The underexploited biotechnology of overexploited Origanum species: Status, knowledge gaps, prospects and potential
DOI:
https://doi.org/10.14719/pst.2020.7.4.816Keywords:
Oregano, Marjoram, Plant regeneration, Genetic transformation, Anticancer, Therapeutic, CarvacrolAbstract
The genus Origanum is a group of phytochemically diverse, aromatic species. Distributed mainly in Eurasia and Mediterranean, they are used in traditional medicine, cosmetics and for culinary purposes. They possess antiproliferative, antioxidant, antiviral, antiseptic, anti-inflammatory, anti-hypertensive properties. The major constituents of Origanum spp. are carvacrol and/or thymol together with ?-terpinene, p-cymene, linalool, terpinene-4-ol and sabinene hydrate. Several flavonoids and glycosides are also found. Although the Origanum spp. can either be cultivated or sourced from nature, high demand has necessitated increased production. Overexploitation from natural habitat has threatened these species. Also, due to its poor viability and small-sized seeds, cross-pollination abilities, less productive vegetative propagation, climate-dependent conventional propagation, its genetic improvement has been limited and thus scientific management of available germplasms through biotechnological approach is necessary. For in-vitro propagation, the literature review showed significant differences in culture protocols, genotypes and their success rates. Studies reported cell culture-based production of secondary metabolites or isolation of active compounds in different species of Origanum, which show antiproliferative activity in cancerous cell lines. However, significant knowledge gaps exist. The urgent need is to use advance technologies in enhancing either plant propagation thus the production of source material for active constituents or for genetic improvement of Origanum germplasms for contents, as well as to validate the therapeutic potential of Origanum constituents. This review critically appraises the status of mostly underexploited biotechnological know-how and research on highly valued medicinal herbs, Origanum and throws light on prospects and potential.
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References
Davuluri S, Dharmarajan TS. Complementary and alternative medicine- herbals and supplements: a review for the primary care physician. Cureus. 2014; 6(6):e184. https://doi.org/10.7759/cureus.184
Balick MJ. Transforming ethnobotany for the new millennium. Ann Missouri Bot Gard. 1996; 83(1): 58–66.. https://doi.org/10.2307/2399968
Voeks RA, Leony A. Forgetting the forest: assessing medicinal plant erosion in Eastern Brazil. Econ Bot. 2004;58 (s): S294–06. https://doi.org/10.1663/00130001(2004)58[S294:FTFA MP]2.0.CO;2
Chishti S, Kaloo ZA, Sultan P. Medicinal importance of genus Origanum: A review. J Pharmacognosy Phytother. 2013;5(10):170–77. https://doi.org/10.5897/JPP2013.0285
Ietswaart JH. A taxonomic revision of the genus Origanum (Labiatae). Leiden Botanical series. Leiden: Leiden University Press; 1980:1–160.https://doi.org/10.1007/978-94-009-9156-9_1
Snogerup S. Evolutionary and plant geographical aspects of Chasmophytic communities. In: Davis PH, Harper PC, Hedge IC, (editors). Plant Life of South–West Asia. Edinburgh: The Botanical Society; 1971:157–70.
Prerna, Vasudeva N. Origanum majorana L. -Phyto-pharmacological review. Indian J Nat Prod Resour. 2015;6(4):261–67.
Kintzios SE. Profile of the multifaceted prince of the herbs. In: Kintzios SE, (editor). Oregano: the genera Origanum and Lippia. London : Taylor & Francis; 2002:236–42.
Fleisher A, Fleisher Z. Identification of Biblical Hyssop and origin of the traditional use of oregano-group herbs in the mediterranean region. Econ Bot. 1988;42(2): 232–41. https://doi.org/10.1007 /BF02858924
Sharma PV. Indian medicine in the classical age. Varanasi: Chaukhamba Amarabharati Prakashan; 2000:134–212.
