Generic placeholder image

The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Research Article

Anastatica hierochuntica Extracts: Promising, Safe and Selective Anticancer Agents

Author(s): Zaynab Al-Eisawi*, Salim M. Abderrahman, Yasmin M. S. Abdelrahim, Reem Al-Abbassi and Yasser K. Bustanji

Volume 12, Issue 1, 2022

Published on: 14 September, 2020

Article ID: e160921185898 Pages: 10

DOI: 10.2174/2210315510999200914153725

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Medicinal plants have been used for many centuries for their significant phytochemical reservoir, forming a foundation for many medicinal drugs. Conventional cancer therapy possesses a number of undesired problems, including poor selectivity, severe side effects and resistance to cancer.

Objective: There is a need for new anticancer drugs, possibly from natural sources such as medicinal plants. A. Hierochuntica L. is rich with phytochemicals and is widely used in traditional medicine.

Methods: The antiproliferative activities of A. hierochuntica whole plant extracts (ethanol, methanol, ethyl acetate, chloroform and water) were determined against a panel of cancer cells and normal primary dermal fibroblasts. The genotoxic effect of A. hierochuntica ethyl acetate on mice bone marrow cells was also evaluated. Genotoxic parameters included chromosomal aberration, mitodepression, micronuclei formation and sister chromatid exchange.

Results: A. hierochuntica exhibited antiproliferative activity against leukemia (K-562) and melanoma (A-375) cells. This is the first study to demonstrate the effect of A. hierochuntica ethyl acetate extract on cancer cell lines, found to be the most cytotoxic of all extracts. Furthermore, the chloroform extract showed notable anti-proliferative effects against most cancer cell lines tested. The extracts proved to be highly safe on human normal skin fibroblasts. Furthermore, A. hierochuntica ethyl acetate extract was also found to have limited genotoxic effects, with these changes seen at very high doses only.

Conclusion: The results indicate that A. hierochuntica extracts have significant selective anticancer activity and that genotoxicity is only observed at very high concentrations.

Keywords: Bioactivity, plant extracts, Anastatica hierochuntica L., cancer, genotoxicity, cells line.

