Cytogenetic activity of methanolic extract of aerial parts of Plumbago europaea on Balb/C Mouse bone marrow cells

Document Type: Original article

Authors

Department of Biological Sciences, Yarmouk University, Irbid, Jordan;

Abstract

Background & Aim: The World Health Organization (WHO) estimated that majority of the inhabitants of the world rely chiefly on folk medicine. It, therefore, approved the use of herbal products for national policies and drug regulatory measures in order to strengthen research and evaluation of the safety and efficacy of herbal products. We have evaluated the cytotoxic, mutagenic and antimutagenic potential of the methanolic extract of the aerial parts of P. europaea, a common species in the Mediterranean and Central Asia.
Experimental: Male Balb/C mice were intraperitoneally (i. v.) injected with varying doses of the extract dissolved in dimethyl sulfoxide (DMSO). The i.v. LD50 of the extract was determined to be 58.33mg/kg body weight. Bone marrow cells were processed and screened for chromosomal aberration and micronucleus formation. Mitomycin C (MMC, 2mg/kg b. w.) and DMSO (0.5%) served as positive and negative control, respectively. Antimutagenecity was followed by administration of 2mg MMC/kg in the beginning of the first or the last 24h of applying 14.6mg/kg of the extract daily for 7 consecutive days.
Results: The selected doses of the extract elevated mitotic index and increased percentage of aberrant cells compared to the negative control. However, at a dose of 14.6mg/kg, the extract was enough to reduce significantly the toxic effects induced by MMC. This indicated that the P.europaea extract by itself is mutagenic, but antimutatgenic probably at small doses and can modulate the mutagenicity of MMC.
Recommended applications/ industries: These data may help in understanding of therapeutic properties of P. europaea claimed by folk medicine. However, caution regarding indiscriminate use of this plant by the public is necessary. Multiple experiences are needed to rule out any possible side effects and to prove health safety of this natural product before introducing it into the market for therapeutic purposes.

Keywords


Article Title [Persian]

فعالیت سیتوژنتیک عصاره متانولی اندامهای هوایی گیاه Plumbago europaea بر روی سلولهای مغز استخوان Balb/C

Authors [Persian]

  • احمد خلیل
  • حنان بشاره
  • احمد ال-اوکلاه
Department of Biological Sciences, Yarmouk University, Irbid, Jordan;
Abstract [Persian]

Background & Aim: The World Health Organization (WHO) estimated that majority of the inhabitants of the world rely chiefly on folk medicine. It, therefore, approved the use of herbal products for national policies and drug regulatory measures in order to strengthen research and evaluation of the safety and efficacy of herbal products. We have evaluated the cytotoxic, mutagenic and antimutagenic potential of the methanolic extract of the aerial parts of P. europaea, a common species in the Mediterranean and Central Asia.
Experimental: Male Balb/C mice were intraperitoneally (i. v.) injected with varying doses of the extract dissolved in dimethyl sulfoxide (DMSO). The i.v. LD50 of the extract was determined to be 58.33mg/kg body weight. Bone marrow cells were processed and screened for chromosomal aberration and micronucleus formation. Mitomycin C (MMC, 2mg/kg b. w.) and DMSO (0.5%) served as positive and negative control, respectively. Antimutagenecity was followed by administration of 2mg MMC/kg in the beginning of the first or the last 24h of applying 14.6mg/kg of the extract daily for 7 consecutive days.
Results: The selected doses of the extract elevated mitotic index and increased percentage of aberrant cells compared to the negative control. However, at a dose of 14.6mg/kg, the extract was enough to reduce significantly the toxic effects induced by MMC. This indicated that the P.europaea extract by itself is mutagenic, but antimutatgenic probably at small doses and can modulate the mutagenicity of MMC.
Recommended applications/ industries: These data may help in understanding of therapeutic properties of P. europaea claimed by folk medicine. However, caution regarding indiscriminate use of this plant by the public is necessary. Multiple experiences are needed to rule out any possible side effects and to prove health safety of this natural product before introducing it into the market for therapeutic purposes.

Keywords [Persian]

  • آنتی موتاژن
  • اختلالات کروموزومی
  • سیتوتوکسیک
  • گیاهان دارویی
  • موتاژن
  • Plumbago
Afifi, F.U., Kasabri, V. and Abu-Dahab, R. 2011. Medicinal plants from Jordan in the treatment of cancer: Traditional uses vs. in vitro and in vivo evaluations--Part 1. Planta Medica.77:1203-1209.

Ahmed, M.2015. Acute toxicity (lethal dose 50 calculation) of herbal drug Somina in rats and mice. Pharmacy and Pharmacology, 6: 185-189.