Tripathy B, Satyanarayana S, Abedulla Khan K, Raja K. An updated review on traditional uses, taxonomy, phytochemistry, pharmacology and toxicology of Origanum majorana. Int J Pharma Res Health Sci. 2017;5:1717–23. https://doi.org/10.21276/ijprhs.2017.04.01
Kordali S, Cakir A, Ozer H, Cakmakci R, Kesdek M, Mete E. Antifungal phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum occidentis and its three components, carvacrol, cymol, p-cymene. Bioresour Technol. 2008;99(18): 8788–95. https://doi.org/10.1016/ j.biortech.2008.04.048
Dudus LE, Bodrug MV, Nemtsanu NN, Kokosh EN, Shashlik sauce. USSR Patent No. 906497, 1982.
Busatta C, Vidal RS, Popiolski AS, Mossi AJ, Dariva C, Rodrigues MR, Corazza FC, Corazza ML, Vladimir Oliveira J, Cansian RL. Application of Origanum majorana L. essential oil as an antimicrobial agent in sausage. Food Microbiol. 2008;25:207–11. https://doi.org/10.1016/j.fm.2007.07.003
Faleiro L, Miguel G, Gomes S, Costa L, Venâncio F, Teixeira A, Figueiredo AC, Barroso JG, Pedro LG. Antibacterial and antioxidant activities of essential oils isolated from Thymbra capitata (L.) Cav. and Origanum vulgare L. J Agric Food Chem. 2005;53(21): 8162–68. https://doi.org/10.1021/ jf0510079
Farrell KT. Spices, condiments, and seasonings. westport: AVI Publishing Company Inc.; 1985:6:415. https://doi.org/10.1002/food.19860301083
Assaf MH, Ali AA, Makboul MA, Beck JP, Anton R. Preliminary study of phenolic glycosides from Origanum majorana, quantitative estimation of arbutin, cytotoxic activity of hydroquinone. Planta Med. 1987;53(4):343–45. https://doi.org/10.1055/s-2006-962734
Ayesh BM, Abed AA, Faris DM. In- vitro inhibition of human leukemia THP-1 cells by Origanum syriacum L. and Thymus vulgaris L. extracts. BMC Res Notes. 2014;7:612. https://doi.org/10.1186/1756-0500-7-612
Benhalilou N, Alsamri H, Alneyadi A, Athamneh K, Alrashedi A, Altamimi N, Al Dhaheri Y, Eid AH, Iratni R. Origanum majorana ethanolic extract promotes colorectal cancer cell death by triggering abortive autophagy and activation of the extrinsic apoptotic pathway. Front Oncol. 2019; 9:795. https://doi.org/10.3389/fonc.2019.00795
Beker R, Dafni A, Eisikowitch D, Ravid U. Volatiles of two chemotypes of Majorana syriaca L. (Labiatae) as olfactory cues for the honeybee. Oecologia. 1989;79(4):446–51. https://doi.org/10.1007/BF00378659
Jablonski B. Nectar secretion and honey productivity of important honey plants in polish conditions. Pszczelnicze Zeszyty Naukowe. 1986;30:195–05.
Long LT, Koeniger N, Fuchs S. Varroa treatment with combination of formic acid and oil of marjoram: laboratory tests and field experiments. Apidologie. 1997;28(3–4):179–81.
