LC-HRMS Phytochemical Analysis and Antiplasmodial Activity of Peronema canescens Jack Leaves
Keywords:
antiplasmodial, hematine, metabolite analysis, fragmentations, peronema canescens leaves, plasmodium 3D7, malaria, Heme Polymerization
Abstract
The increasing number of resistance to antimalarial drugs, including artemisinin, in several countries leads to an urgent need to discover a new compound to treat malaria. Several studies have reported the ability of Peronema canescens Jack leaves to act as an antiplasmodial activity. Therefore, this research aims to assess the chemical properties and antimalarial efficacy of ethanol extract, n-hexane soluble fraction, ethyl acetate soluble fraction, and ethyl acetate insoluble fraction. The phytochemical screening was carried out using thin-layer chromatography (TLC). The phytochemical properties of the ethanolic extract were then investigated by liquid chromatography- high resonance mass spectrometry (LC-HRMS). Subsequently, an in vitro assay was performed to evaluate their antimalarial activity against Plasmodium falciparum strain 3D7 and their ability to inhibit heme polymerization. Phytochemical TLC showed that P. canescens Jack leaves contained chemicals, such as steroids, flavonoids, and terpenoids. Potential antiplasmodial-based metabolites on L-HRMS were terpenoids, flavonoids, and phenolic compounds. The ethanol extracts, ethyl acetate soluble part, n-hexane soluble extract, and ethyl acetate insoluble part exhibited in vitro antiplasmodial activity against the Plasmodium falciparum strain 3D7 at concentrations of 11±0.09 μg/mL, 3.57±0.28μg/mL, 5.43±0.74μg/mL, and 12.12±1.42 μg/mL. Inhibition of heme polymerization activity in the same series was observed at concentrations of 2.77±0.55 mg/mL, 1.11±0.16 mg/mL, 2.04±0.53 mg/mL, and 6.87±1.24 mg/mL. These results suggest that the n-hexane soluble part of P. canescens Jack leaves have the greatest potential as an antimalarial agent and be further investigated to identify the active compound.
References
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Kitagawa I, Simanjuntak P, Hori K, Nagami N, Mahmud T, Shibuya H, & Kobayashi M. (1994). Indonesian medicinal plants. VII. Seven new clerodane-type diterpenoids, peronemins A2, A3, B1, B2, B3, C1, and D1, from the leaves of Peronema canescens (Verbenaceae). https://doi.org/10.1248/cpb.42.1050
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Ramadenti, F., Sundaryono, A., & Handayani, D. (2017). UJI FRAKSI ETIL ASETAT DAUN Peronema canescens TERHADAP Plasmodium berghei PADA Mus musculus. ALOTROP Jurnal Pendidikan Dan Ilmu Kimia, 2, 89–92.
Ribeiro, G. de J. G., Rei Yan, S. L., Palmisano, G., & Wrenger, C. (2023). Plant Extracts as a Source of Natural Products with Potential Antimalarial Effects: An Update from 2018 to 2022. In Pharmaceutics (Vol. 15, Issue 6). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/pharmaceutics15061638
Rudrapal, M., & Chetia, D. (2016). Plant flavonoids as potential source of future antimalarial leads. In Systematic Reviews in Pharmacy (Vol. 8, Issue 1, pp. 13–18). https://doi.org/10.5530/srp.2017.1.4
Saito, A. Y., Marin Rodriguez, A. A., Menchaca Vega, D. S., Sussmann, R. A. C., Kimura, E. A., & Katzin, A. M. (2016). Antimalarial activity of the terpene nerolidol. International Journal of Antimicrobial Agents, 48(6), 641–646. https://doi.org/10.1016/j.ijantimicag.2016.08.017
Sankhuan, D., Niramolyanun, G., Kangwanrangsan, N., Nakano, M., & Supaibulwatana, K. (2022). Variation in terpenoids in leaves of Artemisia annua grown under different LED spectra resulting in diverse antimalarial activities against Plasmodium falciparum. BMC Plant Biology, 22(1). https://doi.org/10.1186/s12870-022-03528-6
Windarsih, A., Suratno, Warmiko, H. D., Indrianingsih, A. W., Rohman, A., & Ulumuddin, Y. I. (2022). Untargeted metabolomics and proteomics approach using liquid chromatography-Orbitrap high resolution mass spectrometry to detect pork adulteration in Pangasius hypopthalmus meat. Food Chemistry, 386. https://doi.org/10.1016/j.foodchem.2022.132856
World Health Organization. (2023, December 4). Malaria. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/malaria
Yang, W., Chen, X., Li, Y., Guo, S., Wang, Z., & Yu, X. (2020). Advances in Pharmacological Activities of Terpenoids. In Natural Product Communications (Vol. 15, Issue 3). https://doi.org/10.1177/1934578X20903555
Zakiah, M., Syarif, R. A., Mustofa, M., Jumina, J., Fatmasari, N., & Sholikhah, E. N. (2021). In vitro antiplasmodial, heme polymerization, and cytotoxicity of hydroxyxanthone derivatives. Journal of Tropical Medicine, 2021. https://doi.org/10.1155/2021/8866681
Zekar, L., & Sharman, tariq. (2022). Plasmodium falciparum Malaria. stat pearls publishing.
