Generic placeholder image

Letters in Drug Design & Discovery

Author(s): Raman Yadav, Punnagai Kumaravelu*, Subburaya Umamaheswari, Viswanathan Subramanian and Suvarna Jyoti Kantipudi

DOI: 10.2174/1570180820666230508163010

DownloadDownload PDF Flyer Cite As
Identification of the Secondary Metabolites of Sargassum Tenerrimum and their Molecular Docking Analysis against the Targets of Anxiety, Depression and Cognitive Disorder

Page: [1819 - 1832] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Objective: This article aimed to identify the bioactive compounds present in the brown algae Sargassum tenerrimum using TLC and HPTLC fingerprinting analysis and followed in silico molecular docking against a potential target of anxiety, depression, and cognitive disorder with identified compounds.

Methods: Bioactive compounds were identified from the methanolic extract of Sargassum tenerrimum through TLC and HPTLC fingerprinting analysis. In silico molecular docking against a potential target of anxiety, depression, and cognitive disorder was performed on the latest version of AutoDock Vina v.1.2.0 software. The pharmacokinetic profile and possible bioactivities of the compounds were predicted using SwissADME.

Results: Fucoxanthin, β-Cryptoxanthin, and Canthaxanthin were identified from the brown algae Sargassum tenerrimum through TLC and HPTLC fingerprinting analysis. Fucoxanthin showed the highest fitness score of -9.7 kcal/mol, -9.6 kcal/mol, and -9.7 kcal/mol against the target protein GABA-A, 5ht2c, and AchE, respectively. β-Cryptoxanthin showed the highest fitness score of -9.4 kcal/mol against target SERT compared with Fucoxanthin and Canthaxanthin. Canthaxanthin exhibited the highest fitness score- 7.5 kcal/mol, -9.0 kcal/mol, -9.7 kcal/mol, -9.1 kcal/mol, -9.1 kcal/mol, -7.4 kcal/mol, -7.9 kcal/mol and - 7.6 kcal/mol against the target receptor trkB, 5ht1A, D2, DAT, MOA-A, COMT, NMDA and 7nAchR respectively on the comparing with Fucoxanthin and β-Cryptoxanthin.

Conclusion: In silico docking and ADME analysis concluded that the canthaxanthin acted through various targets and was safer than the fucoxanthin and β-Cryptoxanthin. Hence, canthaxanthin can be the best potential compound in the therapy of neuropsychological disorders.

[1]
Sagar, R.; Dandona, R.; Gururaj, G.; Dhaliwal, R.S.; Singh, A.; Ferrari, A.; Dua, T.; Ganguli, A.; Varghese, M.; Chakma, J.K.; Kumar, G.A.; Shaji, K.S.; Ambekar, A.; Rangaswamy, T.; Vijayakumar, L.; Agarwal, V.; Krishnankutty, R.P.; Bhatia, R.; Charlson, F.; Chowdhary, N.; Erskine, H.E.; Glenn, S.D.; Krish, V.; Mantilla Herrera, A.M.; Mutreja, P.; Odell, C.M.; Pal, P.K.; Prakash, S.; Santomauro, D.; Shukla, D.K.; Singh, R.; Singh, R.K.L.; Thakur, J.S. ThekkePurakkal, A.S.; Varghese, C.M.; Reddy, K.S.; Swaminathan, S.; Whiteford, H.; Bekedam, H.J.; Murray, C.J.L.; Vos, T.; Dandona, L. The burden of mental disorders across the states of India: The Global Burden of Disease Study 1990–2017. Lancet Psychiatry, 2020, 7(2), 148-161.
[http://dx.doi.org/10.1016/S2215-0366(19)30475-4] [PMID: 31879245]
[2]
Dattani, S.; Ritchie, H.; Roser, M. Mental Health. 2021. Available from: https://ourworldindata.org/mental-health'
[3]
Goodwin, G.M. The overlap between anxiety, depression, and obsessive-compulsive disorder. Dialogues Clin. Neurosci., 2015, 17(3), 249-260.
