Review: Potensi Metabolit Sekunder dari Phaleria macrocarpa dan Fungi Endofitnya sebagai Antikanker

Ikra Agustina; Caterina Siskadewi Lay; Puji Astuti

doi:10.22146/farmaseutik.v20i1.86037

Review: Potensi Metabolit Sekunder dari Phaleria macrocarpa dan Fungi Endofitnya sebagai Antikanker

https://doi.org/10.22146/farmaseutik.v20i1.86037

Ikra Agustina⁽¹⁾, Caterina Siskadewi Lay⁽²⁾, Puji Astuti^(3*)

(1) Magister Ilmu Farmasi, Fakultas Farmasi, Universitas Gadjah Mada
(2) Magister Ilmu Farmasi, Fakultas Farmasi, Universitas Gadjah Mada
(3) Departemen Biologi Farmasi, Fakultas Farmasi, Universitas Gadjah Mada
(*) Corresponding Author

Abstract

Phaleria macrocarpa merupakan tanaman obat Indonesia yang telah digunakan secara empiris untuk pengobatan berbagai penyakit, termasuk kanker. Beberapa metabolit aktif dari Phaleria macrocarpa yang diketahui memiliki aktivitas antikanker diantaranya phalerin, asam galat, fevicordin, dan kaempferol-3-O-β-D-glukosida. Kanker adalah salah satu penyakit yang menjadi masalah global dengan prevalensi dan angka kematian yang tinggi. Terapi pada penderita kanker masih mengalami beberapa keterbatasan seperti aspek biaya yang tinggi, banyaknya efek samping obat sintesis pada kemoterapi, dan adanya resistensi obat kemoterapi. Sumber bahan baku pengobatan kanker di Indonesia juga kebanyakan masih bergantung pada impor. Pencarian senyawa aktif dari bahan alam sangat diperlukan untuk pengembangan bahan baku obat antikanker. Namun, seringkali metabolit aktif yang berasal dari tumbuhan memiliki kelimpahan yang rendah. Penggunaan mikroba endofit dapat menjadi salah satu stategi untuk produksi senyawa metabolit aktif tanpa memerlukan bahan baku dalam jumlah besar. Mikroba endofit dapat bersimbiosis dalam inangnya dan menghasilkan metabolit sekunder yang kemungkinan mirip dengan tanaman inangnya. Artikel ini bertujuan mengkaji metabolit sekunder dari Phaleria macrocarpa dan potensi penggunaan mikroba endofitnya sebagai sumber senyawa antikanker yang berasal dari alam. Metode yang digunakan berupa studi pustaka melalui penelusuran berbagai studi, artikel ilmiah dan penelitian dari database elektronik (Elsevier, Google Scholar, PubMed, Science Direct dan Springer Link). Artikel ini diharapkan menjadi sumber informasi untuk acuan para peneliti di masa mendatang dalam pengembangan riset obat antikanker yang berasal dari alam.

Keywords

Antikanker; Fungi Endofit; Metabolit Sekunder; Phaleria macrocarpa

Full Text:

PDF

References

Abdullah, N., Hassan, N.H., Rahman, S.S.A., Ismail, H., Khalid, R. and Yahya, M.F., 2014. In vitro propagation of Phaleria macrocarpa, God’s Crown. J. Biotechnol. Pharma. Res, 5(2), pp.18-23.

Agung BS, Faried A, Arifin MZ, Wiriadisastra K, Ohta T. 2008. Herbal Medicine Isolation, Phaleria macrocarpa for primary glioblastoma multiforme cells. Ann Epidemiol, 18:708‑41.

Ali RB, Atangwho IJ, Kuar N, Mohamed EAH, Mohamed AJ, et al. 2012. Hypoglycemic and anti-hyperglycemic study of Phaleria macrocarpa fruits pericarp. Journal of Medicinal Plants Research 6: 1982-1990.

Altaf, R., Asmawi, M., Dewa, A., Sadikun, A. and Umar, M., 2013. Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts. Pharmacognosy reviews, 7(13), p.73.

Andrean D, Prasetyo S, Kristijarti AP, Hudaya T. 2014. The Extraction and Activity Test of Bioactive Compounds in Phaleria macrocarpa as Antioxidants. Procedia Chem 9: 94-101.

Aripin, A., Arifin, P.F. and Tjandrawinata, R.R., Dexa Medica PT, 2013. Isolated compounds from Phaleria macrocarpa as anti-cancer agents. U.S. Patent 8,569,382.

Aydın, E., Türkez, H. and Keleş, M.S., 2015. Potential anticancer activity of carvone in N2a neuroblastoma cell line. Toxicology and industrial health, 31(8), pp.764-772.

Cheng, P., Peng, Z.G., Yang, J. and Song, S.J., 2007. The effect of mangiferin on telomerase activity and apoptosis in leukemic K562 cells. Zhong yao cai= Zhongyaocai= Journal of Chinese Medicinal Materials, 30(3), pp.306-309.

