Metabolomic and Cytotoxicity Profiles of Ethanol Extract of Peronema canescens Jack on Human Non-small Lung Cancer Cell A549

Main Article Content

Nuri Anjayani
Senya Putri Amalia
Linda Sukmarini
Hady Anshory Tamhid
Gian Primahana
Asih Triastuti

Abstract

Cancer has a high prevalence and mortality in the world. Cancer treatment is still hampered by high levels of side effects, drug resistance and the lack of affordable prices for anticancer drugs. It is necessary to develop new anticancer drugs to help overcome this problem. One of the plants that has the potential to be developed as an anticancer drug is Sungkai (Peronema canescens Jack). This study aims to determine the cytotoxic activity of sungkai leaf and identify its metabolomic profile. The sungkai leaves were macerated for 24 hours with 96% ethanol. Metabolomic profiles were analyzed with Ultra High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS). Chemical structure identification was performed by MS-DIAL and MS-FINDER platforms. The ethanol extract of sungkai leaves was analyzed for its cytotoxic activity using the MTT test on A549 lung cancer cells and its selectivity on normal HDFa fibroblast cells. The ethanol extract of sungkai showed IC50 105,21 µg/mL on A549 cells and no cytotoxic activity against normal HDFa cells. Based on the metabolomic analysis, 7 furano terpenoid compounds were detected in the ethanol extract, namely peronemin A2; A3; B1; B2; B3: C1; and D1 along with other compounds. In conclusion, the ethanol extract of P. canescens leaves has cytotoxic and selective activity against A549 lung cancer cells, and potential to be further developed as an anticancer drug candidate. Peronemins and other substances like flavonoids and polyphenols may be linked to the cytotoxic properties of sungkai leaves

Article Details

How to Cite
Anjayani, N., Amalia, S. P., Sukmarini, L., Tamhid, H. A., Primahana, G., & Triastuti, A. (2025). Metabolomic and Cytotoxicity Profiles of Ethanol Extract of Peronema canescens Jack on Human Non-small Lung Cancer Cell A549. Jurnal Sains Farmasi & Klinis, 12(1), 7–14. https://doi.org/10.25077/jsfk.12.1.7-14.2025
Section
Research Articles
Author Biographies

Nuri Anjayani, Department of Pharmacy, Universitas Islam Indonesia

Department of Pharmacy, Universitas Islam Indonesia

Senya Putri Amalia, Department of Pharmacy, Sekolah Tinggi Ilmu Kesehatan ISFI, Banjarmasin, South Kalimantan, Indonesia

Department of Pharmacy, Sekolah Tinggi Ilmu Kesehatan ISFI, Banjarmasin, South Kalimantan, Indonesia

Linda Sukmarini, Research Center for Applied Microbiology, National Research and Innovation Agency (BRIN), Bogor, Indonesia

 Research Center for Applied Microbiology, National Research and Innovation Agency (BRIN), Bogor, Indonesia

Hady Anshory Tamhid, Department of Pharmacy, Universitas Islam Indonesia, Yogyakarta, Indonesia

Department of Pharmacy, Universitas Islam Indonesia, Yogyakarta, Indonesia  

References

[1]. WHO. World Health Organization Cancer [Internet]. WHO. 2025 [cited 2025 May 25]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer

[2]. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer Statistics for the Year 2020: An Overview. Int J Cancer. 2021;149(4):1–12. https://doi.org/10.1002/ijc.33588

[3]. CDC. Side Effects of Cancer Treatment [Internet]. CDC. 2023 [cited 2024 Mar 3]. p. 1. Available from: https://www.cdc.gov/cancer/survivors/patients/side-effects-of-treatment.htm

[4]. Fikriansyah M, Nelson N, Latief M, Tarigan I. Anticancer Activities of Seven Peronemins (A2, A3, B1, B2, B3, C1, and D1) from Peronema canescens Jack: A Prediction Studies. Chempublish Journal. 2023;7(1):54–63. https://doi.org/10.22437/chp.v7i1.23726

[5]. Ibrahim A, Hadi K. Identifikasi Metabolit Sekunder dan Aktivitas Antibakteri Ekstrak Daun Sungkai (Peronema canescens Jack.) Terhadap Beberapa Bakteri Patogen. J TropPharmChem. 2012;2(1):8–18. Available from: https://jtpc.ff.unmul.ac.id/index.php/jtpc/article/view/41/35

[6]. Dillasamola D, Aldi Y, Wahyuni F, Rita R, Dachriyanus, Umar S, et al. Study of Sungkai (Peronema canescens, Jack) Leaf Extract Activity as an Immunostimulator with in vivo and in vitro Methods. Pharmacognosy Journal. 2021;13(6):1397–407. https://doi.org/10.5530/PJ.2021.13.177

[7]. Ibrahim A, Siswandono, Bambang P. Cytotoxic Activity of Peronema canescens Jack Leaves on Human Cells: HT-29 and Primary Adenocarcinoma Colon Cancer. Pharmacognosy Journal. 2021;13(6):1389–96. https://doi.org/10.5530/PJ.2021.13.176

[8]. Raimondi M, Randazzo O, Franca M, Barone G, Vignoni E, Rossi D, et al. DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents. Molecules. 2019;24(6):1–19. https://doi.org/10.3390/molecules24061140

[9]. Kubo Y, Adelman J, Clapham D, Jan L, Karschin A, Kurachi Y, et al. International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels. Pharmacol Rev. 2005;57(4):509–26. https://doi.org/10.1124/pr.57.4.11

