The Role of Plant-Derived Compounds in Amplifying Antibiotic Effectiveness

Subject Areas :

Elham Nikouie ¹ , Nadia Kazemipour ^{2 *} , Farokh Rokhbakhsh-Zamin ³

1 - Department of Microbiology, Ke.C., Islamic Azad University, Kerman, Iran
2 - Department of Microbiology, Ke.C., Islamic Azad University, Kerman, Iran
3 - Department of Microbiology, Ke.C., Islamic Azad University, Kerman, Iran

Received: 2025-05-20 Accepted : 2025-08-02 Published : 2025-09-13

Keywords: Synergism, Medicinal plants, Antibiotics, Antimicrobial activity,

Abstract :

Today we are facing an increasing problem related to the antibiotic resistance due to the inappropriate and excessive using antimicrobial drugs. The World Health Organization has declared the antibiotic resistance crisis as one of the greatest threats to global health, and therefore, it is essential to employ effective new methods to combat life threatening infections. Accordingly, researchers are striving to find effective alternatives to address this problem. One promising approach is the use of herbal medicines with antimicrobial properties accompanying with   conventional antibiotics. The potential synergistic effects of using antibiotics with medicinal plants can provide more effective treatment option for dangerous infectious disease caused specially by multidrug resistant bacteria. This research was conducted to draw a clear view about the synergism antibiotics and plants with acceptable effects against important human pathogenic bacteria. Using various herbal essential oils in combination with antibiotics were investigated recently on certain bacteria and it revealed that the synergistic interactions between plant compounds and antibiotics enhance antioxidant and antimicrobial activities. This type of combinations and their dual usage not only increase their antioxidant and antibacterial effects but also significantly reduce the active dose of antibiotics. Outer membrane of Gram-negative bacteria act as an effective barrier against amphipathic agents, making them more resistant to these types of drugs. But their simultaneously plants and antibiotics usage surprisingly permeate the outer membrane making mentioned bacteria more sensitive. Purified plant components in combination with antibiotics enhance their efficacy against target bacteria and provide promising compounds for the development of new effective way for better curing the infectious diseases.

 

References:

1-Sharif S.A., Ismaeil A.S., Ahmad A.A., Synergistic effect of different plant extracts and antibiotics on some pathogenic bacteria, Science journal of university of Zakho ,2020, 8(1):7-11. [Google Scholar]
2- Vipin Ch., Saptami K., Fida F., Mujeeburahiman M., Rao S.S., Athmika , Arun A.B., Rekha P.D., Potential synergistic activity of quercetin with antibiotics against multidrug-resistant clinical strains of Pseudomonas aeruginosa , PLOS ONE ,2020, 15(11): e0241304 https://doi.org/10.1371/journal.pone.0241304 . [Google Scholar] [ResearchGate] [PubMed]
3- El-Wafa W.M.A., Ahmed R.H., Ramadan M.A.H., Synergistic effects of pomegranate and rosemary extracts in combination with antibiotics against antibiotic resistance and biofilm formation of Pseudomonas aeruginosa, Brazilian journal of microbiology,2020, 51:1079-1092. [Google Scholar] [ResearchGate] [PubMed]
4- Alvarez-Martinez F.J., Barrajon-Catalan E., MicolV., Tackling antibiotic resistance with compounds of natural origin: A comprehensive Review, Biomedicines, 2020, 8(10), 405; https://doi.org/10.3390/biomedicines8100405. [Google Scholar] [ResearchGate] [MDPI]
