Synergistic Effect of Antibacterial and Antibiofilm Activity of Oldenlandia corymbosa Combined with Oxytetracycline Against Drug-Resistant Bacteria
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This study evaluated the antioxidant, antibacterial, synergistic, and antibiofilm activities of Oldenlandia corymbosa, a Thai medicinal plant known for hepatoprotective and anti-breast cancer properties. Antibacterial activity and synergy were assessed using broth microdilution and checkerboard assays, with interactions interpreted by fractional inhibitory concentration index (FICI). Antibiofilm activity was determined using the crystal violet assay. The ethanol extract from aerial parts of O. corymbosa exhibited strong antioxidant activity, with a Ferric Reducing Antioxidant Power (FRAP) value of 5.98 ± 0.12 mg FeSO₄/g extract at 0.1 mg/mL and a DPPH IC₅₀ of 0.19 mg/mL. The extract showed antibacterial activity against 10 of 11 opportunistic bacterial strains, with minimum inhibitory concentrations (MICs) ranging from 20 to 80 mg/mL, except for Proteus mirabilis, which was resistant. In combination studies, O. corymbosa extract demonstrated strong synergistic effects with Oxytetracycline against Staphylococcus aureus (FICI = 0.17). However, no effect was observed against drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa. Combination with Ampicillin was largely ineffective, except for S. aureus (FICI = 1.016 as an additive effect). The extract significantly inhibited biofilm formation in both standard and drug-resistant strains, including Escherichia coli ATCC 25922, MRSA, P. aeruginosa, and A. baumannii, with inhibition ranging from 64.15% to 75.86% over 4–24 hours. Notably, combinations with Oxytetracycline or Norfloxacin enhanced antibiofilm activity in resistant strains, achieving approximately 68.23%–75.90% inhibition within 8–12 hours. These findings highlight O. corymbosa as a promising multifunctional antimicrobial and antibiofilm agent.
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Mancuso, G.; Midiri, A.; Gerace, E.; Biondo, C. Bacterial Antibiotic Resistance: The Most Critical Pathogens. Pathogens 2021, 10(10), 1310. https://doi.org/10.3390/pathogens10101310
Gupta, P. D.; Birdi, T. J. Development of Botanicals to Combat Antibiotic Resistance. J. Ayurveda Integr. Med. 2017, 8, 266–275. https://doi.org/10.1016/j.jaim.2017.05.004
Cheesman, M. J.; Ilanko, A.; Blonk, B.; Cock, I. E. Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution? Pharmacogn. Rev. 2017, 11(22), 57–72. https://doi.org/10.4103/phrev.phrev_21_17
Archana, V.; Thomas, N. N.; Rauf, A. A.; Edwin, B. T. Pharmaceutical Properties of Oldenlandia corymbosa Linn. Mater. Today Proc. 2021, 41(3), 698–702. https://doi.org/10.1016/j.matpr.2020.05.585
Sanggeetha, S.; Sivapraksam, K.; Karunakaran, K.; Subburaya, U.; Kuppusamy, S.; Subashini, T. S. A Review of Phytochemical and Pharmacological Profiles of Hedyotis corymbosa Linn. Int. J. Pharm. Sci. Rev. Res. 2014, 26(1), 320–3
Al-Shuhaib, M. B. S.; Al-Shuhaib, J. M. B. Phytochemistry, Pharmacology, and Medical Uses of Oldenlandia (Family Rubiaceae): A Review. Naunyn Schmiedebergs Arch. Pharmacol. 2024. https://doi.org/10.1007/s00210-024-02887-z
Rajalakshmi, K.; Elumalai, A. Phytochemical and Pharmacological Profile of Oldenlandia corymbosa Plant: A Review. Int. J. Pharm. Sci. Res. 2021, 12(6), 3065–3073. https://doi.org/10.13040/IJPSR.0975-8232.12(6).3065-73
Rollando, R. Combination of Hedyotis corymbosa and Tinospora crispa Ethanolic Extract Increases Cisplatin Cytotoxicity on T47D Breast Cancer Cells. Asian J. Pharm. Clin. Res. 2018, 11(7), 171–175. https://doi.org/10.22159/ajpcr.2018.v11i7.25607
Hussain, A. Z.; Kumaresan, S. Phytochemical and Antimicrobial Evaluation of Oldenlandia corymbosa. Asian J. Plant Sci. Res. 2013, 3(4), 155–158
Lahmar, A.; Bedoui, A.; Mokdad-Bzeouich, I.; et al. Combination of Essential Oils and Antibiotics Reduce Antibiotic Resistance in Plasmid-Conferred Multidrug-Resistant Bacteria. Antimicrob. Resist. Infect. Control 2013, 2, 6. https://doi.org/10.1186/2047-2994-2-6
Yap, P. S.; Krishnan, T.; Chan, K. G.; Lim, S. H. Antibacterial Mode of Action of Cinnamomum verum Bark Essential Oil, Alone and in Combination with Piperacillin, against a Multidrug-Resistant Escherichia coli Strain. J. Microbiol. Biotechnol. 2015, 25(8), 1299–1306. https://doi.org/10.4014/jmb.1504.04037
Silva, N. C. C.; Fernandes, J. A. Biological Properties of Medicinal Plants: A Review of Their Antimicrobial Activity. J. Venom. Anim. Toxins Trop. Dis. 2010, 16(3), 402–413. https://doi.org/10.1590/S1678-91992010000300009
Nehme, D.; Li, X.-Z.; Elliot, R.; Poole, K. Assembly of the MexAB-OprM Multidrug Efflux System of Pseudomonas aeruginosa: Identification and Characterization of Mutations in mexA Compromising MexA Multimerization and Interaction with MexB. J. Bacteriol. 2004, 186 (10), 2973–2983. https://doi.org/10.1128/JB.186.10.2973-2983.2004
Sembiring, E. N.; Elya, B.; Sauriasari, R. Phytochemical Screening, Total Flavonoid and Total Phenolic Content, and Antioxidant Activity of Different Parts of Caesalpinia bonduc (L.) Roxb. Pharmacogn. J. 2018, 10 (1), 123–127. https://doi.org/10.5530/pj.2018.10.20.
