Identification of alkaloid compounds arborinine and graveoline from ruta angustifolia (L) pers for their antifungal potential against isocitrate lyase (ICL1) gene of Candida Albicans

Sandai, Doblin

Identification of alkaloid compounds arborinine and graveoline from ruta angustifolia (L) pers for their antifungal potential against isocitrate lyase (ICL1) gene of Candida Albicans

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Title

Identification of alkaloid compounds arborinine and graveoline from ruta angustifolia (L) pers for their antifungal potential against isocitrate lyase (ICL1) gene of Candida Albicans

Type

Article

Main Author

Sandai, Doblin

Additional Authors

Sandai, Rosline

Subject

P Language and Literature

ISSN

0301-486X

Language Code

eng

Bibliographic Details

Place of Production

Tanjung Malim

Publisher

Fakulti Bahasa Dan Komunikasi

Year of publication

2021

Notes

Mycopathologia

Degree Type

Others

Corporate Name

Universiti Pendidikan Sultan Idris

HTTP Link

Access Web Resource

Abstract

Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrient-limited host. The long term usage of fungistatic drugs and the lack of cidal drugs frequently result in strains that could resist commonly used antifungals and display multidrug resistance (MDR). In search of potential therapeutic intervention and novel fungicidals, we have explored a plant alkaloids, namely arborinine and graveoline for its antifungal potential. Alkaloids belongs to Rutaceae family have been reported with numerous antimicrobial activities. In this study, we aimed to isolate and identify the antifungal active alkaloids of R. angustifolia and assess antifungal effect targeting C. albicans isocitrate lyase (ICL) gene which regulates isocitrate lyase, key enzyme in glyoxylate cycle contributing to the virulence potential of C. albicans. Alkaloids were extracted by bioassay guided isolation technique which further identified by TLC profile and compared with the standard through HPLC and NMR analysis. The antifungal activities of the extracted alkaloids were quantified by means of MIC (Minimum Inhibitory Concentration). The gene expression of the targeted gene upon treatment was analysed using RT-qPCR and western blot. Additionally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the isolated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound significantly inhibited the growth of C. albicans at the dose of 250 to 500��g/mL which confirm its antifungal activity. Each alkaloid was found to successfully downregulate the expression of both ICL1 gene CaIcl1 protein. Finally, ADMET analysis suggests a good prediction of chemical properties, namely absorption, distribution, metabolism, excretion and toxicity (ADMET) that will contribute in drug discovery and development later on. ? 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.

References

Adamska-Szewczyk, A., Glowniak, K., & Baj, T. (2016). Furochinoline alkaloids in plants from rutaceae family - A review. Current Issues in Pharmacy and Medical Sciences, 29(1), 33-38. doi:10.1515/cipms-2016-0008

Alotaibi, S. M., Saleem, M. S., & Al-humaidi, J. G. (2018). Phytochemical contents and biological evaluation of ruta chalepennsis L. growing in saudi arabia. Saudi Pharmaceutical Journal, 26(4), 504-508. doi:10.1016/j.jsps.2018.02.008

Brown, A. J. P., Brown, G. D., Netea, M. G., & Gow, N. A. R. (2014). Metabolism impacts upon candida immunogenicity and pathogenicity at multiple levels. Trends in Microbiology, 22(11), 614-622. doi:10.1016/j.tim.2014.07.001

Brown, A. J. P., Budge, S., Kaloriti, D., Tillmann, A., Jacobsen, M. D., Yin, Z., . . . Leach, M. D. (2014). Stress adaptation in a pathogenic fungus. Journal of Experimental Biology, 217(1), 144-155. doi:10.1242/jeb.088930

Carrara, V. S., Filho, L. C., Garcia, V. A. S., Faiões, V. S., Cunha-Júnior, E. F., Torres-Santos, E. C., & Cortez, D. A. G. (2017). Supercritical fluid extraction of pyrrolidine alkaloid from leaves of piper amalago L. Evidence-Based Complementary and Alternative Medicine, 2017 doi:10.1155/2017/7401748

Cheah, H. -., Lim, V., & Sandai, D. (2014). Inhibitors of the glyoxylate cycle enzyme ICL1 in candida albicans for potential use as antifungal agents. PLoS ONE, 9(4) doi:10.1371/journal.pone.0095951

Espinel-Ingroff, A., Chaturvedi, V., Fothergill, A., & Rinaldi, M. G. (2002). Optimal testing conditions for determining MICs and minimum fungicidal concentrations of new and established antifungal agents for uncommon molds: NCCLS collaborative study. Journal of Clinical Microbiology, 40(10), 3776-3781. doi:10.1128/JCM.40.10.3776-3781.2002