5- Alam M., Bano N., Ahmad T., Sharangi A.B., Upadhyay T.K., Alreay Y., Alabdallah N.M., Rauf M.A., Saeed M., Synergistic role of plant extracts and essential oils against multidrug resistance and Gram-Negative bacterial strains producing extended-spectrum β-lactamases, Antibiotics ,2022, 11(7), 855; https://doi.org/10.3390/antibiotics11070855. [Google Scholar] [PubMed] [ResearchGate] [MDPI]
6- Cui Z.H., He H.H., Wu Sh., Dong Ch., Lu S., Shan T., Fang L., Liao X., Liu Y., Sun J., Rapid screening of essential oils as substances which enhance antibiotic activity using a modified well diffusion method, Antibiotics,2021, 10(463):1-11, https://doi.org/10.3390/antibiotics10040463. [Google Scholar] [ResearchGate] [MDPI]
7- Okonkwo I.F., Achilike K.M., Comparative assessment of antimicrobial activities of Allium cepa (Onions) extracts, Agrobiological Records,2022,9:73-79. https://doi.org/10.47278/journal.abr/2022.012 . [Google Scholar]
8- Akullo J.O. , Kiage B. , Nakimbugwe D. , Kinyuru J., Effect of aqueous and organic solvent extraction on in-vitro antimicrobial activity of two varieties of fresh ginger (Zingiber officinale) and garlic (Allium sativum), Heliyon,2022,8 (e10457), https://doi.org/10.1016/j.heliyon.2022.e10457. [Google Scholar] [PubMed]
9- Sharma P.K., Fuloria Sh, Alam S., Sri M.V., Singh A, Sharma V.K., Kumar N., Chemical Composition and Antimicrobial Activity of Oleoresin of Capsicum annuum Fruits, Mindanao Journal of Science and Technology, 2021, 19 (1): 29-43. [Google Scholar] [ResearchGate]
10- Rajaei A., Salarbashi D., Asrari N., Fazly Bazzaz B.S., Aboutorabzade S.M., Shaddel R., Antioxidant, antimicrobial, and cytotoxic activities of extracts from the seed and pulp of Jujube (Ziziphus jujuba) grown in Iran, Food Science and Nutrition,2021, 9:682–691. https://doi.org/10.1002/fsn3.2031. [Google Scholar] [PubMed]
11- Navit O.Sh., Margarita Y., Liki V.O.B., Antimicrobial Activity by a Unique Composition of Cold Pressed Nigella Sativa Seed (Black Cumin) Oil, Food science and nutrition research ,2021,4(2):1-9. [Google Scholar] [ResearchGate]
12- Adarsh A., Chettiyar B., Kanthesh B.M., Raghu N., Phytochemical Screening and Antimicrobial Activity of Cinnamon zeylanicum, International Journal of Pharmaceutical Research and Innovation,2020,13: 22-33. [Google Scholar] [ResearchGate]
13- Qanash H., Yahya R., Bakri M.M., Bazaid A.S., Qanash S., Abdullah F., Shater A.F., Abdelghany T.M., Anticancer, antioxidant, antiviral and antimicrobial activities of Kei Apple (Dovyalis cafra) fruit, Scientific Reports,2022, 12:5914, https://doi.org/10.1038/s41598-022-09993-1. [Google Scholar] [ResearchGate] [PubMed]
14- Shuaib M.J., Shailabi T.I., Borwis E.O., Muhammed A.S., Antimicrobial Activity Evaluation of Citrus Lemon Against Streptococcus Pyogenes and Escherichia Coli, IOSR Journal of Pharmacy,2021, 11(12):11-16. [Google Scholar] [ResearchGate]
15- Nunes A.R., Flores-Felix J.D., Goncalves A.C., Falcao A., Alves G., Silva L.R., Anti-Inflammatory and Antimicrobial Activities of Portuguese Prunus avium L. (Sweet Cherry) By-Products Extracts, Nutrients,2022, 14(21), 4576, https://doi.org/10.3390/nu14214576 . [Google Scholar] [MDPI]
16- Hou T, Sana S.S., Li H., Xing Y., Nanda A., Netala V.R., Zhang Z., Essential oils and its antibacterial, antifungal and anti-oxidant activity application: Areview, Food Biscience ,2022, 47:101716, https://doi.org/10.1016/j.fbio.2022.101716 .[Google Scholar] [ResearchGate] [ScienceDirect]
