Dehydrocostus lactone from the root of Ajuga integrifolia (Buch.-Ham. Ex D. Don): Quantitative determination and in- silico study for anti-breast cancer activity
DOI:
https://doi.org/10.14719/pst.2344Keywords:
Ajuga integrifolia, breast cancer, dehydrocostus lactone, molecular docking, thin layer chromatographyAbstract
Many biological activities were reported for the Ajuga species, specifically for Ajuga integrifolia and its synonyms. These include antioxidant, anti-inflammatory, antidiabetic, antibacterial, blood purifier effects, and anticancer activity. This study quantitatively determines dehydrocostus lactone (DHCL) from the root of Ajuga integrifolia and its in silico study for anti-breast cancer activity. Camag HPTLC was used for TLC – densitometric estimation of dehydrocostus lactone. Estrogen receptor alpha (ER?) protein (PDB ID: 3ERT) was selected for its involvement in cell proliferation within the breast cancer cell. Tamoxifen is a reference drug commonly used in hormonal therapy, and DHCL was used as a ligand. Molecular docking was performed using AutoDock Vina in PyRx v.0.8 to get the best
conformational pose for forming the expected receptor-ligand complex. The docking result visualization was performed using LigPlot v.1.4.5 software for 2D, and the interactive visualization in 3D was done using Biovia Discovery Studio software. The presence of DHCL in the root of A. integrifolia was not reported so far. DHCL content in the root of A. integrifolia was estimated to be 16.5 ± 0.25 mg/g of crude extract using the TLC- densitometric method. From the molecular docking study, DHCL was found to be a promising inhibitor for estrogen receptor interaction in the breast cell and can be selected for further in vivo research to develop an anti-breast cancer drug.
Downloads
References
Dagne E. Natural database for Africa (NDA) Verion 2.0. Addis Ababa; 2011.
Hedberg I. Flora of Ethiopia and Eritrea. Vol. 5, Gentianaceae to Cyclocheilaceae. Hedberg I, Kelbessa E, Edwards S, Demissew S, Persson E, editors. Addis Ababa: The National Herbarium, Biology Department, Science Faculty, Addis Ababa University, Ethiopia. 2006; 528 p.
Ullah MA, Gul FZ, Khan T, Bajwa MN, Drouet S, Tungmunnithum D et al. Differential induction of antioxidant and anti-inflammatory phytochemicals in agitated micro-shoot cultures of Ajuga integrifolia Buch. Ham. ex D.Don with biotic elicitors. AMB Express [Internet]. 2021;11(1). Available from: https://doi.org/10.1186/s13568-021-01297-3
Alene M, Abdelwuhab M, Belay A, Yazie TS. Evaluation of antidiabetic activity of Ajuga integrifolia (Lamiaceae) root extract and solvent fractions in mice. Faisal M, editor. Evidence-Based Complement Altern Med [Internet]. 2020 Dec 22;2020:1-11. Available from: https://www.hindawi.com/journals/ecam/2020/6642588/ https://doi.org/10.1155/2020/6642588
Ahmad GH. Review of the active principles of medicinal and aromatic plants and their disease fighting properties. In: Aftab T, Hakeem KR, editors. Medicinal and Aromatic Plants: Expanding their Horizons through Omics [Internet]. 1st ed. Academic Press. 2021; p. 1-36. Available from: http://dx.doi.org/10.1016/B978-0-12-819590-1/00001-X
Ferrari B, Castilho P, Tomi F, Rodrigues AI, do Ceu Costa M, Casanova J. Direct identification and quantitative determination of costunolide and dehydrocostuslactone in the fixed oil of Laurus novocanariensis by13C-NMR spectroscopy. Phytochem Anal [Internet]. 2005 Mar;16(2):104-07. https://doi.org/10.1002/pca.825
Peng Z, Wang Y, Gu X, Wen Y, Yan C. A platform for fast screening potential anti-breast cancer compounds in traditional Chinese medicines. Biomed Chromatogr [Internet]. 2013 Dec;27(12):1759-66. Available from: https://onlinelibrary.wiley.com/doi/10.1002/bmc.2990 https://doi.org/10.1002/bmc.2990
