Potential Antagonistic Interactions of Cassia alata L. Leaf Extract and Commercial Antibiotics against Staphylococcus aureus: An In Vitro Evaluation
DOI:
10.29303/jppipa.v12i5.14500Published:
2026-05-25Downloads
Abstract
Several in vitro studies have demonstrated that the combination of plant extracts with antibiotics may reduce the minimum inhibitory concentration (MIC) of antibiotics against resistant microorganisms. Interactions between plant extracts and antibiotics can be synergistic, additive, or antagonistic. This study aimed to evaluate the potential interaction between Cassia alata leaves methanol extract and five selected conventional antibiotics in inhibiting the growth of Staphylococcus aureus ATCC 29213. Antibacterial activity was assessed using the well diffusion and paper strip methods. The methanol extract of C. alata leaves, when tested singly at a concentration of 100 mg/mL, produced an average inhibition zone of 11.74 mm. Four antibiotics, namely ciprofloxacin, clindamycin, chloramphenicol, and tetracycline, exhibited stronger antibacterial activity with inhibition zones ranging from 19.56–27.26 mm, whereas co-trimoxazole showed no inhibitory effect. The combination of C. alata leaves methanol extract with ciprofloxacin, clindamycin, chloramphenicol, tetracycline, and cotrimoxazole resulted in inhibition zones of 22.26 ± 0.703 mm, 22.54 ± 1.222 mm, 17.91 ± 1.094 mm, 17.57 ± 0.652 mm, and 9.30 ± 1.180 mm, respectively. The combined treatments have potential antagonistic effects, as the inhibition zones were smaller than the sum of the individual activities of the extract and antibiotics. Therefore, the combination was considered less effective in suppressing growth of S. aureus ATCC 29213
Keywords:
Antibiotics Cassia alata L. Combination effect Staphylococcus aureusReferences
Adfa, M., Gusatyana, N. M. C., Mudyanto, A., Avidlyandi, A., Oktiarni, D., & Yudha, S. S. (2021). Combined Effect of Methanol Extract of Persea americana Seeds and Cassia alata Leaves Against Staphylococcus epidermidis. Proceedings of the International Seminar on Promoting Local Resources for Sustainable Agriculture and Development (ISPLRSAD 2020), 13, 36–40. https://doi.org/10.2991/absr.k.210609.006
Aelenei, P., Miron, A., Trifan, A., Bujor, A., Gille, E., & Aprotosoaie, A. (2016). Essential Oils and Their Components as Modulators of Antibiotic Activity Against Gram-Negative Bacteria. Medicines, 3(19), 1–34. https://doi.org/10.3390/medicines3030019
Alghamdi, B. A., Al-Johani, I., Al-Shamrani, J. M., Alshamrani, H. M., Al-Otaibi, B. G., Almazmomi, K., & Yusof, N. Y. (2023). Antimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus. Saudi Journal of Biological Sciences, 30(103604), 1–12. https://doi.org/10.1016/j.sjbs.2023.103604
Arisurya, I. G. N. K., Permatananda, P. A. K., Dewi, N. W. E. S., & Pandit, I. G. S. (2026). Antibacterial Activity of Tulsi Ethanolic Extract (Ocimum tenuiflorum L.) Against Staphylococcus aureus. Jurnal Penelitian Pendidikan IPA, 12(1), 848–852. https://doi.org/10.29303/jppipa.v12i1.14238
Bahri, S., Umami, R., Qadafi, M., & Partiwi, S. (2023). Comparison of the Effectiveness Antibacterial Test of Natural Ingredients and Antibiotic in Salmonella typhi Isolated from Hospital Waste and Household Waste. Jurnal Penelitian Pendidikan IPA, 9(4), 2068–2074. https://doi.org/10.29303/jppipa.v9i4.3783
Batra, P., Deo, V., Mathur, P., & Gupta, A. K. (2017). Cotrimoxazole, a Wonder Drug in the Era of Multiresistance: Case Report and Review of Literature. Journal of Laboratory Physicians, 9(03), 210–213. https://doi.org/10.4103/0974-2727.208261
