In vitro cytotoxic evaluation of Hypericum perforatum and molecular docking and dynamic analysis of PINK-1 inhibitors on model organism Tribolium castaneum and Homo sapiens

Year 2024, , 880 - 889, 12.10.2024

Fahriye Ercan , Serap Yalcin , Hatice Baş , Seda Yalçınkaya

https://doi.org/10.30910/turkjans.1440915

Abstract

Hypericum species are especially known for their pharmacological characteristic. One of the major component of the plant is hypericin that can be used in tumor inhibition with its potent cytotoxic effects. In this study, the anticancer effect of H. perforatum essential oil on the MCF-7 breast cancer cell line was examined, and the binding potential of the compounds of Hypericum perforatum L., hypericin, hyperoside and hyperforin, to the PINK1 protein of both human and model organism, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) was investigated in silico. Recently, many insect species have been proposed as model organisms, including T. castaneum, that the first species with whole genome sequenced. Worlwide distribution of insects, their environmental importance and realtively inexpensive cultivation have increased the interest in them Therefore, in in silico studies, T. castaneum was used as a model to compare binding similarities with humans and model organisms. In the study, the IC50 concentration of H. perforatum L. on MCF-7 cells was determined to be 98.765 μg/ml. Based on in silico findings, the most favorable binding affinity of -12.5 kcal/mol was observed between the Hypericin molecule and the insect PINK1 protein. The fact that these plant components bind with high energy to the PINK1 protein, which is believed to guard cells from mitochondrial dysfunction triggered by stress, is promising for the development of plant-based medical drugs and biopesticides.

Keywords

Hypericum perforatum, Tribolium castaneum, anticancer effect, in silico, PINK1

Hypericum perforatum'un in vitro sitotoksik değerlendirmesi ve model organizma Tribolium castaneum ve Homo sapiens üzerindeki PINK-1 inhibitörlerinin moleküler kenetleme ve dinamik analizi

Abstract

Hypericum türleri özellikle farmakolojik özellikleriyle bilinmektedir. Bitkinin ana bileşenlerinden biri, güçlü sitotoksik etkileriyle tümör inhibisyonunda kullanılabilen hiperisindir. Bu çalışmada, bu önemli bitki uçucu yağının MCF-7 meme kanseri hücre hattı üzerindeki antikanser etkisi incelenmiş ve H. perforatum L'un bileşikleri olan hiperisin, hiperosid ve hiperforinin hem insan hem de model organizma, Tribolium castaneum'un (Herbst) (Coleoptera: Tenebrionidae) PINK1 proteinine bağlanma potansiyeli in silico olarak araştırılmıştır. Son zamanlarda, tam genom dizilimi yapılan ilk tür olan T. castaneum da dahil olmak üzere pek çok böcek türü model organizma olarak önerilmiştir. Böceklerin dünya çapındaki dağılımları, çevresel önemleri ve üretimlerinin nispeten ucuz olması onlara olan ilgiyi arttırmıştır. Bu nedenle, in silico çalışmalarda, insan ve model organizma ile bağlanma benzerliklerini karşılaştırmak amacıyla T. castaneum model olarak kullanılmıştır. Çalışmada H. perforatum’un MCF-7 hücrelerindeki IC50 konsantrasyonu 98.765 µg/ml olarak belirlenmiştir. In silico bulgularına göre, -12,5 kcal/mol ile en uygun bağlanma afinitesi Hiperisin molekülü ile böcek PINK1 proteini arasında gözlenmiştir. Söz konusu bitki bileşenlerinin hücreleri stres kaynaklı mitokondriyal fonksiyon bozukluğundan koruduğu düşünülen PINK1 proteinine yüksek enerji ile bağlanıyor olması bitkisel orijinli tıbbi ilaçların ve biyopestisitlerin geliştirlmesi için umut vericidir.

Keywords

Hypericum perforatum, Tribolium castaneum, antikanser etki, in silico, PINK1

Supporting Institution

Kırşehir Ahi Evran Üniversitesi

Thanks

This study was financially supported by the Kırşehir Ahi Evran University Research Fund (Project No: ZRT.A4.19.001).