Lin X, Peng Z, Su C. Potential anti-cancer activities and mechanisms of costunolide and dehydrocostuslactone. Int J Mol Sci [Internet]. 2015 May 13;16(12):10888-906. Available from: http://www.mdpi.com/1422-0067/16/5/10888 https://doi.org/10.3390/ijms160510888
Vijayakannan R, Karan M, Dutt S, Jain V, Vasisht K. A rapid densitometric TLC method for simultaneous analysis of costunolide and dehydrocostus lactone in Saussurea costus. Chromatographia [Internet]. 2006 Mar 28;63(5-6):277-81. Available from: http://link.springer.com/10.1365/s10337-006-0733-x https://doi.org/10.1365/s10337-006- 0733-x
Peng Z, Wang Y, Fan J, Lin X, Liu C, Xu Y. Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc / p53 and AKT / 14-3-3 pathway. Sci Rep [Internet]. 2017;7. Available from: http://dx.doi.org/10.1038/srep41254
Li Q, Wang Z, Xie Y, Hu H. Antitumor activity and mechanism of costunolide and dehydrocostus lactone: Two natural sesquiterpene lactones from the Asteraceae family. Biomed Pharmacother [Internet]. 2020;125(January):109955. Available from: https://doi.org/10.1016/j.biopha.2020.109955
Kuo PL, Ni WC, Tsai EM, Hsu YL. Dehydrocostuslactone disrupts signal transducers and activators of transcription 3 through up-regulation of suppressor of cytokine signaling in breast cancer cells. Mol Cancer Ther [Internet]. 2009 May 1;8(5):1328-39. Available from: https://aacrjournals.org/mct/article/8/5/1328/93489/Dehydrocostuslactone-disrupts-signal- transducers https://doi.org/10.1158/1535-7163.MCT-08-0914
Wangchuk P, Keller PA, Pyne SG, Taweechotipatr M, Kamchonwongpaisan S. GC/GC-MS analysis, isolation and identification of bioactive essential oil components from the Bhutanese medicinal plant, Pleurospermum amabile. Nat Prod Commun [Internet]. 2013 Sep 1;8(9):1934578X1300800. https://doi.org/10.1177/1934578X1300800930
Matulyte I, Marksa M, Ivanauskas L, Kalv?nien? Z, Lazauskas R, Bernatoniene J. GC-MS 12 analysis of the composition of the extracts and essential oil from Myristica fragrans seeds using magnesium aluminometasilicate as excipient. Molecules [Internet]. 2019 Mar 18;24(6):1062. Available from: https://www.mdpi.com/1420-3049/24/6/1062
https://doi.org/10.3390/molecules24061062
Tolessa L, Sendo EG, Dinegde NG, Desalew A. Risk factors associated with breast cancer among women in Addis Ababa, Ethiopia: Unmatched case–control study. Int J Womens Health [Internet]. 2021 Jan;Volume 13:101-10. Available from: https://www.dovepress.com/risk-factors-associated-with-breast-cancer-among-women-in-
addis-ababa--peer-reviewed-article-IJWH https://doi.org/10.2147/IJWH.S292588
Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P et al. Breast cancer. Nat Rev Dis Prim [Internet]. 2019 Sep 23;5(1):66. Available from: https://www.nature.com/articles/s41572-019-0111-2 https://doi.org/10.1038/s41572-019- 0111-2
Huang Z, Jiang S, Xiao W. Optimization method of an antibreast cancer drug candidate based on machine learning. Wang J, editor. Comput Math Methods Med [Internet]. 2022 Sep 5;2022:1-13. Available from: https://www.hindawi.com/journals/cmmm/2022/4133663/ https://doi.org/10.1155/2022/4133663
Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SAW et al. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. JNCI J Natl Cancer Inst [Internet]. 2003 Mar 5;95(5):353-61. Available from: https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/95.5.353
Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F. Estrogen receptors alpha (ER?) and beta (ER?): Subtype selective ligands and clinical potential. Steroids [Internet]. 2014;90. Available from: http://dx.doi.org/10.1016/j.steroids.2014.06.012
Luan F, Han K, Li M, Zhang T, Liu D, Yu L et al. Ethnomedicinal uses, phytochemistry, pharmacology and toxicology of species from the genus Ajuga L.: A systematic review. Am J Chin Med [Internet]. 2019 Jan 15;47(05):959-1003. https://doi.org/10.1142/S0192415X19500502
