Cycloartobiloxanthone, a Flavonoid with Antidiabetic, Antibacterial and Anticancer Activities from Artocarpus kemando Miq.

Tati Suhartati, Antin S. Prihatin, Armidla N. Kurniati, Hendri Ropingi, Yandri Yandri, Sutopo Hadi

Abstract


In this present work, a cycloartobiloxanthone compound was isolated from the stem wood and root bark of the Pudau plant (Artocarpus kemando Miq.). The purity of the compound was determined using thin-layer chromatography with three eluent systems and melting point tests. The sample was then analyzed using UV-Vis, IR, and NMR spectroscopy, ensuring that the compound is cycloartobilox-anthone. The cycloartobiloxanthone compound was obtained in a yellow crystalline form with a melting point of 285.1-294°C. The compound was then investigated for antidiabetic, anticancer, and antibacterial properties, showing that the compound has an anti-diabetic effect by reducing the activity of the α-amylase enzyme, with the highest percentage of inhibition of 48.53 ± 1.84% achieved with the use of 1000 ppm of the compound. Cycloartobiloxanthone isolated has an IC50 value of 9.21 µg/mL for anticancer activity against MCF-7 cells, indicating that the compound shows active cytotoxic actions. Staphylococcus aureus was very strongly inhibited by the compound in the antibacterial test at all doses, whereas for Salmonellasp., the activity was categorized as moderate at concentrations of 0.4 and 0.3 mg/disc and strong at 0.5 mg/disc. The anti-diabetic, anti-cancer, and antibacterial bioactivity studies indicated that the cycloartobiloxanthone compound isolated has a broad spectrum of pharmacological actions, indicating that the compound has promising potential.

 

Doi: 10.28991/ESJ-2024-08-01-04

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Keywords


Cycloartobiloxanthone; Antidiabetic; Anticancer; Antibacterial; Artocarpus kemando Miq.

References


Association, A. D. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37(SUPPL.1), 81– 90. doi:10.2337/dc14-S081.

IDF. (2021). IDF Diabetes Atlas 2021 (10th Ed.). International Diabetes Federation, Brussels, Belgium. Available online: www.diabetesatlas.org (accessed on March 2023).

Serbis, A., Giapros, V., Kotanidou, E. P., Galli-Tsinopoulou, A., & Siomou, E. (2021). Diagnosis, treatment and prevention of type 2 diabetes mellitus in children and adolescents. World Journal of Diabetes, 12(4), 344–365. doi:10.4239/wjd.v12.i4.344.

D’Souza, D., Empringham, J., Pechlivanoglou, P., Uleryk, E. M., Cohen, E., & Shulman, R. (2023). Incidence of Diabetes in Children and Adolescents During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis. JAMA Network Open, 6(6), E2321281. doi:10.1001/jamanetworkopen.2023.21281.

Heald, A. H., Stedman, M., Davies, M., Livingston, M., Alshames, R., Lunt, M., Rayman, G., & Gadsby, R. (2020). Estimating life years lost to diabetes: outcomes from analysis of National Diabetes Audit and Office of National Statistics data. Cardiovascular Endocrinology & Metabolism, 9(4), 183–185. doi:10.1097/XCE.0000000000000210.

Tomic, D., Shaw, J. E., & Magliano, D. J. (2022). The burden and risks of emerging complications of diabetes mellitus. Nature Reviews Endocrinology, 18(9), 525–539. doi:10.1038/s41574-022-00690-7.

Ceriello, A., & Prattichizzo, F. (2021). Variability of risk factors and diabetes complications. Cardiovascular Diabetology, 20(1), 101. doi:10.1186/s12933-021-01289-4.

Yang, K., Liu, Z., Thong, M. S. Y., Doege, D., & Arndt, V. (2022). Higher Incidence of Diabetes in Cancer Patients Compared to Cancer-Free Population Controls: A Systematic Review and Meta-Analysis. Cancers, 14(7), 1808. doi:10.3390/cancers14071808.

Sjöholm, K., Carlsson, L. M. S., Svensson, P. A., Andersson-Assarsson, J. C., Kristensson, F., Jacobson, P., Peltonen, M., & Taube, M. (2022). Association of Bariatric Surgery with Cancer Incidence in Patients with Obesity and Diabetes: Long-term Results from the Swedish Obese Subjects Study. Diabetes Care, 45(2), 444–450. doi:10.2337/dc21-1335.

Lega, I. C., Wilton, A. S., Austin, P. C., Fischer, H. D., Johnson, J. A., & Lipscombe, L. L. (2016). The temporal relationship between diabetes and cancer: A population-based study. Cancer, 122(17), 2731–2738. doi:10.1002/cncr.30095.