http://www.ncbi.nlm.nih.gov/books/nbk555962/
Basilico, nicolletta, Pagania, E., Montib, D., Olliaroc, P., & Taramelli, D. (1998). polimerization hematin_malaria. Journal of Antimicrobial Chemotherapy. https://doi.org/10.1093/jac/42.1.55
Batista, R., De Jesus Silva Júnior, A., & De Oliveira, A. B. (2009). Plant-derived antimalarial agents: New leads and efficient phytomedicines. part II. non-alkaloidal natural products. In Molecules (Vol. 14, Issue 8, pp. 3037–3072). https://doi.org/10.3390/molecules14083037
Da, A., Lima Gerlach, C., Gadea, A., Borges Da Silveira, R. M., Clerc, P., & Lohézic-Le Dévéhat, F. (2018). The Use of Anisaldehyde Sulfuric Acid as an Alternative Spray Reagent in TLC Analysis Reveals Three Classes of Compounds in the Genus Usnea Adans. (Parmeliaceae, lichenized Ascomycota). https://doi.org/10.20944/preprints201802.0151.v1
De Villiers, K. A., & Egan, T. J. (2021). Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development. Accounts of Chemical Research, 54(11), 2649–2659. https://doi.org/10.1021/acs.accounts.1c00154
Dillasamola, D., Aldi, Y., Wahyuni, F. S., Rita, R. S., Dachriyanus, Umar, S., & Rivai, H. (2021). Study of Sungkai (Peronema canescens, Jack) leaf extract activity as an immunostimulators with in vivo and in vitro methods. Pharmacognosy Journal, 13(6), 1397–1407. https://doi.org/10.5530/PJ.2021.13.177
Fitriastuti, D., Jumina, & Priatmoko. (2017). Heme polymerization inhibition activity (HPIA) assay of synthesized xanthone derivative as antimalarial compound. AIP Conference Proceedings, 1823. https://doi.org/10.1063/1.4978193
Health Organization, W. (2023). World malaria report 2022. https://www.wipo.int/amc/en/mediation/
Herraiz, T., Guillén, H., González-Peña, D., & Arán, V. J. (2019). Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-51604-z
Hidayati, A. R., Melinda, Ilmi, H., Sakura, T., Sakaguchi, M., Ohmori, J., Hartuti, E. D., Tumewu, L., Inaoka, D. K., Tanjung, M., Yoshida, E., Tokumasu, F., Kita, K., Mori, M., Dobashi, K., Nozaki, T., Syafruddin, D., Hafid, A. F., Waluyo, D., & Widyawaruyanti, A. (2023). Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase. International Journal for Parasitology: Drugs and Drug Resistance, 21, 40–50. https://doi.org/10.1016/j.ijpddr.2022.12.001
Hidayati, A. R., Widyawaruyanti, A., Ilmi, H., Tanjung, M., Widiandani, T., Siswandono, Syafruddin, D., & Hafid, A. F. (2020). Antimalarial activity of flavonoid compound isolated from leaves of artocarpus altilis. Pharmacognosy Journal, 12(4), 835–842. https://doi.org/10.5530/pj.2020.12.120
Ibrahim, A., Hadi Kuncoro, dan, Biologi-Mikrobiologi Farmasi, B., Farmasi, F., Mulawarman, U., & Timur, K. (2012). IDENTIFIKASI METABOLIT SEKUNDER DAN AKTIVITAS ANTIBAKTERI EKSTRAK DAUN SUNGKAI (Peronema canescens JACK.) TERHADAP BEBERAPA BAKTERI PATOGEN. In J. Trop. Pharm. Chem (Vol. 2, Issue 1). https://doi.org/10.25026/jtpc.v2i1.43
Ibrahim, A., Siswandono, & Bambang Prajogo, E. W. (2021). Cytotoxic activity of peronema canescens Jack leaves on human cells: HT-29 and primary adenocarcinoma colon cancer. Pharmacognosy Journal, 13(6), 1389–1396. https://doi.org/10.5530/PJ.2021.13.176
Jensen, J. B., & Trager, W. (1977). Plasmodium falciparum in Culture: Use of Outdated Erythrocytes and Description of the Candle Jar Method. In Source: The Journal of Parasitology (Vol. 63, Issue 5). https://about.jstor.org/terms
Kamaraj, C., Rahuman, A. A., Roopan, S. M., Bagavan, A., Elango, G., Zahir, A. A., Rajakumar, G., Jayaseelan, C., Santhoshkumar, T., Marimuthu, S., & Kirthi, A. V. (2014). Bioassay-guided isolation and characterization of active antiplasmodial compounds from Murraya koenigii extracts against Plasmodium falciparum and Plasmodium berghei. Parasitology Research, 113(5), 1657–1672. https://doi.org/10.1007/s00436-014-3810-3
Kementrian Kesehatan Republik Indonesia. (2024). Kasus Malaria di Indonesia.