References

• Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B. and Lindahl, E. 2015. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, 1-2 19-25.
• Agostinis, P., Vantieghem, A., Merlevede, W., de Witte, P.A. 2002. Hypericin in cancer treatment: More light on the way. International Journal of Biochemistry & Cell Biology, 34:221-241.
• Barnes, J., Anderson, L.A., Phillipson, J.D. 2001. St John’s Wort (Hypericum perforatum L.): A review of its chemistry, pharmacology and clinical properties. Journal of Pharmacy and Pharmacology, 53:583-600.
• Bekker, H., Berendsen, H.J.C., Dijkstra. E.J., Achterop, S., van Drunen, R., van der Spoel, D., Sijbers, A., Keegstra, H. et al. 1993. Gromacs: A parallel computer for molecular dynamics simulations; pp. 252–256 in Physics computing 92. Edited by R.A. de Groot and J. Nadrchal. World Scientific, Singapore.
• Bjelkmar, P., Larsson, P., Cuendet, M.A., Hess, B., Lindahl, E. 2010. Implementation of the CHARMM force field in GROMACS: Analysis of protein stability effects from correction maps, virtual interaction sites, and water models. Journal of Chemical Theory and Computation, 6: 459-466.
• Blank, M., Lavie, G., Mandel, M., Hazan, S., Orenstein, A., Meruelo, D., Keisari, Y. 2004. Antimetastatic activity of the photodynamic agent hypericin in the dark. International Journal of Cancer, 111: 596-603.
• Borawska, M.H., Naliwajko, S.K., Moskwa, J., Markiewicz-Żukowska, R., Puścion-Jakubik, A., Soroczyńska, J. 2016. Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG. B.M.C. Complementary and Alternative Medicine, 16: 367.
• Caballero-Gallardo, K., Olivero-Verbel, J., Stashenko, E.E. 2011. Repellent activity of essential oils and some of their individual constituents against Tribolium castaneum Herbst. Journal of Agricultural and Food Chemistry, 59:1690-1696.
• Crockett, S.L., Robson, N.K. 2011. Taxonomyand chemotaxonomy of the genus Hypericum. Medicinal and Aromatic Plant Science andBiotechnology, 5(Special Issue 1), 1-13.
• Çırak, C., Kurt, D. 2014. Hypericum Species as Important Medicinal Plants, Anadolu, J. of AARI, 24 (1) 2014, 42 – 58.
• Ercan, F., Yalçın, S., Baş, H., Yalçınkaya, S., Ercan, N. 2019. Evaluation of Malondialdehyde, Superoxide Dismutase and Catalase Activity of Tribolium castaneum exposed to essential oil of Hypericum perforatum. 2nd International Erciyes Scientific Research Congress, 27-29 September 2019 Kayseri, p: 89.
• Ferreira, A., Proença, C., Serralheiro, M.L., Araújo, M.E. 2006. The in vitro screening for acetylcholinesterase inhibition and antioxidant activity of medicinal plants from Portugal. Journal of Ethnopharmacology, 108:31-7.
• Guedes, A.P., Franklin, G., Fernandes-Ferreira, M. 2012. Hypericum sp.: Essential oil composition and biological activities. Phytochemistry Reviews, 11:127-152.
• Güller, A., Usta, M., Korkmaz, G., Demirel, S. 2024. In Silico and Molecular Analysis of Some Mosaic Diseases on Cucurbit Plants in Iğdır Province, Türkiye. Türk Tarım ve Doğa Bilimleri Dergisi 11(1): 90–103.
• Huang, K., Yang, X.B., Huang, Z.M. 2008. Research progress in pharmacological activities of hyperoside. Herald Med, 28: 1046-1048.
• Jang, M.H., Lee, T.H., Shin, M.C., Bahn, G.H., Kim, J.W., Shin, D.H., Kim, E.H., Kim, C.J. 2002. Protective effect of Hypericum perforatum Linn (St. John's wort) against hydrogen peroxide-induced apoptosis on human neuroblastoma cells. Neuroscience Letters, 329:177-80.
