Cultivation and genetics of Artemisia annua L. for increased production of the antimalarial artemisinin

Malaria has been treated for over 350 years with quinine and quinine-derived drugs. However, in several areas of the world, some strains of the malarial parasite Plasmodium falciparum have developed resistance against these drugs. Recently, the World Health Organization (WHO) recommended the use of artemisinin-combination treatments (ACT) as the first-line treatment for multidrug-resistant falciparum malaria. The WHO estimates that current supplies of artemisinin are sufficient for only 30 million ACT, and is foreseeing the need for 130-220 million ACT in 2005 (WHO, 2004). Current research on the production of synthetic artemisinin-like compounds by the Roll Back Malaria project, pharmaceutical companies and academia resulted in a promising synthetic artemisinin-like compound (OZ277) which is currently undergoing phase I clinical trials. In about 5 years this drug is expected to be approved and made available to the public, however, meeting current global demands for ACT depends on the immediate availability of affordable artemisinin-derived drugs. This will involve expansion of the area under cultivation of Artemisia annua and improved methods of cultivation and processing of raw material, associated with more efficient methods for extraction and purification of artemisinin from plant material. This review addresses the agricultural, environmental and genetic aspects that may be useful in the successful large-scale cultivation of A. annua and for producing the antimalarial artemisinin in areas where it is urgently needed today. It also includes geographic aspects (latitude and altitude), which will help make decisions about crop establishment in tropical countries, and includes a list of Good Agricultural and Collection Practices for A. annu

Anthelmintic activity of Cymbopogon martinii, Cymbopogon schoenanthus and Mentha piperita essential oils evaluated in four different in vitro tests

AbstractAnthelmintic resistance is a worldwide concern in small ruminant industry and new plant-derived compounds are being studied for their potential use against gastrointestinal nematodes. Mentha piperita, Cymbopogon martinii and Cymbopogon schoenanthus essential oils were evaluated against developmental stages of trichostrongylids from sheep naturally infected (95% Haemonchus contortus and 5% Trichostrogylus spp.) through the egg hatch assay (EHA), larval development assay (LDA), larval feeding inhibition assay (LFIA), and the larval exsheathment assay (LEA). The major constituent of the essential oils, quantified by gas chromatography for M. piperita oil was menthol (42.5%), while for C. martinii and C. schoenanthus the main component was geraniol (81.4% and 62.5%, respectively). In all in vitro tests C. schoenanthus essential oil had the best activity against ovine trichostrongylids followed by C. martini, while M. piperita presented the least activity. Cymbopogon schoenanthus essential oil had LC50 value of 0.045mg/ml in EHA, 0.063mg/ml in LDA, 0.009mg/ml in LFIA, and 24.66mg/ml in LEA. The anthelmintic activity of essential oils followed the same pattern in all in vitro tests, suggesting C. schoenanthus essential oil could be an interesting candidate for nematode control, although in vivo studies are necessary to validate the anthelmintic properties of this oil

Cultivation And Genetics Of Artemisia Annua L. For Increased Production Of The Antimalarial Artemisinin

