Assessment of Antioxidant and Anticancer Activities of  Erythrina variegata  L. Leaves Collected from Ketambe Against A549 Lung Cancer Cell Line

Halimatussakdiah Halimatussakdiah; Ulil Amna; Sara Gustia Wibowo; Misdi Misdi; Vivi Mardina

doi:10.22146/ijc.97718

Assessment of Antioxidant and Anticancer Activities of Erythrina variegata L. Leaves Collected from Ketambe Against A549 Lung Cancer Cell Line

https://doi.org/10.22146/ijc.97718

Halimatussakdiah Halimatussakdiah^(1*), Ulil Amna⁽²⁾, Sara Gustia Wibowo⁽³⁾, Misdi Misdi⁽⁴⁾, Vivi Mardina⁽⁵⁾

(1) Department of Chemistry, Faculty of Science and Technology, Samudra University, Jl. Prof. Syarief Thayeb, Meurandeh, Langsa, Aceh 24416, Indonesia
(2) Department of Chemistry, Faculty of Science and Technology, Samudra University, Jl. Prof. Syarief Thayeb, Meurandeh, Langsa, Aceh 24416, Indonesia
(3) Department of Biology, Faculty of Science and Technology, Samudra University, Jl. Prof. Syarief Thayeb, Meurandeh, Langsa, Aceh 24416, Indonesia
(4) Department of Biology, Faculty of Science and Technology, Samudra University, Jl. Prof. Syarief Thayeb, Meurandeh, Langsa, Aceh 24416, Indonesia
(5) Department of Biology, Faculty of Science and Technology, Samudra University, Jl. Prof. Syarief Thayeb, Meurandeh, Langsa, Aceh 24416, Indonesia
(*) Corresponding Author

Abstract

Erythrina variegata L. (Dadap) has been traditionally utilized as a medicinal plant. In this study, its antioxidant capacity was examined using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against A549 lung cancer cells and Chang normal cells through the MTT assay. The methanolic extract of Dadap leaves showed moderate antioxidant activity with an IC₅₀ of 177.354 ppm. Cytotoxicity tests revealed strong activity against A549 cells with an IC₅₀ of 66.640 ppm, while showing weak toxicity toward Chang cells (IC₅₀ of 324.283 ppm), even slightly promoting normal cell growth. The extract demonstrated a selectivity index (SI) of 4.866, indicating selective cytotoxicity toward lung cancer cells (SI ≥ 2). GC–MS analysis identified 26 compounds, with the predominant bioactive metabolites being neophytadiene, methyl hexadecanoate, methyl (9Z,12Z)-octadecadienoate, phytol, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, and stigmasterol, all of which have been associated with antioxidant and anticancer activities. Complementary LC–HRMS profiling detected 568 compounds, of which 22 were characterized as major constituents, including seven alkaloids—1,2-dimethoxy-6aβ-noraporphine, bohemamine F, peniamidienone, codeinone, sinomenine, 6β-naltrexol, and (S)-corytuberine—and one flavonoid, isovitexin 2''-O-arabinoside. These metabolites support the potential of E. variegata L. methanolic extract as an antioxidant and anticancer agent.

Keywords

antioxidants; cytotoxic; Erythrina variegata L.; ketambe; lung cancer

Full Text:

Full Text PDF

References

[1] World Health Organization, 2025, Cancer, https://www.who.int/news-room/fact-sheets/detail/cancer, accessed on 20 September 2025.

[2] Senhaji, S., Lamchouri, F., and Toufik, H., 2020, Phytochemical content, antibacterial and antioxidant potential of endemic plant Anabasis aretioïdes Coss. & Moq. (Chenopodiaceae), BioMed Res. Int., 2020 (1), 6152932.

[3] Javed, S.B., Alatar, A.A., Anis, M., and Faisal, M., 2017, Synthetic seeds production and germination studies, for short term storage and long distance transport of Erythrina variegata L.: A multipurpose tree legume, Ind. Crops Prod., 105, 41–46.

