Phytochemical Composition, Biological Activity and Molecular Docking Studies of the Endemic Marrubium trachyticum Boiss.

Year 2024, , 117 - 127, 03.04.2024

Ebru Derelli Tüfekçi , Alişan Gürgiç , Emel Ekinci , Ali Rıza Tüfekçi

https://doi.org/10.19159/tutad.1430407

Abstract

In this study, Marrubium trachyticum Boiss., which is an endemic species for Türkiye, belonging to the genus Marrubium selected from the family Lamiaceae, was examined. The phytochemical composition of hexane and methanol:chloroform (MeOH/CHCl3) (1:1) extracts of M. trachyticum were analyzed quantitatively by GC-MS and LC-MS/MS. Antioxidant activities of the plant extracts and inhibitory activities for various enzymes were determined. In addition, molecular docking studies were performed to understand how the phytochemicals may have an effect on tyrosinase, α-amylase and α-glucosidase enzyme activities. Since there are no studies on the phytochemical composition and bioactivities of M. trachyticum, the data obtained from this study will be recorded for the first time. The chemical composition of the extract of M. trachyticum was determined by GC/MS and the major compound was the dotriacontane with a percentage of 20.23% followed by nonacosane (19.94%). Phenolic compound analysis of MeOH/CHCl3 extract of M. trachyticum plant was carried out quantitatively by LC-MS/MS and rutin (1200 mg kg-1 extract), kaempferol-3-O-glucoside (100.2 mg kg-1extract), hesperidin (75.97 mg kg-1 extract) were found to be the most abundant main compounds in this plant. While no inhibitory effect of M. trachyticum hexane extract was observed on all three enzymes, methanol-chloroform extract showed inhibitory effect on -glycosidase and tyrosinase enzymes. The in vitro and in silico results are evaluated, it is seen that compounds such as rutin, hesperidin and isoquercitrin are more abundant in the extract and have the highest potential to inhibit both enzymes. The present study's results indicate that M. trachyticum is an excellent source of flavonoid components and other bioactive substances that may be responsible for the observed antioxidant and specific enzyme inhibitory effects.

Keywords

Antioxidant activity, chemical content, enzyme inhibition, Marrubium trachyticum, molecular docking