Ganan, M., Lorentzen, S. B., Agger, J. W., Heyward, C. A., Bakke, O., Knutsen, S. H., . . . Sørlie, M. (2019). Antifungal activity of well-defined chito-oligosaccharide preparations against medically relevant yeasts. PLoS ONE, 14(1) doi:10.1371/journal.pone.0210208

Ghosh, S., Bishayee, K., & Khuda-Bukhsh, A. R. (2014). Graveoline isolated from ethanolic extract of ruta graveolens triggers apoptosis and autophagy in skin melanoma cells: A novel apoptosis-independent autophagic signaling pathway. Phytotherapy Research, 28(8), 1153-1162. doi:10.1002/ptr.5107

Happi, E. N., Waffo, A. F. K., Wansi, J. D., Ngadjui, B. T., & Sewald, N. (2011). O-prenylated acridone alkaloids from the stems of balsamocitrus paniculata (rutaceae). Planta Medica, 77(9), 934-938. doi:10.1055/s-0030-1250692

Hicham, B. (2019). Yield chemical composition and so antibacterial activity of ruta chalepensis L. essential oil growing spontaneously in algeria. Pharmacy & Pharmacology Int.J, 7(1), 33-36. Retrieved from www.scopus.com

Ishola, O. A., Ting, S. Y., Tabana, Y. M., Ahmed, M. A., Yunus, M. A., Mohamed, R., . . . Sandai, D. (2016). The role of isocitrate lyase (ICL1) in the metabolic adaptation of candida albicans biofilms. Jundishapur Journal of Microbiology, 9(9) doi:10.5812/jjm.38031

Kamal, L. Z. M., Hassan, N. M., Taib, N. M., & Soe, M. K. (2018). Graveoline from ruta angustifolia (L.) pers. and its antimicrobial synergistic potential in erythromycin or vancomycin combinations. Sains Malaysiana, 47(10), 2429-2435. doi:10.17576/jsm-2018-4710-19

Laina Zarisa, M. K., Norazian, M. H., & Nurhayaposter, M. K. S. (2009). Bioassay Guided Isolation of Antimicrobial Active Alkaloid from Ruta Angustifolia [POSTER].in: 4Th National Medical Microbiology Seminar and Workshop.Uni.Putra Malaysia, Retrieved from www.scopus.com

Lam, P., Kok, S. H. L., Lee, K. K. H., Lam, K. H., Hau, D. K. P., Wong, W. Y., . . . Chui, C. H. (2016). Sensitization of candida albicans to terbinafine by berberine and berberrubine. Biomedical Reports, 4(4), 449-452. doi:10.3892/br.2016.608

Lewis, R. E., Lund, B. C., Klepser, M. E., Ernst, E. J., & Pfaller, M. A. (1998). Assessment of antifungal activities of fluconazole and amphotericin b administered alone and in combination against candida albicans by using a dynamic in vitro mycotic infection model. Antimicrobial Agents and Chemotherapy, 42(6), 1382-1386. doi:10.1128/aac.42.6.1382

Liu, X., Ma, Z., Zhang, J., & Yang, L. (2017). Antifungal compounds against candida infections from traditional chinese medicine. BioMed Research International, 2017 doi:10.1155/2017/4614183

Lorenz, M. C., & Fink, G. R. (2001). The glyoxylate cycle is required for fungal virulence. Nature, 412(6842), 83-86. doi:10.1038/35083594

Ncube, N. S., Afolayan, A. J., & Okoh, A. I. (2008). Assessment techniques of antimicrobial properties of natural compounds of plant origin: Current methods and future trends. African Journal of Biotechnology, 7(12), 1797-1806. doi:10.5897/AJB07.613

Nordin, M. -. -., Himratul-Aznita, W. H., & Abdul Razak, F. (2013). Antifungal susceptibility and growth inhibitory response of oral candida species to brucea javanica linn. extract. BMC Complementary and Alternative Medicine, 13 doi:10.1186/1472-6882-13-342

Pfaller, M. A., Diekema, D. J., Jones, R. N., Messer, S. A., & Hollis, R. J. (2002). Trends in antifungal susceptibility of candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY antimicrobial surveillance program, 1997 to 2000. Journal of Clinical Microbiology, 40(3), 852-856. doi:10.1128/JCM.40.3.852-856.2002

Piboonprai, K., Khumkhrong, P., Khongkow, M., Yata, T., Ruangrungsi, N., Chansriniyom, C., & Iempridee, T. (2018). Anticancer activity of arborinine from glycosmis parva leaf extract in human cervical cancer cells. Biochemical and Biophysical Research Communications, 500(4), 866-872. doi:10.1016/j.bbrc.2018.04.175

Pillai-Kastoori, L., Schutz-Geschwender, A. R., & Harford, J. A. (2020). A systematic approach to quantitative western blot analysis. Analytical Biochemistry, 593 doi:10.1016/j.ab.2020.113608