Bronsveld, H. K., Jensen, V., Vahl, P., De Bruin, M. L., Cornelissen, S., Sanders, J., Auvinen, A., Haukka, J., Andersen, M., Vestergaard, P., & Schmidt, M. K. (2017). Diabetes and Breast Cancer Subtypes. PLOS ONE, 12(1), e0170084. doi:10.1371/journal.pone.0170084.

Casqueiro, J., Casqueiro, J., & Alves, C. (2012). Infections in patients with diabetes mellitus: A review of pathogenesis. Indian Journal of Endocrinology and Metabolism, 16(7), 27. doi:10.4103/2230-8210.94253.

Rai, I., Wanjari, A., & Acharya, S. (2021). Recent Advances in Insulin Delivery Devices and Modes of Insulin Therapy. Journal of Pharmaceutical Research International, 33(57B), 358–367. doi:10.9734/jpri/2021/v33i57b34067.

Abalkhail, A., & Elbehiry, A. (2022). Methicillin-Resistant Staphylococcus aureus in Diabetic Foot Infections: Protein Profiling, Virulence Determinants, and Antimicrobial Resistance. Applied Sciences (Switzerland), 12(21), 10803. doi:10.3390/app122110803.

Lienard, A., Hosny, M., Jneid, J., Schuldiner, S., Cellier, N., Sotto, A., La Scola, B., Lavigne, J.-P., & Pantel, A. (2021). Escherichia coli Isolated from Diabetic Foot Osteomyelitis: Clonal Diversity, Resistance Profile, Virulence Potential, and Genome Adaptation. Microorganisms, 9(2), 380. doi:10.3390/microorganisms9020380.

Mohamed, W. F., Askora, A. A., Mahdy, M. M. H., EL-Hussieny, E. A., & Abu-Shady, H. M. (2022). Isolation and Characterization of Bacteriophages Active against Pseudomonas aeruginosa Strains Isolated from Diabetic Foot Infections. Archives of Razi Institute, 77(6), 2187–2200. doi:10.22092/ARI.2022.359032.2357.

Panigrahy, S. K., Bhatt, R., & Kumar, A. (2021). Targeting type II diabetes with plant terpenes: the new and promising antidiabetic therapeutics. Biologia, 76(1), 241–254. doi:10.2478/s11756-020-00575-y.

Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A. H., & Jaremko, M. (2020). Important flavonoids and their role as a therapeutic agent. Molecules, 25(22), 5243. doi:10.3390/molecules25225243.

Santos, E. L., Maia, B. H. L. N. S., Ferriani, A. P., & Teixeira, S. D. (2017). Flavonoids: Classification, Biosynthesis and Chemical Ecology. Flavonoids - From Biosynthesis to Human Health, IntechOpen, London, United Kingdom. doi:10.5772/67861.

Suhartati, T., Fatimah, N., Yandri, Y., Kurniawan, R., Bahri, S., & Hadi, S. (2021). The anticancer, antimalarial, and antibacterial activities of moracalkon a isolated from Artocarpus kemando Miq. Journal of Advanced Pharmacy Education and Research, 11(4), 105–110. doi:10.51847/9NHxpCqzUD.

Suhartati, T., Epriyanti, E., Borisha, I., Yandri, Suwandi, J. F., Yuwono, S. D., Qudus, H. I., & Hadi, S. (2020). In vivo antimalarial test of artocarpin and in vitro antimalarial test of artonin M isolated from artocarpus. Revista de Chimie, 71(5), 400–408. doi:10.37358/RC.20.5.8150.

Suhartati, T., Hernawan, Suwandi, J. F., Yandri, & Hadi, S. (2018). Isolation of Artonin E From the Root Bark of Artocarpus Rigida, Synthesis of Artonin E Acetate and Evaluation of Anticancer Activity. Macedonian Journal of Chemistry and Chemical Engineering, 37(1), 35–42. doi:10.20450/mjcce.2018.1406.

Septama, A., Jantan, I., Panichayupakaranant, P., Aluwi, M. F. M., & Rahmi, E. (2020). Immunosuppressive and antibacterial activities of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Asian Pacific Journal of Tropical Biomedicine, 10(8), 361. doi:10.4103/2221-1691.287162.

Hashim, N., Rahmani, M., Sukari, M. A., Ali, A. M., Alitheen, N. B., Go, R., & Ismail, H. B. M. (2010). Two new xanthones from Artocarpus obtusus. Journal of Asian Natural Products Research, 12(2), 106–112. doi:10.1080/10286020903450411.

Shamaun, S. S., Rahmani, M., Hashim, N. M., Ismail, H. B. M., Sukari, M. A., Lian, G. E. C., & Go, R. (2010). Prenylated flavones from Artocarpus altilis. Journal of Natural Medicines, 64(4), 478–481. doi:10.1007/s11418-010-0427-4.