References

• Akther, N., Shawl, A.S., Sultana, S., Chandan, B.K., Akhter, M., 2013. Hepatoprotective activity of Marrubium vulgare against paracetamol induced toxicity. Journal of Pharmacy Research, 7(7): 565-70.
• Amessis-Ouchemoukh, N., Abu-Reidah, I.M., Quirantes-Pine, R., Madani, K., Segura- Carretero, A., 2014. Phytochemical profiling, in vitro evaluation of totalphenolic contents and antioxidant properties of Marrubium vulgare (horehound) leaves of plants growing in Algeria. Industrial Crops and Products, 61: 120-129.
• Anonymous, 2023. PubChem Database. (http://www. pubchem.ncbi.nlm.nih.gov), (Accessed: 24.10.2023).
• Anonymous, 2024. Protein Data Bank. (http://www.rcsb.org), (Accessed: 18.01.2024).
• Argyropoulou, A., Samara, P., Tsitsilonis, O., Skaltsa, H., 2012. Polar constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their cytotoxic/cytostatic activity. Phytotherapy Research, 26(12): 1800-1806.
• Ballesteros-Vivas, D., Alvarez-Rivera, G., Johanna Morantes, S., del Pilar Sanchez-Camargo, A., Ibanez, E., Parada-Alfonso, F., Cifuentes, A., 2019. An integrated approach for the valorization of mango seed kernel: Efficient extraction solvent selection, phytochemical profiling and antiproliferative activity assessment. Food Research International, 126: 108616.
• Boulila, A., Sanaa, A., Salem, I.B., Rokbeni, N., M’rabet, Y., Hosni, K., Fernandez, X., 2015. Antioxidant properties and phenolic variation in wild populations of Marrubium vulgare L. (Lamiaceae). Industrial Crops and Products, 76: 616-622.
• Bursal, E., Yılmaz, M.A., Izol, E., Türkan, F., Atalar, M.N., Murahari, M., Aras, A., Ahmad, M., 2021. Enzyme inhibitory function and phytochemical profile of Inula discoidea using in vitro and in silico methods. Biophysical Chemistry, 277: 1-7.
• Chemsa, A.E., Zellagui, A., Öztürk, M., Erol, E., Ceylan, O., Duru, M.E., Gherraf, N., 2016. Antibiofilm formation, antioxidant and anticholinesterase activities of essential oil and methanol extract of Marrubium deserti de Noé. Journal of Materials and Environmental Science, 7(3): 993-1000.
• Citoglu, G.S., Aksit, F., 2002. Occurrence of marrubiin and ladanein in Marrubium trachyticum Boiss. Biochemical Systematics and Ecology, 30(9): 885-886.
• Dehbashi, Z., Mazaheri, M., Saeedi, S., Sabbagh, S.K., 2015. Antibacterial activity of Marrubium vulgare L. against antibiotic resistance Klebsiella pneumoniae strains. Advanced Herbal Medicine, 1(3): 9-14.
• Demirtas, I., Tufekci, A.R., Yaglioglu, A.S., Elmastas, M., 2017. Studies on the antioxidant and antiproliferative potentials of Cirsium arvense subsp. vestitum. Journal of Food Biochemistry, 41(1): e12299.
• Elberry, A.A., Harraz, F.M., Ghareib, S.A., Gabr, S.A., Nagy, A.A., Abdel-Sattar, E., 2015. Methanolic extract of Marrubium vulgare ameliorates hyperglycemia and dyslipidemia in streptozotocin-induced diabetic rats. International Journal of Diabetes Mellitus, 3(1): 37-44.
• Fabricant, D.S., Farnsworth, N.R., 2001. The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives, 109(1): 69-75.
• Farzaneh, F., Mosaddegh, M., Motamed, S.M., Abdolbaset, G., 2005. Lamiaceae in folk medicine in Iran: from ethnobotany to pharmacology. Iranian Journal of Pharmautical Research, 4(2): 63-79.
• Golmakani, H., Rabbani Nasab, H., Sharifan, M., Kamali, H., Yadollahi, A., 2016. The essential oil composition and antibacterial activity of Marrubium duabense Murata from North Khorassan province, Iran. Journal of Essential Oil Bearing Plants, 19(4): 963-971.
• Hamedeyazdan, S., Sharifi, S., Nazemiyeh, H., Fathiazad, F., 2014. Evaluating antiproliferative and antioxidant activity of Marrubium crassidens. Advanced Pharmaceutical Bulletin, 4(Supp1): 459-464.