Milhau G, Valentin A, Benoit F, Mallie M, Bastide JM, Pelissier Y, Bessiere JM. In-vitro antimalarial activity of eight essential oils. J Essent Oil Res. 1997;9(3):329–33. https://doi.org/10.1080/10412905.1997.10554252
Baricevic D, Milevoj L, Borstnik J. Insecticidal effect of oregano (Origanum vulgare L. ssp. hirtum Ietswaart) on the dry bean weevil (Acanthos celidesobtectus Say). Int J Hortic Sci. 2001; 7(2): 84–88. https://doi.org/10.31421/IJHS/7/2/272
Shaaya E, Kostjukovski M, Eilberg J, Sukprakarn C. Plant oils as fumigants and contact insecticides for the control of stored-product insects. J Stored Prod Res. 1997; 33(1):7–15. https://doi.org/10.1016/S0022-474X(96)00032-X
Tunc I, Sahinkaya S. Sensitivity of two greenhouse pests to vapours of essential oils. Entomol Exp et Appl. 1998;86(2):183–87. https://doi.org/10.1046/j.1570-7458.1998.00279.x
Isman MB, Wan AJ, Passreiter CM. Insecticidal activity of essential oils to the tobacco cutworm, Spodoptera litura. Fitoterapia. 2001;72:65–68. https://doi.org/10.1016/s0367-326x(00)00253-7
Abd-Elgawad MM, Omer EA. Effect of essential oils of some medicinal plants on phytonematodes. Anz Schadlingsk, Pflanzenschutz, Umweltschutz. 1995;68(4):82–84. https://doi.org/10.1007/BF01908429
Oka Y, Nacar S, Putievsky E, Ravid U, Yaniv Z, Spiegel Y. Nematicidal activity of essential oils and their components against the root-knot nematode. Phytopathology. 2000;90(7):710–15. https://doi.org/10.1094/PHYTO.2000.90.7.710
Hmamouchi M, Lahlou M, Agoumi A. Molluscicidal activity of some Moroccan medicinal plants. Fitoterapia. 2000;71(3): 308–14. https://doi.org/10.1016/S0367-326X(99)00152-5
Benito M, Jorro G, Morales C, Pelaez A, Fernandez A. Labiatae allergy: systemic reactions due to ingestion of oregano and thyme. Ann Allergy Asthma Immunol. 1996;76(5):416–18. https://doi.org/10.1016/S1081-1206(10)63456-4
Farkas J. Perioral dermatitis from marjoram, bay leaf and cinnamon. Contact Derm. 1981;7(2):121. https://doi.org/10.1111/j.1600-0536.1981.tb03993.x
Futrell JM, Rietschel RL. Spice allergy evaluated by results of patch tests. Cutis. 1993;52(5):288–90. PMID: 8299390.
Brinker F. Herb Contraindications and Drug Interactions. Oregon: Eclectic Medical Publications; 1998;263.
Baricevic D, Bartol T. The biological/pharmacological activity of the Origanum genus. In: Kintzios S (editor). Medicinal and Aromatic Plants—Industrial Profiles. London: Taylor & Francis; 2002;177–14.
Bina F, Rahimi R. Sweet marjoram: a review of ethnopharmacology, phytochemistry and biological activities. J Evid Based Complementary Altern Med. 2017;22:175–85. https://doi.org/10.1177/ 2156587216650793
Akgul A, Bayrak A. Constituents of essential oils from Origanum species growing wild in Turkey. Planta Med. 1987;53(1):114. https://doi.org/10.1055/s-2006-962644
Tumen G, Baser KHC. The essential oil of Origanum syriacum L. var. bevanii (Holmes) Ietswaart. J Essent Oil Res. 1993;5:315–16. https://doi.org/10.1080/10412905.1993.9698227
Kokkini S. Taxonomy, diversity and distribution of Origanum species. In: Proceedings of the IPGRI International Workshop on Oregano; 1996 May 8–12; Italy. Bari:CIHEAM; 1997. p.2–12.
Singla P, Vasudeva N. Pharmacognostical and quality control parameters of Origanum majorana Linn. Stem and root, World J Pharm Pharmaceut Sci. 2014;3(6):1428–37.
Mossa AT, Refaie AA, Ramadan A, Bouajila J. Amelioration of prallethrin-induced oxidative stress and hepatotoxicity in rat by the administration of Origanum majorana essential oil. Biomed Res Int. 2013; 2013:859085. https://doi.org/10.1155/2013/859085
Vallverdu-Queralt A, Regueiro J, Rinaldi Alvarenga JF, Martinez-Huelamo M, Leal LN, Lamuela-Raventos RM. Characterization of the phenolic and anti- oxidant profiles of selected culinary herbs and spices: caraway, turmeric, dill, marjoram and nutmeg. Food Sci Technol (Campinas). 2015;35(1):189–95. https://doi.org/10.1590/1678-457X.6580
Erenler R, Sen O, Aksit H, Demirtas I, Yaglioglu AS, Elmastas M, Telci I. Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities. J Sci Food Agric. 2016;96:822–36. https://doi.org/10.1002/jsfa.7155
El-Moursi A, Talaat IM, Balbaa LK. Physiological effect of some antioxidant polyphenols on sweet marjoram (Majorana hortensis) plants. Nusantara Biosci. 2012;4:11–15. https://doi.org/10.13057/ nusbiosci/n040103
Srinivasan K. Role of spices beyond food flavoring: Nutraceuticals with multiple health effects; Food Reviews International, 2005;21:167–88. https://doi.org/10.1081/FRI-200051872
Oliver GW. The world market of oregano. In: Proceedings of the IPGRI International Workshop on Oregano;1996 May 8–12; Italy. Bari: CIHEAM; 1997. p.141–45.