17- Nourbakhsh F., Lotfalizadeh M., Badpeyma M., Shakeri A., Soheili V., From plants to antimicrobials: Natural products against bacterial membranes, Phytotherapy Research,2022,36(1):33-52, https://doi.org/10.1002/ptr.7275 .[Google Scholar] [PubMed]
18- Wang W., Cao J., Yang J., Niu X., Liu X., Zhai Y., Qiang C., Niu Y., li Z., Dong N., Wen B., Ouyang Z., Zhang Y., Li J., Zhao M., Zhao J., Antimicrobial activity of Tannic Acid in vitro and its protective effect on Mice against Clostridioides difficile, American Society for Microbiology,2023, 11(1): e02618-22, https://doi.org/10.1128/spectrum.02618-22 . [Google Scholar] [PubMed]
19- Vaou N., Stavropoulou E., Voidarou Ch., Tsigalou Ch., Bezirtzoglou E., Towards Advances in Medicinal Plant Antimicrobial Activity: A Review Study on Challenges and Future Perspectives, Microorganisms,2021, 9(10), 2041, https://doi.org/10.3390/microorganisms9102041. [Google Scholar] [PubMed] [MDPI]
20- Nikouie E., Kariminik A., Investigating the Antibacterial Effects of Methanolic Extract of Myristica fragrans Against Broad-Spectrum β-lactamase-Producing Staphylococcus aureus Isolates, Quality and durability of agricultural products and food stuffs,2023, 3(1):13-20. [Google Scholar]
21- Jafari-sales A., Pashazadeh M., Study of chemical composition and antimicrobial properties of Rosemary (Rosmarinus officinalis) essential oil on Staphylococcus aureus and Escherichia coli in vitro, international journal of life sciences and biotechnology ,2020, 3(1):62-69. [Google Scholar] [ResearchGate]
22- Li J., Li Ch., Shi C., Aliakbarlu J., Cui H., Antibacterial mechanisms of clove essential oil against Staphylococcus aureus and its application in pork, International journal of food microbiology,2022, 380: 109864, https://doi.org/10.1016/j.ijfoodmicro.2022.109864. [Google Scholar][ScienceDirect]
23- Nikouie E., Kariminik A., Investigating the antibacterial effects of methanolic extract of Myristica fragrans against broad-spectrum β-lactamase-producing Streptococcus pyogenes isolates, new approaches in cellular and molecular sciences, 2023, 1(1):21-26. [Google Scholar]
24- Maqbul M.Sh., Bokhar Y.A., Basalib S.G., Alhelal Sh.N., Omar B.M.M., Khan A.A., Iqubal S.M.Sh., Mohammed T., A Comparative Study of Different Types of Thyme Essential oils Against Streptococcus pyogenes to Determine their Biochemical and Antimicrobial Properties, Oriental journal of chemistry ,2020, 36(2):1-9. [Google Scholar] [ResearchGate]
25- Assegaf S., Kawilarang P., H andajani R., Antibacterial Activity Test of Red Ginger Extract (Zingiber officinale var. rubrum) Against Streptococcus pyogenes in vitro, Biomolecular and health science journal ,2020, 3(1):24-24-27. [Google Scholar] [ResearchGate]
26- Nikouie E., Kariminik A., Antibacterial Effects of Methanolic Extract of Myristica fragrans against Klebsiella pneumoniae and Acinetobacter baumannii Producing broad-spectrum beta-lactamase, Biotechnological journal of environmental microbiology,2023, 1(4):193-200. [Google Scholar]
27- Rafeeq H.F., Sharba Z.A., Study the Effect of Cinnamon and Tea Tree Oils on Biofilm Formation of Klebsiella Pneumoniae, Journal of applied sciences and nanotechnology , 2022, 2(2):16-26. [Google Scholar] [ResearchGate]