Akinboro, A., Baharudeen, I. and Mohamed, K. 2016. Evaluation of cytogenotoxic and antimutagenic Potency of water extract of Centella asiatica Linn. Using the Allium cepa assay. International Food Research Journal, 23(6): 2449-2452.

Alkofahi, A., Batshoun, R., Owais, W. and Najib, N. 1996. Biological activity of some Jordanian, medicinal plant extracts. Fitoterapia, 68:435-442.

Al-Nuri, M.A., Hannoun, M.A., Zatar, N.A., Abu-Eid, M.A., Al-Jondi, W.J. and Hussein, A.I. 1994. Plumbagin, anaturally occurring naphthoquinone: Its isolation, spectrophotometric determination in roots, stems, and leaves in Plumbago europaea L., Spectroscopy Letters, 27:409-416.

Anuf, A.R., Ramachandran, R., Krishnasamy, R., Gandhi, P.S. and Periyasamy, S. 2014. Antiproliferativeeffects of Plumbago rosea and its purified constituent plumbagin on SK-MEL 28 melanoma cell lines. Pharmacognosy Research,6: 312-319.

Aqil, F., Zahin, M. and Ahmad, I. 2008. Antimutagenic activity of methanolic extract of four ayurvedic medicinal plants. Indian Journal of Experimental Biology, 46: 668-672.

Babula, P., Mikelova, R., Adam, V., Kizek, R., Havel, L. and Sladky. Z. 2006. Naphthoquinones--biosynthesis, occurrence and metabolism in plants. Ceska a Slovenskáfarmacie, 55: 151-159.

Berdy, J. 1982. CRC Handbook of Antibiotic Compounds. Volume1-X. CRC Press: Boca Raton, Florida.P. 70.

Castro, F.A.V., Mariani, D., Panek, A.D., Eleutherio, E.C.A. and Pereira, M.D. 2008. Cytotoxicity mechanism of two naphthoquinones (menadione and plumbagin) in Saccharomyces cerevisiae. PLoS One, e 3(12): e3999.

Chaplot, B.B., Dave, A.M. and Jasrai, Y.T. 2006. A Valued medicinal plant-chitrak (Plumbago zeylanica L.): Successful plant regeneration through various explants and field performance. Plant Tissue Culture and Biotechnology, 16:77-84.

Checker, R., Sharma, D., Sandur, S.K., Subrahmanyam, G., Krishnan, S., Poduval, T.B. and Sainis, K.B. 2010.Plumbagin inhibits proliferative and inflammatory responses of T cells independent of ROS generation but by modulating intracellular thiols. Journal of Cellular Biochemistry, 110: 1082-1093.

CSIR. 1969.The Wealth of India. A dictionary of Indian New Materials and Industrial Products. Raw Materials. Ph-Re. Publications and Information Directorate. Council of Scientific Research. New Delhi, India, 8: 394.

Edenharder, R. and Grunhage, D. 2003. Free radical scavenging ability of flavonoids as mechanism of protection against mutagenicity induced by test-butyl hydroxide or Cumene hydroperoxide in Salmonella typhimurium TA 102. Mutation Research, 540: 1-18.

Ganesan, K. and Gani, S.B.2013. Ethnomedical and pharmacological potentials of Plumbago zeylanica L- A Review. American Journal of Phytomedicine and Clinical Therapeutics, 1: 313-337.

Gangabhagirathi, R. and Joshi, R.2015. Antioxidant role of plumbagin in modification of radiation-induced oxidative damage. Oxidants and Antioxidants in Medical Science, 4: 85-90.

Gustafson, D.L. and Pritsos, C.A. 1992. Oxygen radical generation and alkylating ability of mitomycin C bioactivated by xanthine dehydrogenase. Proceedings of the Western Pharmacology Society, 35:147-151.

Karber, G.1931. 50% end-point calculation. Archiv for Experimentelle Pathologie und Pharmakologie, 162: 480-483.

Khalil, A.M. and Dadara, A.A. 1994. The genotoxic and cytotoxic activities of inorganic fluorides in cultured rat bone marrow cells. Archives of Environmental Contamination and Toxicology, 26: 60-63.

Kumar, S., Gautam, S. and Sharma, A.2013. Antimutagenic and antioxidant properties of plumbagin and other naphthoquinones. Mutation Research, 755: 30-41.

Kuroda, Y., Jain, A.K., Tezuka, H. and Kada, T. 1992. Antimutagenicity in cultured mammalian Cells. Mutation Research, 267: 201-209.

Makhafola, T.J. 2014. The in vitro inhibition of genotoxicity by plant extracts and the isolation and characterization of antimutagenic compounds from Combretum microphyllum (Combretaeae). Ph.D.Thesis, Pretoria University.