[http://dx.doi.org/10.31887/DCNS.2015.17.3/ggoodwin] [PMID: 26487806]
[4]
Roberts, A.L.; Kubzansky, L.D.; Chibnik, L.B.; Rimm, E.B.; Koenen, K.C. Association of posttraumatic stress and depressive symptoms with mortality in women. JAMA Netw. Open, 2020, 3(12), e2027935.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.27935] [PMID: 33275156]
[5]
Perini, G.; Cotta Ramusino, M.; Sinforiani, E.; Bernini, S.; Petrachi, R.; Costa, A. Cognitive impairment in depression: Recent advances and novel treatments. Neuropsychiatr. Dis. Treat., 2019, 15, 1249-1258.
[http://dx.doi.org/10.2147/NDT.S199746] [PMID: 31190831]
[6]
Lam, R.W.; Kennedy, S.H.; McIntyre, R.S.; Khullar, A. Cognitive dysfunction in major depressive disorder: Effects on psychosocial functioning and implications for treatment. Can. J. Psychiatry, 2014, 59(12), 649-654.
[http://dx.doi.org/10.1177/070674371405901206] [PMID: 25702365]
[7]
Biswas, S.; Mondol, D.; Jodder, P.; Sana, S.; Saleh, M.A.; Tarafdar, A.K.; Islam, F. Evaluation of neurobehavioral activities of ethanolic extract of Psidium guajava Linn leaves in mice model. Future J. Pharmaceut. Sci., 2021, 7(1), 36.
[http://dx.doi.org/10.1186/s43094-021-00188-5]
[8]
Fitton, J.H. Brown marine algae: A survey of therapeutic potentials. Altern. Complement. Ther., 2003, 9(1), 29-33.
[http://dx.doi.org/10.1089/10762800360520767]
[9]
Miyake, Y.; Tanaka, K.; Okubo, H.; Sasaki, S.; Arakawa, M. Seaweed consumption and prevalence of depressive symptoms during pregnancy in Japan: Baseline data from the Kyushu Okinawa Maternal and Child Health Study. BMC Pregnancy Childbirth, 2014, 14(1), 301.
[http://dx.doi.org/10.1186/1471-2393-14-301] [PMID: 25186917]
[10]
Lee, B.; Shim, I.; Lee, H.; Hahm, D.H. Fucoidan prevents depression-like behavior in rats exposed to repeated restraint stress. J. Nat. Med., 2013, 67(3), 534-544.
[http://dx.doi.org/10.1007/s11418-012-0712-5] [PMID: 23090005]
[11]
Monteiro, V.S.; Teles, F.B.; Coura, C.O.; Souza, R.B.; Lima, C.N.C.; Costa, D.V.S.; Honório, Junior, E.R.; Escudeiro, S.S.; Chaves, E.M.C.; Vasconcelos, S.M.M.; Benevídes, N.M.B. Involvement of the GABAergic system in the anxiolytic effect of sulfated polysaccharides from the red seaweed Gracilaria cornea. J. Appl. Phycol., 2016, 28(3), 1997-2004.
[http://dx.doi.org/10.1007/s10811-015-0724-0]
[12]
Diers, J.A.; Ivey, K.D.; El-Alfy, A.; Shaikh, J.; Wang, J.; Kochanowska, A.J.; Stoker, J.F.; Hamann, M.T.; Matsumoto, R.R. Identification of antidepressant drug leads through the evaluation of marine natural products with neuropsychiatric pharmacophores. Pharmacol. Biochem. Behav., 2008, 89(1), 46-53.
[http://dx.doi.org/10.1016/j.pbb.2007.10.021] [PMID: 18037479]
[13]
Suganthy, N.; Karutha Pandian, S.; Pandima Devi, K. Neuroprotective effect of seaweeds inhabiting South Indian coastal area (Hare Island, Gulf of Mannar Marine Biosphere Reserve): Cholinesterase inhibitory effect of Hypnea valentiae and Ulva reticulata. Neurosci. Lett., 2010, 468(3), 216-219.
