1. Home
  2. Vol 5, No 3 (2024)
  3. Zulfikar

Antimicrobial Potential of Calotropis gigantea Leaf Against Klebsiella pneumoniae in Ventilator-Associated Pneumonia

Teuku Zulfikar, Tongku N. Siregar, Anna Rozaliyani, Amalia Sutriana

Abstract


Calotropis gigantea or biduri has traditional medicinal properties. However, the effect of C. gigantea leaves in assisting the function of antibiotic-resistant ventilator-associated pneumonia (VAP), particularly caused by Klebsiella pneumoniae, has not been evaluated. The purpose of this study was to identify the active compounds of C. gigantea leaf extracts growing in the coastal area of Alue Naga, Banda Aceh, Indonesia, and assess its antimicrobial potential in preventing microbial resistance. C. gigantea leaves were extracted using three different solvents: ethanol, ethyl acetate, and n-hexane. The three extracts of C. gigantea leaves were analyzed for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the active compounds of C. gigantea were identified using gas chromatography-mass spectroscopy (GC-MS). The dominant bioactive compounds of the C. gigantea extract were enrolled for molecular docking analysis. The results of this study showed that the inhibitory concentration 50% (IC50) of the ethanol extract had a higher antioxidant activity (IC50 value of 3.3 ppm) than the ethyl acetate (IC50 value of 22.97 ppm) and n-hexane (IC50 value of 32.9 ppm). Bioactive compound identification using GC-MS from the three extracts showed similar dominant compounds, which were α-amyrin and lup-20(29)-en-3-ol, and these compounds belonged to the class of triterpenoid derivative compounds. Molecular docking analysis showed that α-amyrin (-9.6 Kcal/mol), β-amyrin (-9.6 Kcal/mol), and epilupeol (-9.2 Kcal/mol) in C. gigantea leaves had higher binding free energy values compared to cefixime (-8.7 Kcal/mol). Thus, it could be concluded that C. gigantea leaf extract is assumed to have great potential as an antimicrobial agent and in preventing microbial resistance, particularly in cases of VAP caused by Klebsiella pneumoniae.

 

Doi: 10.28991/HEF-2024-05-03-010

Full Text: PDF


Keywords


Calotropis gigantea; Biduri; Ventilator-Associated Pneumonia (VAP); α-Amyrin; Alue Naga.

References


Papazian, L., Klompas, M., & Luyt, C. E. (2020). Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Medicine, 46(5), 888–906. doi:10.1007/s00134-020-05980-0.

Bailey, K. L., & Kalil, A. C. (2015). Ventilator-Associated Pneumonia (VAP) with Multidrug-Resistant (MDR) Pathogens: Optimal Treatment? Current Infectious Disease Reports, 17(8), 2–7. doi:10.1007/s11908-015-0494-5.

Sani, M. A., & Separovic, F. (2018). Antimicrobial Peptide Structures: From Model Membranes to Live Cells. Chemistry - A European Journal, 24(2), 286–291. doi:10.1002/chem.201704362.

Gupta, R., Malik, A., Rizvi, M., Ahmed, M., & Singh, A. (2017). Epidemiology of multidrug-resistant Gram-negative pathogens isolated from ventilator-associated pneumonia in ICU patients. Journal of Global Antimicrobial Resistance, 9, 47–50. doi:10.1016/j.jgar.2016.12.016.

Murray, C. J., Ikuta, K. S., Sharara, F., Swetschinski, L., Robles Aguilar, G., Gray, A., Han, C., Bisignano, C., Rao, P., Wool, E., Johnson, S. C., Browne, A. J., Chipeta, M. G., Fell, F., Hackett, S., Haines-Woodhouse, G., Kashef Hamadani, B. H., Kumaran, E. A. P., McManigal, B., … Naghavi, M. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet, 399(10325), 629–655. doi:10.1016/S0140-6736(21)02724-0.

Bassetti, M., Echols, R., Matsunaga, Y., Ariyasu, M., Doi, Y., Ferrer, R., Lodise, T. P., Naas, T., Niki, Y., Paterson, D. L., Portsmouth, S., Torre-Cisneros, J., Toyoizumi, K., Wunderink, R. G., & Nagata, T. D. (2021). Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. The Lancet Infectious Diseases, 21(2), 226–240. doi:10.1016/S1473-3099(20)30796-9.