Malaria has been treated for over 350 years with quinine and quinine-derived drugs. However, in several areas of the world, some strains of the malarial parasite Plasmodium falciparum have developed resistance against these drugs. Recently, the World Health Organization (WHO) recommended the use of artemisinin-combination treatments (ACT) as the first-line treatment for multidrug-resistant falciparum malaria. The WHO estimates that current supplies of artemisinin are sufficient for only 30 million ACT, and is foreseeing the need for 130-220 million ACT in 2005 (WHO, 2004). Current research on the production of synthetic artemisinin-like compounds by the Roll Back Malaria project, pharmaceutical companies and academia resulted in a promising synthetic artemisinin-like compound (OZ277) which is currently undergoing phase I clinical trials. In about 5 years this drug is expected to be approved and made available to the public, however, meeting current global demands for ACT depends on the immediate availability of affordable artemisinin-derived drugs. This will involve expansion of the area under cultivation of Artemisia annua and improved methods of cultivation and processing of raw material, associated with more efficient methods for extraction and purification of artemisinin from plant material. This review addresses the agricultural, environmental and genetic aspects that may be useful in the successful large-scale cultivation of A. annua and for producing the antimalarial artemisinin in areas where it is urgently needed today. It also includes geographic aspects (latitude and altitude), which will help make decisions about crop establishment in tropical countries, and includes a list of Good Agricultural and Collection Practices for A. annua. © USDA 2005.32206229Acton, N., Klayman, D.L., Rollman, I.J., Reductive electrochemical HPLC assay for artemisinin (qinghaosu) (1985) Planta Medica, 51, pp. 445-446Akhila, A., Rani, K., Thakur, R.S., Biosynthesis of artemisinic acid in Artemisia annua (1990) Phytochemistry, 29, pp. 2129-2132Chemical studies on qinghaosu (artemisinine): China Cooperative Group on Qinghaosu and its Derivatives as Antimalarials (1982) Journal of Traditional Chinese Medicine, 2, pp. 3-8(2004) Novartis Coartem, , http://www.ifpma.org/Health/malaria/health_coartem_mal.aspx, International Federation of Pharmaceutical Manufacturers and AssociationsAvery, M.A., Chong, W.K.M., Jennings-White, C., Stereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua L. (1992) Journal of the American Chemical Society, 114, pp. 974-979Bryson, C.T., Croom, E.M.J., Herbicide inputs for a new agronomic crop, annual wormwood (Artemisia annua) (1991) Weed Technology, 5, pp. 117-124Cai, Y., Jia, J.-W., Crock, J., Lin, Z.-X., Chen, X.-Y., Croteau, R., A cDNA clone for b-caryophyllene synthase from Artemisia annua (2002) Phytochemistry, 61, pp. 523-529Cantliffe, D.J., Industrial processing of vegetable seeds (1997) Journal of the Korean Society of Horticultural Science, 38, pp. 441-455Caruso, L.V., Pearce, R.C., Gilkinson, B., Bush, L.P., Effect of seed pellet modification on spiral root formation of tobacco seedlings (2001) Agronomy Notes, 33 (2), pp. 1-6Chan, K.L., Teo, K.H., Jinadasa, S., Yuen, K.H., Selection of high artemisinin yielding Artemisia annua (1995) Planta Medica, 61, pp. 185-187Charles, D., Simon, J.E., Wood Kvand Heinstein, P., Germplasm variation in artemisinin content of Artemisia annua using an alternative method of artemisinin analysis from crude plant extracts (1990) Journal of Natural Products, 53, pp. 157-160Charles, D.C., Cebert, E., Simon, J.E., Characterization of the essential oil of Artemisia annua L. (1991) Journal of Essential Oil Research, 3, pp. 33-39Charles, D.J., Simon, J.E., Shock, C.C., Feibert, E.B.G., Smith, R.M., Effect of water stress and post-harvest handling on artemisinin content in the leaves of Artemisia annua L. (1993) New Crops, pp. 640-643. , Janick J and Simon JE (eds), New York: John Wiley and SonsChen, F.I., Zhang, G.H., Studies on several physiological factors in artemisinin synthesis in Artemisia annua L. (1987) Plant Physiology Communications, 5, pp. 26-30Chung, B., Effect of plant population density and rectangularity on the growth and yield of