Rahalison, L., Hamburger, M., Hostettmann, K., Monod, M., & Frenk, E. (1991). A bioautographic agar overlay method for the detection of antifungal compounds from higher plants. Phytochemical Analysis, 2(5), 199-203. doi:10.1002/pca.2800020503

Richardson, J. S. M., Sethi, G., Lee, G. S., & Malek, S. N. A. (2016). Chalepin: Isolated from ruta angustifolia L. pers induces mitochondrial mediated apoptosis in lung carcinoma cells. BMC Complementary and Alternative Medicine, 16(1) doi:10.1186/s12906-016-1368-6

Rodriguez-Tudela, J. L. (2008). EUCAST definitive document EDef 7.1: Method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clinical Microbiology and Infection, 14(4), 398-405. doi:10.1111/j.1469-0691.2007.01935.x

Sandjo, L. P., Kuete, V., Tchangna, R. S., Efferth, T., & Ngadjui, B. T. (2014). Cytotoxic benzophenanthridine and furoquinoline alkaloids from zanthoxylum buesgenii (rutaceae). Cardiovascular Intervention and Therapeutics, 8(1) doi:10.1186/s13065-014-0061-4

Shin, D. -., Kim, S., Yang, H. -., & Oh, K. -. (2005). Cloning and expression of isocitrate lyase, a key enzyme of the glyoxylate cycle, of candida albicans for development of antifungal drugs. Journal of Microbiology and Biotechnology, 15(3), 652-655. Retrieved from www.scopus.com

Shodhganga, S. C. I. I., Distribution, T. H. E., Uses, M., Of, M., & Arborea, G. (2008). The distribution, medicinal uses, morphology and identification of glycosmis arborea [roxb.] DC. The Distribution, Medicinal Uses, Morphology and Identification of Herbs, , 95-96. Retrieved from www.scopus.com

Shuib, N. A., Iqbal, A., Sulaiman, F. A., Razak, I., & Susanti, D. (2015). Antioxidant and antibacterial activities of ruta angustifolia extract. Jurnal Teknologi, 77(25), 101-105. doi:10.11113/jt.v77.6747

Tahia, F., Sikder, A. A., Haque, M. R., Jamil, A. S., Awang, K., & Al-mansur, A. (2015). Alkaloids coumarin and cinnamic acid derivative from. Dhaka Univ J Pharm Sci, 2015, 3-7. Retrieved from www.scopus.com

Tajuddin, A. H. A. (2018). Epidemiology and outcomes of candidaemia among adult patients admitted at hospital universiti sains malaysia (HUSM): A 5-year review. International Medical Journal Malaysia, 17(1), 3-12. Retrieved from www.scopus.com

Tian, Y., Zhang, C., & Guo, M. (2017). Comparative study on alkaloids and their anti-proliferative activities from three zanthoxylum species. BMC Complement Altern Med, 2017, 1-16. Retrieved from www.scopus.com

Tripathi, S. K., Xu, T., Feng, Q., Avula, B., Shi, X., Pan, X., . . . Agarwal, A. K. (2017). Two plant-derived aporphinoid alkaloids exert their antifungal activity by disrupting mitochondrial iron-sulfur cluster biosynthesis. Journal of Biological Chemistry, 292(40), 16578-16593. doi:10.1074/jbc.M117.781773

Tzar, M. N. K., Suhaila, B., Shamsul, A. S., & Azizah, M. (2013). Epidemiology of fungal infections at an infectious disease reference centre in malaysia. International Medical Journal Malaysia, 12(1), 39-42. Retrieved from www.scopus.com

Varamini, P., Doroudchi, M., Mohagheghzadeh, A., Soltani, M., Ghaderi, A., & Doroudchi, M. (2008). Cytotoxic evaluation of four haplophyllum. species with various tumor cell lines cytotoxic evaluation of four haplophyllum species with various. Pharm Biol, 45, 0209. Retrieved from www.scopus.com

Varamini, P., Soltani, M., & Ghaderi, A. (2009). Cell cycle analysis and cytotoxic potential of ruta graveolens against human tumor cell lines. Neoplasma, 56(6), 490-493. doi:10.4149/neo_2009_06_490

Wahyuni, T. S., Widyawaruyanti, A., Lusida, M. I., Fuad, A., Soetjipto, Fuchino, H., . . . Hotta, H. (2014). Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from ruta angustifolia leaves. Fitoterapia, 99, 276-283. doi:10.1016/j.fitote.2014.10.011

Xu, C., Cheng, F., Chen, L., Du, Z., Li, W., Liu, G., . . . Tang, Y. (2012). In silico prediction of chemical ames mutagenicity. Journal of Chemical Information and Modeling, 52(11), 2840-2847. doi:10.1021/ci300400a