Abstract
Background: Ginseng (Panax ginseng) is a herb of medicinal and nutritional importance. Ginseng has been used since ancient times for the treatment of numerous ailments as it has many therapeutic properties. Several phytoconstituents are present in Panax ginseng that possess a variety of beneficial pharmacological properties.
Objective: To explore the potential of phytoconstituents of Panax ginseng in the treatment of depression, a molecular modeling technique was utilized targeting monoamine oxidase-A (MAO-A).
Methods: A total of sixty-one phytoconstituents of ginseng were drawn with the help of ChemBioDraw Ultra 12.0 software and PDBs for MAO-A enzyme were retrieved from the RCSB PDB database. The prepared ligands were screened for MAO-A properties using the software Molegro Virtual Docker (MVD 2010.4.1.0). All the prepared ligands were evaluated for drug-likeliness properties using Swiss ADME.
Results: Among the docking studies of 60 Ginseng phytochemicals including one standard, 15 phytoconstituents with the highest dock score and better binding interactions were selected further for absorption, distribution, metabolism and excretion (ADME) studies. Stachyose (-227.287, 17 interactions), Raffinose (-222.157, 14 interactions), and Ginsenoside Rg1 (-216.593, 10 interactions) were found to possess better interactions as compared to Clorgyline taken as a standard drug.
Conclusion: Stachyose was found to be the most potent inhibitor of MAO-A enzyme under investigation and can be a potential lead molecule for the development of newer phytochemical-based treatment of depression.
Graphical Abstract
[1]
Attele, A.S.; Wu, J.A.; Yuan, C.S. Ginseng pharmacology. Biochem. Pharmacol., 1999, 58(11), 1685-1693.
[http://dx.doi.org/10.1016/S0006-2952(99)00212-9] [PMID: 10571242]
[http://dx.doi.org/10.1016/S0006-2952(99)00212-9] [PMID: 10571242]
[2]
Coon, J.T.; Ernst, E. Panax ginseng. Drug Saf., 2002, 25(5), 323-344.
[http://dx.doi.org/10.2165/00002018-200225050-00003] [PMID: 12020172]
[http://dx.doi.org/10.2165/00002018-200225050-00003] [PMID: 12020172]
[4]
Ru, W.; Wang, D.; Xu, Y.; He, X.; Sun, Y.E.; Qian, L.; Zhou, X.; Qin, Y. Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.). Drug Discov. Ther., 2015, 9(1), 23-32.
[http://dx.doi.org/10.5582/ddt.2015.01004] [PMID: 25788049]
[http://dx.doi.org/10.5582/ddt.2015.01004] [PMID: 25788049]
[5]
Liu, H.; Lu, X.; Hu, Y.; Fan, X. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacol. Res., 2020, 161, 105263.
[http://dx.doi.org/10.1016/j.phrs.2020.105263] [PMID: 33127555]
[http://dx.doi.org/10.1016/j.phrs.2020.105263] [PMID: 33127555]
[6]
Lee, S.Y.; Kim, Y.K.; Park, N.I.; Kim, C.S.; Lee, C.Y.; Park, S.U. Chemical constituents and biological activities of the berry of Panax ginseng. J. Med. Plants Res., 2010, 4(5), 349-353.
[7]
In, G.; Ahn, N.G.; Bae, B.S.; Lee, M.W.; Park, H.W.; Jang, K.H.; Cho, B.G.; Han, C.K.; Park, C.K.; Kwak, Y.S. In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng. J. Ginseng Res., 2017, 41(3), 361-369.
[http://dx.doi.org/10.1016/j.jgr.2016.07.004] [PMID: 28701878]
[http://dx.doi.org/10.1016/j.jgr.2016.07.004] [PMID: 28701878]
[8]
Qi, L.W.; Wang, C.Z.; Yuan, C.S. Isolation and analysis of ginseng: Advances and challenges. Nat. Prod. Rep., 2011, 28(3), 467-495.
[http://dx.doi.org/10.1039/c0np00057d] [PMID: 21258738]
[http://dx.doi.org/10.1039/c0np00057d] [PMID: 21258738]
[9]
Hou, J.P. The chemical constituents of ginseng plants. Comp. Med. East West, 1977, 5(2), 123-145.
[PMID: 608333]
[PMID: 608333]
[10]
Yun, T.K.; Lee, Y.S.; Lee, Y.H.; Kim, S.I.; Yun, H.Y. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J. Korean Med. Sci., 2001, 16(Suppl.), S6-S18.