poppies (Papaver somniferum) (1990) Journal of Agricultural Science, Cambridge, 115, pp. 239-245De Jesus-Gonzalez, L., Weathers, P.J., Tetraploid Artemisia annua hairy roots produce more artemisinin than diploids (2003) Plant Cell Reports, 21, pp. 809-813Debrunner, N., Dvorak, V., Magalhães, P., Delabays, N., Selection of genotypes of Artemisia annua L. for the agricultural production of artemisinin (1996) Proceedings of An International Symposium on Breeding Research on Medicinal and Aromatic Plants, Quedlinburg, Germany, 30 June-4 July, pp. 222-225. , Pank F (ed.). Quedlinburg: Bundesanstalt für Züchtungsforchung an KulturpflanzenDelabays, N., (1997) Biologie de la Reproducion Chez l'Artemisia annua L. et Génétique de la Production en Artémisinine: Contribution à la Domestication et à l'Amélioration Géné tique de l'Espèce, , PhD Thesis, Faculté des Sciences, Lausanne UniversityDelabays, N., Blanc, C., Collet, G., La culture et la selection d'Artemisia annua L. en vue de la production d'artemisinine (1992) Revue Suisse de Viticulture, Arboriculture et Horticulture, 24, pp. 245-251Delabays, N., Benakis, A., Collet, G., Selection and breeding for high artemisinin (qinghaosu) yielding strains of Artemisia annua (1993) Acta Horticulturae, 330, pp. 203-207Delabays, N., Simonnet, X., Gaudin, M., The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars (2001) Current Medicinal Chemistry, 8, pp. 1795-1801Delabays, N., Darbellay, C., Galland, N., Variation and heritability of artemisinin content in Artemisia annua L. (2002) Artemisia, pp. 197-209. , Wright CW (ed.). London: Taylor & FrancisDelhaes, L., Benoit-Vical, F., Camus, D., Capron, M., Meunier, B., Chloroquine and artemisinin: Six decades of research - What next? (2003) IDrugs, 6, pp. 674-680Dhingra, V., Pakki, S.R., Narasu, M.L., Antimicrobial activity of artemisinin and its precursors (2000) Current Science, 78, pp. 709-713Dong, N.H., Thuan, N.V., Breeding of a high leaf and artemisinin yielding Artemisia annua variety (2003) International Conference on Malaria: Current Status and Future Trends, , Chulabhorn Research Institute, Bangkok, ThailandDuke, M.V., Paul, R.N., Elsohly, H.N., Sturtz, G., Duke, S.O., Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. (1994) International Journal of Plant Sciences, 155, pp. 365-372Duke, S., Paul, R., Development and fine structure of the glandular trichomes of Artemisia annua L. (1993) International Journal of Plant Sciences, 154, pp. 107-118Efferth, T., Dunstan, H., Sauerbrey, A., Miyachi, H., Chitambar, C.R., The anti-malarial artesunate is also active against cancer (2001) International Journal of Oncology, 18, pp. 767-773Elhag, H., Abdel-Sattar, E., El-Domiaty, M., El-Olemy, M., Mosa, J.S., Selection and micropropagation of high artemisinin producing clones of Artemisia annua L. Part II. Follow up of the performance of micropropagated clones (1997) Arab Gulf Journal of Scientific Research, 15, pp. 683-693Elsohly, H.N., A large-scale extraction technique of artemisinin from Artemisia annua (1990) Journal of Natural Products, 53, pp. 1560-1564Farooqi, A.H.A., Shukla, A., Sharma, S., Khan, A., Effect of plant age and GA3 on artemisinin and essential oil yield in Artemisia annua L. (1996) Journal of Herbs, Spices and Medicinal Plants, 4, pp. 73-81Ferreira, J.F.S., (1994) Production and Detection of Artemisinin in Artemisia annua, , PhD Thesis, Purdue University, West Lafayette, INFerreira, J.F.S., Janick, J., Floral morphology of Artemisia annua with special reference to trichomes (1995) International Journal of Plant Sciences, 156, pp. 807-815Ferreira, J.F.S., Janick, J., Production and detection of artemisinin from Artemisia annua (1995) Acta Horticulturae, 390, pp. 41-49Ferreira, J.F.S., Janick, J., Immunoquantitative analysis of artemisinin from Artemisia annua using polyclonal antibodies (1996) Phytochemistry, 41, pp. 