Ee, G. C. L., Teo, S. H., Rahmani, M., Lim, C. K., Lim, Y. M., & Go, R. (2011). Artomandin, a new xanthone from Artocarpus kemando (Moraceae). Natural Product Research, 25(10), 995–1003. doi:10.1080/14786419.2010.534471.

Seo, E. K., Lee, D., Young, G. S., Chai, H. B., Navarro, H. A., Kardono, L. B. S., Rahman, I., Cordell, G. A., Farnsworth, N. R., Pezzuto, J. M., Kinghorn, A. D., Wani, M. C., & Wall, M. E. (2003). Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Archives of Pharmacal Research, 26(2), 124–127. doi:10.1007/bf02976656.

Suhartati, T., Andriyani, N., Yandri, Y., & Hadi, S. (2023). Xanthoangelol, geranilated chalcone compound, isolation from pudau leaves (Artocarpus kemando Miq.) as antibacterial and anticancer. Physical Sciences Reviews. doi:10.1515/psr-2022-0259.

Lotulung, P. D. N., Mozef, T., Risdian, C., & Darmawan, A. (2014). In vitro antidiabetic activities of extract and isolated flavonoid compounds from Artocarpus altilis (Parkinson) Fosberg. Indonesian Journal of Chemistry, 14(1), 7–11. doi:10.22146/ijc.21261.

Hmidene, A. Ben, Smaoui, A., Abdelly, C., Isoda, H., & Shigemori, H. (2017). Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: Structure-activity relationship and synergistic potential. Bioscience, Biotechnology and Biochemistry, 81(3), 445–448. doi:10.1080/09168451.2016.1254538.

Martinez-Gonzalez, A. I., Díaz-Sánchez, G., de la Rosa, L. A., Bustos-Jaimes, I., & Alvarez-Parrilla, E. (2019). Inhibition of α-amylase by flavonoids: Structure activity relationship (SAR). Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 206, 437–447. doi:10.1016/j.saa.2018.08.057.

Fuwa, H. (1954). A new method for microdetermination of amylase activity by the use of amylose as the substrate. Journal of Biochemistry, 41(5), 583–603. doi:10.1093/oxfordjournals.jbchem.a126476.

Mwakalukwa, R., Amen, Y., Nagata, M., & Shimizu, K. (2020). Postprandial hyperglycemia lowering effect of the isolated compounds from olive mill wastes - An inhibitory activity and kinetics studies on α-glucosidase and α-amylase enzymes. ACS Omega, 5(32), 20070–20079. doi:10.1021/acsomega.0c01622.

Bauer, A. W., Kirby, W. M., Sherris, J. C., & Turck, M. (1966). Antibiotic susceptibility testing by a standardized single disk method. American Journal of Clinical Pathology, 45(4), 493–496. doi:10.1093/ajcp/45.4_ts.493.

Mabry, T., Markham, K. R., & Thomas, M. B. (2012). The systematic identification of flavonoids. Springer Science & Business Media, Berlin, Germany.

Suhartati, T. & Yandri, Y. (2007). Cycloartobilosanthone from stem bark and flavonoids in several parts of Artocarpus dadah which grows in Lampung. Jurnal Sains MIPA, 2(13), 82-86. (In Indonesian).

Sastrohamidjojo, H. (1991). Chromatography. Liberti, Yogyakarta, Indonesia.

Silverstein, R. W., & Bassler, G. C. (1962). Spectrometric identification of organic compounds. Journal of Chemical Education, 39(11), 546–553. doi:10.1021/ed039p546.

Yadav, L. D. S. (2005). Organic Spectroscopy. Springer Science Business Media, Berlin, Germany.

Makmur, L., Syamsurizal, S., Tukiran, T, Syamsu, Y., Achmad, S. A., Aimi, N., Hakim, E. H., Kitajima, M., Mujahidin, D., & Takayama, H. (1999). Artonol B and cycloartobiloxanthone from the plant Artocarpus teysmanii MIQ. Proccedings ITB. 31(2), 63-68.

Nasution, R., Bahi, M., Saidi, N., & Junina, I. (2015, November). β-Sitosterol from Bark of Artocarpus camansi and its Antidiabetic Activity. Proceedings of The Annual International Conference, 9-11 September, 20 5, Banda Aceh, Indonesian.

Idris, M., Sukandar, E. R., Purnomo, A. S., Martak, F., & Fatmawati, S. (2022). Antidiabetic, cytotoxic and antioxidant activities of Rhodomyrtus tomentosa leaf extracts. RSC Advances, 12(39), 25697–25710. doi:10.1039/d2ra03944c.

Mahnashi, M. H., Alqahtani, Y. S., Alqarni, A. O., Alyami, B. A., Alqahtani, O. S., Jan, M. S., Hussain, F., Islam, Z. U., Ullah, F., Ayaz, M., Abbas, M., Rashid, U., & Sadiq, A. (2022). Phytochemistry, anti-diabetic and antioxidant potentials of Allium consanguineum Kunth. BMC Complementary Medicine and Therapies, 22(1), 154. doi:10.1186/s12906-022-03639-5.

