The Effectiveness of Antibiofilm Synergy of Parijoto Leaf Extract (Medinilla speciosa) and Gentamicin on Methicillin-Resistant Staphylococcus aureus (MRSA) from Diabetic Ulcers

Authors

  • Arina Lis Sa'adah Diploma IV Medical Laboratory Technology Study Program, Faculty of Health Sciences, Muhammadiyah University of Kudus, Indonesia
  • Fariza Yulia Kartika Sari Bachelor of Nutrition Study Program, Faculty of Health Sciences, Muhammadiyah University of Kudus, Indonesia
  • Bintari Tri Sukoharjanti Bachelor of Pharmacy Study Program, Faculty of Health Sciences, Muhammadiyah University of Kudus, Indonesia
  • Sri Darmawati Magister of Medical Laboratory Science Study Program, Postgraduate Program, Universitas Muhammadiyah of Semarang, Indonesia

DOI:

https://doi.org/10.32382/medkes.v20i2.1715

Keywords:

Parijoto leaf extract, MRSA, Antibiofilm activity, Synergistic effect

Abstract

Diabetic foot ulcers (DFU) are chronic complications of diabetes that are generally accompanied by bacterial infections. Methicillin-Resistant Staphylococcus aureus (MRSA) is one of the most dominant pathogenic bacteria isolated from DFU wounds. The significant number of MRSA bacteria and the formation of bacterial biofilms result in prolonged wound treatment and high amputation rates. Several medicinal plants in the Muria Mountains have the potential to be alternative antibiofilms supporting gentamicin antibiotic treatment, one of which is the parijoto plant (Medinilla speciosa). This study aims to evaluate the effectiveness of the combination of parijoto leaf extract with gentamicin in inhibiting the growth of MRSA biofilms isolated from DFU. Parijoto leaves were extracted using the UAE (Ultrasound-Assisted Extraction) technique, followed by phytochemical tests and antibiofilm inhibition tests using the microdilution method. The results of phytochemical identification showed that there were saponin, flavonoid, tannin, alkaloid, quinone, and phenol compounds. The combination of gentamicin and parijoto leaf extract with several variations obtained the highest percentage of biofilm inhibition, namely 95%. The IC50 value in the antibiofilm inhibition test of the combination of parijoto leaf extract and gentamicin was 6.90 μg/mL. The chemical bioactive content in parijoto leaf extract can synergize as a supporting treatment with gentamicin to accelerate the treatment of diabetic ulcer wound infections. Further research needs to be carried out to explore and further study to determine the QS (Quorum Sensing) mechanism against MRSA (Methicillin-Resistant Staphylococcus aureus) bacteria by bioactive compounds in parijoto leaf extract and invivo test.

References

Kharroubi AT, Darwish HM. Diabetes mellitus: The epidemic of the century. World J Diabetes. 2015 Jun;6(6):850–67.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045 : Results from the International Diabetes Federation Diabetes Atlas , 9 th edition. Diabetes Res Clin Pract [Internet]. 2019;157:107843. Available from: https://doi.org/10.1016/j.diabres.2019.107843

Motala AA, Mbanya JC, Ramaiya K, Pirie FJ, Ekoru K. Type 2 diabetes mellitus in sub-Saharan Africa: challenges and opportunities. Nat Rev Endocrinol. 2022 Apr;18(4):219–29.

Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun;376(24):2367–75.

Zhou S, Hu X, Wang Y, Fei W, Sheng Y, Que H. The Global Prevalence of Methicillin-Resistant Staphylococcus aureus in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis. Diabetes, Metab Syndr Obes. 2024;17(January):563–74.

Raja JM, Maturana MA, Kayali S, Khouzam A, Efeovbokhan N. Diabetic foot ulcer: A comprehensive review of pathophysiology and management modalities. World J Clin cases. 2023 Mar;11(8):1684–93.

