Evaluation of extracts of wild Cannabis sativa L. for genotoxicity and phytochemical composition
Keywords:Medicinal cannabis, Phenolics, Modulatory effects, Cyclophosphamide, Ethyl methanesulphonate, Lesotho.
Cannabis sativa L. is used as medicine and narcotic in Lesotho. Phytochemical composition and total phenolics content (TPC) for hexane, chloroform, ethyl acetate a methanol extracts of aerial parts of C. sativa were determined. Ethyl acetate extract (0.1875, 0.375 and 0.75 mg mL-1) and methanol extract (0.75, 1.5 and 3.0 mg mL-1) were evaluated for cytotoxicity, genotoxicity and modulation of cyclophosphamide (CP, 1.25 mg mL-1)- and ethylmethane sulphonate (EMS, 0.25 mg mL-1)-induced genotoxicity using Allium cepa root meristem assay. CP or EMS did not reduce mitotic index (MI) of cells, hence not cytotoxic when compared with negative control using the t-test (p>0.05), but genotoxic. Both extracts were genotoxic with methanol extract also being cytotoxic. Genotoxicity was the number of aberrant cells per 100 mitotic cells. The modulatory effect (ME) was obtained by comparing mutagen-induced genotoxicity with mixture-induced genotoxicity and expressed as the number of units of mutagen-induced genotoxicity that equalled the mixture-induced genotoxicity. ME was either positive or negative and significant only if ME = ≥ 2. Both extracts were genotoxic with methanol extract also being cytotoxic. Aberrations observed were sticky chromosomes, c-metaphase, anaphase and telophase bridges, chromosome fragments and laggards. Mixture of methanol extract with CP or EMS was more genotoxic (+ME range = 1.61-11.89) than the mutagen or extract alone which suggested synergistic interaction. Mixture of ethyl acetate extract with CP induced insignificant +ME. Mixture of ethylacetate extract with EMS was significantly more genotoxic (+ME = 2.20) than EMS only at high extract concentration. TPCs for hexane, chloroform, ethyl acetate and methanol extracts were 39831.46, 2544.94, 2438.20 and 56601.12 mg GAE/gram dry weight respectively. The differences in the cytotoxicity and MEs of the extracts were attributed to differences in phytochemical composition.
Keywords: Medicinal cannabis, Phenolics, Modulatory effects, Cyclophosphamide, Ethyl methanesulphonate, Lesotho.
Abraham S, Kosly MP. 1979. Mutagenic potential of green chilies. Cytologia. 44(1):221–225.
Adams M, Gmünder F, Hamburger M. 2007. Plants traditionally used in age related brain disorders - a survey of ethnobotanical literature.Journal of Ethnopharmacology. 113 (363–381): 3.
Akeem A, Mohamed KB, Asmawi MZ, Sofiman OA. 2011. Mutagenic and antimutagenic potentials of fruit juices of five medicinal plants in Allium cepa L.: Possible influence of DPPH free radical scavengers. African Journal of Biotechnology. 10(51):10520-10529.
Akinboro A, Bakare AA. 2007. Cytotoxic and genotoxic effects of aqueous extracts of five medicinal plants on Allium cepa Linn. Journal of Ethopharmacology. 112(3):470–475.
Akintonwa A, Awodele O, Afolayan G, Coker HA. 2009. Mutagenic screening of some commonly used medicinal plants in Nigeria. Journal of Ethopharmacology. 125(3): 461-470.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. 2008. Molecular Biology of the Cell, 1601, Garland Science, New York.
Andre CM, Hausman J-F, Guerriero G. 2016. Cannabis sativa: the plant of the thousand and one molecule. Frontiers in Plant Science. 7:19-26.
Asche C. 2005. Antitumour quinones. Mini Reviews in Medicinal Chemistry. 5(5): 449-467.
Ashton CH. 2001. Pharmacology and effects of cannabis: a brief review. The British Journal of Psychiatry. 178: 101-106.
Asita AO, Heisi DH, Tjale T. 2015. Modulation of Mutagen-Induced Genotoxicity by two Lesotho Medicinal Plants in Allium cepa L. Environment and Natural Resources Research. 5(3): 37-55.