[4] Yuwono, E.H., Susanto, P., Saleh, C., Andayani, N., Prasetyo, D., and Atmoko, S.S.U., 2007, Guidelines for Better Management Practices on Avoidance, Mitigation and Management of Human-Orangutan Conflict in and around Oil Palm Plantations, WWF-Indonesia, Jakarta, Indonesia.

[5] Thongmee, P., and and Itharat, A., 2016, Anti-inflammatory activities of Erythrina variegata bark ethanolic extract, J. Med. Assoc. Thailand, 99 (Suppl. 4), S166–S171.

[6] Herlina, T., Nurlelasari, N., Kurnia, D., Supratman, U., and Udin, Z., 2011, In vitro anticancer and antimalarial Erystagallin-A from Erythrina variegata (L.) stem bark, Med. Plants – Int. J. Phytomed. Relat. Ind., 3 (1), 9–13.

[7] Martins, J., and Brijesh, S., 2020, Anti-depressant activity of Erythrina variegata bark extract and regulation of monoamine oxidase activities in mice, J. Ethnopharmacol., 248, 112280.

[8] Santhiya, N., Priyanga, S., Hemmalakshmi, S., Devaki, K., 2016, Phytochemical analysis, anti inflammatory activity, in vitro antidiabetic activity and GC-MS profile of Erythrina variegata L. bark, J. Appl. Pharm. Sci., 6 (7), 147–155.

[9] Baranitharan, M., Sawicka, B., and Gokulakrishnan, J., 2019, Phytochemical profiling and larval control of Erythrina variegata methanol fraction against malarial and filarial vector, Adv. Prev. Med., 2019 (1), 2641959.

[10] Kumar, A., Lingadurai, S., Shrivastava, T.P., Bhattacharya, S., and Haldar, P.K., 2011, Hypoglycemic activity of Erythrina variegata leaf in streptozotocin-induced diabetic rats, Pharm. Biol., 49 (6), 577–582.

[11] John, R., Kariyil, B.J., Usha, P.T.A., and Surya, S., 2021, Apoptosis mediated cytotoxic potential of Erythrina variegata L. stem bark in human breast carcinoma cell lines, Indian J. Exp. Biol., 59 (7), 437–447.

[12] Halimatussakdiah, H., Amna, U., and Mardina, V., 2020, Antioxidant activity of methanol extract of Diplazium esculentum (Retz.) Sw. leaves collected from Aceh, IOP Conf. Ser.: Mater. Sci. Eng., 725 (1), 012082.

[13] Lee, J.E., Jayakody, J.T., Kim, J.I., Jeong, J.W., Choi, K.M., Kim, T.S., Seo, C., Azimi, I., Hyun, J., and Ryu, B., 2024, The influence of solvent choice on the extraction of bioactive compounds from Asteraceae: A comparative review, Foods, 13 (19), 3151.

[14] Bhandary, S.K., Suchetha Kumari, N., Bhat, V.S., Sharmila, K.P., and Bekal, M.P., 2012, Preliminary phytochemical screening of various extracts of Punica granatum peel, whole fruit and seeds, Nitte Univ. J. Health Sci., 2 (4), 34–38.

[15] Fransina, E.G., Tanasale, M.F.J.D.P., Latupeirissa, J., Malle, D., and Tahapary, R., 2019, Phytochemical screening of water extract of gayam (Inocarpus edulis) bark and its amylase inhibitor activity assay, IOP Conf. Ser.: Mater. Sci. Eng., 509 (1), 012074.

[16] Safrina, U., Wardiyah, W., and Cartika, H., 2022, Evaluation of total flavonoid, total phenolic, and antioxidant activity of Etlingera elatior (Jack) R.M.Sm flower, fruit, and leaf, Trad. Med. J., 27 (1), 51–59.

[17] Priya, V., Krishnan, M., and Gopika Nair, M., 2024, Exploring the phytochemical properties and therapeutic potential of Cheilanthes swartzii: A novel fern from the Western Ghats, JMPB, 13 (4), 1103–1110.