Baig MS, Banu A, Zehravi M, Rana R, Burle SS, Khan SL, et al. An Overview of Diabetic Foot Ulcers and Associated Problems with Special Emphasis on Treatments with Antimicrobials. Life (Basel, Switzerland). 2022 Jul;12(7).

Kananizadeh P, Moghadam SO, Sadeghi Y, Foroushani AR, Adibi H, Pourmand MR. Molecular characteristics of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from diabetic foot infection. Iran J Pathol. 2019;14(4):329–37.

Anvarinejad M, Pouladfar G, Japoni A, Bolandparvaz S, Satiary Z, Abbasi P, et al. Isolation and Antibiotic Susceptibility of the Microorganisms Isolated from Diabetic Foot Infections in Nemazee Hospital, Southern Iran. J Pathog. 2015;2015:1–7.

Du F, Ma J, Gong H, Bista R, Zha P, Ren Y, et al. Microbial Infection and Antibiotic Susceptibility of Diabetic Foot Ulcer in China: Literature Review. Front Endocrinol (Lausanne). 2022;13:881659.

Cheung GYC, Bae JS, Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence. 2021 Dec;12(1):547–69.

Khariunnisa R, Soleha TU, Ramadhian MR. Identifikasi dan Uji Resistensi Staphylococcus aureus pada Ulkus Diabetik di Instalasi Penyakit Dalam RSUD Dr. H. Abdul Moeloek Identification and Resistency Test of Staphylococcus aureus on Diabetic Ulcer in Internal Medicine Installation at Dr. J Agromedicine Unila. 2020;7:1–6.

Iyamba JML, Bassom VMHN, Lukukula CM, Unya JW, Ngbandani BK, Vihembo GM, et al. Study of Biofilm Formation and Antibiotic Resistance Pattern of Bacteria Isolated from Diabetic Foot Ulcers in Hôpital de Référence Saint Joseph, Kinshasa, Democratic Republic of Congo. Adv Microbiol [Internet]. 2021; Available from: https://api.semanticscholar.org/CorpusID:236582449

Banu A, Noorul Hassan MM, Rajkumar J, Srinivasa S. Spectrum of bacteria associated with diabetic foot ulcer and biofilm formation: A prospective study. Australas Med J. 2015;8(9):280–5.

Papadopoulou V, Sidders AE, Lu KY, Velez AZ, Durham PG, Bui DT, et al. Overcoming biological barriers to improve treatment of a Staphylococcus aureus wound infection. Cell Chem Biol [Internet]. 2023;30(5):513-526.e5. Available from: https://doi.org/10.1016/j.chembiol.2023.04.009

Wahyuni RA, Putri IY, Jayadi EL, Prastiyanto ME. Antibacterial Activity Of Parijoto Fruit Extract (Medinilla Speciosa) On Bacteria Extended Spectrum Betalactamase (Esbl) Escherichia Coli And Methicillin Resistant Staphylococcus aureus (MRSA J Media Anal Kesehat. 2019;10(2):106.

Bheemavarapu H, Mohammad A, Ahmad A, Patel I. Nosocomial Infections in India: The Unaddressed Lacunae! J Pharm Pract Community Med. 2018 Jun 10;4:43.

Lu L, Zhao Y, Yi G, Li M, Liao L, Yang C, et al. Quinic acid: a potential antibiofilm agent against clinical resistant Pseudomonas aeruginosa. Chin Med [Internet]. 2021;16. Available from: https://consensus.app/papers/quinic-acid-a-potential-antibiofilm-agent-against-lu-zhao/88303a2880aa5feebcf70438f1616a3c/

Wan B, Zhu Y, Tao J, Zhu F, Chen J, Li L, et al. Biological and Medical Applications of Materials and Interfaces Alginate-lyase Guided Silver Nanocomposites for Eradicating Pseudomonas aeruginosa from lung. 2020;