Moussaoui, F., & Alaoui, T. (2016). Evaluation of antibacterial activity and synergistic effect between antibiotic and the essential oils of some medicinal plants. Asian Pacific Journal of Tropical Biomedicine, 6(1), 32–37. doi:10.1016/j.apjtb.2015.09.024.

Qaid, M. M., Al-Mufarrej, S. I., Azzam, M. M., & Al-Garadi, M. A. (2021). Anticoccidial effectivity of a traditional medicinal plant, Cinnamomum verum, in broiler chickens infected with Eimeria tenella. Poultry Science, 100(3), 100902. doi:10.1016/j.psj.2020.11.071.

Hajarnavis, A. M., & Bulakh, P. M. (2020). Anticataract effects of S. cumini and A. marmelos on goat lenses in an experimental diabetic cataract model. Journal of Ayurveda and Integrative Medicine, 11(4), 421–425. doi:10.1016/j.jaim.2019.08.001.

Hakim, R. F., Fakhrurrazi, & Dinni. (2019). Effect of Carica papaya Extract toward Incised Wound Healing Process in Mice (Mus musculus) Clinically and Histologically. Evidence-Based Complementary and Alternative Medicine, 2019. doi:10.1155/2019/8306519.

Adnan, M., Patel, M., Deshpande, S., Alreshidi, M., Siddiqui, A. J., Reddy, M. N., Emira, N., & De Feo, V. (2020). Effect of Adiantum philippense Extract on Biofilm Formation, Adhesion with Its Antibacterial Activities Against Foodborne Pathogens, and Characterization of Bioactive Metabolites: An in vitro-in silico Approach. Frontiers in Microbiology, 11(May), 1–19. doi:10.3389/fmicb.2020.00823.

Sivapalan, S., Dharmalingam, S., Venkatesan, V., Angappan, M., & Ashokkumar, V. (2023). Phytochemical analysis, anti-inflammatory, antioxidant activity of Calotropis gigantea and its therapeutic applications. Journal of Ethnopharmacology, 303, 115963. doi:10.1016/j.jep.2022.115963.

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), 2041. doi:10.3390/microorganisms9102041.

Basavegowda, N., & Baek, K. H. (2022). Combination Strategies of Different Antimicrobials: An Efficient and Alternative Tool for Pathogen Inactivation. Biomedicines, 10(9), 2219. doi:10.3390/biomedicines10092219.

Kamatou, G. P. P., Viljoen, A. M., van Vuuren, S. F., & van Zyl, R. L. (2006). In vitro evidence of antimicrobial synergy between Salvia chamelaeagnea and Leonotis leonurus. South African Journal of Botany, 72(4), 634–636. doi:10.1016/j.sajb.2006.03.011.

Reda, F. M., El-Zawahry, Y., & Omar, A. (2017). Synergistic Effect of Combined Antibiotic and Methanol Extract of Eucalyptus camaldulensis leaf Against Staphylococcus aureus and Pseudomonas aeruginosa. International Journal of Applied Sciences and Biotechnology, 5(4), 486–497. doi:10.3126/ijasbt.v5i4.18620.

USDA. (1992). Dr. Duke’s Phytochemical and Ethnobotanical Databases. United States Department of Agriculture, United States. Available online: https://phytochem.nal.usda.gov/ (accessed on August 2024).

Kemala, P., Idroes, R., Khairan, K., Tallei, T. E., Ramli, M., & Efendi, R. (2022). Green synthesis of silver nanoparticles using Calotropis gigantea and its characterization using UV-Vis Spectroscopy. IOP Conference Series: Earth and Environmental Science, 951(1), 12090. doi:10.1088/1755-1315/951/1/012090.

Rajamohan, S., Kalaivanan, P., Sivangnanam, H., & Rajamanickam, M. (2014). Antioxidant, Antimicrobial activities and GC-MS analysis of Calotropis gigantea white flowers. J. Phytopharmacol, 3, 405-409.

Ningsih, D. S., Idroes, R., Bachtiar, B. M., Khairan, K., Tallei, T. E., & Muslem, M. (2022). In vitro cytotoxicity of ethanolic extract of the leaf of Calotropis gigantea from Ie Jue Geothermal Area, Aceh-Indonesia, and its mouthwash formulation against dental pulp cells. Journal of Applied Pharmaceutical Science, 12(2), 133–143. doi:10.7324/JAPS.2021.120213.

Bairagi, S., Ghule, P., & Gilhotra, R. (2022). Molecular Docking, In vitro Antioxidant, and In vivo Hepatoprotective Activity of Methanolic Extract of Calotropis gigantea leaves in Carbon Tetrachloride-induced Liver Injury in Rats. Current Enzyme Inhibition, 18(2), 110–126. doi:10.2174/1573408018666220511170125.