Matthys, J.K., Wim, Q.J. and Oliver, K. 2007. The engineering of medicinal plants: Prospects and limitations of medicinal plant biotechnology, in: Kayser, O., Quax, W.J. (Eds.). Medicinal Plant Biotechnology, Volume (1), Part (1), Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim, 3.

Muhammad, H.M., Kawkab, Y. and Naqishbandi, A.M. 2009. Quantitative and qualitative analysis of plumbagin in the leaf and root of Plumbago europaea growing naturally in Kurdistan by HPLC. Iraqi Journal of Pharmaceutical Sciences, 18 (Suppl.): 47-53.

Musarrat, J., Aqil, F. and Ahmad, I. 2006. Mutagenicity and antimutagenicity of medicinal plants, In: Ahmad, I., Aqil, F., Owais, M. (Eds.).Modern Phytomedicine: Turning Medicinal Plants into Drug. Wiley-VCH, Germany, pp.271–286.

Nile, S.H. and VeKhobragade, C.N. 2010. Antioxidant activity and flavonoid derivatives of Plumbago zeylanica. Journal of Natural Products, 3: 130-133.

Noel, S., Kasinathan, M. and Rath, S.K. 2006. Evaluation of apigenin using in vitro cytochalasin-Blocked micronucleus assay. Toxicology in Vitro, 20: 1168-1172.

Oran, S.A.S. and Al-Eisawi, D. 2015. Ethnobotanical survey of the medicinal plants in the central mountains (North-South) in Jordan. Journal of Biodiversity and Environmental Sciences, 6:381-400.

Pravin, B., Tushar, D., Vijay, P. and Kishanchnad, K. 2013. Review on plumbagin obtained from Plumbago zeylanica Linn. International Journal of Pharmaceutical Sciences Review and Research, 18: 116-120.

Santhakumari, G., Saralamma, P.G. and Radhakrishnan, N.1980. Effect of plumbagin on cellgrowth and mitosis. Indian Journal of Experimental Biology, 18: 215-218.

Serrilli, A.M., Sanfilippo, V., Ballero, M., Sanna, C., Poli F., Scartezzini, P., Serafini, M. and Bianco, A. 2010. Polar and antioxidant fraction of Plumbago europaea L., a spontaneous plant of Sardinia. Natural Product Research, 24: 633-639.

Shatoor, A.S.2011. Acute and sub-acute toxicity of Crataegus aronia Syn. Azarolus (L.) whole plant aqueous extract in wistar rats. American Journal of Pharmacology and Toxicology, 6: 37-45.

Shawarb, N., Jaradat, N., Abu-Qauod, H., Alkowni, R. and Hussein, F. 2017. Investigation of antibacterial and antioxidant activity for methanolic extract from different edible plant species in Palestine. Moroccan Journal of Chemistry, 5(4):573-579.

Siddique, Y.H., Ara, G., Faisal, M. and Afzal, M. 2011. Protective role of Plumbago zeylanica extract against the toxic effects of ethinylestradiol in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg9 and cultured human peripheral blood lymphocytes. Alternative Medicine Studies, 1:e7.

Siva Kumar, V. and Devaraj, S.N. 2006. Protective effect of Plumbago zeylanica against cyclophosphamide-induced genotoxicity and oxidative stress in Swiss albino mice. Drug and Chemical Toxicology, 29: 279-288.

Solomon, F.E., Sharada, A.C. and Uma Devi, P.1993. Toxic effects of crude root extract of Plumbago rosea (Raktachitraka) on mice and rats. Journal of Ethnopharmacology, 38: 79-84.

Subramaniya, B.R., Srinivasan, G., Sadullah, S.S.M., Davis, N., Subhadara, L.B.R., Halagowder, D., Sivasitambaram, N.D. 2011. Apoptosis inducing effect of plumbagin on colonic cancer cells depends on expression of COX-2. PLoS One, 6:1-11.

Sundari, B.K.R., Telapolu, S., Dwarakanath, B.S. and Thyagarajan, S.P. 2017. Cytotoxic and antioxidant effects in various tissue extracts of Plumbago zeylanica: Implications for anticancerpotential. Pharmacognosy Journal, 9(5):706-712.

Tawaha, K.A. 2006. Cytotoxicity evaluation of Jordanian wild plants using brine shrimp lethality test. Jordanian Journal of Applied Science,8:12-17.

Thitiorul, S., Ratanavalachai, T., Tanuchit, S., Itharat, A. and Sakpakdeejaroenet, I. 2013. Genotoxicity and interference with cell cycle activities by an ethanolic extract from Thai Plumbago indica roots in human lymphocytes in vitro. Asian Pacific Journal of Cancer Prevention, 14 (4): 2487-2490.

Wang, C.C., Chiang, Y.M., Sung, S.C., Hsu, Y.L., Chang, J.K. and Kuo, P.L. 2008. Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Letters, 259: 82-98.