Berenbaum, M. C. (1977). Synergy, Additivism and Antagonism in Immunosuppression: A Critical Review. Clinical and Experimental Immunology, 28(1), 1–18. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC1540873/
Burt, S. (2004). Essential Oils: Their Antibacterial Properties and Potential Applications in Foods - A Review. International Journal of Food Microbiology, 94(3), 223–253. https://doi.org/10.1016/j.ijfoodmicro.2004.03.022
El-Sakhawy, M. A. M. (2023). Combinational Effect of Selected Medicinal Plants and Antibiotics Against Pathogenic Bacteria. Pakistan Journal of Biological Sciences, 26(3), 108–118. https://doi.org/10.3923/pjbs.2023.108.118
Esposito, S., Bassetti, M., Concia, E., Simone, G. D., Rosa, F. G. D>, Grossi, P., Novelli, A., Menichetti, F., Petrosillo, N., Tinelli, M., Tumbarello, M., Sanguinetti, M., Viale, P., Venditti, M., & Viscoli, C. (2017). Diagnosis and Management of Skin and Soft-Tissue infections (SSTI). A Literature Review and Consensus Statement: an Update. Journal of Chemotherapy, 29(4), 197–214. https://doi.org/10.1080/1120009X.2017.1311398
Fatmawati, S., Yuliana, Y., Purnomo, A. S., & Bakar, M. F. A. (2020). Chemical Constituents, Usage and Pharmacological Activity of Cassia alata. Heliyon, 6, 1–11. https://doi.org/10.1016/j.heliyon.2020.e04396
Fitriani, I. R., Fitriana, F., & Nuryanti, S. (2023). Aktivitas Antibakteri Ekstrak Etanol Daun Ketepeng Cina (Cassia alata L.) Terhadap Beberapa Bakteri Penyebab Infeksi Kulit. Makassar Natural Product Journal (MNPJ), 1(4), 22–28. https://doi.org/10.33096/mnpj.v1i1.8
Gnanamani, A., Hariharan, P., & Maneesh, P.-S. (2018). Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach. Journal of Global Infectious Diseases, 3, 1–26. http://dx.doi.org/10.5772/67338
Hamni, L., Avidlyandi, A., Banon, C., Wiradimafan, K., Triawan, D. A., Wibowo, R. H., & Adfa, M. (2022). Kombinasi Ekstrak Metanol Daun Ketepeng Cina (Cassia alata Linn.) dengan Enam Ekstrak Tumbuhan Terpilih dalam Menghambat Pertumbuhan Bakteri Staphylococcus aureus. BIOEDUSAINS: Jurnal Pendidikan Biologi dan Sains, 5(2), 350–362. https://doi.org/10.31539/bioedusains.v5i2.3996
Handarni, D., Putri, S. H., & Tensiska, T. (2020). Skrining Kualitatif Fitokimia Senyawa Antibakteri pada Ekstrak Daun Jambu Biji (Psidiium guajava L.). Jurnal Keteknikan Pertanian Tropis dan Biosistem, 8(2), 182–188. https://doi.org/10.21776/ub.jkptb.2020.008.02.08
Hanifa, A. P., Erliana, D., Avidlyandi, A., Rizka, M., Triawan, D. A., Yudha S, S. P., & Adfa, M. (2022). Efektivitas Ekstrak Metanol Daun Ketepeng Cina (Cassia alata L.) dalam Menghambat Pertumbuhan Bakteri Staphylococcus epidermidis Secara Tunggal dan Kombinasi. Jurnal Biosilampari: Jurnal Biologi, 5(1), 57–66. https://doi.org/10.31540/biosilampari.v5i1.1787
Ishak, A., Mazonakis, N., Spernovasilis, N., Akinosoglou, K., & Tsioutis, C. (2025). Bactericidal Versus Bacteriostatic Antibacterials: Clinical Significance, Differences and Synergistic Potential in Clinical Practice. Journal of Antimicrobial Chemotherapy, 80(1), 1–17. https://doi.org/10.1093/jac/dkae380
Khurm, M., Wang, X., Zhang, H., Hussain, S. N., Qaisar, M. N., Hayat, K., Saqib, F., Zhang, X., Zhan, G., & Guo, Z. (2021). The Genus Cassia L.: Ethnopharmacological and Phytochemical Overview. Phytotherapy Research, 35(5), 2336–2385. https://doi.org/10.1002/ptr.6954