Asita AO, Moramang S, Rants’o T, Magama S. 2017. Modulation of mutagen-induced genotoxicity by vitamic C and medicinal plants in Allium cepa, L. Caryologia. 70(2): 151-165.
Audu BS, Ofojekwu PC, Ujah A, Ajima MNO. 2014. Phytochemical, proximate composition, amino acid profile and characterization of Marijuana (Cannabis sativa L.). The Journal of Phytopharmacology. 3(1):35-43.
Aydemir N, Çelikler S, Summak S, Yılmaz D, Özer Ö. 2008. Evaluation of clastogenicity of 4,6-Dinitro-ocresol (DNOC) in Allium root tip test. Journal of Biodiversity and Environmental Sciences. 2(5): 59-63.
Azwanida N. 2015. A review on the extraction methods use in medicinal plants, principle, strength and limitation. Medicinal and Aromatic Plants. 4(3):196-202.
Babich H, Segall MA, Fox KD. 1997. The Allium test— a simple, eukaryote genotoxicity assay. American Biology Teacher. 59(9): 580-583.
Balandrin MF, Klocke JA, Wurtele ES, Bollinger WH. 1985. Natural plant chemicals: sources of industrial and medicinal materials. Science. 228 (4704):1154-1160.
Bang RP, Rosario RMD, Palmes ND. 2015. Phytochemical profiles and antioxidant activity of selected indigenous vegetables in Northern Mindanao, Philippines. International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering 9(8): 855-860.
Bedini S, Flamini G, Cosci F, Ascrizzi R, Benelli G, Conti B. 2016. Cannabis sativa and Humulus lupulus essential oils as novel control tools against the invasive mosquito Aedes albopictus and fresh water snail Physella acuta.Industrial Crops and Products. 85:318-323.
Bennett C. 2010. Early/ancient history. In: Holland J, ed. The Pot Book: A Complete Guide to Cannabis. Rochester, Vermont: Park Street Press.
Bidau CJ, Amat AG, Yajia M, Marti DA, Riglos AG, Silvestroni A. 2004. Evaluation of the genotoxicity of aqueous extracts of Ilex paraguariensis St. Hil. (Aquifoliaceae) using the Allium test.Cytologia. 69(2):109-117.
Bloomer J. 2019. Turning Cannabis Into Cash: Agrarian Change and Lesotho’s Evolving Experience. EchoGéo. 48(48). URL : http:// journals.openedition.org/echogeo/17612
Bonciu E, Firbas P, Fontanetti CS, Wusheng J, Karaismailoğlu MC, Liu D, Menicucci F, Pesnya DS, Popescu A, Romanovsky AV, Schiff S, Ślusarczyk J, de Souza CP, Srivastava A, Sutan A, Papini A. 2018. An evaluation for the standardization of the Allium cepa test as cytotoxicity and genotoxicity assay. Caryologia. 71(3): 191-209.
Bourgaud F, Gravot A, Milesi S, Gontier E. 2001. Production of plant secondary metabolites: A historical perspective. Plant Science. 161(5):839-851.
Boyer J, Liu RH. 2004. Apple phytochemicals and their health benefits. Nutrition Journal. 3: 5-19.
Brand EJ, Zhao Z. 2017. Cannabis in Chinese medicine: are some traditional indications referenced in ancient literature related to cannabinoids? Frontiers in Pharmacology. 8:108-118.
Bridgeman MB, Abazia DT. 2017. Medicinal Cannabis: History, Pharmacology, and Implications for the Acute Care Setting. Pharmacy and Therapeutics. 42(3): 180-188.
Brito GS, Neves ES, Oberlaender G. 1996. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. The Journal of Nervous & Mental Disease. 184(2):86-94.
Busch FW, Seid DA, Wei ET. 1979. Mutagenic activity of marijuana smoke condensates. Cancer Letters. 6(6):319-324.
Camparoto ML, Teixeira RO, Mantovani MS, Vicentini VEP. 2002. Effects of Maytenus ilicifolia Mart. and Bauhinia candicans Benth infusions on onion root-tip and rat bone-marrow cells. Genetics and Molecular Biology. 25(1):85-89.
Cauhan LKS, Saxena PN, Gupta SK. 1999. Cytogenetic effects of cypermetrin and fenvalerate on the root meristem cells of Allium cepa. Environmental and Experimental Botany. 42(3):181-189.