97-104Ferreira, J.F.S., Janick, J., Distribution of artemisinin in Artemisia annua (1996) Progress in New Crops, pp. 579-584. , Janick J (ed.). Arlington: ASHS PressFerreira, J.F.S., Janick, J., Production of artemisinin from in vitro cultures of Artemisia annua L. (2002) Biotechnology in Agriculture and Forestry, 51, pp. 1-12Ferreira, J.F.S., Simon, J.E., Janick, J., Developmental studies of Artemisia annua: Flowering and artemisinin production under greenhouse and field conditions (1995) Planta Medica, 61, pp. 167-170Ferreira, J.F.S., Simon, J.E., Janick, J., Relationship of artemisinin content of tissue-cultured, greenhouse-grown, and field-grown plants of Artemisia annua (1995) Planta Medica, 61, pp. 351-355Ferreira, J.F.S., Simon, J.E., Janick, J., Artemisia annua: Botany, horticulture, pharmacology (1997) Horticultural Reviews, 19, pp. 319-371Ferreira, J.F.S., Dhingra, V., Wood, A.J., Biochemistry and genetics of Artemisia annua L. and the production of artemisinin (2004) Genetic Resources and Biotechnology, pp. 270-281. , Thangadurai D, Pullaiah T and Balatti PA (eds). New Delhi: Regency PublicationsFigueira, G.M., Mineral nutrition, production, and artemisinin content in Artemisia annua L. (1996) Acta Horticulturae, 426, pp. 573-577. , Proceedings of the International Symposium on Medicinal and Aromatic PlantsFranz, C., Preface (1983) Acta Horticulturae, 132, p. 13. , Third International Symposium on Spices and Medicinal Plants, Freising-Weihenstephan, Germany, 19 August-4 September 1982Fritz, D., Welcoming address (1978) Acta Horticulturae, 73, pp. 15-16. , First International Symposium on Spices and Medicinal Plants, Freising-Weihenstephan, Germany, 31 July-4 August 1977Galambosi, B., Results of cultural trials with Artemisia annua (1982) Herba Hungarica, 21 (2-3), pp. 119-125Gallup, J.L., Sachs, J.D., The economic burden of malaria (2001) American Journal of Tropical Medicine and Hygiene, 64, pp. 85-96Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M., Barrell, B., Genome sequence of the human malaria parasite Plasmodium falciparum (2002) Nature, 419, pp. 498-511Green, M.D., Mount, D.L., Wirtz, R.A., Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method (2001) Tropical Medicine and International Health, 6, pp. 980-982Haynes, R.K., Vonwiller, S.C., The development of new peroxide antimalarials (1991) Chemistry in Australia, 58 (2), pp. 64-67Hirt, H.M., (2001) Artemisia annua Anameda Plant with Antimalarial Properties (Document), , Winnenden: AnamedHolliday, R., Plant population and crop yield (1960) Nature, 186, pp. 22-24Hua, L., Matsuda, S.P.T., The molecular cloning of 8-epicedrol synthase from Artemisia annua (1999) Archives of Biochemistry and Biophysics, 369, pp. 208-212Jia, J.-W., Crock, J., Lu, S., Croteau, R., Chen, X.-Y., (3R)-Linalool synthase from Artemisia annua L.: CDNA isolation, characterization, and wound induction (1999) Archives of Biochemistry and Biophysics, 372, pp. 143-149Kawamoto, H., Sekine, H., Furuya, T., Production of artemisinin and related sesquiterpenes in Japanese Artemisia annua during a vegetation period (1999) Planta Medica, 65, pp. 88-89Klayman, D.L., Weeding out malaria (1989) Natural History, OCTOBER, pp. 18-26Klayman, D.L., Artemisia annua: From weed to respectable antimalarial plant (1993) Human Medicinal Agents from Plants, pp. 242-255. , Kinghorn AD and Balandri MF (eds). Washington, DC: American Chemical SocietyKlayman, D.L., Lin, A.J., Acton, N., Scovill, J.P., Hock, J.M., Milhous, W.K., Theoharides, A.D., Isolation of artemisinin (qinghaosu) from Artemisia annua growing in the United States (1984) Journal of Natural Products, 47, pp. 715-717Kohler, M., Haerdi, W., Christen, P., Veuthey, J.