Mokbel, M. S.; Hashinaga, F. Antibacterial and Antioxidant Activities of Banana (Musa, AAA cv. Cavendish) Fruit Peel. Am. J. Biochem. Biotechnol. 2005, 1(3), 125–131. https://doi.org/10.3844/ajbbsp.2005.125.131
Sokamte, A.; et al. Screening and Characterization of Phenolic Compounds from Banana Peels and Their Antioxidant Activities. Antioxidants 2021, 10 (1), 1. https://doi.org/10.3390/antiox10010001
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: CLSI Supplement M100S, 26th ed.; CLSI: Wayne, PA, 2016.
Padalia, H.; Anjali, T.; Chanda, S. Antimicrobial Activity of Some Medicinal Plant Extracts and Its Synergistic Interaction with Some Antibiotics. J. Pharm. Res. 2016, 10, 211–220.
Das, A.; Das, M. C.; Sandhu, P.; et al. Antibiofilm Activity of Parkia javanica against Pseudomonas aeruginosa: A Study with Fruit Extract. RSC Adv. 2017, 7(9), 5497–5513. https://doi.org/10.1039/C6RA24603F
Al Bashera, M.; Moulick, S. P.; Islam, M. B.; Jahan, F.; Uddin, M. N.; Rana, G. M.; et al. Antimicrobial and Antioxidant Properties of Oldenlandia corymbosa L. Ethanolic Extract: A Comprehensive Study with Molecular Docking and GC-MS Analysis. Heliyon 2025, 11(5), e42901. https://doi.org/10.1016/j.heliyon.2025.e42901
Sasikumar, J. M.; Maheshu, V.; Aseervatham, G. S.; Darsini, D. T. In Vitro Antioxidant Activity of Hedyotis corymbosa (L.) Lam. Aerial Parts. Indian J. Biochem. Biophys. 2010, 47(1), 49–52.
Njinga, N. S.; Attah, F.; Shittu, A. O.; et al. Phytochemical and Antioxidant Activity of Water and Methanol Extracts of Oldenlandia corymbosa. J. Basic Soc. Pharm. Res. 2024, 3(2), 53–60. https://doi.org/10.52968/27459072
Archana, V.; Thomas, N. N.; Rauf, A. A.; Edwin, B. T. Fatty Acid Derivative of Methanol Extract of Oldenlandia corymbosa: A Potential Compound against Klebsiella pneumoniae and MCF Cell Lines. Int. J. Res. Appl. Sci. Biotechnol. 2020, 7(3), 46–52. https://doi.org/10.31033/ijrasb.7.3.8
Piekarska-Radzik, L.; Klewicka, E. Mutual Influence of Polyphenols and Lactobacillus spp. Bacteria in Food: A Review. Eur. Food Res. Technol. 2021, 247(1), 9–24. https://doi.org/10.1007/s00217-020-03603-y
Bakry, S. M.; El-Shiekh, R. A.; Hatem, S.; Mandour, A. A.; El-Dessouki, A. M.; Bishr, A.; et al. Therapeutic Applications of Ursolic Acid: A Comprehensive Review and Utilization of Predictive Tools. Futur. J. Pharm. Sci. 2025, 11, 48. https://doi.org/10.1186/s43094-025-00796-5
Devi, K. P.; Nisha, S. A.; Sakthivel, R.; Pandian, S. K. Eugenol Acts as an Antibacterial Agent against Salmonella typhi by Disrupting the Cellular Membrane. J. Ethnopharmacol. 2010, 130(1), 107–115. https://doi.org/10.1016/j.jep.2010.04.025
Gill, A. O.; Holley, R. A. Disruption of Escherichia coli, Listeria monocytogenes, and Lactobacillus sakei Cellular Membranes by Plant Oil Aromatics. Int. J. Food Microbiol. 2006, 108(1), 1–9. https://doi.org/10.1016/j.ijfoodmicro.2005.12.029
Osei-Owusu, H.; Rondevaldova, J.; Houdkova, M.; Kudera, T.; Needham, T.; Mascellani, A.; Kokoska, L. Evaluation of In Vitro Synergistic Effects of Tetracycline with Alkaloid-Related Compounds against Diarrheic Bacteria. Int. J. Mol. Sci. 2024, 25(11), 6038. https://doi.org/10.3390/ijms25116038
Malik, M.; Das, S.; Paul, P.; Chakraborty, P.; Roy, R.; Maity, A.; et al. Cuminaldehyde in Combination with Tetracycline Shows Promising Antibiofilm Activity against Drug-Resistant Pseudomonas aeruginosa. Biofouling 2024, 40(10), 862–881. https://doi.org/10.1080/08927014.2024.2422874
Shinde, S.; Lee, L. H.; Chu, T. Inhibition of Biofilm Formation by the Synergistic Action of EGCG-S and Antibiotics. Antibiotics 2021, 10(2), 102. https://doi.org/10.3390/antibiotics10020102