Cetin B, Cakmaci S, and Cakmakci R. The investigation of antimicrobial activity of thyme and oregano essential oils. Turkish Journal of Agriculture and Forestry. 2011;35(2):145–54. https://doi.org/10.3906/tar-0906-162
Ozkan G, Sagd?c O, Ek?c? l, Ozturk I, Ozcan MM. Phenol?c compounds of Or?ganum s?pyleum L. extract and ?ts ant?ox?dant and ant?bacter?al act?v?t?es. J Food Lipids. 2007;141(2):157–69. https://doi.org/10.1111/j.1745-4522.2007.00077.x
Farashah HD, Afshari RT, Sharifzadeh F, Chavoshinasab S. Germination improvement and ?-amylase and ?-1,3-glucanase activity in dormant and non-dormant seeds of Oregano (Origanum vulgare). Aust J Crop Sci. 2011;5(4):421–27.
Anonymous. Origanum majorana, The Wealth of India-A Dictionary of Indian Raw Material, New Delhi, Council of Scientific and Industrial Research. 1992;98:226–27.
Nanova Zh, Slavova Y. Mass Vegetative Propagation of Winter Marjoram (Origanum vulgare ssp. hirtum (Link) Ietswaart. Bulg J Agric Sci. 2006;12:531–36.
Tejvathi DH, Padma AV. In-vitro multiplication of Majorana hortensis Moench- An aromatic medicinal herb. Indian J Plant Sci. 2012;1(1):48-56.
Leelavathi D, Kuppan N. Callus induction and regeneration of multiple shoots from in-vitro apical bud explant of Origanum vulgare, An important medicinal plant. Int J Res Pharm Chem. 2013;3(4):898–03.
Oluk EA, Çak?r A. Micropropagation of Origanum sipyleum L., an endemic medicinal herb of Turkey. African J Biotechnol. 2009; 8(21): 5769–72. https://doi.org/10.5897/AJB09.1216
Murashige T, Skoog F. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant. 1962;15:473–97. https://doi.org/10.1111/j.1399-3054.1962.tb08052.x
Becker H. Studies on the formation of volatile substances in plant tissue cultures. Biochem. Physiol Pflanzen. 1970;161:425–41. https://doi.org/10.1016/S0015-3796(17)31070-3
Kumari N, Saradhi PP. Regeneration of plants from callus cultures of Origanum vulgare L. Plant Cell Rep. 1992; 11 (9): 476–79. https://doi.org/10.1007/BF00232694
Sajina A, Geetha SP, Minoo D, Rema J, Nirmalbabu K, Sadanandan AK, Ravindran PN. Micropropagation of some important herbal species. In: Proceedings of Biotechnology of Spices, Medicinal and Aromatic Plants; 1996 Apr 24-25; India. Calicut: Indian Society for Spices; 1997. p. 79–86.
Iyer PV, Pai JS. Micropropagation of sweet marjoram (Majorana hortensis Moench). J Spices Aromat Crops. 1998;7(1):47–49.
Iyer PV, Pai JS. In vitro regeneration of Majorana hortensis Moench from callus and nodal segments. J Spices Aromat Crops. 2000;9 (1):47–50.
Yashodabai S, Gayatri MC, Leelavathi D. In-vitro propagation of Oreganum majorana using axillary bud explants. J Cytol Genet. 2011;12:71–75.
