Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Compounds with Anti-Alzheimer Activity Isolated for the First Time from Melaleuca leucodendron (L.) Leaves

Author(s): Asmaa S. Abdel Elkarim*, Amal H. Ahmed and Wael M. ELsayed

Volume 24, Issue 14, 2023

Published on: 03 May, 2023

Page: [1836 - 1845] Pages: 10

DOI: 10.2174/1389201024666230331083751

Price: $65

Abstract

Objective: To discover a drug from natural triterpenes that has no side effects and is effective in treating Alzheimer's disease. We predict that the drug will be put on the market soon and achieve success.

Methods: The methanolic extract of M. leucodendron leaves was fractionated and subjected to different chromatographic techniques to isolate two new triterpene glycosides alongside five known compounds kaempferol 3, quercetin 4, quercetin3-O-β-D-glucopyranoside 5, kaempferol3- O-β-D-glucopyranoside 6 and kaempferol3-O-α-L-rhamnoside 7. The structures of compounds 1 and 2 were elucidated by spectroscopic analysis and chemical means.

Results: Two new triterpene glycosides, 21-O-α-L-rhamnopyranosyl-olean-12-ene-3-O-[α-Lrhamnopyranosyl (1-4) β-D-galactopyranosyl (1-4) β-D-glucouronopyranoside]1 and 21-O-α-Lrhamnopyranosyl- olean-12-ene-3-O-[α-L-rhamnopyranosyl (1→4) β-D-galactopyra-nosyl (1→4) β-D-galactopyranoside] 2, were isolated for the first time from 70% aqueous methanolic extract (AME) of M. leucodendron leaves. The inhibitory activities of the said compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were then assayed. Both compounds exhibited significant inhibitory activities toward the two enzymes, and evidence indicated that compound 2 was a more effective inhibitor than compound 1.

Conclusion: Compounds 1 and 2 have a significant role in inhibiting the enzymes acetylcholinesterase and butyrylcholinesterase.

Keywords: M. leucodendron, triterben glycosides, flavonoids, cholinesterase, acetylcholinesterase (AChE), Alzheimer's disease.