Pal A, Jadon M, Katare YK, Singour PK, Rajak H, Chaurasiya PK et al. Ajuga bracteosa wall?: A review on its ethnopharmacological and phytochemical studies. Der Pharm Sin [Internet]. 2011;2(2):1-10. Available from: www.pelagiaresearchlibrary.com
Tuasha N, Petros B, Asfaw Z. Plants used as anticancer agents in the Ethiopian traditional medical practices: A systematic review. Evidence-Based Complement Altern Med [Internet]. 2018; Available from: https://doi.org/10.1155/2018/6274021
Chen T, Diao QY, Yu HZ, Jiao CL, Ruan J. Phytochemical, cytotoxic and chemotaxonomic study on Ajuga forrestii Diels (Labiatae). Nat Prod Res [Internet]. 2018;32(8):977-81. Available from: https://doi.org/10.1080/14786419.2017.1371161
Hussain H, Green IR, Saleem M, Raza ML, Nazir M. Therapeutic potential of iridoid derivatives: Patent review. Inventions [Internet]. 2019 May 16;4(2):29. Available from: https://www.mdpi.com/2411-5134/4/2/29 https://doi.org/10.3390/inventions4020029
Sheng W, Mao H, Wang C, Yang N, Zhang Z, Han J. Dehydrocostus lactone enhances chemotherapeutic potential of doxorubicin in lung cancer by inducing cell death and limiting metastasis. Med Sci Monit [Internet]. 2018 Nov 2;24:7850-61. Available from: https://www.medscimonit.com/abstract/index/idArt/911410 https://doi.org/10.12659/MSM.911410
Zhang Y, Cai P, Cheng G, Zhang Y. A brief review of phenolic compounds identified from plants: Their extraction, analysis and biological activity. Nat Prod Commun [Internet]. 2022 Jan 5;17(1):1934578X2110697. https://doi.org/10.1177/1934578X211069721
Fitriah A, Holil K, Syarifah U, Fitriyah, Utomo DH. In silico approach for revealing the anti- breast cancer and estrogen receptor alpha inhibitory activity of Artocarpus altilis. In: AIP Conference Proceedings [Internet]. 2018; p. 070003. https://doi.org/10.1063/1.5062801
Omosa LK, Amugune B, Ndunda B, Milugo TK, Heydenreich M, Yenesew A et al. Antimicrobial flavonoids and diterpenoids from Dodonaea angustifolia. South African J Bot [Internet]. 2014;91:58-62. Available from: http://dx.doi.org/10.1016/j.sajb.2013.11.012
Karthika K, Paulsamy S. TLC and HPTLC fingerprints of various secondary metabolites in the stem of the traditional medicinal climber, Solena amplexicaulis. Indian J Pharm Sci [Internet]. 2015;111-16. Available from: www.ijpsonline.com https://doi.org/10.4103/0250- 474X.151591
Patel NG, Patel KG, Patel K V, Gandhi TR. Validated HPTLC method for quantification of luteolin and apigenin in Premna mucronata Roxb., Verbenaceae. Adv Pharmacol Sci [Internet]. 2015;2015:1-7. Available from: http://www.hindawi.com/journals/aps/2015/682365/ https://doi.org/10.1155/2015/682365
Gören AC, Zhou BN, Topçu G, Kökdil G, Kingston DGI. DNA damaging activities of methanol extract of Ajuga postii and iridoid glucoside reptoside. Nat Prod Res [Internet]. 2005 Jul 1;19(5):457-60. https://doi.org/10.1080/14786410412331272095
Dallakyan S, Olson A. Chemical biology [Internet]. Hempel JE, Williams CH, Hong CC, editors. Chemical biology methods and protocols. New York, NY: Springer New York. Methods in Molecular Biology. 2015;1263:243-50. Available from: http://link.springer.com/10.1007/978-1-4939-2269-7 https://doi.org/10.1007/978-1-4939-
-7_19
Iman M, Saadabadi A, Davood A. Molecular docking analysis and molecular dynamics simulation study of ameltolide analogous as a sodium channel blocker. TURKISH J Chem [Internet]. 2015;39(2):306-16. Available from:
https://journals.tubitak.gov.tr/chem/vol39/iss2/10 https://doi.org/10.3906/kim-1402-37
Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol [Internet]. 2004 Dec;1(4):337-41. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1740674904000551