Çelik TA, Aslantürk ȌS (2010). Evaluation of cytotoxicity and genotoxicity of Inula viscosa leaf extracts with Allium Test. BioMed Research International. 2010(1):1-9.
Celik TA, Aslanturk ȌS. 2006. Anti-mitotic and antigenotoxic effects of Plantago lanceolata aqueous extract on Allium cepa root tip meristem cells. Biologia. 61(6):693–697.
Çelik TA, Aslantürk ȌS. 2007. Cytotoxic and genotoxic effects of Lavandula stoechas aqueous extracts. Biologia Bratislava. 62(3): 292-296.
Chukwudi IE, Yusha’u M. 2016. Phytochemical screening and brine shrimp lethality assay of the leaf extracts of Cucurbita maxima, Euphorbia hirta, Leptadenia hastata and Mitracarpus scaber. International Journalof Current Research in Life Sciences. 5(5): 579-583.
Chutel L. 2017. This country is tapping into the lucrative marijuana industry that could make Africa rich. The Marijuana Report. News source: https://qz.com/1080156/legalize-weed-lesotho-malawi-and-south-africa-are-all-closer-to-africas-first-legal-marijuana-license/ .
Constantin MJ, Owen ET. 1982. Introduction and perspectives of plant genetic and cytogenetic assay, A report of US EPA Gene-Tox programme. Mutation Research. 99(1):1-12.
Copeland J, Clement N. 2014. The use of cannabis for medical purposes. National Cannabis Prevention and Information Centre Bulletin (NCPIC) (18). Available from: https://www.dalgarnoinstitute.org.au/images/resources/pdf/aod/cannabis-documents/NCPICBulletincannabis-for-medical-purposes.pdf
Debisri S, Archana S, Geeta T. 1996. Plant extracts as modulators of genotoxic effects. The Botanical Review. 62(4):275–300.
Dziwenka M, Coppock R, McCorkle A, Palumbo E, Ramirez C, Lermer S. 2020. Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat- Dose Toxicity Studies in Sprague-Dawley Rats. Toxicology Reports. 7: 376-385.
Efferth T, Koch E. 2011. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Current Drug Targets. 12(1):122–132.
Eid SY, El-Readi MZ, Wink M. 2012. Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells. Phytomedicine. 19(14):1288-1297.
El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M, Slade D, Khan I, ElSohly M, Ross S. 2010. Antidepressant-like effect of Δ9- tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology Biochemistry and Behavior. 95 (4): 434–442.
ElSohly M, Gul W. 2014 In: Roger Pertwee, Editor. Handbook of Cannabis. Published to Oxford Scholarship Online: January 2015. Available from: https://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780199662685.001.0001/acprof-9780199662685-chapter-1?print=pdf
ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. 2017. Phytochemistry of Cannabis sativa L. Progress in the Chemistry of Organic Natural Products. 103:1-36.
ElSohly MA, Slade D. 2005. Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sciences. 78(5):539-48..
Fachinetto JM, Bagatini MD, Silva ACF, Tedesco SB. 2007. Efeito anti-proliferativo das infusões de Achyrocline satureioides DC (Asteraceae) sobre o ciclo celular de Allium cepa. Revista Brasileira de Farmacognosia 17(1):49-54.
Fachinetto JM, Tedesco SB. 2009. Atividade antiproliferativa e mutagênica dos extratos aquosos de Baccharis trimera (Less.) A. P. de Candolle e Baccharis articulate (Lam.) Pers. (Asteraceae) sobre o sistema teste de Allium cepa. Revista Brasileira de Plantas Medicinais 11( 4):360-367.
Fastner J, Flieger I, Neumann U. 1998. Optimised extraction of microcystins from field samples—a comparison of different solvents and procedures. Water Research. 32(10):3177-3181.
Fayera S, Babu NG, Dekebo A, Bogale Y. 2018. Phytochemical Investigation and Antimicrobial Study of Leaf Extract of Plantago lanceolata. Natural Products Chemistry & Research. 6(2): 1-8.
Fiskesjö G. 1985. The Allium test as a standard in environmental monitoring. Hereditas. 102(1):99-112.