Arisa, I. I., Fitriani, F., Agustina, S., Karina, S., & Devira, C. N. (2021). The effect Calotropis gigantea leaf extract on eggs hatchability and survival of Barbonymus gonionotus larvae. IOP Conference Series: Earth and Environmental Science, 869(1), 12029. doi:10.1088/1755-1315/869/1/012029.

Sharma, M., Delta, A. K., & Kaushik, P. (2022). Phytochemistry and Pharmacology of Calotropis gigantea — An update. Indian Journal of Biochemistry and Biophysics, 59(6), 611–618. doi:10.56042/ijbb.v59i6.56922.

Alafnan, A., Sridharagatta, S., Saleem, H., Khurshid, U., Alamri, A., Ansari, S. Y., Zainal Abidin, S. A., Ansari, S. A., Alamri, A. S., Ahemad, N., & Anwar, S. (2021). Evaluation of the Phytochemical, Antioxidant, Enzyme Inhibition, and Wound Healing Potential of Calotropis gigantea (L.) Dryand: A Source of a Bioactive Medicinal Product. Frontiers in Pharmacology, 12. doi:10.3389/fphar.2021.701369.

Kumar, G., Karthik, L., & Bhaskara Rao, K. V. (2010). Antibacterial activity of aqueous extract of Calotropis gigantea leaves - An in vitro study. International Journal of Pharmaceutical Sciences Review and Research, 4(2), 141–144.

Bush, K., & Bradford, P. A. (2020). Epidemiology of β-lactamase-producing pathogens. Clinical Microbiology Reviews, 33(2). doi:10.1128/CMR.00047-19.

Lund, B. A., Thomassen, A. M., Carlsen, T. J. O., & Leiros, H. K. S. (2017). Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis. Acta Crystallographica Section F:Structural Biology Communications, 73(10), 579–587. doi:10.1107/S2053230X17013838.

Maulydia, N. B., Tallei, T. E., Ginting, B., Idroes, R., Illian, D. N., & Faradilla, M. (2022). Analysis of flavonoid compounds of Orange (Citrus sp.) peel as anti-main protease of SARS-CoV-2: A molecular docking study. IOP Conference Series: Earth and Environmental Science, 951(1), 12078. doi:10.1088/1755-1315/951/1/012078.

Zeb, M. A., Rahman, T. U., Sajid, M., Xiao, W., Musharraf, S. G., Bibi, S., Akitsu, T., & Liaqat, W. (2021). GC-MS Analysis and In Silico Approaches of Indigofera heterantha Root Oil Chemical Constituents. Compounds, 1(3), 116–124. doi:10.3390/compounds1030010.

Maulydia, N. B., Khairan, K., Tallei, T. E., Estevam, E. C., Patwekar, M., Mohd Fauzi, F., & Idroes, R. (2023). GC-MS Analysis Reveals Unique Chemical Composition of Blumea balsamifera (L.) DC in Ie-Jue Geothermal Area. Grimsa Journal of Science Engineering and Technology, 1(1), 9–16. doi:10.61975/gjset.v1i1.6.

Jasmine, J. M., & Vanaja, R. (2013). In silico analysis of phytochemical compounds for optimizing the inhibitors of HMG CoA reductase. Journal of Applied Pharmaceutical Science, 3(9), 43–47. doi:10.7324/JAPS.2013.3908.

Gulcin, İ. (2020). Antioxidants and antioxidant methods: an updated overview. Archives of Toxicology, 94(3), 651–715. doi:10.1007/s00204-020-02689-3.

Harlita, T. D., & Asnani, A. (2018). The antibacterial activity of dayak onion (Eleutherine palmifolia (L.) merr) towards pathogenic bacteria. Tropical life sciences research, 29(2), 39. doi:10.21315/tlsr2018.29.2.4.

Lefebvre, T., Destandau, E., & Lesellier, E. (2021). Selective extraction of bioactive compounds from plants using recent extraction techniques: A review. Journal of Chromatography A, 1635, 461770. doi:10.1016/j.chroma.2020.461770.

Atolani, O., Oguntoye, H., Areh, E. T., Adeyemi, O. S., & Kambizi, L. (2019). Chemical composition, anti-toxoplasma, cytotoxicity, antioxidant, and anti-inflammatory potentials of cola gigantea seed oil. Pharmaceutical Biology, 57(1), 154–160. doi:10.1080/13880209.2019.1577468.