https://malaria.kemkes.go.id/case (accessed, June 22, 2024)
Khasanah, U., Waruyanti, A. W., Hafd, A. F., & Tanjung, M. (2017). Antiplasmodial activity of isolated polyphenols from Alectryon serratus leaves against 3D7 Plasmodium falciparum. Pharmacognosy Research, 9(5), S57–S60. https://doi.org/10.4103/pr.pr_39_17
Kitagawa I, Simanjuntak P, Hori K, Nagami N, Mahmud T, Shibuya H, & Kobayashi M. (1994). Indonesian medicinal plants. VII. Seven new clerodane-type diterpenoids, peronemins A2, A3, B1, B2, B3, C1, and D1, from the leaves of Peronema canescens (Verbenaceae). https://doi.org/10.1248/cpb.42.1050
Koffi, J. A., Silué, K. D., Tano, D. K., Dable, T. M., & Yavo, W. (2020). Evaluation of antiplasmodial activity of extracts from endemic medicinal plants used to treat malaria in Côte d’Ivoire. BioImpacts, 10(3), 151–157. https://doi.org/10.34172/bi.2020.19
Latief, M., Anggun, ;, Fisesa, T., Putri, ;, Sari, M., Indra, ;, & Tarigan, L. (2021). Jurnal Farmasi Sains dan Praktis AKTIVITAS ANTIINFLAMASI EKSTRAK ETANOL DAUN SUNGKAI (PERONEMA CANESCENS JACK) PADA MENCIT TERINDUKSI KARAGENAN ANTI-INFLAMMATORY ACTIVITY OF SUNGKAI LEAVES (PERONEMA CANESCENS JACK) ETHANOL EXTRACT IN CARRAGEENAN INDUCED MICE. In JFSP (Vol. 7, Issue 2). http://journal.ummgl.ac.id/index.php/pharmacy
Latief, M., Sari, P. M., Fatwa, L. T., Tarigan, I. L., & Rupasinghe, H. P. V. (n.d.). Antidiabetic Activity of Sungkai (Peronema canescens Jack) Leaves Ethanol Extract on the Male Mice Induced Alloxan Monohydrate. Pharmacology and Clinical Pharmacy Research. https://doi.org/10.15416/pcpr.v4i3.31666
Muharni, M., Ferlinahayati, F., & Yohandini, H. (2021). Antioxidant, antibacterial, total phenolic and flavonoid contents of sungkai leaves (Paronema canescens). Tropical Journal of Natural Product Research, 5(3), 528–533. https://doi.org/10.26538/tjnpr/v5i3.18
Noreen, N., Ullah, A., Salman, S. M., Mabkhot, Y., Alsayari, A., & Badshah, S. L. (2021). New insights into the spread of resistance to artemisinin and its analogues. In Journal of Global Antimicrobial Resistance (Vol. 27, pp. 142–149). Elsevier Ltd. https://doi.org/10.1016/j.jgar.2021.09.001
Nurhasanah, D., Fakhrudin, N., Retnoaji, B., & Nugroho, A. E. (2023). Antiangiogenic Activity of n-hexane Insoluble Fraction and Its Tylophorine Component from Ficus septica Leaves in Chicken Chorioallantoic Membrane Induced by bFGF. Asian Pacific Journal of Cancer Prevention, 24(1), 75–80. https://doi.org/10.31557/APJCP.2023.24.1.75
Okfrianti, Y., Irnameria, D., Studi DIV Gizi, P., Kesehatan Bengkulu, P., Studi DIII Farmasi, P., Kesehatan Lampung, P., Okfrianti Porgram Studi DIV Gizi, Y., & Kesehatan Kemenkes Bengkulu, P. (n.d.). Aktivitas Antioksidan Ekstrak Etanol Daun Sungkai (Peronema canescens Jack) Antioxidant Activity of Sungkai Leaf (Peronema canescens Jack) Ethanol Extract. In Jurnal Kesehatan (Vol. 13, Issue 2). Online. http://ejurnal.poltekkes-tjk.ac.id/index.php/JK
Paul, S., Hwang, J. K., Kim, H. Y., Jeon, W. K., Chung, C., & Han, J. S. (2013). Multiple biological properties of macelignan and its pharmacological implications. In Archives of Pharmacal Research (Vol. 36, Issue 3, pp. 264–272). https://doi.org/10.1007/s12272-013-0048-z