Hales BE. 1982. Comparison of the mutagenicity and teratogenicity of cyclophosphamide and its active metabolites, 4 hydroxycyclophosphamide, phosphoramide mustard and acrolein. Cancer Research. 42(8):3016-3021.
Harborne AJ. 1998. Phytochemical Methods A Guide to Modern Techniques of Plant Analysis. Dordrecht: Springer: 1-302.
Herrera-Ruiz M, Roman-Ramos R, Zamilpa A, Tortoriello J, Jimenez-Ferrer JE. 2008. Flavonoids from Tilia americana with anxiolytic activity in plus-maze test. Journal of Ethopharmacology. 118(2):312-317.
Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. 1993. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen elderly study. Lancet. 342(8878):1007-1011.
Higashi K. 1988. Metabolic activation of environmental chemicals by microsomal enzymes of higher plants. Mutation Research. 197(2):273-288.
Higashimoto M, Purintrapiban J, Kataoka K, Kinouchi T, Vinitketkumnuen U, Akimoto S, Matsumoto H, Ohnishi Y. 1993. Mutagenicity and antimutagenicity of extracts of three spices and a medicinal plant in Thailand. Mutation Research. 303(3):135–142.
Ho YS, So KF, Chang RCC. 2010. Anti-aging herbal medicine - how and why can they be used in aging-associated neurodegenerative diseases? Ageing Research Reviews. 9(3):354-362.
Hussein RA, El-Anssary AA. 2018. Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants, Herbal Medicine, Philip F. Builders, IntechOpen. Available from: https://www.intechopen.com/books/herbal-medicine/plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants
Kabarity A, El-Bayoumi A, Habib AA. 1974. Effect of morphine sulphate on mitosis of Allium cepa L. root tips. Biologia Plantarum. 16(4):275–282.
Kassie F, Parzefall W, Musk S, Johnson I, Lamprecht G, Sontag G, Knasmuller S. 1996. Genotoxic effects of crude juices from Brassica vegetables and juices and extracts from phytopharmaceutical preparations and spices of cruciferous plants origin in bacterial and mammalian cells. Chemico-Biological Interactions. 102(1):1–16.
Kauderer B, Zamith H, Paumgartten FJ, Speit G, Holden H. 1991. Evaluation of the mutagenicity of β-myrcene in mammalian cells in vitro. Environmental and Molecular Mtagenesis. 18(1): 28-34.
Kim J C, Bendixen EL. 1987. Effect of haloxyfop and CGA82725 on ciss cycle and cell division of oat (Avena sativa) root tips. Weed Science. 35(6): 769-774.
Knoll MF, Silva ACF, Tedesco SB, Canto-Dorow TS. 2006. Effects of Pterocaulon polystachyum DC. (Asteraceae) on onion (Allium cepa) root-tip cells. Genetics and Molecular Biology. 29(3):539-542.
Laniel L. 1999. Cannabis in Lesotho: a preliminary survey. “Discussion Paper n°34”, Management of Social Transformations connected to the international drug problem (MOST-Drugs), Unesco, Paris. Available from: http://laniel.free.fr/INDEXES/PapersIndex/Cannabis_in_Lesotho_MOST.htm
Leme MD, Marin-Morales MA. 2009. Allium cepa test in environmental monitoring: a review on its application. Mutation Research. 682 (1): 71-81.
Levan A. 1938. The effect of colchicine on root mitoses in Allium. Hereditas. 24(4):471–486.
Liu RH. 2013. Health-promoting components of fruits and vegetables in the diet. Advances in Nutrition. 4(3):384S-392S.
Lu Y, Knoo T, Wiart C. 2014. Phytochemical analysis and antioxidant activity determination on crude extracts of Melodinus eugeniifolus barks and leaves from Malaysia. Pharmacology & Pharmacy. 5(8):773-780.
Magama S, Rants’o T, Asita AO, Taole M. 2018. Evaluation of Procavia capensis hyraceum used in traditional medicine for antioxidant activity. Journal of Medicinal Plants Research. 12(19):248-257.
Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. 2003. Effect of St. John's Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme. Journal of the American Medical Association. 290(11):1500–1504.
Marselos M, Karamanakos P. 1999. Mutagenicity, developmental toxicity and carcinogenicity of cannabis. Addiction Biology. 4(1): 5-12.