-L., Extraction of artemisinin and artemisinic acid from Artemisia annua L. using supercritical carbon dioxide (1997) Journal of Chromatography, 785, pp. 353-360Kumar, S., Gupta, S.K., Singh, P., Bajpai, P., Gupta, M.M., Singh, D., Gupta, A.K., Sharma, S., High yields of artemisinin by multi-harvest of Artemisia annua crops (2004) Industrial Crops and Products, 19, pp. 77-90Laughlin, J.C., The effect of band placed nitrogen and phosphorus fertilizer on the yield of poppies (Papaver somniferum L.) grown on krasnozem soil (1978) Acta Horticulture, 73, pp. 165-172Laughlin, J.C., Effect of agronomic practices on plant yield and antimalarial constituents of Artemisia annua L. (1993) Acta Horticulturae, 331, pp. 53-61Laughlin, J.C., Agricultural production of artemisinin - A review (1994) Transactions of the Royal Society of Tropical Medicine and Hygiene, 88, pp. 21-22Laughlin, J.C., The influence of distribution of antimalarial constituents in Artemisia annua L. on time and method of harvest (1995) Acta Horticulturae, 390, pp. 67-73Laughlin, J.C., Post-harvest drying treatment effects on anti-malarial constituents of Artemisia annua L. (2002) Acta Horticulturae, 576, pp. 315-320Laughlin, J.C., Chung, B., Nitrogen and irrigation effects on the yield of poppies (Papaver somniferum L.) (1992) Acta Horticulturae, 306, pp. 466-473Laughlin, J.C., Munro, D., The effect of Sclerotinia stem infection on morphine production and distribution in poppy (Papaver somniferum L.) plants (1983) Journal of Agricultural Science, Cambridge, 100, pp. 299-303Laughlin, J.C., Heazlewood, G.N., Beattie, B.M., Cultivation of Artemisia annua L. (2002) Artemisia, pp. 159-195. , Wright CW (ed.). London: Taylor & FrancisLawrence, B.M., Progress in essential oils (1990) Perfumer & Flavorist, 15, pp. 63-64Lee, J.M., Advances in seed treatments (2004) Chronica Horticulturae, 44 (2), pp. 11-20Liersch, R., Soicke, H., Stehr, C., Tullner, H.V., Formation of artemisinin in Artemisia annua during one vegetation period (1986) Planta Medica, 52, pp. 387-390Lin, A.J., Klayman, D.L., Hoch, J.M., Silverton, J.V., George, C.F., Thermal rearrangement and decomposition products of artemisinin (qinghaosu) (1985) Journal of Organic Chemistry, 50, pp. 4504-4508Liu, C.-Z., Guo, C., Wang, Y., Ouyang, F., Factors influencing artemisinin production from shoot cultures of Artemisia annua L. (2003) World Journal of Microbiology and Biotechnology, 19, pp. 535-538Luo, X.-D., Shen, C.-C., The chemistry, pharmacology, and clinical applications of qinghaosu (artemisinin) and its derivatives (1987) Medicinal Research Reviews, 7, pp. 29-52Madhusudanan, K.P., Mass spectral studies on artemisinin, dihydroartemisinin and arteether (1989) Indian Journal of Chemistry, 28 B, pp. 751-754Magalhães, P.M., A experimentação agricola com plantas medicinais e aromáticas (1994) Atualidades Científicas (CPQBA/UNICAMP, Campinas, Brazil), 3, pp. 31-56Magalhães, P.M., (1996) Selecão, Melhoramento, e Nutrição Da Artemisia annua L. para Cultivo Em Região Intertropical, , PhD Thesis, University of Campinas, BrazilMagalhães, P.M., Delabays, N., The selection of Artemisia annua L. for cultivation in intertropical regions (1996) Proceedings of An International Symposium on Breeding Research on Medicinal and Aromatic Plants, Quedlinburg, Germany, 30 June-4 July, pp. 185-188. , Pank F (ed.). Quedlinburg: Bundesanstalt für Züchtungsforchung an KulturpflanzenMagalhães, P.M., Raharinaivo, J., Delabays, N., Influences de la dose et du type d'azote sur la production en artemisinine de l'Artemisia annua L. (1996) Revue Suisse de Viticulture, Arboriculture et Horticulture, 28, pp. 349-353Marchese, J.A., (1999) Produção e Detecção de Artemisinina Em Plantas de Artemisia annua L. Submetidas a Estresses Abióticos, , MS Thesis, Campinas, BrazilMarchese, J.A., Casiraghi, V., Lira, R., Tedesco, A.C., Rehder, V.L.G., Flowering of Artemisia annua L. plants submitted to different photoperiod and temperature conditions (2002) Acta Horticulturae, 569, pp. 275-280. , Proceedings of the 1st Latin American Symposium on