Advistasari YD, Vifta RL. Uji Antidiabetes Ekstrak Etanol Buah Parijoto (Medinilla speciosa B.) dan Fraksinya. Repos STIFAR [Internet]. 2019 Dec 2;0(0 SE-Articles). Available from: https://repository.stifar.ac.id/Repository/article/view/173

Astutik P, Yuswantina R, Vifta RL. Perbandingan Aktivitas Antifungi Ekstrak Etanol 70% Dan 96% Buah Parijoto (Medinilla speciosa) Terhadap Candida albicans. J Holistics Heal Sci [Internet]. 2021; Available from: https://api.semanticscholar.org/CorpusID:236750202

Sugiarti L, Pujiastuti E. Uji Aktivitas Antibakteri Ektrak Etanol Buah Parijoto (Medinilla Speciosa Blume) terhadap Bakteri Staphylococcus aureus dan Echerichia coli. Cendekia J Pharm. 2017 Nov 30;1:25–33.

Milanda T, Lestari K, Tarina NTI. Antibacterial Activity of Parijoto (Medinilla speciosa Blume) Fruit Against Serratia marcescens and Staphylococcus aureus. Indones J Pharm Sci Technol. 2021;8(2):76.

Anastasia FF, Aziz IR, Oktaviola V, Iswara A. Antibacterial Activity Of Combination Cold Plasma And Parijoto (Medinilla speciosa) against Staphylococcus aureus and Pseudomonas aeruginosa on diabetic ulcer. El-Hayah. 2020;7(4):133–8.

Anas Y, Rakhmawati D, Fuadah L, Rahayu NC. Efek Antidiare Ekstrak Etanol Daun Parijoto (Medinilla Speciosa Blume) Pada Mencit Jantan Galur Balb/C. JIFFK J Ilmu Farm dan Farm Klin. 2019;16(01):28.

Sa’adah AL, Kartikasari FY, Mundriyastutik Y, Hayati DN, Faizal IA. Potensi Ekstrak Daun Parijoto ( Medinilla Speciosa ) Sebagai Penghambatan Biofilm Methicillin-resistant Staphylococcus aureus ( MRSA ). J ILMU Kedokt DAN Kesehat. 2025;12(10):2025.

Zhu M, Tse MW, Weller J, Chen J, Blainey PC. The future of antibiotics begins with discovering new combinations. Ann N Y Acad Sci. 2021;1496(1):82–96.

Septiani, Yulia KSF. Pengaruh Sinbiotik Terhadap Mikrobiota Saluran Cerna Pada Anak Stunting. J Med Indones. 2023;4(2):23–9.

Nazari M, Taheri M, Nouri F, Bahmanzadeh M, Alikhani MY. The antimicrobial and antibiofilm effects of gentamicin, imipenem, and fucoidan combinations against dual-species biofilms of Staphylococcus aureus and Acinetobacter baumannii isolated from diabetic foot ulcers. Ann Clin Microbiol Antimicrob. 2024;23(1).

Bonincontro G, Scuderi SA, Marino A, Simonetti G. Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Pharmaceuticals. 2023;16(11).

Li Z. Antibacterial Activity of Surfactin and Synergistic Effect with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus aureus Isolated from Patients with Diabetic Foot Ulcers [Response to Letter]. Diabetes, Metab Syndr Obes. 2023;16(November):4233–4.

Turangan ATM, Wewengkang DS, Yudistira A. Uji Aktivitas Antioksidan Ekstrak Etanol Kulit Batang Mahoni (Swietenia Mahagoni Jacq.) Menggunakan Metode DPPH (1,1 diphenyl-2-picrylhydrazyl). Pharmacon. 2019;8(3):548.

Noer S, Pratiwi RD, Gresinta E. Penetapan Kadar Senyawa Fitokimia (Tanin, Saponin dan Flavonoid) sebagai Kuersetin Pada Ekstrak Daun Inggu (Ruta angustifolia L.). J Eksakta. 2018;18(1):19–29.