• Jaric, S., Popović, Z., Macukanović-Jocić, M., Djurdjević, L., Mijatović, M., Karadzić, B., Mitrović, M., Pavlović, P. 2007. An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia). Journal of Ethnopharmacology, 111:160-75.
• Khan, A., Islam, M.H., Islam, M.E., Al-Bari, M.A.A., Parvin, M.S., Sayeed, M.A., Islam, M.N., Haque, M.E. 2014. Pesticidal and pest repennency activities of rhizomes of Drynaria quercifolia (J. Smith) against Tribolium castaneum (Herbst). Biological Research, 47:51.
• Kimira, M., Arai, Y., Shimoi, K., Watanabe, S. 1998. Japanese intake of flavonoids and isoflavonoids from foods. Journal of Epidemiology, 8:168-175.
• Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J.L., Dorr, R.O., Shaw, D.E. 2010. Improved side-chain torsion potentials for the AMBER ff99SB protein force field. PROTEINS: Struct. Funct. Gen, 78: 1950-1958.
• McKenna, D.D. 2018. Beetle genomes in the 21st century: prospects, progress and priorities. Current Opinion in Insect Science, 25:76-82.
• Medina, M.A., Martínez-Poveda, B., Amores-Sánchez, M.I., Quesada, A.R. 2006. Hyperforin: More than an antidepressant bioactive compound? Life Sciences, 79: 105–111.
• Mirmalek, S.A., Azizi, M.A., Jangholi, E., Yadollah-Damavandi, S., Javidi, M.A., Parsa, Y., Parsa, T., Salimi-Tabatabaee, S.A., Ghasemzadeh Kolagar, H., Alizadeh-Navaei, R. 2016. Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line. Cancer Cell International, 16:3.
• Miskovsky, P. 2002. Hypericin, a new antiviral and antitumor photosensitizer: mechanism of action and interaction with biological macromolecules. Current Drug Targets, 3: 55-84.
• Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., Olson, A.J. 1998. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19, 1639-1662.
• Oostenbrink, C., Villa, A., Mark, A.E., Van Gunsteren, W.F. 2004. A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6. Journal of Computational Chemistry, 25(13): 1656-1676.
• Parchin, R.A., Ebadollahi, A. 2016. Biological Activities of Hypericum perforatum L. Essential Oil Against Red Flour Beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Journal of Entomology, 13:91-97.
• Rouis, Z., Laamari, A., Abid, N., Elaissi, A., Cioni, P.L., Flamini, G., Aouni, M. 2013. Chemical composition and larvicidal activity of several essential oils from Hypericum species from Tunisia. Parasitology Research, 112:699-705.
• Thomsen, R., Christensen, M.H. 2006. MolDock: a new technique for high-accuracy molecular docking. Journal of Medicinal Chemistry, 49: 3315-3321.
• Tribolium Genome Sequencing Consortium. 2008. The genome of the model beetle and pest Tribolium castaneum. Nature, 452:949-955.
• Trott, O., Olson, A.J. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31: 455-461.
• Yuca, H., Aydın, B., Tekman, E., Göger, G., Karakaya, S., Güvenalp, Z., Özkan, A.M.G. 2022. Peganum harmala L. (Nitrariaceae) Bitkisinin α-Amilaz ve α-Glukozidaz Enzim İnhibisyon, Antioksidan ve Antimikrobiyal Aktivitelerinin Değerlendirilmesi. Türk Tarım ve Doğa Bilimleri Dergisi 9(4): 925–932.
• Zhou, T., Chen, B., Fan, G., Chai, Y., Wu, Y. 2006. Application of high-speed counter-current chromatography coupled with high-performance liquid chromatography–diode array detection for the preparative isolation and purification of hyperoside from Hypericum perforatum with online purity monitoring. Journal of Chromatography A, 1116: 97-101.