Kuok, C. F., Hoi, S. O., Hoi, C. F., Chan, C. H., Fong, I. H., Ngok, C. K., Meng, L. R., & Fong, P. (2017). Synergistic Antibacterial Effects of Herbal Extracts and Antibiotics on Methicillin-Resistant Staphylococcus aureus: A Computational and Experimental Study. Experimental Biology and Medicine, 242(7), 731–743. https://doi.org/10.1177/1535370216689828
Lacey, K. A., Geoghegan, J. A., & McLoughlin, R. M. (2016). The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens. Pathogens, 5(1). https://doi.org/10.3390/pathogens5010022
Lathifah, Q. A., Turista, D. D. R., & Puspitasari, E. (2021). Daya Antibakteri Ketepeng Cina (Cassia alata L.) Terhadap Staphylococcus aureus, Pseudomonas aerugenosa, dan Klebsiella pneumonia. Jurnal Analis Kesehatan, 10(1), 29. https://doi.org/10.26630/jak.v10i1.2718
Li, J., Lu, T., Chu, Y., Zhang, Y., Zhang, J., Fu, W., Sun, J., Liu, Y., Liao, X. P., & Zhou, Y. F. (2024). Cinnamaldehyde Targets SarA to Enhance β-lactam Antibiotic Activity Against Methicillin-Resistant Staphylococcus aureus. MLife, 3(2), 291–306. https://doi.org/10.1002/mlf2.12121
Li, T., Lu, Y., Zhang, H., Wang, L., Beier, R. C., Jin, Y., Wang, W., Li, H., & Hou, X. (2021). Antibacterial Activity and Membrane-Targeting Mechanism of Aloe-Emodin Against Staphylococcus epidermidis. Frontiers in Microbiology, 12(621866), 1–14. https://doi.org/10.3389/fmicb.2021.621866
Lin, S., Li, H., Tao, Y., Liu, J., Yuan, W., Chen, Y., Liu, Y., & Liu, S. (2020). In Vitro and In Vivo Evaluation of Membrane-Active Flavone Amphiphiles: Semisynthetic Kaempferol-Derived Antimicrobials Against Drug-Resistant Gram-Positive Bacteria. Journal of Medicinal Chemistry, 63(11), 5797–5815. https://doi.org/10.1021/acs.jmedchem.0c00053
Malmir, M., Serrano, R., & Silva, O. M. D. (2017). Anthraquinones as Potential Antimicrobial Agents-A Review. In A. M. Vilas (Ed.), Antimicrobial Research: Novel Bioknowledge and Educational Programs (Issue 1, pp. 55–61). FORMATEX.
Nandhini, P., Kumar, P., Mickymaray, S., Alothaim, A. S., Somasundaram, J., & Rajan, M. (2022). Recent Developments in Methicillin-Resistant Staphylococcus aureus (MRSA) Treatment: A Review. Antibiotics, 11(606), 1–21. https://doi.org/10.3390/antibiotics11050606
Nurhasana, D., Febriansyah, R., Avidlyandi, A., S., S. Y., Banon, C., Oktiarni, D., & Adfa, M. (2023). In-Vitro Antibacterial Activity of Excoecaria cochinchinensis Lour’s Methanol Extract and Its Combination with Commercial Drugs. Jurnal Ilmu Kefarmasian Indonesia, 21(2), 179–185. https://doi.org/10.35814/jifi.v21i2.1383
Nurwahida, W. O., Muslihin, A. M., & Hardia, L. (2025). Antibacterial Activity Testing of Methanol Extract of Yellow Rope Barb (Anamirta cocculus). Jurnal Penelitian Pendidikan IPA, 11(4), 451–458. https://doi.org/10.29303/jppipa.v11i4.10760
Periferakis, A., Periferakis, K., Badarau, I. A., Petran, E. M., Popa, D. C., Caruntu, A., Costache, R. S., Scheau, C., Caruntu, C., & Costache, D. O. (2022). Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications. International Journal of Molecular Sciences, 23(15054), 1–39. https://doi.org/10.3390/ijms232315054
Ponce, A. G., Fritz, R., Valle, C. D., & Roura, S. I. (2003). Antimicrobial Activity of Essential Oils on the Native Microflora of Organic Swiss Chard. Lebensm.-Wiss. u.-Techno, 36(7), 679–684. https://doi.org/10.1016/S0023-6438(03)00088-4
Sanhueza, L., Melo, R., Montero, R., Maisey, K., Mendoza, L., & Wilkens, M. (2017). Synergistic Interactions between Phenolic Compounds Identified in Grape Pomace Extract with Antibiotics of Different Classes Against Staphylococcus aureus and Escherichia coli. PLoS ONE, 12(2), 1–15. https://doi.org/10.1371/journal.pone.0172273