Farida DO, Suyanto S. Skrining Fitokimia, Kandungan Flavonoid Total, Dan Aktivitas Antioksidan Ekstrak Etanol Tumbuhan Selaginella doederleinii. J Kim Ris. 2021;6(2):141–53.

Wigati EI, Pratiwi E, Nissa TF, Utami NF. Uji Karakteristik Fitokimia Dan Aktivitas Antioksidan Biji Kopi Robusta (Coffea canephora Pierre) Dari Bogor, Bandung Dan Garut Dengan Metode DPPH (1,1-diphenyl-2-picrylhydrazyl). Fitofarmaka J Ilm Farm [Internet]. 2018;Vol. 8(1):59–66. Available from: https://repositorio.ufsc.br/bitstream/handle/123456789/186602/PPAU0156-D.pdf?sequence=-1&isAllowed=y%0Ahttp://journal.stainkudus.ac.id/index.php/equilibrium/article/view/1268/1127%0Ahttp://www.scielo.br/pdf/rae/v45n1/v45n1a08%0Ahttp://dx.doi.org/10.1016/j

Asmara AP. Uji Fitokimia Senyawa Metabolit Sekunder Dalam Ekstrak Metanol Bunga Turi Merah (Sesbania grandiflora L. Pers). Al-Kimia. 2017;5(1):48–59.

Dewi ZY, Nur A, Hertriani T. Efek antibakteri dan penghambatan biofilm ekstrak sereh (Cymbopogon nardus L.) terhadap bakteri Streptococcus mutans. 2015;3:136–41.

Nafi’ah LN. Review Article: Aktivitas Farmakologi Tanaman Parijoto (Medinilla speciosa). J Ris Rumpun Ilmu Kesehat. 2022;1(1):09–18.

Qudsiya A, Lutfiani D, Da’i M. Penetapan Kadar Flavonoid Dan Fenolik Ekstrak Etanol Tanaman Parijoto (Medinilla Speciosa) Serta Aktivitas Sitotoksiknya Terhadap Sel Kanker Serviks Hela Determination Of Flavonoid And Phenolic Content Of Ethanol Extract Of Parijoto Plant (Medinilla speciosa). Usadha J Pharm [Internet]. 2022;1(4):505–20. Available from: https://jsr.lib.ums.ac.id/index.php/ujp

Hurlow JJ, Humphreys GJ, Bowling FL, McBain AJ. Diabetic foot infection: A critical complication. Int Wound J. 2018 Oct;15(5):814–21.

Pouget C, Dunyach-Remy C, Pantel A, Schuldiner S, Sotto A, Lavigne JP. Biofilms in Diabetic Foot Ulcers: Significance and Clinical Relevance. Microorganisms. 2020 Oct;8(10).

Afonso AC, Oliveira D, Saavedra MJ, Borges A, Simões M. Biofilms in Diabetic Foot Ulcers: Impact, Risk Factors and Control Strategies. Int J Mol Sci. 2021 Jul;22(15).

Roszell S, Jones C. Intravenous administration issues: a comparison of intravenous insertions and complications in vancomycin versus other antibiotics. J Infus Nurs Off Publ Infus Nurses Soc. 2010;33(2):112–8.

Joseph WS, Kosinski MA, Rogers LC. Parenteral Vancomycin in the Treatment of MRSA-Associated Diabetic Foot Infections: An Unnecessary Risk. Int J Low Extrem Wounds. 2023 Oct;15347346231207552.

Fadel MN, Huda N, Hasriyani, Besan EJ, Ayuningsih S. Aktivitas Antibakteri Ekstrak Etanol Daun Parijoto (Medinilla speciosa blume) Pada Sediaan Gel Hand Sanitizer. IJF (Indonesia J Farm. 2024;9:1–12.

Zhou H, Chen L, Ouyang K, Zhang Q, Wang W. Antibacterial activity and mechanism of flavonoids from Chimonanthus salicifolius S. Y. Hu. and its transcriptome analysis against Staphylococcus aureus. Front Microbiol. 2023;13(January).