[http://dx.doi.org/10.1016/j.neulet.2009.11.001] [PMID: 19897016]
[14]
Yoon, N.Y.; Chung, H.Y.; Kim, H.R.; Choi, J.S. Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera. Fish. Sci., 2008, 74(1), 200-207.
[http://dx.doi.org/10.1111/j.1444-2906.2007.01511.x]
[15]
Bhargava, A.; Shrivastava, P.; Tilwari, A. HPTLC analysis of Fumaria parviflora (Lam.) methanolic extract of whole plant. Future J. Pharmaceut. Sci., 2021, 7(1), 1-9.
[http://dx.doi.org/10.1186/s43094-020-00150-x]
[16]
Salo-Ahen, O.M.H.; Alanko, I.; Bhadane, R.; Bonvin, A.M.J.J.; Honorato, R.V.; Hossain, S.; Juffer, A.H.; Kabedev, A.; Lahtela-Kakkonen, M.; Larsen, A.S.; Lescrinier, E.; Marimuthu, P.; Mirza, M.U.; Mustafa, G.; Nunes-Alves, A.; Pantsar, T.; Saadabadi, A.; Singaravelu, K.; Vanmeert, M. Molecular dynamics simulations in drug discovery and pharmaceutical development. Processes (Basel), 2020, 9(1), 71.
[http://dx.doi.org/10.3390/pr9010071]
[17]
Elias, E.; Zhang, A.Y.; Manners, M.T. Novel pharmacological approaches to the treatment of depression. Life (Basel), 2022, 12(2), 196.
[http://dx.doi.org/10.3390/life12020196] [PMID: 35207483]
[18]
Leelananda, S.P.; Lindert, S. Computational methods in drug discovery. Beilstein J. Org. Chem., 2016, 12(1), 2694-2718.
[http://dx.doi.org/10.3762/bjoc.12.267] [PMID: 28144341]
[19]
Albratty, M.; Alhazmi, H.A.; Meraya, A.M.; Najmi, A.; Alam, M.S.; Rehman, Z.; Moni, S.S. Spectral analysis and Antibacterial activity of the bioactive principles of Sargassum tenerrimum J. Agardh collected from the Red sea, Jazan, Kingdom of Saudi Arabia. Braz. J. Biol., 2023, 83, e249536.
[http://dx.doi.org/10.1590/1519-6984.249536] [PMID: 34669913]
[20]
Mtunzi, F.M.; Ejidike, I.P.; Ledwaba, I.; Ahmed, A.; Pakade, V.E.; Klink, M.J.; Modise, S.J. Solvent–solvent fractionations of Combretum erythrophyllum (Burch.) leave extract: Studies of their antibacterial, antifungal, antioxidant and cytotoxicity potentials. Asian Pac. J. Trop. Med., 2017, 10(7), 670-679.
[http://dx.doi.org/10.1016/j.apjtm.2017.07.007] [PMID: 28870343]
[21]
Rajauria, G.; Abu-Ghannam, N. Isolation and partial characterization of bioactive fucoxanthin from Himanthalia elongata brown seaweed: A TLC-based approach. Int. J. Anal. Chem., 2013, 2013, 802573.
[http://dx.doi.org/10.1155/2013/802573] [PMID: 23762062]
[22]
Rajalakshmi, R.; Lalitha, P.; Sharma, S.C.; Rajiv, A.; Chithambharan, A.; Ponnusamy, A. In silico studies: Physicochemical properties, drug score, toxicity predictions and molecular docking of organosulphur compounds against Diabetes mellitus. J. Mol. Recognit., 2021, 34(11), e2925.
[http://dx.doi.org/10.1002/jmr.2925] [PMID: 34302410]
[23]
Gupta, N.; Choudhary, S.K.; Bhagat, N.; Karthikeyan, M.; Chaturvedi, A. In silico prediction, molecular docking and dynamics studies of steroidal alkaloids of holarrhena pubescens wall. ex G. don to guanylyl cyclase C: Implications in designing of novel antidiarrheal therapeutic strategies. Molecules, 2021, 26(14), 4147.