« Previous
Graphical Abstract

[1]
Jamir, K.; Ganguly, R.; Seshagirirao, K. ZCPG, a cysteine protease from Zingiber montanum rhizome exhibits enhanced anti-inflammatory and acetylcholinesterase inhibition potential. Int. J. Biol. Macromol., 2020, 163, 2429-2438.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.09.097] [PMID: 32979448]
[2]
Ahmed, S.; Khan, S.T.; Zargaham, M.K.; Khan, A.U.; Khan, S.; Hussain, A.; Uddin, J.; Khan, A.; Al-Harrasi, A. Potential therapeutic natural products against Alzheimer’s disease with Reference of Acetylcholinesterase. Biomed. Pharmacother., 2021, 139(8), 111609.
[http://dx.doi.org/10.1016/j.biopha.2021.111609] [PMID: 33915501]
[3]
Liu, C.; Hou, W.; Li, S.; Tsao, R. Extraction and isolation of acetylcholinesterase inhibitors from Citrus limon peel using an in vitro method. J. Sep. Sci., 2020, 43(8), 1531-1543.
[http://dx.doi.org/10.1002/jssc.201901252] [PMID: 31999045]
[4]
Bhagat, J.; Kaur, A.; Kaur, R.; Yadav, A.K.; Sharma, V.; Chadha, B.S. Cholinesterase inhibitor (Altenuene) from an endophytic fungus Alternaria alternata: Optimization, purification and characterization. J. Appl. Microbiol., 2016, 121(4), 1015-1025.
[http://dx.doi.org/10.1111/jam.13192] [PMID: 27248836]
[5]
Petrachaianan, T.S.; Chaiyasirisuwan, S.; Athikomkulchai, S.; Sareedenchai, V. Screening of acetylcholinesterase inhibitory activity in essential oil from Myrtaceae. T J P S., 2019, 43(1), 63-68.
[http://dx.doi.org/10.1371/journal.pone.0162139]
[6]
Khan, H.; Marya; Amin, S.; Kamal, M.A.; Patel, S. Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects. Biomed. Pharmacother., 2018, 101, 860-870.
[http://dx.doi.org/10.1016/j.biopha.2018.03.007] [PMID: 29635895]
[7]
Yılmaz, A.; Boğa, M.; Topcu, G. Novel terpenoids with potential anti-alzheimer activity from Nepeta obtusicrena. Rec. Nat. Prod., 2016, 10(5), 530-541.
[8]
Hou, W.; Zhang, W.; Chen, G.; Luo, Y. Optimization of extraction conditions for maximal phenolic, flavonoid and antioxidant activity from Melaleuca bracteata leaves using the response surface methodology. PLoS One, 2016, 11(9), e0162139.
[http://dx.doi.org/10.1371/journal.pone.0162139] [PMID: 27611576]
[9]
Brophy, J.J.; Craven, L.A.; Doran, J.C. Melaleucas: their botany, essential oils and uses. Australian Centre for International Agricultural Research; ACIAR, 2013, p. 415.
[10]
Edwards, R.D.; Crisp, M.D.; Cook, L.G. Species limits and cryptic biogeographic structure in a widespread complex of Australian monsoon tropics trees (broad-leaf paperbarks: Melaleuca, Myrtaceae). Aust. Syst. Bot., 2018, 31(6), 495-503.
[http://dx.doi.org/10.1071/SB18032]
[11]
Lee, C.K. A new norlupene from the leaves of Melaleuca leucadendron. J. Nat. Prod., 1998, 61(3), 375-376.
[http://dx.doi.org/10.1021/np9606052] [PMID: 9548878]
[12]
Jang, H.N.; Park, S.N. Antimicrobial activity of niaouli (Melaleuca quinquenervia) leaf extracts against skin flora. J. Soc. Cosmet. Sci. Korea, 2014, 40(3), 313-320.
[http://dx.doi.org/10.15230/SCSK.2014.40.3.313]
[13]
Fang, S.; Hao, C.; Liu, Z.; Song, F.; Liu, S. Application of electrospray ionization mass spectrometry combined with sequential tandem mass spectrometry techniques for the profiling of steroidal saponin mixture extracted from Tribulus terrestris. Planta Med., 1999, 65(1), 068-073.
[http://dx.doi.org/10.1055/s-1999-13966] [PMID: 17260238]
[14]
Cui, M.; Sun, W.; Song, F.; Liu, Z.; Liu, S. Multi-stage mass spectrometric studies of triterpenoid saponins in crude extracts from Acanthopanax senticosus Harms. Rapid Commun. Mass Spectrom., 1999, 13(10), 873-879.
[http://dx.doi.org/10.1002/(SICI)1097-0231(19990530)13:10<873::AID-RCM571>3.0.CO;2-2]
[15]
Ellman, G.L.; Courtney, K.D.; Andres, V., Jr; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7(2), 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[16]
Obregon, A.D.C.; Schetinger, M.R.C.; Correa, M.M.; Morsch, V.M.; Silva, J.E.P.; Martins, M.A.P.; Bonacorso, H.G.; Zanatta, N. Effects per se of organic solvents in the cerebral acetylcholinesterase of rats. Neurochem. Res., 2005, 30(3), 379-384.
[http://dx.doi.org/10.1007/s11064-005-2612-5] [PMID: 16018582]
[17]