Marx TK, Reddeman R, Clewell AE, Endres JR, Béres E, Vértesi A, Glávits R, Hirka G, Szakonyiné IP. 2018. An Assessment of the Genotoxicity and Subchronic Toxicity of a Supercritical Fluid Extract of the Aerial Parts of Hemp. Journal of Toxicology. 2018:1-27
McClatchey WC, Mahady G, Bennett BC, Shiels L, Savo V. 2009. Ethnobotany as a pharmacological research tool and recent developments in CNS-active natural products from ethnobotanical sources. Pharmacology & Therapeutics. 123(2):239–254.
McDonald S, Prenzler PD, Autolovich M, Robards K. 2001. Phenolic
content and antioxidant activity of olive extracts. Food Chemistry.
Merlin MD. 2003. Archaeological evidence for the tradition of psychoactive plant use in the old world. Economic Botany. 57(3):295–323.
Mihailović V, Matić S, Mišić D, Solujić S, Stanić S, Katanić J, Mladenović M, Stanković N. 2013. Chemical composition, antioxidant and antigenotoxic activities of different fractions of Gentiana asclepiadea L. roots extract. Experimental and Clinical Sciences Journal. 12:807-823.
Mitić-Ćulafić D, Žegura B, Nikolić B, Vuković-Gačić B, Knežević-Vukčević J, Filipič M. 2009. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells. Food and Chemical Toxicology. 47(1):260-266.
Mkpenie VN, Essien EE, Udoh II. 2012. Effect of Extraction Conditions on Total Polyphenol Contents, Antioxidant and Antimicrobial Activities of Cannabis sativa L. Electronic Journal of Environmental, Agricultural and Food Chemistry. 11(4): 300 – 307.
Mohn GR, Ellenberger J. 1976. Genetic effects of cyclophosphamide, ifosfamide and trofosfamide. Mutat Res. 32(3-4):331-360.
Moyo M, Amoo SO, Ncube B, Ndhlala AR, Finnie JF, Van Staden J.
2013. Phytochemical and antioxidant properties of unconventional
leafy vegetables consumed in southern Africa. South African Journal
of Botany. 84:65-71.
Mulyaningsih S, Sporer F, Zimmermann S, Reichling J, Wink M. 2010. Synergistic properties of the terpenoids aromadendrene and 1, 8- cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens. Phytomedicine. 17(13):1061-1066.
Mustafa Y, Suna Arikan ES. 2008. Genotoxicity testing of quizalofop-P-ethyl herbicide using the Allium cepa anaphase-telophase chromosome aberration assay. Caryologia. 61(1):45–52.
National Institute on Drug Abuse (NIDA). 2018. Marijuana as Medicine. Available from:https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine.
Nwaoguikpe RN, Ujowundu CO, Emejulu AA. 2014. The antioxidant and free radical scavenging effects of extracts of seeds of some neglected legumes of south-east Nigeria. Scholars Academic Journal of Biosciences. 2(1): 51-59.
Oliveira FdeS, de Freitas TS, da Cruz RP, do Socorro Costa M, Pereira RLS, Quintans-Junior LJ, de Araujo Andrade T, dos Passos Menezes P, de Sousa, Hipolito BM, Nunes PS. 2017. Evaluation of the antibacterial and modulatory potential of α-bisabolol, β- cyclodextrin and α-bisabolol/β-cyclodextrin complex. Biomedicine and Pharmacotherapy. 92: 1111-1118.
Oyedare BM, Bakare AA, Akinboro A. 2009. Genotoxicity assessment of water extracts of Ocimum gratissimum, Morinda lucida and Citrus medica using the Allium cepa assay. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas. 8(2): 97-103.
Padhi L, Panda SK. 2015. Antibacterial activity of Eleutherine bulbosa against multidrug-resistant bacteria. Journal of Acute Medicine. 5(3): 53-61.
Padmanabhan P, Sujana KA. 2008. Animal products in traditional medicine from Attappady hills of Western Ghats. Indian Journal of Traditional Knowledge. 7(2):326-329.