[http://dx.doi.org/10.3390/molecules26144147] [PMID: 34299422]
[24]
Devaraj, S.N.; Jamuna, S.; Rathinavel, A.; Mohammed Sadullah, S.S. In silico approach to study the metabolism and biological activities of oligomeric proanthocyanidin complexes. Indian J. Pharmacol., 2018, 50(5), 242-250.
[http://dx.doi.org/10.4103/ijp.IJP_36_17] [PMID: 30636827]
[25]
Ralte, L.; Khiangte, L.; Thangjam, N.M.; Kumar, A.; Singh, Y.T. GC–MS and molecular docking analyses of phytochemicals from the underutilized plant, Parkia timoriana revealed candidate anti-cancerous and anti-inflammatory agents. Sci. Rep., 2022, 12(1), 3395.
[http://dx.doi.org/10.1038/s41598-022-07320-2] [PMID: 35233058]
[26]
Simhadri, N.; Muniappan, M.; Kannan, I.; Viswanathan, S. Phytochemical analysis and docking study of compounds present in a polyherbal preparation used in the treatment of dermatophytosis. Curr. Med. Mycol., 2017, 3(4), 6-14.
[http://dx.doi.org/10.29252/cmm.3.4.6] [PMID: 29707673]
[27]
Sahila, M.; Babitha, P.P.; Bandaru, S.; Nayarisseri, A.; Doss, V.A. Molecular docking based screening of GABA (A) receptor inhibitors from plant derivatives. Bioinformation, 2015, 11(6), 280-289.
[http://dx.doi.org/10.6026/97320630011280] [PMID: 26229288]
[28]
Singla, R.K.; Scotti, L.; Dubey, A.K. In silico studies revealed multiple neurological targets for the antidepressant molecule ursolic acid. Curr. Neuropharmacol., 2017, 15(8), 1100-1106.
[PMID: 28034283]
[29]
Casarotto, P.C.; Girych, M.; Fred, S.M.; Kovaleva, V.; Moliner, R.; Enkavi, G.; Biojone, C.; Cannarozzo, C.; Sahu, M.P.; Kaurinkoski, K.; Brunello, C.A.; Steinzeig, A.; Winkel, F.; Patil, S.; Vestring, S.; Serchov, T.; Diniz, C.R.A.F.; Laukkanen, L.; Cardon, I.; Antila, H.; Rog, T.; Piepponen, T.P.; Bramham, C.R.; Normann, C.; Lauri, S.E.; Saarma, M.; Vattulainen, I.; Castrén, E. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell, 2021, 184(5), 1299-1313.e19.
[http://dx.doi.org/10.1016/j.cell.2021.01.034] [PMID: 33606976]
[30]
Waqar, M.; Batool, S. In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer’s disease. J. Venom. Anim. Toxins Incl. Trop. Dis., 2017, 23(1), 42.
[http://dx.doi.org/10.1186/s40409-017-0132-9] [PMID: 28943883]
[31]
Gulsevin, A.; Papke, R.L.; Horenstein, N. In silico modeling of the α7 nicotinic acetylcholine receptor: New pharmacological challenges associated with multiple modes of signaling. Mini Rev. Med. Chem., 2020, 20(10), 841-864.
[http://dx.doi.org/10.2174/1389557520666200130105256] [PMID: 32000651]
[32]
Zulkipli, N.N.; Zakaria, R.; Long, I.; Abdullah, S.F.; Muhammad, E.F.; Wahab, H.A.; Sasongko, T.H. In silico analyses and cytotoxicity study of asiaticoside and asiatic acid from malaysian plant as potential mTOR inhibitors. Molecules, 2020, 25(17), 3991.