Graphical Abstract
[1]
Sofowora, A.; Ogunbodede, E.; Onayade, A. The role and place of medicinal plants in the strategies for disease prevention. Afr. J. Tradit. Complement. Altern. Med., 2013, 10(5), 210-229.
[http://dx.doi.org/10.4314/ajtcam.v10i5.2] [PMID: 24311829]
[2]
Oyebode, O.; Kandala, N.B.; Chilton, P.J.; Lilford, R.J. Use of traditional medicine in middle-income countries: A WHO-SAGE study. Health Policy Plan., 2016, 31(8), 984-991.
[http://dx.doi.org/10.1093/heapol/czw022] [PMID: 27033366]
[3]
Abat, J.K.; Kumar, S.; Mohanty, A. Ethnomedicinal, phytochemical and ethnopharmacological aspects of four medicinal plants of malvaceae used in indian traditional medicines: A review. Medicines (Basel), 2017, 4(4), E75.
[http://dx.doi.org/10.3390/medicines4040075] [PMID: 29057840]
[4]
Abbott, R. Documenting traditional medical knowledgeWorld intellectual property organization; , 2014. Available from: https://ssrn.com/abstract=2406649
[5]
Kumar, B.; Singh, S.; Skvortsova, I.; Kumar, V. Promising targets in anti-cancer drug development: recent updates. Curr. Med. Chem., 2017, 24(42), 4729-4752.
[PMID: 28393696]
[6]
Akinsanya, B.; Utoh, O.U.; Ukwa, U.D. Toxicological, phytochemical and anthelminthic properties of rich plant extracts on Clarias gariepinus. J. Basic Appl. Zool., 2016, 74(Suppl. C), 75-86.
[http://dx.doi.org/10.1016/j.jobaz.2016.09.003]
[7]
Stearns, D.M. Evaluation of chromium(III) genotoxicity with cell culture and in vitro assays. The Nutritional Biochemistry of Chromium (III); Vincent, J.B., Ed.; Elsevier: Amsterdam, 2007, pp. 209-224.
[http://dx.doi.org/10.1016/B978-044453071-4/50011-4]
[8]
Romansik, E.M.; Reilly, C.M.; Kass, P.H.; Moore, P.F.; London, C.A. Mitotic index is predictive for survival for canine cutaneous mast cell tumours. Vet. Pathol., 2007, 44(3), 335-341.
[http://dx.doi.org/10.1354/vp.44-3-335] [PMID: 17491075]
[9]
Zhou, J.; Ouedraogo, M.; Qu, F.; Duez, P. Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: an overview. Phytother. Res., 2013, 27(12), 1745-1755.
[http://dx.doi.org/10.1002/ptr.4942] [PMID: 23420770]
[10]
Yoshikawa, M.; Xu, F.; Morikawa, T.; Ninomiya, K.; Matsuda, H. Anastatins A and B, new skeletal flavonoids with hepatoprotective activities from the desert plant Anastatica hierochuntica. Bioorg. Med. Chem. Lett., 2003, 13(6), 1045-1049.
[http://dx.doi.org/10.1016/S0960-894X(03)00088-X] [PMID: 12643908]
[11]
AlGamdi, N.; Mullen, W.; Crozier, A. Tea prepared from Anastatica hirerochuntica seeds contains a diversity of antioxidant flavonoids, chlorogenic acids and phenolic compounds. Phytochemistry, 2011, 72(2-3), 248-254.
[http://dx.doi.org/10.1016/j.phytochem.2010.11.017] [PMID: 21176927]
[12]
Daur, I. Chemical properties of the medicinal herb Kaff Maryam (Anastatica hierochuntica L.) and its relation to folk medicine use. Afr. J. Microbiol. Res., 2012, 6, 5048-5051.
[13]
Zin, S.R.M.; Kassim, N.M.; Alshawsh, M.A.; Hashim, N.E.; Mohamed, Z. Biological activities of Anastatica hierochuntica L. : A systematic review. Biomed. Pharmacother., 2017, 91, 611-620.
[http://dx.doi.org/10.1016/j.biopha.2017.05.011] [PMID: 28486192]
[14]
Abou-Elella, F.; Hanafy, E.A.; Gavamukulya, Y. Determination of antioxidant and anti-inflammatory activities, as well as in vitro cytotoxic activities of extracts of Anastatica hierochuntica (Kaff Maryam) against HeLa cell lines. J. Med. Plants Res., 2016, 10(7), 77-87.
[http://dx.doi.org/10.5897/JMPR2015.6030]
[15]
Alatshan, A.; Qnais, E.; Wedyan, M.; Bseiso, Y.; Alzyoud, E.; Banat, R. Antinociceptive and antiinflammatory activities of Anastatica hierochuntica and possible mechanism of action. Indian J. Pharm. Sci., 2018, 80(4), 637-646.
[http://dx.doi.org/10.4172/pharmaceutical-sciences.1000403]
[16]
Hajjar, D.; Kremb, S.; Sioud, S.; Emwas, A.H.; Voolstra, C.R.; Ravasi, T. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging. PLoS ONE, 2017, 12(6), e0177316.