[10]. Triastuti A, Pradana D, Saputra D, Lianika N, Wicaksono H, Anisari T, et al. Anti-rheumatoid Activity of a Hexane-insoluble Fraction from Plantago Major in Female Wistar Rats Induced by Complete Freund’s Adjuvant. J Tradit Complement Med. 2022;12(3):219–24. https://doi.org/10.1016/j.jtcme.2021.07.006

[11]. Triastuti A, Haddad M, Barakat F, Mejia K, Rabouille G, Fabre N, et al. Dynamics of Chemical Diversity during Co-Cultures: An Integrative Time-Scale Metabolomics Study of Fungal Endophytes Cophinforma mamane and Fusarium solani. Chem Biodivers. 2021;18(2). https://doi.org/10.1002/cbdv.202000672

[12]. Triastuti A, Vansteelandt M, Barakat F, Amasifuen C, Jargeat P, Haddad M. Untargeted metabolomics to evaluate antifungal mechanism: a study of Cophinforma mamane and Candida albicans interaction. Nat Prod Bioprospect. 2023;13(1). https://doi.org/10.1007/s13659-022-00365-w

[13]. Tsugawa H, Kind T, Nakabayashi R, Yukihira D, Tanaka W, Cajka T, et al. Hydrogen Rearrangement Rules: Computational MS/MS Fragmentation and Structure Elucidation Using MS-FINDER Software. Anal Chem. 2016;88(16):7946–58. https://doi.org/10.1021/acs.analchem.6b00770

[14]. Lee J, Thilini J, Jayakody M, Kim JI, Jeong JW, Choi KM, et al. The Influence of Solvent Choice on the Extraction of Bioactive Compounds from Asteraceae : A Comparative Review. Foods. 2024;13:1–21. https://doi.org/10.3390/ foods13193151

[15]. Ibrahim A, Siswandono, Bambang P. Anticancer activity of Peronema canescens Jack leaves extracts against human cells: HT-29 and HeLa in vitro. Res J Pharm Technol. 2022;15(10):4739–45. https://doi.org/10.52711/0974-360X.2022.00796

[16]. Triastuti A, Sari M, Khasanah N, Chabib L, Fajriyah R, Fitria A. Development of Hand Sanitizer Formulated with Essential Oil from Piper betle Grown in Yogyakarta, Indonesia. Natural Volatiles & Essent Oils. 2021;8(5):12816–27. Available from: https://www.nveo.org/index.php/journal/article/view/3988

[17]. Mancilla T, Davis L, Aune G. Doxorubicin-induced p53 Interferes with Mitophagy in Cardiac Fibroblasts. Plos One. 2020;1–27. https://doi.org/10.1371/journal.pone.0238856

[18]. Wang S, Wang Y, Zhang Z, Liu Q, Gu J. Cardioprotective Effects of Fibroblast Growth Factor 21 Against Doxorubicin-induced Toxicity via the SIRT11/LKB1/AMPK Pathway. Cell Death Dis. 2017;8(8). https://doi.org/10.1038/cddis.2017.410

[19]. Dista R, Larasati C, Ayuningsih S, Anggraeni N, Batubara I. Formulation and Characterization of Sungkai Leaf Extract Nanoemulsion (Peronema canscens Jack). Jurnal UIN Alauddin . 2022;10(2):192–200. https://doi.org/10.24252/al-kimiav10i2.33482

[20]. Rahmi, Santoni, Jaswandi, Juanssilfero. GC-MS Screening of Sungkai Leaves and Relation with Its Antioxidant Capacity. IOP Conf Ser Earth Environ Sci. 2023;1182(1):1–7. https://doi.org/10.1088/1755-1315/1182/1/012014

[21]. Blaženović I, Kind T, Torbašinović H, et al. Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: Database boosting is needed to achieve 93% accuracy. J Cheminform. 2017;9:1–12. https://doi.org/10.1186/s13321-017-0219-x

[22]. Zhang M, Zhou J, Wang L, Li B, Guo J, Guan X, et al. Caffeic Acid Reduces Cutaneous Tumor Necrosis Factor Alpha (TNF-α), IL-6, and IL-1β Levels and Ameliorates Skin Edema in Acute and Chronic Models of Cutaneous Inflammation in Mice. Biol Pharm Bull. 2014;37(3):347–54. Available from: https://pubmed.ncbi.nlm.nih.gov/24583856/

[23]. Liang N, Kitts D. Role of Chlorogenic Acids in Controlling Oxidative and Inflammatory Stress Conditions. Nutrients. 2015;8(1):1–20. https://doi.org/10.3390/nu8010016

[24]. Baranowska M, Koziara Z, Suliborska K, Chrzanowski W, Wormstone M, Namieśnik J, et al. Interactions between Polyphenolic Antioxidants Quercetin and Naringenin Dictate the Distinctive Redox-related Chemical and Biological Behaviour of their Mixtures. Sci Rep. 2021;11(1):1–18. https://doi.org/10.1038/s41598-021-89314-0

[25]. Tarigan I, Sutrisno, Rumaida, Aini I, Latief M. Isolation of a Flavone Apigenin and a Steroid Squalene from Peronema canescens Jack Leaves with Anti-Inflammatory Activities. Pharmacognosy Journal. 2022;14(6):744–52. https://doi.org/10.5530/pj.2022.14.162