Panigrahy SK, Jatawa S, Tiwari A. 2011. Modulatory effect of chenopodium album extract against cyclophosphamide induced genotoxicity damage in cultured mammalian cells. International Journal of Pharmacy and Pharmaceutical Sciences. 4(1): 541-542.
Parry EM, Mumba LE, Asita A, Parry JM. 1999. Mechanisms of Action of Aneuploidy Inducing Chemicals with Particular Reference to Spindle Inhibitors and Neurotoxins. In: Trends in Environmental Mutagenesis. Sobti RC, Obe G, Quillardet P. (Eds., Tausco Book distributors, New Delhi, India, pp.101-110.
Patil B C, Bhat GI. 1992. A comparative study of MH and EMS in the induction of chromosomal aberration on lateral root meristem in Clitoriatematea L. Cytologia. 57: 295-264.
Pavela R. 2016. History, presence and perspective of using plant extracts as commercial botanical insecticides and farm products for protection against insects—a review. Plant Protection Science. 52:229-241.
Plewa MJ, Gentile JM. 1982. The activation of chemical mutagens by Green plants. In A. Hollander, & F. J. de Serres (Eds.), Chemical Mutagens, Principles and Methods for Their Detection (pp. 401-420). Plenum Vol. VII, New York.
Polit J T, Maszewski J, Kazmierczak A. 2003. Effect of BAP and IAA on the experssion of G1 and G2 control points and G1-S and G2-M transitions in root meristem cells of Vicia faba. Cell Biology International. 27(7): 559-566.
Pollastro F, Minassi A, Fresu L. 2018. Cannabis Phenolics and their Bioactivities. Current Medicinal Chemistry. 25(10):1160-1185.
Priyanka, Mohanka R, Kumari P, Kumar B. 2019. Cytotoxicity Evaluation Of Aqueous Extracts Of Medicinal Plants On Allium cepa L. IOSR Journal of Biotechnology and Biochemistry. 5(2):35-49.
Ramelet A-A. 2015. Chap. 14. Veno-active drugs. In Goldman MP, Guex JJ, Weiss RA. Sclerotherapy, 5th ed. Saunders-Elsevier. Available from: https://clinicalgate.com/venoactive-drugs/
Ranotsi A, Makatjane T, Aiyuk S. 2012. The Extent of Drug Abuse in Lesotho: The Case of Mapoteng Community. Lesotho Medical Association Journal. 10(1):11-18.
Razak MR, Afzan A, Ali R, Jajaluddin A, Wasiman M, Zahari S, Abdullah N, Ismail Z. 2014. Effect of selected local medicinal plants on the asexual blood stafe of chloroquine resistant Plasmodium falciparum. BMC Complimentary and Alternative Medicine 14: 492.
Rios MDD, Katz F. 1975. Some relationships between music and hallucinogenic ritual. The “jungle gym” in consciousness. Ethos. 3(1):64-76.
Salim AA, Chin Y-W, Kinghorn AD. 2008. Drug Discovery from Plants. Bioactive Molecules and Medicinal Plants. Berlin, Heidelberg: Springer. Chapter 1 pp. 1-24
Salvadori DMF, Ribeiro LR, Oliveira MDM, Pereira CAB, Beçak W. 1992. The protective effect of β-carotene on genotoxicity induced by cyclophosphamide. Mutation Research. 265(2):237-244.
Schimmer O, Kruger A, Paulini H, Haefele F. 1994. An evaluation of 55 commercial plant extracts in the Ames mutagenicity test. Pharmazie. 49(6):448–451.
Schultes RE, Hofmann A, Rätsch C. 2001. Plants of the gods: their sacred, healing, and hallucinogenic powers(pp. 124-135). Rochester, VT: Healing Arts Press.
Shale TL, Stirk WA, Van Staden J. 1999. Screening of medicinal plants used in Lesotho for anti-bacterial and anti-inflammatory activity. Journal of Ethnopharmacology. 67(3): 347–354.
Shanmuganathan B, Suryanarayanan V, Sathya S, Narenkumar M, Singh SK, Ruckmani K, Devi KP. 2018. Anti-amyloidogenic and antiapoptotic effect of α-bisabolol against Aβ induced neurotoxicity in PC12 cells. European Journalof Medicinal Chemistry. 143: 1196-1207.