[http://dx.doi.org/10.3390/molecules25173991] [PMID: 32887218]
[33]
Eswaramoorthy, R.; Hailekiros, H.; Kedir, F.; Endale, M. In silico molecular docking, DFT analysis and ADMET studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A potent inhibitor for quorum sensing. Adv. Appl. Bioinform. Chem., 2021, 14, 13-24.
[http://dx.doi.org/10.2147/AABC.S290912] [PMID: 33584098]
[34]
Mahendran, S.; Sankaralingam, S.; Sethupathi, S.M.; Kathiresan, D.; Muthumani, M.; Kousalya, L.; Palpperumal, S.; Harinathan, B. Evaluation of antioxidant and cytotoxicity activities of polyphenol extracted from brown seaweed Sargassum tenerrimum biomass. Biom. Conv. Bio-refin., 2022, 17, 1-7.
[35]
Galasso, C.; Orefice, I.; Pellone, P.; Cirino, P.; Miele, R.; Ianora, A.; Brunet, C.; Sansone, C. On the neuroprotective role of astaxanthin: New perspectives? Mar. Drugs, 2018, 16(8), 247.
[http://dx.doi.org/10.3390/md16080247] [PMID: 30042358]
[36]
Lin, J.; Huang, L.; Yu, J.; Xiang, S.; Wang, J.; Zhang, J.; Yan, X.; Cui, W.; He, S.; Wang, Q. Fucoxanthin, a marine carotenoid, reverses scopolamine-induced cognitive impairments in mice and inhibits acetylcholinesterase in vitro. Mar. Drugs, 2016, 14(4), 67.
[http://dx.doi.org/10.3390/md14040067] [PMID: 27023569]
[37]
Zhao, X.; Zhang, S.; An, C.; Zhang, H.; Sun, Y.; Li, Y.; Pu, X. Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death. J. Chin. Pharm. Sci., 2015, 24, 467-474.
[38]
Maeda, H.; Hosokawa, M.; Sashima, T.; Takahashi, N.; Kawada, T.; Miyashita, K. Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Int. J. Mol. Med., 2006, 18(1), 147-152.
[http://dx.doi.org/10.3892/ijmm.18.1.147] [PMID: 16786166]
[39]
Hosokawa, M.; Kudo, M.; Maeda, H.; Kohno, H.; Tanaka, T.; Miyashita, K. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARγ ligand, troglitazone, on colon cancer cells. Biochim. Biophys. Acta, Gen. Subj., 2004, 1675(1-3), 113-119.
[http://dx.doi.org/10.1016/j.bbagen.2004.08.012] [PMID: 15535974]
[40]
Martin, H.L.; Mounsey, R.B.; Mustafa, S.; Sathe, K.; Teismann, P. Pharmacological manipulation of peroxisome proliferator-activated receptor γ (PPARγ) reveals a role for anti-oxidant protection in a model of Parkinson’s disease. Exp. Neurol., 2012, 235(2), 528-538.
[http://dx.doi.org/10.1016/j.expneurol.2012.02.017] [PMID: 22417924]
[41]
Carta, A.R. PPAR-γ: Therapeutic prospects in Parkinson’s disease. Curr. Drug Targets, 2013, 14(7), 743-751.
[http://dx.doi.org/10.2174/1389450111314070004] [PMID: 23469878]
[42]
Kang, S.S.; Ahn, E.H.; Zhang, Z.; Liu, X.; Manfredsson, F.P.; Sandoval, I.M.; Dhakal, S.; Iuvone, P.M.; Cao, X.; Ye, K. α‐Synuclein stimulation of monoamine oxidase‐B and legumain protease mediates the pathology of Parkinson’s disease. EMBO J., 2018, 37(12), e98878.
[http://dx.doi.org/10.15252/embj.201798878] [PMID: 29769405]
[43]
Zhang, P.; Xu, S.; Zhu, Z.; Xu, J. Multi-target design strategies for the improved treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 176, 228-247.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.020] [PMID: 31103902]
[44]
Zhang, H.; Tang, Y.; Zhang, Y.; Zhang, S.; Qu, J.; Wang, X.; Kong, R.; Han, C.; Liu, Z. Fucoxanthin: A promising medicinal and nutritional ingredient. Evid. Based Complement. Alternat. Med., 2015, 2015, 723515.