Naeem A, Ming Y, Pengyi H, Jie K, Yali L, Haiyan Z, et al. The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability. Crit Rev Food Sci Nutr. 2021 Apr 13;62:1–18.

Chen X, Jia X, Yang S, Zhang G, Li A, Du P, et al. Optimization of ultrasonic-assisted extraction of flavonoids, polysaccharides, and eleutherosides from Acanthopanax senticosus using response surface methodology in development of health wine. Lwt [Internet]. 2022;165(June):113725. Available from: https://doi.org/10.1016/j.lwt.2022.113725

Wang Z, Zheng Y, Hu Y, Yang L, Liu X, Zhao R, et al. Improvement of antibacterial activity of polysaccharides via chemical modification: A review. Int J Biol Macromol. 2024 Jun;269(Pt 2):132163.

Wang Z, Zhou X, Liang X, Zheng X, Shu Z, Sun Q, et al. Antioxidant and antibacterial activities of a polysaccharide produced by Chaetomium globosum CGMCC 6882. Int J Biol Macromol [Internet]. 2023;233:123628. Available from: https://www.sciencedirect.com/science/article/pii/S0141813023005214

Sa’adah AL, Kartikasari FY, Mundriyastutik Y, Defi Hayati N, Faizal IA. Potensi Ekstrak Daun Parijoto (Medinilla speciosa) Sebagai Penghambatan Biofilm Methicillin-resistant Staphylococcus aureus (MRSA). J Ilmu Kedokt dan Kesehat [Internet]. 2025;12(10):2306–12. Available from: https://ejurnalmalahayati.ac.id/index.php/kesehatan/article/view/20935

Jamal M, Ahmad W, Andleeb S, Jalil F, Imran M, Nawaz MA, et al. Bacterial biofilm and associated infections. J Chinese Med Assoc [Internet]. 2018;81(1):7–11. Available from: https://doi.org/10.1016/j.jcma.2017.07.012

Singh S, Singh SK, Chowdhury I, Singh R. Understanding the Mechanism of Bacterial Biofilms Resistance to Antimicrobial Agents. Open Microbiol J. 2017;11(1):53–62.

Roy R, Das A, Ganguly D, Chakraborty P, Paul P, Das S, et al. Cuminaldehyde synergistically enhances the antimicrobial and antibiofilm potential of gentamicin: A direction towards an effective combination for the control of biofilm-linked threats of Staphylococcus aureus. Brazilian J Microbiol [publication Brazilian Soc Microbiol. 2025 Jun;56(2):1033–48.

Kungwani NA, Panda J, Mishra AK, Chavda N, Shukla S, Vikhe K, et al. Combating bacterial biofilms and related drug resistance: Role of phyto-derived adjuvant and nanomaterials. Microb Pathog. 2024 Oct;195:106874.

Zhou K, Shi M, Chen R, Zhang Y, Sheng Y, Tong C, et al. Natural phytochemical-based strategies for antibiofilm applications. Chinese Med (United Kingdom). 2025;20(1).

Nikolic I, Aleksic Sabo V, Gavric D, Knezevic P. Anti-Staphylococcus aureus Activity of Volatile Phytochemicals and Their Combinations with Conventional Antibiotics Against Methicillin-Susceptible S. aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA) Strains. Antibiot (Basel, Switzerland). 2024 Oct;13(11).

Downloads

Published

2025-12-03

How to Cite

Sa’adah, A. L., Sari, F. Y. K., Sukoharjanti, B. T., & Darmawati, S. (2025). The Effectiveness of Antibiofilm Synergy of Parijoto Leaf Extract (Medinilla speciosa) and Gentamicin on Methicillin-Resistant Staphylococcus aureus (MRSA) from Diabetic Ulcers. Media Kesehatan Politeknik Kesehatan Makassar, 20(2), 330–338. https://doi.org/10.32382/medkes.v20i2.1715
Abstract viewed: 20
PDF downloaded: 16