[18] Kumari, P., Singh, S.K., and Kumari, C., 2017, Phytochemical screening and antibacterial activity of Erythrina variegata L. (leaf extract), Int. J. Curr. Microbiol. Appl. Sci., 6 (6), 2500–2505.

[19] Ramila Devi, M., and Manoharan, A., 2011, Phytochemical investigation of Erythrina variegata and Ficus racemosa leaves, J. Chem. Pharm. Res., 3, 166–172.

[20] Wang, Y., Zhang, S., Ma, Y., Du, X., Zong, Q., Lin, D., Lai, M., Huang, T., Luo, Q., Yang, L., Li, Z., and Zuo, Z., 2024, Solvent effects on terpenoid compositions and antioxidant activities of Cinnamomum camphora (L.) J. Presl extracts and the main antioxidant agent evaluation through in vitro and in vivo assay, Chem. Biol. Technol. Agric., 11 (1), 2.

[21] Ilemona, A.J., Gbekele-Oluwa, A.R., Ojo, O.A., and Habila, J.D., 2017, Chemical investigation and antioxidant activity of fractions of Lannea humilis (Oliv.) Engl., J. Turk. Chem. Soc., Sect. A, 4 (2), 563–572.

[22] Nirmalraj, S., and Perinbam, K., 2015, Studies on phytochemical screening and in vitro antioxidant activity of ethyl acetate leaf extract of Justicia gendarussa Burm. F., Res. J. Bot., 10 (1), 30–36.

[23] Alruwad, M.I., Sabry, M.M., Gendy, A.M., El-Dine, R.S., and El Hefnawy, H.M., 2023, In vitro cytotoxic potential of selected Jordanian flora and their associated phytochemical analysis, Plants, 12 (8), 1626.

[24] Wan Yusof, W.N.S., Abdullah, H., 2020, Phytochemicals and cytotoxicity of Quercus infectoria ethyl acetate extracts on human cancer cells, Trop. Life Sci. Res., 31 (1), 69–84.

[25] Stein, S.E., Brown, R.L., 2025, “Structures and Properties Group Additivity Model” in NIST Chemistry WebBook, NIST Standard Reference Database Number 69, Eds. Linstrom, P.J., and Mallard, W.G., National Institute of Standards and Technology, Gaithersburg, MD, US, https://webbook.nist.gov/chemistry/grp-add/, accessed on 11 April 2025.

[26] Pratama, O.A., Sri Tunjung, W.A., Sutikno, S., and Daryono, B.S., 2019, Bioactive compound profile of melon leaf extract (Cucumis melo L. ‘Hikapel’) infected by downy mildew, Biodiversitas, 20 (11), 3448–3453.

[27] To’bungan, N., Jati, W.N., and Zahida, F., 2022, Acute toxicity and anticancer potential of knobweed (Hyptis capitata) ethanolic leaf extract and fraction, Plant Sci. Today, 9 (4), 955–962.

[28] El-fayoumy, E.A., Shanab, S.M.M., Gaballa, H.S., Tantawy, M.A., and Shalaby, E.A., 2021, Evaluation of antioxidant and anticancer activity of crude extract and different fractions of Chlorella vulgaris axenic culture grown under various concentrations of copper ions, BMC Complementary Med. Ther., 21 (5), 51.

[29] Gonzalez-Rivera, M.L., Barragan-Galvez, J.C., Gasca-Martínez, D., Hidalgo-Figueroa, S., Isiordia-Espinoza, M., and Alonso-Castro, A.J., 2023, In vivo neuropharmacological effects of neophytadiene, Molecules, 28 (8), 3457.

[30] Maheswari, B.U., and Kalaiselvi, G., 2024, Exploring Neophytadiene from Ampelocissus araneosa: A molecular docking approach to inhibit biofilm formation in Staphylococcus aureus, Uttar Pradesh J. Zool., 45 (3), 59–70.