[http://dx.doi.org/10.1155/2015/723515] [PMID: 26106437]
[45]
Zhu, C.B.; Carneiro, A.M.; Dostmann, W.R.; Hewlett, W.A.; Blakely, R.D. p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process. J. Biol. Chem., 2005, 280(16), 15649-15658.
[http://dx.doi.org/10.1074/jbc.M410858200] [PMID: 15728187]
[46]
Ge, H.; Yang, T.; Sun, J.; Zhang, D. Associations between dietary carotenoid intakes and the risk of depressive symptoms. Food Nutr. Res., 2020, 64, 64.
[http://dx.doi.org/10.29219/fnr.v64.3920] [PMID: 33447180]
[47]
Chan, K.; Mong, M.; Yin, M. Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J. Food Sci., 2009, 74(7), H225-H231.
[http://dx.doi.org/10.1111/j.1750-3841.2009.01274.x] [PMID: 19895474]
[48]
Laruelle, M. Imaging dopamine transmission in schizophrenia. A review and meta-analysis. Q. J. Nucl. Med., 1998, 42(3), 211-221.
[PMID: 9796369]
[49]
Axelrod, J.; Tomchick, R. Enzymatic O-methylation of epinephrine and other catechols. J. Biol. Chem., 1958, 233(3), 702-705.
[http://dx.doi.org/10.1016/S0021-9258(18)64731-3] [PMID: 13575440]
[50]
Opmeer, E.M.; Kortekaas, R.; Aleman, A. Depression and the role of genes involved in dopamine metabolism and signalling. Prog. Neurobiol., 2010, 92(2), 112-133.
[http://dx.doi.org/10.1016/j.pneurobio.2010.06.003] [PMID: 20558238]
[51]
Lakhan, S.E.; Caro, M.; Hadzimichalis, N. NMDA receptor activity in neuropsychiatric disorders. Front. Psychiatry, 2013, 4, 52.
[http://dx.doi.org/10.3389/fpsyt.2013.00052] [PMID: 23772215]
[52]
Bacher, I.; Wu, B.; Shytle, D.R.; George, T.P. Mecamylamine – a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Expert Opin. Pharmacother., 2009, 10(16), 2709-2721.
[http://dx.doi.org/10.1517/14656560903329102] [PMID: 19874251]
[53]
Sałaciak, K.; Pytka, K. Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases? Pharmacol. Ther., 2021, 227, 107872.
[http://dx.doi.org/10.1016/j.pharmthera.2021.107872] [PMID: 33905796]
[54]
Miyashita, K.; Hosokawa, M. 12 beneficial health effects of seaweed carotenoid, fucoxanthin. In: Marine nutraceuticals and functional foods; Barrow, C.; Shahidi, F., Eds.; Boca Raton, Florida: CRC Press, 2007; p. 297.
[55]
Pangestuti, R.; Kim, S.K. Neuroprotective effects of marine algae. Mar. Drugs, 2011, 9(5), 803-818.
[http://dx.doi.org/10.3390/md9050803] [PMID: 21673890]
[56]
Das, M.; Prakash, S.; Nayak, C.; Thangavel, N.; Singh, S.K.; Manisankar, P.; Devi, K.P. Dihydroactinidiolide, a natural product against Aβ25-35 induced toxicity in Neuro2a cells: Synthesis, in silico and in vitro studies. Bioorg. Chem., 2018, 81, 340-349.
[http://dx.doi.org/10.1016/j.bioorg.2018.08.037] [PMID: 30189414]
[57]
Baek, S.Y.; Kim, S.J.; Kim, M.R. Phytochemicals and antioxidant properties of Enteromorpha prolifera extract in Korea. J. Korean Soc. Food Sci. Nutrit., 49(5), 462-472.