[http://dx.doi.org/10.1371/journal.pone.0177316]
[17]
Nakashima, S.; Matsuda, H.; Oda, Y.; Nakamura, S.; Xu, F.; Yoshikawa, M. Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells. Bioorg. Med. Chem., 2010, 18(6), 2337-2345.
[http://dx.doi.org/10.1016/j.bmc.2010.01.046] [PMID: 20189399]
[18]
Afifi-Yazar, F.U.; Kasabri, V.; Abu-Dahab, R. Medicinal plants from Jordan in the treatment of cancer: traditional uses vs. in vitro and in vivo evaluations-part 1. Planta Med., 2011, 77(11), 1203-1209.
[http://dx.doi.org/10.1055/s-0030-1270832] [PMID: 21347997]
[19]
Alves-Silva, J.M.; Romane, A.; Efferth, T.; Salgueiro, L. North african medicinal plants traditionally used in cancer therapy. Front. Pharmacol., 2017, 8, 383.
[http://dx.doi.org/10.3389/fphar.2017.00383] [PMID: 28694778]
[20]
Mohammd, T.U.; Baker, R.K.; Al-Ameri, K.A.; Abd-Ulrazzaq, S.S. Cytotoxic effect of aqueous extract of Anastatica hierochuntica L. on AMN-3 cell line in vitro. Adv. Life. Sci. Technol., 2015, 31, 59-63.
[21]
El Sayed, R.A.; Hanafy, Z.E.; Abd El Fattah, H.F.; Amer, A.K. Possible antioxidant and anticancer effects of plant extracts from Anastatica hierochuntica, Lepidium sativum and Carcia papaya against Ehrlich ascites carcinoma cells. Cancer Biology, 2020, 10(1), 1-16.
[22]
Yang, L.; Wen, K.S.; Ruan, X.; Zhao, Y.X.; Wei, F.; Wang, Q. Response of plant secondary metabolites to environmental factors. Molecules, 2018, 23(4), 762.
[http://dx.doi.org/10.3390/molecules23040762] [PMID: 29584636]
[23]
Tharib, S.; Al-Migirab, S. Physicochemical investigations on natural products, 1st ed;
[24]
Dickerson, M.D. NRC Guide for the Care and Use of Laboratory Animals, 8th ed; The National Academies Press: Washington, DC, 2011.
[25]
Rossi, A.; Romano, M.; Zaccaro, L.; Pulci, R.; Salmona, M. DNA synthesis, mitotic index, drug-metabolising systems and cytogenetic analysis in regenerating rat liver: Comparison with bone marrow test after in vivo treatment with cyclophosphamide. Mut. Res. Enviro. Muta. Rel. Sub., 1987, 182(2), 75-82.
[26]
Dobson, K.R.; Reading, L.; Haberey, M.; Marine, X.; Scutt, A. Centrifugal isolation of bone marrow from bone: An improved method for the recovery and quantitation of bone marrow osteoprogenitor cells from rat tibiae and femurae. Calcif. Tissue Int., 1999, 65(5), 411-413.
[http://dx.doi.org/10.1007/s002239900723] [PMID: 10541770]
[27]
Abderrahman, S.M.; Modallal, N. Genotoxic effects of Catha edulis (Khat) extract on mice bone marrow cells. Jordan J. Biol. Sci., 2008, 1(4), 165-172.
[28]
Gundy, S.; Varga, L.P. Chromosomal aberrations in healthy persons. Mutat. Res., 1983, 120(2-3), 187-191.
[http://dx.doi.org/10.1016/0165-7992(83)90162-8] [PMID: 6843581]
[29]
Kabarity, A.; El-Bayoumi, A.; Habib, A. C-Tumours and polyploidy induced by some alkaloids of opium and cannabis. Cytologia (Tokyo), 1980, 45(3), 497-506.
[http://dx.doi.org/10.1508/cytologia.45.497]
[30]
Hart, J.W.; Engberg-Pedersen, H. Statistics of the mouse bone-marrow micronucleus test: counting, distribution and evaluation of results. Mutat. Res., 1983, 111(2), 195-207.
[http://dx.doi.org/10.1016/0027-5107(83)90063-5] [PMID: 6633550]
[31]
Allen, J.W.; Shuler, C.F.; Latt, S.A. Bromodeoxyuridine tablet methodology for in vivo studies of DNA synthesis. Somatic Cell Genet., 1978, 4(4), 393-405.
[http://dx.doi.org/10.1007/BF01538862] [PMID: 356290]
[32]
Goto, K.; Maeda, S.; Kano, Y.; Sugiyama, T. Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma, 1978, 66(4), 351-359.
[http://dx.doi.org/10.1007/BF00328535] [PMID: 77756]
[33]
Geran, R. Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother. Rep., 1972, 3, 17-27.
[34]
Boik, J. Natural compounds in cancer therapy: Promising nontoxic antitumor agents from plants and other natural sources. J. Nat. Prod., 2001, 64(12), 1605-1606.
[35]
Sajjadi, S.E.; Ghanadian, M.; Mouhebat, L. Cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells. J. Herb. Med. pharm., 2015, 4, 15-19.