Choi EJ, Kim G-H., 2009. Apigenin induces apoptosis through a mitochondria/caspase-pathway in human breast cancer MDA-MB-453 cells. J Clin Biochem Nutr 44(3): 260–265.

Christina, Y.I., Nafisah, W., Atho’illah, M. F., Rifa’i, M., Widodo, N., and Djati, S., 2021. Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies. Journal of Pharmacy & Pharmacognosy Research, 9(6), pp.824-845.

Christina, Y.I., Rifa’i, M., Widodo, N. and Djati, M.S., 2022. Comparative Study of Antiproliferative Activity in Different Plant Parts of Phaleria macrocarpa and the Underlying Mechanism of Action. The Scientific World Journal.

Cragg, G.M. and Newman, D.J., 2013. Natural products: a continuing source of novel drug leads. Biochimica et Biophysica Acta (BBA)-General Subjects, 1830(6), pp.3670-3695.

Diantini, A., Subarnas, A., Supriyatna, L.J., Abdulah, R., Achmad, T.H., Faried, A., Faried, L.S., Julaeha, E., Kurnia, D., Wardhani, S.R. and Koyama, H., 2012. Cytotoxicity of fevicordin-A from Phaleria macrocarpa (Scheff.) Boerl. on P388, HeLa, Caski, TE-2, TE-8 and Prepuce’s Fibroblast cells. J Med Res, 1, pp.1-5.

Dzobo, K., 2022. The role of natural products as sources of therapeutic agents for innovative drug discovery. Comprehensive Pharmacology, p.408.

Faried, A., Kurnia, D., Faried, L.S., Usman, N., Miyazaki, T., Kato, H. and Kuwano, H., 2007. Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. International journal of oncology, 30(3), pp.605-613.

Gasong, B. T., & Tjandrawinata, R. R. 2016. Production of secondary metabolite E2. 2 from Phaleria macrocarpa endophytic fungus. Asian Pacific Journal of Tropical Biomedicine, 6(10), 881-885.

Globocan, 2021, The Global Cancer Obsevatory; Indonesia 2020. https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf

Govindappa M. 2015. Diabetes and metabolism: A review on role of plant(s) extracts and its phytochemicals for the management of Diabetes. Jour of Diab and Metab 6: 565.

Hanifah, R.S., Novitarani, N.A., Harmen, F., Tedjo, A., Azizah, N.N., Putrianingsih, R., Fachri, W. and Kusmardi, K., 2019. The inhibition of ethanol extract of Phaleria macrocarpa stem bark on COX-2 expression of HCT116 colorectal cancer cell line. Research Journal of Pharmacy and Technology, 12(6), pp.2902-2906.

Harmanto, N., 2005. Mahkota Dewa Obat Pusaka Para Dewa [A Medicine the Legacy of the Gods (6th Edition)], Agro Media Pustaka, Jakarta.

He, Z., Chen, A.Y., Rojanasakul, Y., Rankin, G.O. and Chen, Y.C., 2016. Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells. Oncology reports, 35(1), pp.291-297.

Katrin, E., Selvie, S. and Winarno, H., 2011. Chromatogram profiles and cytotoxic activity of irradiated Mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl) leaves. Atom Indonesia, 37(1), pp.17-23.

Kumala, S. and Pratiwi, A.A., 2014. Efek antimikroba dari kapang endofit ranting tanaman biduri. Jurnal Farmasi Indonesia, Vol, 7(2), p.112.

Kumar, A., Patil D., Rajamohanan, P.R., dan Ahmad, A., 2013. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus, PLoS One, 8(9), 71805.

Kusari, S., Zühlke, S., & Spiteller, M. 2009. An Endophytic Fungus from Camptotheca acuminata That Produces Camptothecin and Analogues. Journal of Natural Products, 72(1), 2–7. doi:10.1021/np800455b

Lay, M.M., Karsani, S.A. and Abd Malek, S.N., 2014b. Induction of apoptosis of 2, 4′, 6-trihydroxybenzophenone in HT-29 colon carcinoma cell line. BioMed research international, 2014.

Lay, M.M., Karsani, S.A., Banisalam, B., Mohajer, S. and Abd Malek, S.N., 2014a. Antioxidants, phytochemicals, and cytotoxicity studies on Phaleria macrocarpa (Scheff.) Boerl seeds. BioMed research international.

Lu, Y., Jiang, F., Jiang, H., Wu, K., Zheng, X., Cai, Y., Katakowski, M., Chopp, M. and To, S.S.T., 2010. Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells. European journal of pharmacology, 641(2-3), pp.102-107.

Muchtaridi, M., Yusuf, M., Diantini, A., Choi, S.B., Al-Najjar, B.O., Manurung, J.V., Subarnas, A., Achmad, T.H., Wardhani, S.R. and Wahab, H.A., 2014. Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) boerl. Seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies. International journal of molecular sciences, 15(5), pp.7225-7249.