Kadhim, M. J., Sosa, A. A., & Hameed, I. H. (2016). Evaluation of anti-bacterial activity and bioactive chemical analysis of Ocimum basilicum using Fourier transform infrared (FT-IR) and gas chromatographymass spectrometry (GC-MS) techniques. Journal of Pharmacognosy and Phytotherapy, 8(6), 127–146. doi:10.5897/JPP2015.0366.

Filimonov, D. A., Lagunin, A. A., Gloriozova, T. A., Rudik, A. V., Druzhilovskii, D. S., Pogodin, P. V., & Poroikov, V. V. (2014). Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chemistry of Heterocyclic Compounds, 50(3), 444–457. doi:10.1007/s10593-014-1496-1.

Rehman, N., Haq, F., & Faisal, S. (2023). Phytochemical Analysis and Antioxidant Potential of Calotropis procera and Calotropis gigantea. Asian Journal of Biological Sciences, 16(3), 254–263. doi:10.3923/ajbs.2023.254.263.

Vuolo, M. M., Lima, V. S., & Maróstica Junior, M. R. (2019). Phenolic Compounds. Bioactive Compounds, 33–50. Elsevier, Amsterdam, Netherlands. doi:10.1016/B978-0-12-814774-0.00002-5.

Li, H., Zhang, D., Tan, L. H., Yu, B., Zhao, S. P., & Cao, W. G. (2017). Comparison of the antioxidant properties of various solvent extracts from Dipsacus asperoides and identification of phenolic compounds by LC-ESI-QTOF-MS–MS. South African Journal of Botany, 109, 1–8. doi:10.1016/j.sajb.2016.12.018.

Sumczynski, D., Kotásková, E., Orsavová, J., & Valášek, P. (2017). Contribution of individual phenolics to antioxidant activity and in vitro digestibility of wild rices (Zizania aquatica L.). Food Chemistry, 218, 107–115. doi:10.1016/j.foodchem.2016.09.060.

Heim, K. E., Tagliaferro, A. R., & Bobilya, D. J. (2002). Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships. Journal of Nutritional Biochemistry, 13(10), 572–584. doi:10.1016/S0955-2863(02)00208-5.

Madhavan, S. A., Vinotha, P., & Uma, V. (2020). Phytochemical screening and comparative gc–ms analysis of bioactive compounds present in methanolic leaf and latex extract Calotropis gigantea (L). Asian Journal of Advances in Medical Science, 2(1), 31-43.

Idroes, G. M., Tallei, T. E., Idroes, R., Muslem, Riza, M., & Suhendrayatna. (2021). The study of Calotropis Gigantea leaf metabolites from Ie Brouk geothermal area Lamteuba-Aceh Besar using molecular docking. IOP Conference Series: Earth and Environmental Science, 667(1), 12072. doi:10.1088/1755-1315/667/1/012072.

Allafchian, A., Jalali, S. A. H., Hosseini, F., & Massoud, M. (2017). Ocimum basilicum mucilage as a new green polymer support for silver in magnetic nanocomposites: production and characterization. Journal of environmental chemical engineering, 5(6), 5912-5920. doi:10.1016/j.jece.2017.11.023.

Usman, M., Abdulrahman, M. D., Hamad, S. W., Hama, H. A., & Lema, A. A. (2022). Antioxidants, Anti-inflammation, Anti-hyperglycemia and Chemical Evaluation of the whole plant extracts of Anisopus mannii N.E.Br. Zanco Journal of Pure and Applied Sciences, 34(5), 114–122. doi:10.21271/ZJPAS.34.5.10.

Viet, T.D., Xuan, T.D., & Anh, L.H. (2021). α-Amyrin and β-Amyrin Isolated from Celastrus hindsii Leaves & Their Antioxidant, Anti-Xanthine Oxidase, and Anti-Tyrosinase Potentials. Molecules, 26(23), 7248. doi:10.3390/molecules26237248.

Wawer, I. (2008). Solid-State Measurements of Drugs and Drug Formulations. NMR Spectroscopy in Pharmaceutical Analysis, Elsevier, Amsterdam, Netherlands. doi:10.1016/b978-0-444-53173-5.00009-3.

Nogueira, A. O., Oliveira, Y. I. S., Adjafre, B. L., de Moraes, M. E. A., & Aragão, G. F. (2019). Pharmacological effects of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum: a literature review. Fundamental & Clinical Pharmacology, 33(1), 4–12. doi:10.1111/fcp.12402.