[31] Nagabhushana, S., Yohannan, A.S.K., Malammanavar, S.G., Mookkan, P., and Iwarx, K., 2025, Phytochemistry, bioactive potential and chemical characterization of culturable freshwater microalgae Chlorococcum infusionum (Schrank) Meneghini, Not. Sci. Biol., 17 (1), 12276.

[32] Wan Alias, W.A.S., Ismail, N., Hasan, H.B., Nik Abdul Ghani, N.R., Abdulrazak, M.H., and Hassan, S.A., 2024, Phytochemical composition and antimicrobial efficacy of Salvadora persica root extracts against Carbapenem-resistant Acinetobacter baumannii, Cureus, 16 (4), e58660.

[33] Hadi, M.Y., Mohammed, G.J., and Hameed, I.H., 2016, Analysis of bioactive chemical compounds of Nigella sativa using gas chromatography-mass spectrometry, J. Pharmacogn. Phytother., 8 (2), 8–24.

[34] Gupta, V., Tyagi, S., and Tripathi, R., 2023, Hexadecanoic acid methyl ester, a potent hepatoprotective compound in leaves of Pistia stratiotes L., Appl. Biol. Chem. J., 4 (4), 118–120.

[35] Budi, H.S., Anitasari, S., Ulfa, N.M., Setiabudi, R., Ramasamy, R., Wu, C.Z., and Shen, Y.K., 2022, Palmitic acid of Musa paradisiaca induces apoptosis through caspase-3 in human oral squamous cell carcinoma, Eur. Rev. Med. Pharmacol. Sci., 26 (19), 7099–7114.

[36] Kaushik, B., Sharma, J., Yadav, K., Kumar, P., and Shourie, A., 2021, Phytochemical properties and pharmacological role of plants: Secondary metabolites, Biosci., Biotechnol. Res. Asia, 18 (1), 23–35.

[37] Sun, J., Zhan, X., Wang, W., Yang, X., Liu, Y., Yang, H., Deng, J., and Yang, H., 2024, Natural aporphine alkaloids: A comprehensive review of phytochemistry, pharmacokinetics, anticancer activities, and clinical application, J. Adv. Res., 63, 231–253.

[38] Rodrigues-Junior, D.M., de Almeida Pontes, N.M., de Albuquerque, G.E., Carlin, V., Perecim, G.P., Raminelli, C., and Vettore, A.L., 2020, Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells, Invest. New Drugs, 38 (1), 70–78.

[39] Adrian, A., Lubis, M.F., Syahputra, R.A., Astyka, R., Sumaiyah, S., Yudha Harahap, M.A., and Aini, Z., 2024, The potential effect of aporphine alkaloids from Nelumbo nucifera Gaertn. as anti-breast cancer based on network pharmacology and molecular docking, Int. J. Appl. Pharm., 16 (1), 280–287.

[40] Fu, P., La, S., and MacMillan, J.B., 2016, 1,3-Oxazin-6-one derivatives and bohemamine-type pyrrolizidine alkaloids from a marine-derived Streptomyces spinoverrucosus, J. Nat. Prod., 79 (3), 455–462.

[41] Maeda, K., Sugai, T., Tokuda, A., Kajino, K., Saitoh, T., Nagase, H., and Kutsumura, N., 2024, Design and synthesis of unique morphinan-type molecules: Their application to the search for the unexplored binding domain between opioid receptors and morphinan ligands, Bioorg. Med. Chem. Lett., 99, 129611.

[42] Kajino, K., Tokuda, A., and Saitoh, T., 2024, Morphinan evolution: The impact of advances in biochemistry and molecular biology, J. Biochem., 175 (4), 337–355.

[43] Hitosugi, N., Nagasaka, H., Sakagami, H., Matsumoto, I., and Kawase, M., 2003, Analysis of apoptosis signaling pathway in human cancer cells by codeinone, a synthetic derivative of codeine, Anticancer Res, 23 (3B), 2569–2576.

[44] Yang, S., Peng, L.Y., Peng, W., Huang, C., Wei, D.N., Mou, M.T., Liang, F., and Gao, Y.X., 2019, Anticancer potentials of sinomenine from Sinomenium acutum: A mini-review, Trop. J. Pharm. Res., 17 (12), 2519–2526.