Korkor AM, Mohamed SA, Abd Al-Kafie OM, Gohar AA. Adaptation of the in-vitro culture of Origanum majorana L. for production of phenolic acids. Journal of Pharmacy and Biological Sciences. 2017;12(2):30–38. https://doi.org/10.9790/3008-1202013038
Iconomou-Petrovich GN, Nianiou-Obeidat I. Micropropagation of Origanum vulgare subsp. hirtum (Mt. Taygetos). In: Tsekos I, Moustakas M, (editors). Progress in Botanical Research; 1998; Germany. Berlin: Springer; 1998. p. 509–12. https://doi.org/10.1007/978-94-011-5274-7_116
Goleniowski ME, Falmarique C, Bima P. Micropropagation of Oregano (Origanum vulgare x applii) from meristem tips. In-vitro Cell Dev Biol- Plant. 2003;39:125–28. https://doi.org/10.1079/ IVP2002361
Habibi P, Grossi de Sa MF, Lopes da Silva AL, Makhzoum A, da Luz Costa J, Borghetti IA, Soccol CR. Efficient genetic transformation and regeneration system from hairy root of Origanum vulgare. Physiol Mol Biol Plants. 2016;22(2):271–77. https://doi.org/10.1007/s12298-016-0354-2
Sevindik B, Izgu T, Simsek O, Tutunku M, Curuk P, Yilmaz O, Kaynak, G, Aka Cakar Y, Teixeira da Silva JA and Mendi YY. In-vitro Culture of Turkish Origanum sipyleum L. American Journal of Plant Biology. 2017; 2(5-1):32–36. https://doi.org/10.11648/j.ajpb.s.2017020501.16
Ozkum D. In-vitro shoot regeneration of Oregano (Origanum minutiflorum O. Schwarz & Davis). Hacettepe J Biol Chem. 2007;35(2):97–100.
Yildirim MU. Micropropagation of Origanum acutidens (Hand.-Mazz.) Ietswaart using stem node explants. Sci World J. 2013:1-3. https://doi.org/10.1155/2013/276464
El Beyrouthy M, Elian G, AbouJaoudeh C, Chalak, L. In-vitro propagation of Origanum syriacum and Origanum ehrenbergii. Acta Hortic. 2015;1083:169–72. https://doi.org/10.17660/ActaHortic.2015.1083.19
Abdallah SAS, Yakoup MYA and Abdalla MYH. Micropropagation of Oregano (Origanum syriacum L.) through tissue culture technique. J Plant Prod, Mansoura Univ. 2017; 8 (5): 635 –39. https://doi.org/10.21608/jpp.2017.40497
Avtar H, Colgecen H. Regeneration in Origanum onites L. by Plant Tissue Culture. Karaelmas Sci Eng J 2019;9(2):177–80. http://dx.doi.org/10.7212%2Fzkufbd.v9i2.1237
Arafeh RM, Shibli RA, Al-Mahmoud M, Shatnawi MA. Callusing, cell suspension culture and secondary metabolites production in Persian Oregano (Origanum vulgare L.) and Arabian Oregano (O. syriacum L.). Jordan J Agric Sci. 2006;2(3):274–81.
El-Gengaihi S, Taha HS, Kamel AM. In-vivo and in-vitro comparative studies of Origanum species. J Food Agric Environ. 2006;4 (3&4):127–34.
Hussein Y, Amin G, Hashem E-S, Youssef K. In-vitro Cultivation of Marjoram (Origanum majorana L.) under influence of 2, 4-D (2, 4-Dichlorophenoxy Acetic Acid) as herbicide. Life Sci J. 2014;11(2):249–57.