Putranto, A. M. H. (2014). EXAMINATION OF THE SUNGKAI’S YOUNG LEAF EXTRACT (Peronema canescens) AS AN ANTIPIRETIC, IMMUNITY, ANTIPLASMODIUM AND TERATOGENITY IN MICE (Mus.muculus). International Journal of Science and Engineering, 7(1). https://doi.org/10.12777/ijse.7.1.30-34
Quadros, H. C., Çapcı, A., Herrmann, L., D’alessandro, S., Fontinha, D., Azevedo, R., Villarreal, W., Basilico, N., Prudêncio, M., Tsogoeva, S. B., & Moreira, D. R. M. (2021). Studies of potency and efficacy of an optimized artemisinin-quinoline hybrid against multiple stages of the plasmodium life cycle. Pharmaceuticals, 14(11). https://doi.org/10.3390/ph14111129
Ramadenti, F., Sundaryono, A., & Handayani, D. (2017). UJI FRAKSI ETIL ASETAT DAUN Peronema canescens TERHADAP Plasmodium berghei PADA Mus musculus. ALOTROP Jurnal Pendidikan Dan Ilmu Kimia, 2, 89–92.
Ribeiro, G. de J. G., Rei Yan, S. L., Palmisano, G., & Wrenger, C. (2023). Plant Extracts as a Source of Natural Products with Potential Antimalarial Effects: An Update from 2018 to 2022. In Pharmaceutics (Vol. 15, Issue 6). Multidisciplinary Digital Publishing Institute (MDPI). https://doi.org/10.3390/pharmaceutics15061638
Rudrapal, M., & Chetia, D. (2016). Plant flavonoids as potential source of future antimalarial leads. In Systematic Reviews in Pharmacy (Vol. 8, Issue 1, pp. 13–18). https://doi.org/10.5530/srp.2017.1.4
Saito, A. Y., Marin Rodriguez, A. A., Menchaca Vega, D. S., Sussmann, R. A. C., Kimura, E. A., & Katzin, A. M. (2016). Antimalarial activity of the terpene nerolidol. International Journal of Antimicrobial Agents, 48(6), 641–646. https://doi.org/10.1016/j.ijantimicag.2016.08.017
Sankhuan, D., Niramolyanun, G., Kangwanrangsan, N., Nakano, M., & Supaibulwatana, K. (2022). Variation in terpenoids in leaves of Artemisia annua grown under different LED spectra resulting in diverse antimalarial activities against Plasmodium falciparum. BMC Plant Biology, 22(1). https://doi.org/10.1186/s12870-022-03528-6
Windarsih, A., Suratno, Warmiko, H. D., Indrianingsih, A. W., Rohman, A., & Ulumuddin, Y. I. (2022). Untargeted metabolomics and proteomics approach using liquid chromatography-Orbitrap high resolution mass spectrometry to detect pork adulteration in Pangasius hypopthalmus meat. Food Chemistry, 386. https://doi.org/10.1016/j.foodchem.2022.132856
World Health Organization. (2023, December 4). Malaria. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/malaria
Yang, W., Chen, X., Li, Y., Guo, S., Wang, Z., & Yu, X. (2020). Advances in Pharmacological Activities of Terpenoids. In Natural Product Communications (Vol. 15, Issue 3). https://doi.org/10.1177/1934578X20903555
Zakiah, M., Syarif, R. A., Mustofa, M., Jumina, J., Fatmasari, N., & Sholikhah, E. N. (2021). In vitro antiplasmodial, heme polymerization, and cytotoxicity of hydroxyxanthone derivatives. Journal of Tropical Medicine, 2021. https://doi.org/10.1155/2021/8866681
Zekar, L., & Sharman, tariq. (2022). Plasmodium falciparum Malaria. stat pearls publishing.
http://www.ncbi.nlm.nih.gov/books/nbk555962/
Published
2026-05-04
How to Cite
Nurrochmad, A., Ramadhani, N., Rohman, A., & Lukitaningsih, E. (2026). LC-HRMS Phytochemical Analysis and Antiplasmodial Activity of Peronema canescens Jack Leaves. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.16914
Issue
Section
Research Article