• Herrera-Arellano, A., Aguilar-Santamaria, L., Garcia-Hernandez, B., Nicasio-Torres, P., Tortoriello, J., 2004. Clinical trial of Cecropia obtusifolia and Marrubium vulgare leaf extracts on blood glucose and serum lipids in type 2 diabetics. Phytomedicine, 11(7-8): 561-566.
• Irawan, C., Putri, I.D., Sukiman, M., Utami, A., Putri, R.K., Lisandi, A., Pratama, A.N., 2022. Antioxidant activity of DPPH, CUPRAC, and FRAP methods, as well as activity of alpha-glucosidase inhibiting enzymes from Tinospora crispa (L.) stem ultrasonic extract. Pharmacognosy Journal, 14(5): 511-520.
• Islam, M.T., Ali, E.S., Uddin, S.J., Shaw, S., Islam, M.A., Ahmed, M.I., Chandra Shill, M., Karmakar, U.K., Yarla, N.S., Khan, I.N., Billah M.M., Pieczynska, M.D., Zengin, G., Malainer, C., Nicoletti, F., Gulei, D., Berindan-Neagoe, I., Apostolov, A., Banach, M., Yeung, A.W.K., Strzałkowska, N., Marchewka, J., Rengasamy, K.R.R., Horbańczuk, J., Kamal, M.A., Mubarak, M.S., Mishra, S.K., Shilpi, J.A., Atanasov, A.G., 2018. Phytol: A review of biomedical activities. Food and Chemical Toxicology, 121(14): 82-94.
• Karioti, A., Protopappa, A., Megoulas, N., Skaltsa, H., 2007. Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorganic and Medicinal Chemistry, 15(7): 2708-2714.
• Kaurinovic, B., Vlaisavljevic, S., Popovic, M., Vastag, D., Djurendic-Brenesel, M., 2010. Antioxidant properties of Marrubium peregrinum L. (Lamiaceae) essential oil. Molecules, 15(9): 5943-5955.
• Kim, Y.-J., Uyama, H., 2005. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future. Cellular and Molecular Life Sciences, 62(15): 1707-1723.
• Laouer, H., Yabrir, B., Djeridane, A., Yousfi, M., Beldovini, N., Lamamra, M., 2009. Composition, antioxidant and antimicrobial activities of the essential oil of Marrubium deserti. Natural Product Communication, 4(8): 1133-1138.
• Loizzo, M.R., Saab, A.M., Tundis, R., Menichini, F., Bonesi, M., Piccolo, V., Statti, G.A., de Cindio, B., Houghton, P.J., Menichini, F., 2008. In vitro inhibitory activities of plants used in Lebanon traditional medicine against angiotensin converting enzyme (ACE) and digestive enzymes related to diabetes. Journal of Ethnopharmacology, 119(1): 109-116.
• Maiti, B., Bidinger, M., 1981. Performance metrics in machine learning. Journal of Chemical Information and Modeling, 53(9): 1689-1699.
• Mesquita, L.S.S., Luz, T.R.S.A, Mesquita, J.W.C., Coutinho, D.F., Amaral, F.M.M., Ribeiro, M.N.S., Malik, S., 2019. Exploring the anticancer properties of essential oils from family Lamiaceae. Food Reviews International, 35(2): 105-131.
• Mohammadi, S., Piri, K., Dinarvand, M., 2019. Identification of chemical compositions in some medicinal plants by GC/MS analysis. Lebanese Science Journal, 20(1): 161-172.
• Namjoyan, F., Azemi, M.E., Abdollahi, E., Goudarzi, N., Nikan, K., 2015. Angiotensin I converting enzyme ıinhibitory activities of hydroalcoholic extract of Nardostachys jatamansi, Prangos ferulacea and Marrubium vulgare. Jundishapur Journal of Natural Pharmaceutical Products, 10(2): e17255.
• Özyazıcı, G., Uçar, E., Eruygur, N., 2023. Effects of 80% ethanol extract on biological activitie coriander (Coriandrum sativum L.) plant. EU 3rd International Conference on Health, Engineering and Applied Sciences, November 17-19, Tiran, pp. 247-252.
• Petrović, S., Pavlović, M., Maksimović, Z., Milenković, M., Couladis, M., Tzakouc, O., Niketić, M., 2009. Composition and antimicrobial activity of Marrubium incanum Desr. (Lamiaceae) essential oil. Natural Product Communication, 4(3): 431-434.
• Saad, S., Ouafi, S., Chabane, D., 2016. Anti-inflammatory and acute toxicity evaluation of aqueous infusion extract obtained from aerial parts of Marrubium deserti de noé growing in Algeria. African Journal of Traditional, Complementary and Alternative Medicines, 13(1): 71-5.
• Sarikurkcu, C., Kirkan, B., Ozer, M.S., Ceylan, O., Atilgan, N., Cengiz, M., Tepe, B., 2018. Chemical characterization and biological activity of Onosma gigantea extracts. Industrial Crops and Products, 115: 323-329.