MAPMarchese, J.A., Broetto, F., Ming, L.C., Ducatti, C., Rodella, R.A., Ventrella, M.C., Gomes, G.D.R., Franceschi, L., Carbon isotope composition and leaf anatomy as a tool to characterize the photosynthetic mechanism of Artemisia annua L. (2005) Brazilian Journal of Plant Physiology, 17, pp. 187-190Martin, V.J.J., Pitera, D.J., Withers, S.T., Newman, J.D., Keasling, J.D., Engineering a mevalonate pathway in Escherichia coli for production of terpenoids (2003) Nature Biotechnology, 21, pp. 796-802Martinez, B.C., Staba, J., The production of artemisinin in Artemisia annua L. tissue cultures (1988) Advances in Cell Culture, 6, pp. 69-87Matsushita, Y., Kang, W., Charlwood, B.V., Cloning and analysis of a cDNA encoding farnesyl diphosphate synthase from Artemisia annua (1996) Gene, 172, pp. 207-209Maynard, L., Malaria cure (1985) Pharmacy Report, the University of Mississippi School of Pharmacy, 7 (1), pp. 10-13McVaugh, R., A descriptive account of the vascular plants of Western Mexico (1984) Flora Novo-Galiciana Vol. 12. Compositae, 12. , Andersohn WR (ed.). Ann Arbor: University of Michigan PressMercke, P., Crock, J., Croteau, R., Brodelius, P.E., Cloning, expression, and characterization of epi-cedrol synthase, a sesquiterpene cyclase from Artemisia annua L. (1999) Archives of Biochemistry and Biophysics, 369, pp. 213-222Mercke, P., Bengtsson, M., Bouwmeester, H.J., Posthumus, M.A., Brodelius, P.E., Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. (2000) Archives of Biochemistry and Biophysics, 381, pp. 173-180Moore, J.C., Lai, H., Li, J.-R., Ren, R.-L., McDougall, J.A., Singh, N.P., Chou, C.-K., Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat (1995) Cancer Letters, 98, pp. 83-87Morales, M.R., Charles, D.J., Simon, J.E., Seasonal accumulation of artemisinin in Artemisia annua L. (1993) Acta Horticulturae, 344, pp. 416-420Mueller, M.S., Karhagomba, I.B., Hirt, H.M., Wemakor, E., The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: Agricultural, chemical and clinical aspects (2000) Journal of Ethnopharmacology, 73, pp. 487-493Mueller, M.S., Runyambo, N., Wagner, I., Borrmann, S., Dietz, K., Heide, L., Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria (2004) Transactions of the Royal Society of Tropical Medicine and Hygiene, 98, pp. 318-321Newton, P., Proux, S., Green, M., Smithuis, F., Rozendaal, J., Prakongpan, S., Chotivanich, K., White, N.J., Fake artesunate in southeast Asia (2001) The Lancet, 357, pp. 1948-1950Nussenzweig, R.S., Long, C.A., Malaria vaccines: Multiple targets (1994) Science, 265, pp. 1381-1383O'Neill, P.M., A worthy adversary for malaria (2004) Nature, 430, p. 838Status of the malaria programs in the Americas, XLVI Report (1998) 25th Pan American Sanitary Conference, , 50th session of the regional committee, PAHO/WHO, Washington, DCPras, N., Visser, J.F., Batterman, S., Woerdenbag, H.J., Malingre, T.M., Laboratory selection of Artemisia annua L. for high artemisinin yielding types (1991) Phytochemical Analysis, 2, pp. 80-83Prasad, A., Kumar, D., Anwar, M., Singh, D.V., Jain, D.C., Response of Artemisia annua L. to soil salinity (1997) Journal of Herbs, Spices and Medicinal Plants, 5, pp. 49-55Prasad, A., Ram, M., Gupta, N., Kumar, S., Effect of different soil characteristics on the essential oil yield of Artemisia annua (1998) Journal of Medicinal and Aromatic Plant Sciences, 20, pp. 703-705Ram, M., Gupta, M.M., Dwivedi, S., Kumar, S., Effect of plant density on the yields of artemisinin and essential oil in Artemisia annua cropped under low input cost management in north-central India (1997) Planta Medica, 63, pp. 372-374Ratkowsky, D.A., (1983) Non-linear Regression Modeling: A Unified Practical Approach, , New York: Marcel DekkerRavindranathan, T., Kumar, Ma., Menon, R.B., Hiremath, S.V., Stereoselective synthesis of artemisinin (1990) Tetrahedron Letters, 31, pp. 755-758Roll Back Malaria (2004) Malaria in Africa, , http://www.rbm.who.int/cmc_upload/0/000/015/370/RBMInfosheet_3.htmRoth, R.J., Acton, N., A simple conversion of artemisinic acid into artemisinin (1989) Journal of Natural Products, 52, pp. 1183-1185Schmid, G., Hofheinz, W., Total synthesis of qinghaosu (1983) Journal of the American Chemical Society, 105, pp. 624-625Simon, J.E., Cebert, E., Artemisia annua: A production guide (1988) Third National Herb Growing and Marketing Conference, pp. 78-83. , Simon JE and Clavio LZ (eds). Purdue University Agricultural Experimental Station Bulletin No. 552. West Lafayette, IN: Purdue UniversitySimon, J.E., Charles, D., Cebert, E., Grant, L., Janick, J., Whipkey, A., Artemisia annua L.: A promising aromatic and medicinal (1990) Advances in New Crops, pp. 522-526. , Janick J and Simon J (eds). Portland, OR: Timber PressSimonnet, X., Gaudin, M., Hausammann, H., Vergéres, C., Le fanage au champ d'Artemisia annua L.: Élever la teneur en artémisinine et abaisser les coûts de production (2001) Revue Suisse de Viticulture, Arboriculture et Horticulture, 33, pp. 263-268Singh, A., Kaul, V.K., Mahajan, V.P., Singh, A., Misra, L.N., Thakur, R.S., Husain, A., Introduction of Artemisia annua in India and isolation of artemisinin, a promising antimalarial drug (1986) Indian Journal of Pharmaceutical Sciences, 48, pp. 137-138Singh, A., Vishwakarma, R.A., Husain, A., Evaluation of Artemisia annua strains for higher artemisinin production (1988) Planta Medica

Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas

Germination and growth of spinach under potassium deficiency and irrigation with high-salinity water

WOS:000603106200001PubMed ID:33317110Information is scarce on the interaction of mineral deficiency and salinity. We evaluated two salt-tolerant spinach cultivars under potassium (K) doses (0.07, 0.15, 0.3, and 3.0 mmolc L?1) and saline irrigation (5, 30, 60, 120, and 160 mmolc L?1 NaCl) during germination and growth. There was no interaction between salinity and K. Salinity decreased germination percent (GP), not always significantly, and drastically reduced seedling biomass. ‘Raccoon’ significantly increased GP at 60 mmolc L?1 while ‘Gazelle’ maintained GP up to 60 or 120 mmolc L?1. After 50 days under saline irrigation, shoot biomass increased significantly at 30 and 60 mmolc L?1 at the lowest K dose but, in general, neither salinity nor K dose affected shoot biomass, suggesting that salinity supported plant growth at the most K-deficient dose. Salinity did not affect shoot N, P, or K but significantly reduced Ca, Mg, and S, although plants had no symptoms of salt toxicity or mineral deficiency. Although spinach seedlings are more sensitive to salt stress, plants adjusted to salinity with time. Potassium requirement for spinach growth was less than the current crop recommendation, allowing its cultivation with waters of moderate to high salinity without considerable reduction in yield, appearance, or mineral composition. © 2020 by the authors.U.S. Department of Agriculture, USDA CRIS 2036–13210-006–00DFunding: This research was funded by the United States Department of Agriculture (USDA-ARS) as part of the internal project: CRIS 2036–13210-006–00D; Enhancing Special Crop Tolerance to Saline Irrigation Waters.Acknowledgments: We acknowledge the financial support of a grant provided by TUBITAK (2219 International Postdoctoral Research Scholarship Program) for Kadir Uçgun’s work on this project at the US Salinity Laboratory (USDA-ARS), Riverside, USA. We also acknowledge the help of Alysia Soria, Kimberly Wilkerson, and Noah Gangoso for their assistance with harvest, saline solutions and sample preparation and Pangki Xiong for the analyses of macro/micronutrients and of Na and Cl in tissues of spinach. We also acknowledge the help of Ray Anderson and Dennise Jenkins for the confirmation of greenhouse light intensity