[45] Zhu, J., Zhu, H., and Gao, J., 2023, The anti-tumor potential of sinomenine: A narrative review, Transl. Cancer Res., 12 (9), 2393–2404.

[46] Jiang, P., Zahra, A., Guo, X., and Wu, J., 2024, Recent advances in the therapeutic potential of sinomenine for cancer treatment, Pharmacology, 109 (2), 76–85.

[47] Kiptoo, P.K., Paudel, K.S., Hammell, D.C., Hamad, M.O., Crooks, P.A., and Stinchcomb, A.L., 2008, In vivo evaluation of a transdermal codrug of 6-β-naltrexol linked to hydroxybupropion in hairless guinea pigs, Eur. J. Pharm. Sci., 33 (4), 371–379.

[48] Ciwun, M., Tankiewicz-Kwedlo, A., and Pawlak, D., 2024, Low-dose naltrexone as an adjuvant in combined anticancer therapy, Cancers, 16 (6), 1240.

[49] Lv, H., Yu, Z., Zheng, Y., Wang, L., Qin, X., Cheng, G., and Ci, X., 2016, Isovitexin exerts anti-inflammatory and anti-oxidant activities on lipopolysaccharide-induced acute lung injury by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways, Int. J. Biol. Sci., 12 (1), 72–86.

[50] Li, J., Shang, L., Zhou, F., Wang, S., Liu, N., Zhou, M., Lin, Q., Zhang, M., Cai, Y., Chen, G., and Yang, S., 2023, Herba Patriniae and its component Isovitexin show anti-colorectal cancer effects by inducing apoptosis and cell-cycle arrest via p53 activation, Biomed. Pharmacother., 168, 115690.

[51] Ghanbari-Movahed, M., Shafiee, S., Burcher, J.T., Lagoa, R., Farzaei, M.H., and Bishayee, A., 2023, Anticancer potential of apigenin and isovitexin with focus on oncogenic metabolism in cancer stem cells, Metabolites, 13 (3), 404.

[52] Gulcin, İ., and Alwasel, S.H., 2023, DPPH radical scavenging assay, Processes, 11 (8), 2248.

[53] Hemmalakshmi, S., Priyanga, S., Vidya, B., Gopalakrishnan, V.K., and Devaki, K., 2016, Screening of the antioxidant potential of the leaves and flowers extract of Erythrina variegata L.: A comparative study, Int. J. Pharm. Sci. Rev. Res., 40 (2), 186–191.

[54] Widyawati, P.S., 2016, Determination of antioxidant capacity in Pluchea indica less leaves extract and its fractions, Int. J. Pharm. Pharm. Sci., 8 (9), 32–36.

[55] Flora, S.J.S., 2009, Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure, Oxid. Med. Cell. Longevity, 2 (4), 873634.

[56] Muniyandi, K., George, E., Sathyanarayanan, S., George, B.P., Abrahamse, H., Thamburaj, S., and Thangaraj, P., 2019, Phenolics, tannins, flavonoids and anthocyanins contents influenced antioxidant and anticancer activities of Rubus fruits from Western Ghats, India, Food Sci. Hum. Wellness, 8 (1), 73–81.

[57] Di Marco, B., Marchetti, F., Costa, S., Baldini, E., Baldisserotto, A., Gugel, I., Vertuani, S., Strettoi, E., and Manfredini, S., 2025, Dual-action steroid derivatives with anti-inflammatory and antioxidant potency: An in vitro study, Biomed. Pharmacother., 186, 117940.

[58] Pekkoh, J., Phinyo, K., Thurakit, T., Lomakool, S., Duangjan, K., Ruangrit, K., Pumas, C., Jiranusornkul, S., Yooin, W., Cheirsilp, B., Pathom-aree, W., Srinuanpan, S., 2022, Lipid profile, antioxidant and antihypertensive activity, and computational molecular docking of diatom fatty acids as ACE inhibitors, Antioxidants, 11 (2), 186.