[36]
Manosroi, A.; Akazawa, H.; Akihisa, T.; Jantrawut, P.; Kitdamrongtham, W.; Manosroi, W.; Manosroi, J. In vitro anti-proliferative activity on colon cancer cell line (HT-29) of Thai medicinal plants selected from Thai/Lanna medicinal plant recipe database “MANOSROI III”. J. Ethnopharmacol., 2015, 161, 11-17.
[http://dx.doi.org/10.1016/j.jep.2014.11.038] [PMID: 25481081]
[37]
Benyagoub, E.; Razni, D.; Moghtet, S. Phytochemical composition of Anastatica hierochuntica L., can it fight the toxigenic bacterial agents responsible for food poisoning? Microbes Health., 2017, 6(1), 5-8.
[http://dx.doi.org/10.3329/mh.v6i1.34063]
[38]
Grigalius, I.; Petrikaite, V. Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules, 2017, 22(12), E2169.
[http://dx.doi.org/10.3390/molecules22122169] [PMID: 29215574]
[39]
Tiwari, P.; Kumar, B.; Kaur, M.; Kaur, G.; Kaur, H. Phytochemical screening and extraction: A review. Int. Pharm. Sci., 2011, 1(1), 98-106.
[40]
Roopashree, K.M.; Naik, D. Advanced method of secondary metabolite extraction and quality analysis. J. Pharm. Phytochem, 2019, 8(3), 1829-1842.
[41]
Hanganu, D.; Vlase, L.; Filip, L.; Sand, C.; Mirel, S.; Indrei, L.L. The study of some polyphenolic compounds from Melissa officinalis L. (Lamiaceae). Rev. Med. Chir. Soc. Med. Nat. Iasi, 2008, 112(2), 525-529.
[PMID: 19295032]
[42]
Chua, L.S.; Lau, C.H.; Chew, C.Y.; Dawood, D.A.S. Solvent fractionation and acetone precipitation for crude saponins from Eurycoma longifolia extract. Molecules, 2019, 24(7), 1416.
[http://dx.doi.org/10.3390/molecules24071416] [PMID: 30974893]
[43]
Yan, X.; Qi, M.; Li, P.; Zhan, Y.; Shao, H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell Biosci., 2017, 7(1), 50.
[http://dx.doi.org/10.1186/s13578-017-0179-x] [PMID: 29034071]
[44]
Chung Weng, P.; Nurestri, S.; Abd Malek, S.N.; Ibrahim, H.; Wahab, N. Antioxidant properties of crude and fractionated extracts of Alpinia mutica rhizomes and their total phenolic content. Afr. J. Pharm. Pharmacol., 2010, 5, 842-852.
[45]
Nordin, M.L.; Abdul Kadir, A.; Zakaria, Z.A.; Abdullah, R.; Abdullah, M.N.H. In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231. BMC Complement. Altern. Med., 2018, 18(1), 87.
[http://dx.doi.org/10.1186/s12906-018-2153-5] [PMID: 29530022]
[46]
Sun, Z.X.; Zhang, Y.H.; Cheng, S.; Ma, Q.W.; Guo, S.L.; Zhang, J.B. Anti-tumor effect of ethanol extracts from Thymus quinquecostatus Celak on human leukemia cell line. J. Chin. Integr. Med., 2005, 3(5), 382-385.
[http://dx.doi.org/10.3736/jcim20050513]
[47]
Rawat, P.; Saroj, L.M.; Kumar, A.; Singh, T.D.; Tewari, S.K.; Pal, M. Phytochemicals and cytotoxicity of Launaea procumbens on human cancer cell lines. Pharmacogn. Mag., 2016, 12(Suppl. 4), S431-S435.
[http://dx.doi.org/10.4103/0973-1296.191452] [PMID: 27761070]
[48]
Hatmal, Mm; Aderrahman, S; Alsholi, D. Determining the anti-tumor effects of differnt extracting methods of Arum palaestinum on different cancer cell lines by in vitro assay. Pharmacologyonline, 2017, 2017, 1.
[49]
Saranya, R.; Ali, M.; Anuradha, V. Phytochemical, fluorescence screening and gc-ms analysis of various crude extracts of Anastatica hierochuntica. J. Pharma. Chem. Bio. Sci., 2019, 7(1), 44-56.
[50]
Bolton, J.L.; Dunlap, T. Formation and biological targets of quinones: Cytotoxic versus cytoprotective effects. Chem. Res. Toxicol., 2017, 30(1), 13-37.
[http://dx.doi.org/10.1021/acs.chemrestox.6b00256] [PMID: 27617882]
[51]
Chen, P.Y.; Tien, H.J.; Chen, S.F.; Horng, C.T.; Tang, H.L.; Jung, H.L.; Wu, M.J.; Yen, J.H. Response of myeloid leukemia cells to luteolin is modulated by differentially expressed pituitary tumor-transforming gene 1 (PTTG1) oncoprotein. Int. J. Mol. Sci., 2018, 19(4), 1173.
[http://dx.doi.org/10.3390/ijms19041173] [PMID: 29649138]
[52]