Takahama, U., & Hirota, S. (2018). Interactions of flavonoids with α-amylase and starch slowing down its digestion. Food & Function, 9(2), 677–687. doi:10.1039/c7fo01539a.

Atjanasuppat, K., Wongkham, W., Meepowpan, P., Kittakoop, P., Sobhon, P., Bartlett, A., & Whitfield, P. J. (2009). In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand. Journal of Ethnopharmacology, 123(3), 475–482. doi:10.1016/j.jep.2009.03.010.

Losuwannarak, N., Sritularak, B., & Chanvorachote, P. (2018). Cycloartobiloxanthone induces human lung cancer cell apoptosis via mitochondria-dependent apoptotic pathway. In Vivo, 32(1), 71–78. doi:10.21873/invivo.11206.

Jiang, C. H., Sun, T. L., Xiang, D. X., Wei, S. S., & Li, W. Q. (2018). Anticancer activity and mechanism of xanthohumol: A prenylated flavonoid from hops (Humulus lupulus L.). Frontiers in Pharmacology, 9. doi:10.3389/fphar.2018.00530.

Chethankumara, G. P., Nagaraj, K., & Krishna, V. (2021). In vitro cytotoxic potential of alkaloid and flavonoid rich fractions of alseodaphne semecarpifolia against MCF-7 cells. Biomedical and Pharmacology Journal, 14(2), 557–565. doi:10.13005/bpj/2158.

Nugraha, A. T., Ramadani, A. P., Werdyani, S., Pratiwi, I. A., Juniardy, T., Arfadila, S., & Mahardhika, M. R. P. (2021). Cytotoxic activity of flavonoid from local plant Eriocaulon cinereum R.B against MCF-7 breast cancer cells. Journal of Advanced Pharmaceutical Technology & Research, 12(4), 425–429. doi:10.4103/japtr.japtr_69_21.

Slika, H., Mansour, H., Wehbe, N., Nasser, S. A., Iratni, R., Nasrallah, G., Shaito, A., Ghaddar, T., Kobeissy, F., & Eid, A. H. (2022). Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomedicine & Pharmacotherapy, 146, 112442. doi:10.1016/j.biopha.2021.112442.

Davis, W. W., & Stout, T. R. (1971). Disc Plate Method of Microbiological Antibiotic Assay. Applied Microbiology, 22(4), 659–665. doi:10.1128/am.22.4.659-665.1971.

Wu, X., Tang, Y., Osman, E. E. A., Wan, J., Jiang, W., Yang, G., Xiong, J., Zhu, Q., & Hu, J. F. (2022). Bioassay-Guided Isolation of New Flavonoid Glycosides from Platanus × acerifolia Leaves and Their Staphylococcus aureus Inhibitory Effects. Molecules, 27(17), 5357. doi:10.3390/molecules27175357.

Yu, J. S., Kim, J. H., Rashan, L., Kim, I., Lee, W., & Kim, K. H. (2021). Potential Antimicrobial Activity of Galloyl-Flavonoid Glycosides from Woodfordia uniflora Against Methicillin-Resistant Staphylococcus aureus. Frontiers in Microbiology, 12, 784504. doi:10.3389/fmicb.2021.784504.

Iwansyah, A. C., Desnilasari, D., Agustina, W., Pramesti, D., Indriati, A., Mayasti, N. K. I., Andriana, Y., & Kormin, F. B. (2021). Evaluation on the physicochemical properties and mineral contents of averrhoa bilimbi l. Leaves dried extract and its antioxidant and antibacterial capacities. Food Science and Technology (Brazil), 41(4), 987–992. doi:10.1590/fst.15420.

Abdallah, M. S., Mustafa, M., Nallappan, M. A., Choi, S., Paik, J. H., & Rusea, G. (2021). Determination of Phenolics and Flavonoids of Some Useful Medicinal Plants and Bioassay-Guided Fractionation Substances of Sclerocarya birrea (A. Rich) Hochst Stem (Bark) Extract and Their Efficacy Against Salmonella typhi. Frontiers in Chemistry, 9, 670530. doi:10.3389/fchem.2021.670530.

Bouarab-Chibane, L., Forquet, V., Lantéri, P., Clément, Y., Léonard-Akkari, L., Oulahal, N., Degraeve, P., & Bordes, C. (2019). Antibacterial properties of polyphenols: Characterization and QSAR (Quantitative structure-activity relationship) models. Frontiers in Microbiology, 10. doi:10.3389/fmicb.2019.00829.


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DOI: 10.28991/ESJ-2024-08-01-04

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