28- Baptista C.T., Cerveira M.M., Santos B.V., Ferrer E.M.K., Miller R.G., Souza T.T., Zank P.D., Blanke A.O., Klein V.P., Rosado R.P., Silveira R.M., Melo L.G., Pereira C.M.P., Lopes L.Q., Giongo J.L., Vaucher R.A., A systematic review of essential oils’ antimicrobial and antibiofilm activity against Klebsiella pneumoniae, Current research in complementary and alternative medicine ,2022,6(3):1-11, WWW.doi.org/10.29011/2577-2201.100062. [Google Scholar]
29- Stefanovic O.D., Synergistic Activity of Antibiotics and Bioactive Plant Extracts: A Study Against Gram-Positive and Gram-Negative Bacteria, Bacterial pathogenesis and antibacterial control ,2017, 23-48. [Google Scholar] [ResearchGate]
30- Sharma N., Sheik Z.N., Alamri S., Singh B., Kesawat M.S., Guleria S., Chemical composition, antibacterial and combinatorial effects of the essential oils from Cymbopogon spp. and Mentha arvensis with conventional antibiotics, Agronomy,2023, 13(4), 1091, https://doi.org/10.3390/ agronomy13041091. [Google Scholar] [ResearchGate] [MDPI]
31- Sharma K., Guleria S., Razdan V.K., Babuc V., Synergistic antioxidant and antimicrobial activities of essential oils of some selected medicinal plants in combination and with synthetic compounds, Industrial crop and products,2020, 154:112569 https://doi.org/10.1016/j.indcrop.2020.112569. [Google Scholar] [ScienceDirect]
32- Dumlupinara B., Celikc D.D., Karatoprak G.S., Gurer U.S., Synergy between Pelargonium endlicherianum essential oil and conventional antibiotics against Neisseria meningitidis and Haemophilus influenzae, South African journal of Botany ,2022, 146:243-253, https://doi.org/10.1016/j.sajb.2021.10.006. [Google Scholar] [ScienceDirect]
33- Dumlupinara B., Karatoprak G.S., Celikc D.D., Gurer U.S., Demirci B., Gurbuz B., Rayamanc P., Kurtuluse E.M., Synergic potential of Pelargonium endlicherianum Fenzl. Essential oil andantibiotic combinations against Klebsiella pneumonia, South African journal of Botany , 2020, 135:117-126. [Google Scholar] [ResearchGate] [ScienceDirect]
34- Feudjieu E.G., Gislaine k., Tchinda F.C., Armelle T.D., Moni E.D.F.N, Sonia M.G., Agbor G.A., Synergistic effects of essential oils and antibiotics against some bacterial strains, Journal of drug delivery and therapeutics,2023, 13(6):73-82. [Google Scholar] [ResearchGate]
35- Chukwudi I.N., Ebenezer K.I., Uchenna K.A., Onyetugo C.A., Kenneth U., In-vitro Antibacterial and synergistic activities of extracts Allium cepa and Allium sativum with selected antibiotics on Escherichia coli and Staphylococcus aureus, South Asian journal of research in microbiology ,2021,10(2):32-44, DOI: 10.9734/SAJRM/2021/v10i230227. [Google Scholar] [ResearchGate]
36- Tanavar H., Barzegar H., Alizadeh Behbahani B., Mehrnia M.A., Evaluation of the antimicrobial activity of Menthapulegium essential oil on some foodborne pathogens and its interaction with gentamicin and chloramphenicol in vitro, Food Science and Technology,2020, 97(16):77-87, DOI: 10.29252/fsct.16.97.77. [Google Scholar] [ResearchGate]
37- Boren K., Crown A.A., Carlson R., Multidrug and pan-antibiotic resistance the role of antimicrobial and synergistic essential oils: A Review, Natural product communications,2020, 15(10):1-19, https://doi.org/10.1177/1934578X20962595. [Google Scholar] [ResearchGate]
38- Amirian F., KazemiPour N., Khoshroo S.M.R., Sayadi A., Karmostaji A., Mousavi S.M., Synergistic effect and antibacterial activities of extracts of Salvia and Rosemary officinalis against Escherichia coli Isolated from clinical urinary tract infection, Annals of Military and Health Sciences Research,2017,15(4): e80148, http://dx.doi.org/10.5812/amh.80148. [Google Scholar]