Santosaningsih, D., Santoso, S., Setijowati, N., Rasyid, H. A., Budayanti, N. S., Suata, K., Widhyatmoko, D. B., Purwono, P. B., Kuntaman, K., Damayanti, D., Prakoeswa, C. R. S., Laurens, M., Nierop, J. W. I. V., Nanninga, G. L., Oudenes, N., Regt, M. D., Snijders, S. V., Verbrugh, H. A., & Severin, J. A. (2018). Prevalence and Characterisation of Staphylococcus aureus Causing Community-Acquired Skin and Soft Tissue Infections on Java and Bali, Indonesia. Tropical Medicine and International Health, 23(1), 34–44. https://doi.org/10.1111/tmi.13000
Saputra, T. R., Ngatin, A., & Sarungu, Y. T. (2018). Penggunaan Metode Ekstraksi Maserasi dan Partisi pada Tumbuhan Cocor Bebek (Kalanchoe pinnata) dengan Kepolaran Berbeda. Fullerene Journal of Chemistry, 3(1), 1–4. https://doi.org/10.37033/fjc.v3i1.26
Setiawan, V., Triono, N., Agustina, A. K., & Moira, L. A. (2025). The Antibacterial Activities of Piper betle and Allium cepa Extracts Against Staphylococcus aureus. Jurnal Penelitian Pendidikan IPA, 11(9), 97–102. https://doi.org/10.29303/jppipa.v11i9.10850
Shari, W., Erliana, D., Azizah, K., Banon, C., Avidlyandi, A., Wiradimafan, K., S, S. Y., & Adfa, M. (2025). Effectiveness of Cinnamomum porrectum Roxb. Kosterm Pyroligneous Acid and Its Compounds in Staphylococcus aureus Growth Inhibition. Yuzuncu Yil University Journal of Agricultural Sciences, 35(3), 392–402. https://doi.org/10.29133/yyutbd.1601765
Susanti, S., & Asri, M. T. (2024). Aktivitas Antibakteri Kombinasi Ekstrak Kulit Alpukat dan Daun Kemangi Terhadap Pertumbuhan Staphylococcus epidermidis. Lenterabio, 13(2), 236–243. https://doi.org/10.26740/lenterabio.v13n2.p236-243
Taura, D. W., Hassan, A., Yayo, A. M., & Takalmawa, H. (2013). Bacterial Isolates of the Respiratory Tract Infection and Their Current Sensitivity Pattern Among Patients Attending Aminu Kano Teaching Hospital Kano-Nigeria. International Research Journal of Microbiology, 4(9), 226–231. http:/dx.doi.org/10.14303/irjm.2013.048
Vaou, N., Stavropoulou, E., Voidarou, C., Tsigalou, C., & Bezirtzoglou, E. (2021). Towards Advances in Medicinal Plant Antimicrobial Activity: A Review Study on Challenges and Future Perspectives. Microorganisms, 9(10), 1–28. https://doi.org/10.3390/microorganisms9102041
Yon, J. A. L., Lee, S. K., Keng, J. W., Chow, S. C., Liew, K. B., Teo, S. S., Mossadeq, W. M. S., Marriott, P. J., Akowuah, G. A., Ming, L. C., Goh, B. H., & Chew, Y. L. (2023). Cassia alata (Linnaeus) Roxburgh for Skin: Natural Remedies for Atopic Dermatitis in Asia and Their Pharmacological Activities. Cosmetics, 10(5), 1–15. https://doi.org/10.3390/cosmetics10010005
Yuliana, B., Ania, H., & Habiburrahim, H. (2025). Effectiveness of Secang Wood Isolate in Combination with Amoxicillin Against MRSA. Jurnal Penelitian Pendidikan IPA, 11(10), 766–772. https://doi.org/10.29303/jppipa.v11i10.12206
License
Copyright (c) 2026 Oki Rokhim Mawakhid, Putri Ramanda, Samuel Billie Tua Sinaga, Winda Shari, Avidlyandi Avidlyandi, Khafit Wiradimafan, Salprima Yudha S., Risky Hadi Wibowo, Morina Adfa

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with Jurnal Penelitian Pendidikan IPA, agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC-BY License). This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Jurnal Penelitian Pendidikan IPA.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).