• Sarikurkcu, C., Ozer, M. S., Tlili, N., 2020. Comparison of the influence of the solvent on the extraction of the bioactive compounds from Marrubium lutescens using liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Analytical Letters, 53(14): 2222-2234.
• Sarikurkcu, C., Tepe, B., Daferera, D., Polissiou, M., Harmandar, M., 2008. Studies on the antioxidant activity of the essential oil and methanol extract of Marrubium globosum subsp. globosum (Lamiaceae) by three different chemical assays. Bioresource Technology, 99(10): 4239-4246.
• Swantara, M.D., Rita, W.S., Suartha, N., Agustina, K.K., 2019. Anticancer activities of toxic isolate of Xestospongia testudinaria sponge. Veterinary World, 12(9): 1434-1440.
• Tlili, N., Kirkan, B., Sarikurkcu, C., 2019. LC-ESI-MS/MS characterization, antioxidant power and inhibitory effects on a-amylase and tyrosinase of bioactive compounds from hulls of Amygdalus communis: The influence of the extracting solvents. Industrial Crops and Products, 128(1): 147-152.
• Tsvetkov, D., Dmitrenok, A., Tsvetkov, Y.E., Menshov, V., Yashunsky, D., Yashin, A.Y., Yashin, I.Y., Kumar, R., Varshney, V.K., Nifantiev, N.E., 2016. Phenylethanoid glycosides from teak wood knots and their antioxidant activity. Journal of Biologically Active Products from Nature, 6(4): 272-281.
• Tüfekçi, A.R., Akşit, H., Gül, F., Demirtaş, İ., 2018. Determination of phenolic profile of Cirsium arvense (L.) scop. subsp. vestitum (Wimmer et Grab.) petrak plant. Eurasian Journal of Biological and Chemical Sciences, 1(2): 33-36.
• Tüfekçi, A.R., Akşit, H., Şimşek, S., Karakoç, Ö.C., Adem, Ş., Hameed, Z.A., Atalar, M.N., Topkara, A.R., 2023. Evaluation of insecticidal and enzyme activity potentials of essential oils and extracts of Chenopodium botrys against storage products pests. Bulletin of Biotechnology, 4(1): 7-12.
• Ullah, R., Alqahtani, A.S., 2022. GC-MS analysis, heavy metals, biological, and toxicological evaluation of Reseda muricata and Marrubium vulgare methanol extracts. Evidence-Based Complementary and Alternative Medicine, 2284328.
• Uysal, A., Zengin, G., Mahomoodally, M. F., Picot-Allain, C., Jekő, J., Cziáky, Z., Rodrigues, M.J., Ak, G., Polat, R., Urusan, Z., Sinan, K.I., Custodio, L., 2021. A comparative study on biological properties and chemical profiles of different solvent extracts from Centaurea bingoelensis, an endemic plant of Turkey. Process Biochemistry, 102(3): 315-324.
• Venkatachalam, R., Kalimuthu, K., Chinnadurai, V., Saravanan, M., Radhakrishnan, R., Shanmuganathan, R., Pugazhendhi, A., 2020. Various solvent effects on phytochemical constituent profiles, analysis of antioxidant and antidiabetic activities of Hopea parviflora. Process Biochemistry, 89(2): 227-232.
• Yuan, Y., Zhang, J., Fan, J., Clark, J., Shen, P., Li, Y., Zhang, C., 2018. Microwave assisted extraction of phenolic compounds from four economic brown macroalgae species and evaluation of their antioxidant activities and inhibitory effects on a-amylase, a-glucosidase, pancreatic lipase and tyrosinase. Food Research International, 113(11): 288-297.
• Zaabat, N., A. Hay, S. Michalet, N. Darbour, C. Bayet, I. Skandrani, L. Chekir-Ghedira, S. Akkal, Dijoux-Franca, M.G., 2011. Antioxidant and antigenotoxic properties of compounds isolated from Marrubium deserti de Noé. Food and Chemical Toxicology, 49(12): 3328-3335.
• Zhang, H., Tsao, R., 2016. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Current Opinion in Food Science, 8(2): 33-42.
• Zhang, L., Zhao, X., Tao, G.-J., Chen, J., Zheng, Z.-P., 2017. Investigating the inhibitory activity and mechanism differences between norartocarpetin and luteolin for tyrosinase: A combinatory kinetic study and computational simulation analysis. Food Chemistry, 223(10): 40-48.