39- Shirzad Z., Niakan M., Rahimi F., Haghiralsadat F., Eevaluation of the effectiveness of the combination of the antibiotic meropenem and the ethanolic extract of Vaccinum arctostaphylus plant on the standard strain of Acintobacter baumannii bacteria, Daneshvar medicine: Basic and Clinical Research Journal, 2023, 31(1): 78-87, https://doi.org/10.22070/daneshmed.2023.16814.1274. [Google Scholar]
40- Bekka-Hadji F., Bombarda I., Djoudi F., Bakour S., Touati A., Chemical composition and synergistic potential of Mentha pulegium L. and Artemisia herba-alba Asso. Essential oils and antibiotic against multi-drug-resistant bacteria, Molecules,2022, 27(3), 1095, https://doi.org/10.3390/molecules27031095. [Google Scholar] [ResearchGate] [MDPI]
41- Sreepian A., Popruk S., Nutalai D., Phutthanu Ch., Sreepian P.M., Antibacterial activities and synergistic interaction of Citrus essential oils and Limonene with Gentamicin against clinically isolated Methicillin-resistant Staphylococcus aureus, Hindawi the Scientific World Journal,2022, https://doi.org/10.1155/2020/8418287. [Google Scholar] [ScienceDirect] [PubMed]
42- Mohammadpour P., Ahmadi M.H., Niakan M., Rahimi F., Haghirsadat F., Survey the synergistic effect of the Cotrimoxazole and Nigella sativa extract on Methicillin resistant Staphylococcus aureus bacteria, Daneshvar medicine: Basic and Clinical Research Journal ,2023, 31(1):13-22. [Google Scholar]
43- Coimbra A., Miguel S., Ribeiro M., Coutinho P., Silva L., Duarte P., Ferreira S., Thymus zygis essential oil: Phytochemical characterization, bioactivity evaluation and synergistic effect with antibiotics against Staphylococcus aureus, Antibiotics, 2022, 11(2): 146, https://doi.org/103390/antibiotics11020146 .[Google Scholar] [MDPI]
44- Zaharieva M.M., Kaleva M., Kroumov A., Slavkova M., Benbassat N., Yoncheva K., Najdenski H., Advantageous combinations of Nanoencapsulated Oregano Oil with selected antibiotics for skin treatment, Pharmaceutics, Pharmaceutics,2022, 14(12), 2773, https://doi.org/10.3390/pharmaceutics14122773 .[Google Scholar] [ResearchGate] [MDPI]
45- Mahmoodi S.M.M., Javanmardi F., Study of antibacterial effect of Peganum harmala extract on Streptococcus sanguinis and study of its synergistic effect with some common antibiotics, Alborz university of medical sciences journal, 2022, 12(3):304-311. [Google Scholar] [ResearchGate]
46- John S., Lee J.W., Lamichhane P., Dinh T., Nolan T., Yoon T., Potential synergistic inhibition of Enterococcus faecalis by essential Oils and antibiotics, Applied sciences, 2023, 13(19), 11089, https://doi.org/10.3390/app131911089. [Google Scholar] [ResearchGate] [MDPI]
47- Liu Y., Rena H., Wang D., Zhang M., Sun Sh., Zhao Y., The synergistic antifungal effects of gypenosides combined with fluconazole against resistant Candida albicans via inhibiting the drug efflux and biofilm formation, Biomedicine and Pharmacotherapy,2020, https://doi.org/10.1016/j.biopha.2020.110580 [Google Scholar] [ScienceDirect] [PubMed]
48- Yong J., Zu R., Huang X., Ge Y., Li Y., Synergistic Effect of Berberine Hydrochloride and Fluconazole Against Candida albicans Resistant Isolates, Frontiers in Microbiology,2020, 11:1498, https://doi.org/10.3389/fmicb.2020.01498. [Google Scholar] [PubMed]
