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Daulay, Wardiyah
Faculty Of Nursing Universitas Sumatera Utara
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Synergistic mechanism of Phyllanthus emblica extract and tetracycline against multidrug-resistant Acinetobacter baumannii Nasution, Haris M.; Yulyana, Ana; Utama, Rezza F.; Bangar, Roy I.; Kaban, Vera E.; Daulay, Wardiyah; Astyka, Ririn; Lubis, Muhammad F.
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1939

Abstract

The rising incidence of multidrug-resistant (MDR) Acinetobacter baumannii infections underscores the urgent need for novel antimicrobial strategies. The aim of this study was to investigate the synergistic effects between a polyphenol-rich extract from Phyllanthus emblica fruit and tetracycline against MDR A. baumannii strains. The extraction process was optimized using the Box-Behnken design approach to maximize the total phenolic content (TPC) of the P. emblica extract. Key variables, including ethanol concentration, extraction time, and solid-to-liquid ratio (w/v), were determined through single-factor experiments. The antimicrobial activity of the extract, both alone and in combination with tetracycline, was evaluated against A. baumannii. Mechanistic studies focusing on bacterial lysis and efflux pump inhibition were conducted to assess the extract's effects and its combined potential with tetracycline. The Box-Behnken design successfully optimized the extraction conditions, yielding the highest TPC at 68.92% ethanol concentration, 1.85 days of extraction time, and a 1:9.58 w/v ratio. The predicted and experimentally verified TPC values of the extract were 129.19 and 130.76±2.46 mg GAE/g samples, respectively, with no significant difference (p>0.05). The extract contained several phenolic compounds identified using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). It exhibited antimicrobial activity against MDR Acinetobacter baumannii, either alone or in combination with tetracycline. The combination demonstrated a synergistic effect against MDR A. baumannii, with a fractional inhibitory concentration index (FICI) of 0.37. Moreover, the combination showed superior bacteriolytic effects against MDR A. baumannii cells, as evidenced by increased release of nucleic acid components and membrane destabilization, compared to the extract or tetracycline alone (p<0.0001 for all comparisons). Additionally, the combination significantly enhanced the efflux pump inhibition effect compared to the extract or tetracycline alone (p<0.05 for both). These findings support the potential use of polyphenol-rich P. emblica extracts as adjuncts to conventional antibiotics in treating drug-resistant bacterial infections.
Co-Authors Agatha Novelia Simamora Ansela, Rasninta Devi Anwar, Anwar Astyka, Ririn Azzahra, Putri Karini Bangar, Roy I. Boru Tarigan, Juliati Daulay, Niken Malinda Putri Dwi Eka Putri Einjel Tiyo Marlina Damanik Fadhila, Filza Forwaty, Erni Harianja, Susi Junita Jenny M Purba Jenny Marlindawani Purba Kaban, Vera E. Kontoko R Rochadi Lailan Nasution, Mahnum Lia Debora Manihuruk Lilik Supriati, Lilik Lubis, Ade Sulistya Lubis, Muhammad F. M. Surya Husada Mahnum Lailan Mahnum Lailan Nasution Mahnum Lailan Nasution Mahnum Lailan Nst Marbun, Betty Nurita Marlindawani Purba, Jenny Marlindawani, Jenni Marlindawani, Jenny Muhaini Atmayana Purba Nababan, Riko Hengki Nadya, Cici Naibaho, Amelia Elisabeth Nasution, Haris M. Nasution, Mahnum Lailan Nasution, Sakinah Al Muniroh Nasution, Siti Saidah Nia Khusniyati Nst, Mahnum Lailan Oktariani, Falinda Purba, Jenny Marlindawani Purba, Jenny Marlindawany Putri, Nazela Nanda Rasninta Devi Ansela Ria Rahmawati Riko Hengki Nababan Rinaldi Ginting Safira, Annisa Safra Satilla Rambe Santika, Ririn Dewi Sari, Dewi Keumala Silalahi, Evayanti Ratna Dewi Siregar, Ismail Wildansyah Siregar, Nadiyah Afrah Sitanggang, Rahmatia Siti Saidah Nasution Sitorus, Pranciska Sri Adriana A Siahaan Sri Adriana Siahaan Sri Depi Ulinta Br Ginting Sri Eka Wahyuni Sri Eka Wahyuni Sri Eka Wahyuni Sri Eka Wahyuni Sri Eka Wahyuni Sri Eka Wahyuni Sri Eka Wahyuni Usraleli, Usraleli Utama, Rezza F. VEVI SURYENTI PUTRI, VEVI SURYENTI Wahyuni, Sri Eka Wulantari, Masrina Naomi Yohana Beatry Sitanggang Yulyana, Ana Yuswardi, Yuswardi