[http://dx.doi.org/10.3346/jkms.2001.16.S.S6] [PMID: 11748383]
[http://dx.doi.org/10.3346/jkms.2001.16.S.S6] [PMID: 11748383]
[11]
Sun, Y.; Yang, Y.; Liu, S.; Yang, S.; Chen, C.; Lin, M.; Zeng, Q.; Long, J.; Yao, J.; Yi, F.; Meng, L.; Ai, Q.; Chen, N. New therapeutic approaches to and mechanisms of ginsenoside rg1 against neurological diseases. Cells, 2022, 11(16), 2529.
[http://dx.doi.org/10.3390/cells11162529] [PMID: 36010610]
[http://dx.doi.org/10.3390/cells11162529] [PMID: 36010610]
[12]
Kim, D.H. Chemical diversity of panax ginseng, panax quinquifolium, and panax notoginseng. J. Ginseng Res., 2012, 36(1), 1-15.
[http://dx.doi.org/10.5142/jgr.2012.36.1.1] [PMID: 23717099]
[http://dx.doi.org/10.5142/jgr.2012.36.1.1] [PMID: 23717099]
[13]
Mehta, SD; Rathore, P; Rai, G Ginseng: Pharmacological action and phytochemistry prospective. In: Ginseng in Medicine; Intech, 2021.
[http://dx.doi.org/10.5772/intechopen.99646]
[http://dx.doi.org/10.5772/intechopen.99646]
[14]
Hou, J.H.; Shin, H.; Shin, H.; Kil, Y.; Yang, D.H.; Park, M.K.; Lee, W.; Seong, J.Y.; Lee, S.H.; Cho, H.S.; Yuk, S.H.; Lee, K.Y. Influence of Panax ginseng formulation on skin microbiota: A randomized, split face comparative clinical study. J. Ginseng Res., 2022, 46(2), 296-303.
[http://dx.doi.org/10.1016/j.jgr.2021.12.002] [PMID: 35509819]
[http://dx.doi.org/10.1016/j.jgr.2021.12.002] [PMID: 35509819]
[15]
Checkoway, H.; Lundin, J.I.; Kelada, S.N. Neurodegenerative diseases. IARC Sci. Publ., 2011, (163), 407-419.
[PMID: 22997874]
[PMID: 22997874]
[16]
Finberg, J.; Youdim, M.B. Selective mao a and b inhibitors: Their mechanism of action and pharmacology. Neuropharmacology, 1983, 22(3), 441-446.
[http://dx.doi.org/10.1016/0028-3908(83)90194-6] [PMID: 6304562]
[http://dx.doi.org/10.1016/0028-3908(83)90194-6] [PMID: 6304562]
[17]
Wadood, A.; Ahmed, N.; Shah, L.; Ahmad, A.; Hassan, H.; Shams, S. In-silico drug design: An approach which revolutionarised the drug discovery process. OA Drug Des Deliv, 2013, 1(1), 3.
[18]
Karmazyn, M.; Gan, X.T. Chemical components of ginseng, their biotransformation products and their potential as treatment of hypertension. Mol. Cell. Biochem., 2021, 476(1), 333-347.
[http://dx.doi.org/10.1007/s11010-020-03910-8] [PMID: 32940821]
[http://dx.doi.org/10.1007/s11010-020-03910-8] [PMID: 32940821]
[19]
Lee, S.M.; Bae, B.S.; Park, H.W.; Ahn, N.G.; Cho, B.G.; Cho, Y.L.; Kwak, Y.S. Characterization of korean red ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. J. Ginseng Res., 2015, 39(4), 384-391.
[http://dx.doi.org/10.1016/j.jgr.2015.04.009] [PMID: 26869832]
[http://dx.doi.org/10.1016/j.jgr.2015.04.009] [PMID: 26869832]
[20]
Rani, N.; Singh, R.; Kumar, P. Molecular modeling study for the evaluation of natural compounds as potential lanosterol 14α-demethylase inhibitors. Lett. Drug Des. Discov., 2022, 19(5), 459-471.
[http://dx.doi.org/10.2174/1570180818666211027114007]
[http://dx.doi.org/10.2174/1570180818666211027114007]
[21]
Rani, N; Kumar, P; Singh, R. Molecular modeling studies of halogenated imidazoles against 14α-demethylase from candida albicans for treating fungal infections. Infect. Disord. Drug Targets, 2020, 21(1), 90-117.
[22]
Rani, N.; Dahiya, R.S.; Kumar, P. In silico studies of plant-derived bioactive compounds of wedelia species. Antiinfect. Agents, 2022, 20(5), e170522204885.
[http://dx.doi.org/10.2174/2211352520666220517094604]
[http://dx.doi.org/10.2174/2211352520666220517094604]