49- Biernasiuk A., Baj T., Malm A., Clove Essential Oil and Its Main Constituent, Eugenol, as Potential Natural Antifungals against Candida spp. Alone or in Combination with Other Antimycotics Due to Synergistic Interactions, Molecules,2023, 28(1), 215, https://doi.org/10.3390/molecules28010215. [Google Scholar] [ResearchGate] [MDPI]
50- Alnour T.M.S., Ahmed-Abakur E.H., Elssaig E.H., Abuduhier F.M., Ullah M.F., Antimicrobial synergistic effects of dietary flavonoids rutin and quercetin in combination with antibiotics Gentamicin and Ceftriaxone against E. coli (MDR) and P. mirabilis (XDR) strains isolated from human infections: Implications for food–medicine interactions, Italian Journal of Food Science ,2022, 34 (2): 34–42. [Google Scholar] [ResearchGate]
51- Mahmoudi H., Fahim N.Z., Alikhani M.Y., Shokoohizadeh L., Investigation of antimicrobial effect of Berberine on Ciprofloxacin and Imipenem resistance Acinetobacter baumannii isolated from Hamadan Hospitals, Iranian journal of medical microbiology ,2020, 14(1):44-54, http://dx.doi.org/10.30699/ijmm.14.1.44. [Google Scholar] [ResearchGate]
52- Asadi S., Nayer Fasaei B., Zahraei Salehi T., yahya Rayat R., Shams N., Evaluation of the antibacterial effect of Carvacrol alone and in combination with the antibiotic Cefixime against Escherichia coli O157:H7, Journal of Veterinary Research ,2023, 78(1):67-76, https://doi.org/10.22059/jvr.2022.333699.3207. [Google Scholar]
53- Zamanpour Boroujeni A., Alizadeh Behbahani B., Mehrnia M.A., Hojjati M., Noshad M., Evaluation of antioxidant activity and antimicrobial effect of Nigella sativa oil on some pathogenic bacteria and its interaction with chloramphenicol antibiotic, Journal of Food Science and Technology (Iran) ,2023, 145(20):111-121, http://dx.doi.org/10.22034/FSCT.20.145.111. [Google Scholar]
54- Nafis A., Kasrati A., Jamali Ch.A., Custodio L., Vitalini S., Iriti M., Hassani L., A comparative study of the in vitro antimicrobial and synergistic effect of essential oils from Laurus nobilis L. and Prunus armeniaca L. from morocco with antimicrobial drugs: new approach for health promoting products, Antibiotics,2020,9(4), 140, https://doi.org/10.3390/antibiotics9040140. [Google Scholar] [ResearchGate] [PubMed] [MDPI]
55- Dumlupinar B., Karatoprak G.S., Demirci B., Akkol E.K., Sobarzo-Sanchez E., Antioxidant activity and chemical composition of Geranium oil and its synergistic potential against Pneumococci with various antibiotic combinations, Plants,2023, 12(17), 3080, https://doi.org/10.3390/plants12173080. [Google Scholar] [ResearchGate] [MDPI]
56- Dera A.A., Ahmad I., Rajagopalan P., Al Shahrani M., Saif A., Alshahrani M.Y., Alraey Y., Alamri A.M., Alasmari S., Makkawi M., Alkhathami A.G., Zaman G., Hakami A., Alhefzi R., Alfhili M.A., Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug-resistant isolates, Saudi medical journal,2021, 42(2):196-204. doi: 10.15537/smj.2021.2.25706. [Google Scholar] [ResearchGate] [PubMed]
57- Magrys A., Olender A., Tchorzewska D., Antibacterial properties of Allium sativum L. against the most emerging multidrug‑resistant bacteria and its synergy with antibiotics, Archives of Microbiology,2021, 203:2257–2268, https://doi.org/10.1007/s00203-021-02248-z. [Google Scholar] [ResearchGate] [PubMed]
58- Amassmoud O., Abbad I., Iriti M., Hassani L., Mezrioui N., Abbad A., Antibacterial activity of essential oils combinations based on Thymus broussonnetii, and their synergism with some antibiotics, Current Microbiology,2023, 80:398, https://doi.org/10.1007/s00284-023-03510-x. [Google Scholar] [ResearchGate]