[59] Kintya, P.K., Burtseva, S.A., Koval’chuk, L.P., Mashchenko, N.E., and Bobeiko, V.A., 1982, Search for steroidal glycoside antioxidants, Pharm. Chem. J., 16 (1), 65–67.

[60] Marimuthu, T., Manikandan, R., and Anburaj, G., 2022, Phytochemical analysis, anti oxident, in vitro anti-cancer activity of Erythrina variegata L. leaves, World J. Pharm. Life Sci., 8 (9), 111–119.

[61] Pakka, S., Magar, A.B., Shrestha, D., Sharma, T., and Sharma, K.R., 2024, Phytochemical analysis and biological activities of solvent extracts of two traditionally used medicinal plants, BIBECHANA, 21 (2), 113–123.

[62] Rajia, S., Alamgir, M., Shahriar, M., and Chouduri, M.S.K., 2006, Bioactivity of the methanol extract of Excoecaria agallocha Linn. (Euphorbiaceae), Orient. Pharm. Exp. Med., 6 (2), 102–107.

[63] Kumar, P., Nagarajan, A., and Uchil, P.D., 2018, Analysis of cell viability by the MTT assay, Cold Spring Harb. Protoc., 2018 (6), pdb.prot095505.

[64] Pires, F.C.S., de Oliveira, J.C., Menezes, E.G.O., Silva, A.P.S., Ferreira, M.C.R., Siqueira, L.M.M., Almada-Vilhena, A.O., Pieczarka, J.C., Nagamachi, C.Y., and de Carvalho Junior, R.N., 2021, Bioactive compounds and evaluation of antioxidant, cytotoxic and cytoprotective effects of murici pulp extracts (Byrsonima crassifolia) obtained by supercritical extraction in HepG2 cells treated with H₂O₂, Foods, 10 (4), 737.

[65] Kundishora, A., Sithole, S., and Mukanganyama, S., 2020, Determination of the cytotoxic effect of different leaf extracts from Parinari curatellifolia (Chrysobalanaceae), J. Toxicol., 2020 (1), 8831545.

[66] Gao, M., Huang, Y., Hu, C., Hu, J., Wang, Y., Chen, Y., Huang, Y., Song, G., Song, Z., and Wang, Z., 2021, Selective anticancer effect of Phellinus linteus on epidermoid cell lines studied by atomic force microscopy: Anticancer activity on A431 cancer cells and low toxicity on HaCat normal cells, IEEE Nanatechnol. Mag., 15 (1), 4–16.

[67] Suttithumsatid, W., Toriumi, T., Sukketsiri, W., Nagasaki, Y., and Panichayupakaranant, P., 2024, Enhanced stability of α-mangostin-rich extract and selective cytotoxicity against cancer cells via encapsulation in antioxidant nanoparticles (AME@Nano^AOX), ACS Biomater. Sci. Eng., 10 (8), 5027–5038.

[68] Vaishali Rai, M., Pai, V.R., Kevin, S., and Kedilaya, H.P., 2017, In vitro evaluation of anticancer potential of Erythrina variegata L. on breast cancer cell lines, Asian J. Pharm. Clin. Res., 10 (7), 305–310.

[69] Zahra, M., Abrahamse, H., and George, B.P., 2024, Flavonoids: Antioxidant powerhouses and their role in nanomedicine, Antioxidants, 13 (8), 922.

[70] Thawabteh, A., Juma, S., Bader, M., Karaman, D., Scrano, L., Bufo, S.A., and Karaman, R., 2019, The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens, Toxins, 11 (11), 656.

[71] Fitri, L., Fauziah, F., Dini, F., Mauludin, S.A., and Dita, S.F., 2023, The Potential of tapak dara (Catharanthus roseus) leaves endophytic bacteria BETD5 as antioxidant and anticancer against T47D breast cancer cells, Indones. J. Pharm., 34 (2), 245–252.

DOI: https://doi.org/10.22146/ijc.97718