertheless, its interactions are extract-, antibiotic-, concentration-, and strain-dependent. Further studies using checkerboard assays, fractional inhibitory concentration indices, time-kill assays, resistant clinical isolates, and in vivo models are required before clinical application.
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