Gyawali, R., Bhattarai, B., Bajracharya, S., Bhandari, S., Bhetwal, P., Bogati, K., Neupane, S., Shrestha, S., Shrestha, A. K., Joshi, R., & Paudel, P. N. (2020). α-Amylase Inhibition, Antioxidant Activity and Phytochemical Analysis of Calotropis gigantea (L.) Dryand. Journal of Health and Allied Sciences, 10(1), 77–81. doi:10.37107/jhas.143.

Lim, T. K. (2012). Moringa oleifera. Edible Medicinal and Non-Medicinal Plants, 453–485. Springer Netherlands. doi:10.1007/978-94-007-2534-8_61.

Karadağ, A. E., Demirci, B., Polat, D. Ç., & Okur, M. E. (2018). Characterization of Opuntia ficus-indica (L.) Mill. fruit volatiles and antibacterial evaluation. Natural Volatiles and Essential Oils, 5(4), 35–38.

Wongves, K., Chongcharoen, W., & Chandrachai, A. (2023). Development of Herbal Topical Anesthetic Mucoadhesive Spray for oral Cavity using Customer-Centric Approach. Journal of Human, Earth, and Future, 4(3), 274-289. doi:10.28991/HEF-2023-04-03-02.

Alam, S., Emon, N. U., Rashid, M. A., Arman, M., & Haque, M. R. (2020). Investigation of biological activities of Colocasia gigantea Hook.f. leaves and PASS prediction, in silico molecular docking with ADME/T analysis of its isolated bioactive compounds, Biorxiv, Amsterdam, Netherlands. doi:10.1101/2020.05.18.101113.

Tallei, T. E., Tumilaar, S. G., Niode, N. J., Fatimawali, Kepel, B. J., Idroes, R., Effendi, Y., Sakib, S. A., & Emran, T. Bin. (2020). Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. Scientifica, 2020, 1–18. doi:10.1155/2020/6307457.

Kumar, D., Chandel, V., Raj, S., & Rathi, B. (2020). In silico identification of potent FDA approved drugs against Coronavirus COVID-19 main protease: A drug repurposing approach. Chemical Biology Letters, 7(3), 166-175.

Tyagi, R., Srivastava, M., Jain, P., Pandey, R. P., Asthana, S., Kumar, D., & Raj, V. S. (2022). Development of potential proteasome inhibitors against Mycobacterium tuberculosis. Journal of Biomolecular Structure and Dynamics, 40(5), 2189–2203. doi:10.1080/07391102.2020.1835722.

Sharma, P., & Modi, G. (2018). in Vitro Assessment of Antibacterial Activity of Calotropis Gigantea. International Journal of Current Research in Life Sciences, 07(06), 2347–2350.

Govindasamy, G. A., Mydin, R. B. S. M. N., Sreekantan, S., & Harun, N. H. (2021). Compositions and antimicrobial properties of binary ZnO–CuO nanocomposites encapsulated calcium and carbon from Calotropis gigantea targeted for skin pathogens. Scientific Reports, 11(1), 99. doi:10.1038/s41598-020-79547-w.

Bui, T., Patel, P., & Preuss, C. V. (2024). Cephalosporins. StatPearls Publishing LLC, St. Petersburg, United States.

Ladeira Ázar, R. I. S., Morgan, T., dos Santos, A. C. F., de Aquino Ximenes, E., Ladisch, M. R., & Guimarães, V. M. (2018). Deactivation and activation of lignocellulose degrading enzymes in the presence of laccase. Enzyme and Microbial Technology, 109, 25–30. doi:10.1016/j.enzmictec.2017.09.007.

Maulydia, N. B., Idroes, R., Khairan, K., Tallei, T. E., & Mohd Fauzi, F. (2024). Ecotoxicological insight of phytochemicals, toxicological informatics, and heavy metal concentration in Tridax procumbens L. in geothermal areas. Global Journal of Environmental Science and Management, 10(1), 369–384. doi:10.22034/gjesm.2024.01.23.


Full Text: PDF

DOI: 10.28991/HEF-2024-05-03-010

Refbacks

  • There are currently no refbacks.


Copyright (c) 2024 Teuku Zulfikar, Tongku Nizwan Siregar, Tongku Nizwan Siregar, Anna Rozaliyani, Anna Rozaliyani, Amalia Sutriana, Amalia Sutriana