https://doi.org/10.1016/j.ddtec.2004.11.007
Dayrit FM, Dios AC de. 1H and 13C NMR for the profiling of natural product extracts: Theory and applications. In: Sharmin E, Zafar F, editors. Spectroscopic analyses - Developments and applications [Internet]. InTech; 2017. Available from: http://www.intechopen.com/books/spectroscopic-analyses-developments-and-
applications/1h-and-13c-nmr-for-the-profiling-of-natural-product-extracts-theory-and-applications https://doi.org/10.5772/intechopen.71040
Guccione C, Ros G, Gallori S, Bergonzi MC, Bilia AR. Rapid and efficient extraction and HPLC analysis of sesquiterpene lactones from Aucklandia lappa root. Nat Prod Commun [Internet]. 2017 Feb 1;12(2):1934578X1701200. https://doi.org/10.1177/1934578X1701200218
Anita Y, Radifar M, Kardono LB, Hanafi M, Istyastono EP. Structure-based design of eugenol analogs as potential estrogen receptor antagonists. Bioinformation [Internet]. 2012 Oct 1;8(19):901-06. Available from: http://www.bioinformation.net/008/97320630008901.htm
https://doi.org/10.6026/97320630008901
Llorent-Martínez EJ, Zengin G, Ortega-Barrales P, Zakariyyah Aumeeruddy M, Locatelli M, Mollica A et al. Characterization of the phytochemical profiles and biological activities of Ajuga chamaepitys subsp. chia var. chia and Ajuga bombycina by high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry . Anal Lett [Internet]. 2019;52(5):852-68. Available from: https://doi.org/10.1080/00032719.2018.1500581
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev [Internet]. 2012 Dec;64:4-17. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0169409X12002797
https://doi.org/10.1016/j.addr.2012.09.019
Patrick G. BIOS instant notes in medicinal chemistry. Bosher A, editor. New York: Taylor & Francis; 2019. https://doi.org/10.1201/9780429188572
Milanetti E, Raimondo D, Tramontano A. Prediction of the permeability of neutral drugs inferred from their solvation properties. Bioinformatics [Internet]. 2016 Apr 15;32(8):1163- 69. Available from: https://academic.oup.com/bioinformatics/article- lookup/doi/10.1093/bioinformatics/btv725
van Lipzig MMH, ter Laak AM, Jongejan A, Vermeulen NPE, Wamelink M, Geerke D et al. Prediction of ligand binding affinity and orientation of xenoestrogens to the estrogen receptor by molecular dynamics simulations and the linear interaction energy method. J Med Chem [Internet]. 2004 Feb 1;47(4):1018-30. https://doi.org/10.1021/jm0309607
Laskowski RA, Swindells MB. LigPlot+: Multiple ligand–protein interaction diagrams for drug discovery. J Chem Inf Model [Internet]. 2011 Oct 24;51(10):2778-86. https://doi.org/10.1021/ci200227u
Lazzeroni M, Serrano D, Dunn BK, Heckman-Stoddard BM, Lee O, Khan S et al. Oral low dose and topical tamoxifen for breast cancer prevention: modern approaches for an old drug. Breast Cancer Res [Internet]. 2012 Oct 29;14(5):214. Available from: http://breast-cancer- research.biomedcentral.com/articles/10.1186/bcr3233 https://doi.org/10.1186/bcr3233
Downloads
Published
Versions
- 01-01-2024 (2)
- 01-10-2023 (1)
How to Cite
Issue
Section
License
Copyright (c) 2022 Fekade Beshah Tessema , Yilma Hunde Gonfa, Tilahun Belayneh Asfaw, Mesfin Getachew Tadesse, Archana Joshi Bachheti, Abdel Nasser Singab, Rakesh Kumar Bachheti
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright and Licence details of published articles
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Open Access Policy
Plant Science Today is an open access journal. There is no registration required to read any article. All published articles are distributed under the terms of the Creative Commons Attribution License (CC Attribution 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (https://creativecommons.org/licenses/by/4.0/). Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