Konoshima, T.; Lee, K.H. Antitumor agents, 82. cytotoxic sapogenols from Aesculus hippocastanum. J. Nat. Prod., 1986, 49(4), 650-656.
[http://dx.doi.org/10.1021/np50046a015] [PMID: 3783160]
[18]
Markam, K.R. Techniques of flavonoid identification; Academic Press: Cambridge, 1982, pp. 41-47.
[19]
Guvenalp, Z.; Demirezer, L. O. Flavonol glycosides from Asperula arvensis L. Turkish J. Chem., 2005, 29(2), 163-169.
[20]
Chaturvedula, V.S.P.; Prakash, I. Triterpene glycosides from the aerial parts and seeds of bupleurumfalcatum. IOSR J. Pharm., 2013, 3(4), 34-37.
[http://dx.doi.org/10.9790/3013-034203437]
[21]
Aisyah, L.S.; Yun, Y.F.; Julaeha, E.; Herlina, T.; Zainuddin, A.; Hermawan, W.; Supratman, U.; Hayashi, H. Flavonoids from the fresh leaves of Kalanchoe tomentosa (Crassulaceae). Open Chem. J., 2015, 2(1), 36-39.
[http://dx.doi.org/10.2174/1874842201502010036]
[22]
Si, C.L.; Du, Z.G.; Fan, S.; An, L.L. Isolation and structure elucidation of a new flavonol glycoside from Sophora japonica. Chem. Nat. Compd., 2016, 52(5), 794-797.
[http://dx.doi.org/10.1007/s10600-016-1780-7]
[23]
Kim, J. W.; Kim, T. B.; Yang, H.; Sung, S. H. Phenolic compounds isolated from Opuntiaficus-indica fruits. Nat. Prod.t Sci., 2016, 22(2), 117-121.
[http://dx.doi.org/10.20307/nps.2016.22.2.117]
[24]
Lin, L.; Huang, X.; Lv, Z. Isolation and identification of flavonoids components from Pteris vittata L. Springerplus, 2016, 5(1), 1649.
[http://dx.doi.org/10.1186/s40064-016-3308-9] [PMID: 27722067]
[25]
Furusawa, M.; Tanaka, T.; Ito, T.; Nakaya, K.; Iliya, I.; Ohyama, M.; Iinuma, M.; Murata, H.; Inatomi, Y.; Inada, A.; Nakanishi, T.; Matsushita, S.; Kubota, Y.; Sawa, R.; Takahashi, Y. Flavonol glycosides in leaves of two Diospyros species. Chem. Pharm. Bull., 2005, 53(5), 591-593.
[http://dx.doi.org/10.1248/cpb.53.591] [PMID: 15863940]
[26]
Wang, J.; Gao, H.; Zhao, J.; Wang, Q.; Zhou, L.; Han, J.; Yu, Z.; Yang, F. Preparative separation of phenolic compounds from Halimodendron halodendron by high-speed counter-current chromatography. Molecules, 2010, 15(9), 5998-6007.
[http://dx.doi.org/10.3390/molecules15095998] [PMID: 20877205]
[27]
Tuzimski, T.; Petruczynik, A. Determination of anti-Alzheimer’s disease activity of selected plant ingredients. Molecules, 2022, 27(10), 3222.
[http://dx.doi.org/10.3390/molecules27103222] [PMID: 35630702]
[28]
Mcgleenon, B.M.; Dynan, K.B.; Passmore, A.P. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br. J. Clin. Pharmacol., 1999, 48(4), 471-480.
[http://dx.doi.org/10.1046/j.1365-2125.1999.00026.x]
[29]
Noori, T.; Dehpour, A.R.; Sureda, A.; Sobarzo-Sanchez, E.; Shirooie, S. Role of natural products for the treatment of Alzheimer's disease. Eur. J. Pharmacol., 2021, 5(898), 173974.
[http://dx.doi.org/10.1016/j.ejphar.2021.173974]
[30]
Basnet, R.; Khadka, S.; Basnet, B.B.; Gupta, R. Perspective on acetylcholinesterase: A potential target for Alzheimer’s disease intervention. Curr. Enzyme Inhib., 2020, 16, 1-8.
[http://dx.doi.org/10.2174/1573408016999200801021329]
[31]
Tabet, N. Acetylcholinesterase inhibitors for Alzheimer’s disease: Anti inflammatories in acetylcholine clothing. Age Ageing, 2006, 35(4), 336-338.
[http://dx.doi.org/10.1093/ageing/afl027]
[32]
Silman, I.; Sussman, J.L. Acetylcholinesterase: ‘Classical’ and ‘non-classical’ functions and pharmacology. Curr. Opin. Pharmacol., 2005, 5(3), 293-302.
[http://dx.doi.org/10.1016/j.coph.2005.01.014] [PMID: 15907917]
[33]
Bartus, R.T. The cholinergic hypothesis of geriatric memory dysfunction. Sci., 1982, 217, 408-417.
[http://dx.doi.org/10.1126/science.7046051]
[34]
Roy, A. Role of medicinal plants against Alzheimer’s disease. Int. J. Complement. Altern. Med., 2018, 11(4), 205-208.
[http://dx.doi.org/10.15406/ijcam.2018.11.00398]
[35]
Magina, M.D.A.; Dalmarco, E.M.; Dalmarco, J.B.; Colla, G.; Pizzolatti, M.G.; Brighente, I.M.C. Bioactive triterpenes and phenolics of leaves of Eugenia brasiliensis. Quim. Nova, 2012, 35(6), 1184-1188.
[http://dx.doi.org/10.1590/S0100-40422012000600022]

Rights & Permissions Print Cite
Article Metrics
21
2
World Brain Tumor Day
© 2024 Bentham Science Publishers | Privacy Policy