Sharma A, Sen S. 2002. Chromosome Botany, Science, Enfield, NH, USA.
Siegel RK. 1977. Cocaine: recreational use and intoxication. Pp. 119-136 in R.C. Petersen and R.C. Stillman, eds., Cocaine: 1977. NIDA Research Monograph 13. DHHS Pub. No. (ADM) 77-741. Rockville, Md.: National Institute on Drug Abuse.
Singh RJ. 2003. Plant Cytogenetics, CRC Press, Boca Raton, Fla, USA: CRC Press.
Soliman MI. 2001. Genotoxicity testing of neem plant (Azadirachta indica A. Juss.) using the Allium cepa chromosome aberration assay. Journal of Biological Sciences. 1(11):1021-1027.
Soni A, Sheetal S. 2013. Phytochemical analysis and free radical scavenging potential of herbal and medicinal plant extracts. Journal of Pharmacognosy and Phytochemistry. 2(4): 22-29.
Sopova M, Sekovski Z, Jovanovska M. 1983. Cytological effects of tobacco leaf extract on root-tip cells of Allium sativum. Acta Biologiae et Medicinae Experimentalis.8:49-56.
Stubbs L, Carver EA, Cacheiro NL, Shelby M, Generoso W. 1997. Generation and characterization of heritable reciprocal translocations in mice. Methods. 13(4): 397-408.
Suk K. 2005. Regulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseases. A focus on traditional medicines and flavonoids. Neurosignals. 14(1-2):23-33
Tedesco SB, Laughinghouse IVHD. 2012. Bioindicator of genotoxicity: the Allium cepa test. In: Srivastava J, editor.Environmental contamination. Croatia: InTech:p. 137– 156.
Trease GE, Evans CW. 1984. Pharmacognos, 12th ed. Balliere Tindall, London, UK, London.
Trease GE, Evans WC. 2002. Textbook of Pharmacognosy. 15th Ed. Saunders Publishers, London.
Turner CE, ElSohly MA, Boeren EG. 1980. Constituents of Cannabis sativa L. XVII. A review of the natural constituents. Journal of Natural Products. 43(2):169–234.
Uddin G, Feroz S, Ali J, Rauf A. 2014. Antioxidant, antimicrobial activity and phytochemical investigation of Pterospermum acerifolium (Leaf petiole). Wudpecker Journal Agriculture Resource. 3(3): 058-062.
van Wyk B-E, Wink M. 2015. Phytomedicines, Herbal Drugs and Poisons. Briza, Kew Publishing, Cambridge University Press:Cambridge, UK.
Van’t Hof J. 1968. The action of IAA and Kinetine on the mitotic cycle of proliferative and stationary phase excided root meristems. Experimental Cell Research. 51(1): 167-176.
Wink M. 2015. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines, 2(3):251-286
Wong FC, Chai TT, Hoo YW (2012). Antioxidation and cytotoxic activities of selected medicinal herbs used in Malaysia. Journal of Medicinal Plants Research. 6(16): 3169-3175.
Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D. 2015. Chromothripsis from DNA damage in micronuclei. Nature. 522:179–184.
Zhang Z, Chang Q, Zhu M, Huang Y, Ho WKK, Chen ZY. 2001. Characterization of antioxidants present in hawthorn fruits. The Journal of Nutritional Biochemistry. 12(3): 144-152.
Zimmerman S, Zimmerman A. 1990. Genetic Effects of Marijuana. International Journal of Addictions. 25(1): 19-33.
Zink T, Chaffin J. 1998. Herbal health products: what family physicians need to know. American Family Physician. 58(5):1133-1140.
How to Cite
Copyright (c) 2021 Asita Asita, Dr. S. Magama, Thato Moahloli, Selometsi Baholo
This work is licensed under a Creative Commons Attribution 4.0 International License.
- Copyright on any open access article in a journal published byCaryologia is retained by the author(s).
- Authors grant Caryologia a license to publish the article and identify itself as the original publisher.
- Authors also grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details and publisher are identified.
- The Creative Commons Attribution License 4.0 formalizes these and other terms and conditions of publishing articles.
- In accordance with our Open Data policy, the Creative Commons CC0 1.0 Public Domain Dedication waiver applies to all published data in Caryologia open access articles.