Gamborg OL, Miller RA, Ojima K. Nutrient requirements of suspension cultures of soybean root cells. Exp Cell Res. 1968;50:151- 58. https://doi.org/10.1016/0014-4827(68)90403-5
Nitsch JP, Nitsch C. Haploid plants from pollen grains. Science. 1969; 163: 85–87. https://doi.org/10.1126/science.163.3862.85
Phillips GC, Collins GB. In-vitro tissue culture of selected legumes and plant regeneration from callus of Red clover. Crop Sci. 1979;19:59–64. https://doi.org/10.2135/cropsci1979. 0011183X001900010014x
Linsmaier EM, Skoog F. Organic growth factor requirements of tobacco tissue cultures. Physiol Plant. 1965; 18:100–27. https://doi.org/10.1111/j.1399-3054.1965.tb06874.x
Shetty K, Curtis OF, Levin RE, Witkowski R, Ang W. Prevention of vitrification associated with in-vitro shoot culture of Oregano (Origanum vulgare) by Pseudomonas spp. J Plant Physiol. 1995;147(3-4):447–51. https://doi.org/10.1016/S0176-1617(11)82181-4
Shetty K, Curtis O F and Levin RE. Specific interaction of mucoid strains of Pseudomonas spp. with oregano (Origanum vulgare) clones and the relationship to prevention of hyperhydricity in tissue culture. J Plant Physiol. 1996;149(5):605–11. https://doi.org/10.1016/S0176-1617(96)80341-5
Ueno K, Shetty K. Effect of selected polysaccharide-producing soil bacteria on hyperhydricity control in Oregano tissue cultures. Appl Environ Microbiol. 1997; 63(2): 767–70. https://doi.org/10.1128/AEM.63.2.767-770.1997
Bafana A. Diversity and metabolic potential of culturable root-associated bacteria from Origanum vulgare in sub-Himalayan region. World J Microbiol Biotechnol. 2013;29:63–74. https://doi.org/10.1007/s11274-012-1158-3
Abdel-Massih RM, Fares R, Bazzi S, El-Chami N, Baydoun E. The apoptotic and anti-proliferative activity of Origanum majorana extracts on human leukemic cell line. Leukemia Research. 2010;34:1052–56. https://doi.org/10.1016/j.leukres.2009.09.018
Hussain AI, Anwar F, Rasheed S, Nigam PS, Janneh O, Sarker SD. Composition, antioxidant and chemotherapeutic properties of the essential oils from two Origanum species growing in Pakistan. Rev Bras Farmacogn. 2011; 21(6):943–52. https://doi.org/10.1590/S0102-695X2011005000165
El Babili F, Bouajila J, Souchard JP, Bertrand C, Bellvert F, Fouraste I, Moulis C, Valentin A. Oregano: Chemical analysis and evaluation of its antimalarial, antioxidant and cytotoxic activities. J Food Sci. 2011;76:512–18. https://doi.org/10.1111/j.1750-3841.2011.02109.x
Dhaheri YA, Attoub S, Arafat K, AbuQamar S, Viallet J, Saleh A, Agha HA, Eid A, Iratni R. Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: Inhibition of NF?B signaling and reduction of nitric oxide production. Plos One. 2013;8(7):e68808. https://doi.org/10.1371/journal.pone.0068808
Rao S, Timsina B, Nadumane VK. Evaluation of the anticancer potentials of Origanum marjorana on fibrosarcoma (HT-1080) cell line. Asian Pac J Trop Dis. 2014;4(1):S389–S394. https://doi.org/10.1016/S2222-1808(14)60476-X
Elshafie HS, Armentano MF, Carmosino M, Bufo SA, De Feo V, Camele I. Cytotoxic activity of Origanum vulgare L. on hepatocellular carcinoma cell line HepG2 and evaluation of its biological activity. Molecules. 2017; 22:1435:1–16. https://doi.org/10.3390/molecules22091435
Makrane H, El Messaoudi M, Melhaoui A, El Mzibri M, Benbacer L, Aziz M. Cytotoxicity of the aqueous extract and organic fractions from Origanum majorana on human breast cell line MDA-MB-231 and human colon cell line HT-29. Adv Pharmacol Sci. 2018;3297193:1–9. https://doi.org/10.1155/2018/3297193
Spyridopoulou K, Fitsiou E, Bouloukosta E, Tiptiri-Kourpeti A, Vamvakias M, Oreopoulou A, Papavassilopoulou E, Pappa A, Chlichlia K. Extraction, chemical composition and anticancer potential of Origanum onites L. Essential Oil Molecules. 2019;24:2612:1–15. https://doi.org/10.3390/molecules24142612
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