Othman, S.N.A.M., Bohari, S.P.M. and Basar, N., 2013, March. Chemical Constituents and Cytotoxicity Activity of Phaleria Macrocarpa (SCHEFF) Boerl. Fruits on MCF-7 Cell Line. In The Open Conference Proceedings Journal (Vol. 4, No. 1).

Othman, S.N.A.M., Sarker, S.D., Nahar, L. and Basar, N., 2014. The ethnomedicinal, phytochemical and pharmacological properties of Phaleria macrocarpa (Scheff). Boerl. CELLMED, 4(4), pp.22-1.

Palem, P.P.C., Kuriakose, G.C., dan Jayabaskaran, C., 2015. An Endophytic Fungus Talaromyces radicus, isolated from Catharanthus roseus, produces vincristine and vinblastine, which induce apoptotic cell death, PLoS One, 10 (12), 0144476

Puri, S.C., Nazir, A., Chawla, R., & Arora, R. 2006. The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. Journal of Biotechnology, 122(4), pp.494–510.

Radji, M., 2005. Peranan bioteknologi dan mikroba endofit dalam pengembangan obat herbal. Majalah ilmu kefarmasian, 2(3), p.1.

Rahmawati, E., Dewoto, H.R. and Wuyung, P.E., 2006. Anticancer activity study of ethanol extract of Mahkota dewa fruit pulp (Phaleria macrocarpa (Scheff.) Boerl.) in C3H mouse mammary tumor induced by transplantation. Medical Journal of Indonesia, 15(4), pp.217-22.

Seo H-S, Ku JM, Choi H-S, Woo J-K, Jang B-H, Go H, Shin YC, Ko S-G., 2015. Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells. Mol Med Rep 12(2): 2977–2984.

Siao A, Hou CWR, Kao Y-H, Jeng KC., 2015. Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer MCF-7 cells. Asian Pac J Cancer Prev 16(9): 3779–3783.

Siegel, R.L., Miller, K.D. and Jemal, A., 2016. Cancer statistics, 2016. CA: a cancer journal for clinicians, 65(1), pp.5-29.

Singh, N., Baby, D., Rajguru, J. P., Patil, P. B., Thakkannavar, S. S., & Pujari, V. B. 2019. Inflammation and cancer. Annals of African medicine, 18(3), 121. https://doi.org/10.4103/aam.aam_56_18

Stierle, A., Strobel, G. and Stierle, D., 1993. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science, 260(5105), pp.214-216.

Strobel, G.A., 2004, Natural Products from Endophyc microorganism. Journal of natural products, 67; 67:257-268.

Sumarawati, T., Riwanto, I., Hadisaputro, S., Dharmana, E., & Nasihun, T. 2020. Effect of Phaleria macrocapa on Atrophy and Apoptosis of Intestinal Mucous Cell and Phalerin Concentration at Portal Vein and Systemic Circulation in Adenocarcinoma Mice following Adriamycine and Cyclophosphamide Treatment. Pharmacognosy Journal, 12(3).

Syarmalina, S., Lely, W. and Laupa, N., 2007. Uji Sitotoksik Hasil Fermentasi Kapang Endofit Buah Mahkota Dewa (Phaleria macrocarpa) terhadap Sel MCF-7. Jurnal Ilmu Kefarmasian Indonesia, 5(1), pp.23-30.

Tjandrawinata, R.R., Arifin, P.F., Tandrasasmita, O.M., Rahmi, D. and Aripin, A., 2010. DLBS1425, a Phaleria macrocarpa (Scheff.) Boerl. extract confers anti proliferative and proapoptosis effects via eicosanoid pathway. J Exp Ther Oncol, 8(3), pp.187-201.

Winarno, H., 2009. Benzophenone glucoside isolated from the ethyl acetate extract of the bark of mahkota dewa [Phaleria macrocarpa (Scheff.) Boerl.] and its inhibitory activity on leukemia L1210 cell line. Indonesian Journal of Chemistry, 9(1), pp.142-145.

You, B.R., Moon, H.J., Han, Y.H. and Park, W.H., 2010. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food and Chemical Toxicology, 48(5), pp.1334-1340.

Zhang, S.Y., Zhang, Q.H., Zhao, W., Zhang, X., Zhang, Q., Bi, Y.F. and Zhang, Y.B., 2012. Isolation, characterization and cytotoxic activity of benzophenone glucopyranosides from Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl). Bioorganic & medicinal chemistry letters, 22(22), pp.6862-6866.

Zhang, Y.B., Xu, X.J. and Liu, H.M., 2006. Chemical constituents from Mahkota dewa. Journal of Asian natural products research, 8(1-2), pp.119-123.

DOI: https://doi.org/10.22146/farmaseutik.v20i1.86037