Danışman Kalındemirtaş, F.; Birman, H.; Candöken, E.; Bilgiş Gazioğlu, S.; Melikoğlu, G.; Kuruca, S. Cytotoxic effects of some flavonoids and imatinib on the k562 chronic myeloid leukemia cell line: Data analysis using the combination index method. Balkan Med. J., 2019, 36(2), 96-105.
[http://dx.doi.org/10.4274/balkanmedj.galenos.2018.2017.1244] [PMID: 30396879]
[53]
Ahvazi, M.; Khalighi-Sigaroodi, F.; Charkhchiyan, M.M.; Mojab, F.; Mozaffarian, V-A.; Zakeri, H. Introduction of medicinal plants species with the most traditional usage in alamut region. Iran. J. Pharm. Res., 2012, 11(1), 185-194.
[PMID: 24250441]
[54]
Artun, F.; Karagoz, A. In vitro anticancer and cytotoxic activities of some plant extracts on hela and vero cell lines. In: Proc (MPDI); , 2017; 1, p. (10)1019.
[55]
Alsemari, A.; Alkhodairy, F.; Aldakan, A.; Al-Mohanna, M.; Bahoush, E.; Shinwari, Z.; Alaiya, A. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement. Altern. Med., 2014, 14, 114.
[http://dx.doi.org/10.1186/1472-6882-14-114] [PMID: 24679057]
[56]
Williams, G.H.; Stoeber, K. The cell cycle and cancer. J. Pathol., 2012, 226(2), 352-364.
[http://dx.doi.org/10.1002/path.3022] [PMID: 21990031]
[57]
Shah, A. Kaff-E-Maryam (Anastatica hierochuntica L. ): Evaluation of gastro-protective activity and toxicity in different experimental models. Biol. Med., 2014, 6, 1000197.
[58]
Botham, P.A. Acute systemic toxicity prospects for tiered testing strategies. Toxicol. In Vitro., 2004, 18(2), 227-230.
[http://dx.doi.org/10.1016/S0887-2333(03)00143-7] [PMID: 14757114]
[59]
Patlolla, B.P.; Patlolla, A.K.; Tchounwou, P.B. Cytogenetic effects of 1,1-dichloroethane in mice bone marrow cells. Int. J. Environ. Res. Public Health., 2005, 2(1), 101-106.
[http://dx.doi.org/10.3390/ijerph2005010101] [PMID: 16705807]
[60]
Culvenor, C.C.; Dann, A.T.; Dick, A.T. Alkylation as the mechanism by which the hepatotoxic pyrrolizidine alkaloids act on cell nuclei. Nature, 1962, 195, 570-573.
[http://dx.doi.org/10.1038/195570a0] [PMID: 13882603]
[61]
Abderrahman, S.M.; Abdallah, S. M.M H. Genotoxic and cytotoxic effects of alkaloids extracted from Rubia cordifolia roots on mice bone marrow cells. Toxicol. Lett., 2016, 258, S94.
[http://dx.doi.org/10.1016/j.toxlet.2016.06.1410]
[62]
Shehab, A.; Adam, Z. Mitotic effect of water extract of Anastatica hierochuntica L. on Allium cepa. Cytologia (Tokyo), 1983, 48(2), 343-348.
[http://dx.doi.org/10.1508/cytologia.48.343]
[63]
Jois, H.S.; Kale, A.D.; Mohan Kumar, K. Micronucleus as potential biomarker of oral carcinogenesis. IJDA, 2010, 2(2), 197-202.
[64]
Zaizuhana, S.; Puteri J Noor, M.B.; Noral’ashikin, Y.; Muhammad, H.; Rohana, A.B.; Zakiah, I. The in vivo rodent micronucleus assay of Kacip Fatimah (Labisia pumila) extract. Trop. Biomed., 2006, 23(2), 214-219.
[PMID: 17322824]
[65]
Nefic, H.; Musanovic, J.; Metovic, A.; Kurteshi, K. Chromosomal and nuclear alterations in root tip cells of Allium cepa L. Induced by alprazolam. Medical archives, 2013, 67(6), 388-392.
[66]
Abderrahman, S.; Soliman, S.; Mohammad, M. Genotoxic effects of Peganum harmala L. in relation to traditional use. J. Pharm. Phyto., 2018, 10, 167-173.
[67]
Tucker, J.D.; Auletta, A.; Cimino, M.C.; Dearfield, K.L.; Jacobson-Kram, D.; Tice, R.R.; Carrano, A.V. Sister-chromatid exchange: Second report of the Gene-Tox Program. Mutat. Res., 1993, 297(2), 101-180.
[http://dx.doi.org/10.1016/0165-1110(93)90001-4] [PMID: 7687323]
[68]
Giri, S.; Giri, A.; Sharma, G.D.; Prasad, S.B. Induction of sister chromatid exchanges by cypermethrin and carbosulfan in bone marrow cells of mice in vivo. Mutagenesis, 2003, 18(1), 53-58.
[http://dx.doi.org/10.1093/mutage/18.1.53] [PMID: 12473735]
[69]
Abderrahman, S.M.; Shbailat, S.J. Genotoxic and cytotoxic effects of Artemisia herba-alba on mammalian cells. Caryologia, 2014, 67(4), 265-272.
[http://dx.doi.org/10.1080/0144235X.2014.974355]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy