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Current Nutrition & Food Science

Editor-in-Chief

ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Review Article

Phytochemical and Pharmacological Attributes of Nerium oleander: A Review

Author(s): Amita Pandey, Shazia Usmani*, Mohd Ahmad, Shabana Khatoon, Shadma Wahab and Om Prakash

Volume 20, Issue 5, 2024

Published on: 01 August, 2023

Page: [570 - 585] Pages: 16

DOI: 10.2174/1573401319666230522160742

Price: $65

Abstract

Background: Nerium Oleander is an Indian folk medicine popularly known as oleander, contains numerous phytoconstituents and nutritional agents for the treatment of multiple ailments.

Objective: The prime objective for the current comprehensive review is to focus on the elaboration of phytochemistry along with the Pharmacological significance of N. oleander.

Methods: As per literature investigations it was noticed that plant contains various phytochemical constituents, including Oleandric acid, Kaneroside, Cardenolide, Nerizoside, Neritaloside, Odoroside- H,3-Ocaffeoylquinic acid along with structural isomer, 5-Ocaffeoylquinic acid, α-tocopherol, Oleandrin, Digitoxgenin along with nutritional ingredients viz essential fatty acids like omega- 3 fatty acids, and other polyphenols reported in N. oleander.

Results: In recent investigations, it was observed that oleander possesses a wide range of medicinal attributes viz. anti-inflammatory, larvicidal, anti-cancer, Antidiabetic, Cellular/humoral immune response, Hepatoprotective, Wound healing, Anti-microbial, Antioxidant, Antinociceptive, Locomotor, Diuretic, and Anti leukemic activities.

Conclusion: N. oleander could be an excellent candidate for discovering new medications because of its wide range of pharmacological action and the large diversity of active phytochemicals. However, to disclose the favorable therapeutic, safety, and pharmacological virtues of N. oleander and its phytoconstituents, more clinical and experimental investigations are needed.

Graphical Abstract

[1]
Akerlee O. WHO guidelines for the assessment of the herbal medicines. Fitoterapia 1996; 63: 99-110.
[2]
Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and homoeopathy, ministry of health and family welfare, Govt of India.
[3]
Hseini S, Kahouadji A. Ethnobotanical study of medicinal flora in the region of Rabat (Morocco Western). Lazaroa 2007; 28: 79-92.
[4]
El Sawi NM, Geweely NS, Qusti S, Mohamed M, Kamel A. Cytotoxicity and antimicrobial activity of Nerium oleander extracts. J Appl Anim Res 2010; 37(1): 25-31.
[http://dx.doi.org/10.1080/09712119.2010.9707089]
[5]
Dey P, Roy S, Chaudhuri TK. A quantitative assessment of bioactive phytochemicals of Nerium indicum: An ethnopharmacological herb. Int J Res Pharm Sci 2012; 3: 579-87.
[6]
Duke JA. Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press 1985.
[7]
Lans C. Ethnomedicines used in trinidad and tobago for reproductive problems. J Ethnobiol Ethnomed 2007; 3(1): 13.
[http://dx.doi.org/10.1186/1746-4269-3-13] [PMID: 17362507]
[8]
Nanyingi MO, Mbaria JM, Lanyasunya AL, et al. Ethnopharmacological survey of Samburu district, Kenya. J Ethnobiol Ethnomed 2008; 4(1): 14.
[http://dx.doi.org/10.1186/1746-4269-4-14] [PMID: 18498665]
[9]
Tagarelli G, Tagarelli A, Piro A. Folk medicine used to heal malaria in Calabria (southern Italy). J Ethnobiol Ethnomed 2010; 6(1): 27.
[http://dx.doi.org/10.1186/1746-4269-6-27] [PMID: 20849654]
[10]
Muthu C, Ayyanar M, Raja N, Ignacimuthu S. Medicinal plants used by traditional healers in Kancheepuram District of Tamil Nadu, India. J Ethnobiol Ethnomed 2006; 2(1): 43.
[http://dx.doi.org/10.1186/1746-4269-2-43] [PMID: 17026769]
[11]
Bnouham M, Mekhfi H, Legssyer A, Ziyyat A. Medicinal plants used in the treatment of diabetes in Morocco. Int J Diabetes Metab 2002; 10: 33-50.
[12]
Tantiado RG. Survey on ethnopharmacology of medicinal plants in Iloilo, Philippines. Int J Biosci Biotechnol 2012; 4: 11-26.
[13]
Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province). J Ethnopharmacol 2007; 110(1): 105-17.
[http://dx.doi.org/10.1016/j.jep.2006.09.011] [PMID: 17052873]
[14]
Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain 2008; 137(3): 473-7.
[http://dx.doi.org/10.1016/j.pain.2008.04.025] [PMID: 18583048]
[15]
Bayne K. Assessing pain and distress: A veterinary behaviorist's perspective. Definition of pain and distress and reporting requirements for laboratory animals. Proceedings of the Workshop.
[16]
Kiran C, Prasad DN. A review on: Nerium oleander Linn. (Kaner). International J of Pharmacogn and Phytochem Res 2014; 6(3): 593-7.
[17]
Garima Z, Amla B. A review on chemistry and pharmacological activity of Nerium oleander L. J Chem Pharm Res 2010; 2(6): 351-8.
[18]
Vikas G, Payal M. Phytochemical and pharmacological potential of Nerium oleander: A review. Int J Pharm Sci Res 2010; 1(3): 21-7.
[19]
Farkhondeh T, Kianmehr M, Kazemi T, Samarghandian S, Khazdair MR. Toxicity effects of Nerium oleander, basic and clinical evidence: A comprehensive review. Hum Exp Toxicol 2020; 39(6): 773-84.
[http://dx.doi.org/10.1177/0960327120901571] [PMID: 31971021]
[20]
Shah SMA, Akram M, Riaz M, Munir N, Rasool G. Cardioprotective potential of plant-derived molecules: A scientific and medicinal approach. Dose Response 2019; 17(2): 1559325819852243.
[http://dx.doi.org/10.1177/1559325819852243] [PMID: 31205459]
[21]
Sabira B. Bio-active cardenolides from the leaves of Nerium oleander. Science 1998; 2(98): 00523-8.
[22]
Huq MM, Jabbar A, Rashid MA, Hasan CM. A novel antibacterial and cardiac steroid from the roots of Nerium oleander. Fitoterapia 1999; 70(1): 5-9.
[http://dx.doi.org/10.1016/S0367-326X(98)00013-6]
[23]
Derwic E, Benziane Z, Boukir A. Antibacterial activity and chemical composition of the essential oil from flowers of Nerium Oleander. J Env Agricult Food Chem 2010; 9(6): 1074-84.
[24]
Yamauchi T, Abe F. Cardiac glycosides and pregnanes from Adenium obesum (Studies on the constituents of Adenium. I). Chem Pharm Bull 1990; 38(3): 669-72.
[http://dx.doi.org/10.1248/cpb.38.669] [PMID: 2347008]
[25]
Torbjordnr A. Structural studies of digitoxin and related cardenolides by two-dimensional. Nmr Can J Chem 1990; 68: V90-V037.
[26]
Tymiak AA, Norman JA, Bolgar M, et al. Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus. Proc Natl Acad Sci USA 1993; 90(17): 8189-93.
[http://dx.doi.org/10.1073/pnas.90.17.8189] [PMID: 8396262]
[27]
Ibrahim A, Khalifa SI, Khafagi I, et al. Microbial metabolism of biologically active secondary metabolites from Nerium oleander L. Chem Pharm Bull 2008; 56(9): 1253-8.
[http://dx.doi.org/10.1248/cpb.56.1253] [PMID: 18758096]
[28]
Quan Y. A Hydroxylated Lupeol-based triterpenoid ester isolated from the Scurrul aparasitica parasitic on Nerium indicum. Verlag Helvetica Chimicaacta AG Zurich 2015; 2(98): 627-32.
[29]
Sujata R, Aelt B. Constitution of proceragenin A- A trirepenoid sapogenin from albizzia procera brinth. Tetrahedron Lett 1966; 46: 5743-50.
[30]
Hougen TJ, Lloyd BL, Smith TW. Effects of inotropic and arrhythmogenic digoxin doses and of digoxin-specific antibody on myocardial monovalent cation transport in the dog. Circ Res 1979; 44(1): 23-31.
[http://dx.doi.org/10.1161/01.RES.44.1.23] [PMID: 758230]
[31]
Blum LM, Rieders F. Oleandrin distribution in a fatality from rectal and oral Nerium oleander extract administration. J Anal Toxicol 1987; 11(5): 219-21.
[http://dx.doi.org/10.1093/jat/11.5.219] [PMID: 3682781]
[32]
Haynes BE, Bessen HA, Wightman WD. Oleander tea: Herbal draught of death. Ann Emerg Med 1985; 14(4): 350-3.
[http://dx.doi.org/10.1016/S0196-0644(85)80103-7] [PMID: 4039113]
[33]
Eddleston M, Ariaratnam CA, Sjöström L, et al. Acute yellow oleander (Thevetia peruviana) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital. Br Heart J 2000; 83(3): 301-6.
[http://dx.doi.org/10.1136/heart.83.3.301] [PMID: 10677410]
[34]
Singh S, Shenoy S, Nehete PN, et al. Nerium oleander derived cardiac glycoside oleandrin is a novel inhibitor of HIV infectivity. Fitoterapia 2013; 84: 32-9.
[http://dx.doi.org/10.1016/j.fitote.2012.10.017] [PMID: 23127567]
[35]
Fonseka MM, Seneviratne SL, de Silva CE, Gunatilake SB, de Silva HJ. Yellow oleander poisoning in Sri Lanka: Outcome in a secondary care hospital. Hum Exp Toxicol 2002; 21(6): 293-5.
[http://dx.doi.org/10.1191/0960327102ht257oa] [PMID: 12195932]
[36]
Al-Snafi AE. Bioactive ingredients and pharmacological effects of Nerium oleander. IOSR J Pharm 2020; 10(9): 19-32.
[37]
Yamauchi T, Takata N, Mimura T. Cardiac glycosides of the leaves of Nerium odorum. Phytochemistry 1975; 14(5-6): 1379-82.
[http://dx.doi.org/10.1016/S0031-9422(00)98630-8]
[38]
Rashan LJ, Franke K, Khine MM, et al. Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum. J Ethnopharmacol 2011; 134(3): 781-8.
[http://dx.doi.org/10.1016/j.jep.2011.01.038] [PMID: 21291990]
[39]
Siddiqui BS, Khatoon N, Begum S, et al. Flavonoid and cardenolide glycosides and a pentacyclic triterpene from the leaves of Nerium oleander and evaluation of cytotoxicity. Phytochemistry 2012; 77(77): 238-44.
[http://dx.doi.org/10.1016/j.phytochem.2012.01.001] [PMID: 22281382]
[40]
Bakir ÇN, Yalçin E. Çavuşoğlu K, Sipahi KS. Qualitative and quantitative phytochemical screening of Nerium oleander L. extracts associated with toxicity profile. Sci Rep 2022; 12(1): 21421.
[http://dx.doi.org/10.1038/s41598-022-26087-0] [PMID: 36504046]
[41]
Smith TW, Antman EM, Friedman PL, Blatt CM, Marsh JD, Part I. Digitalis glycosides: Mechanisms and manifestations of toxicity. Prog Cardiovasc Dis 1984; 26(5): 413-58.
[http://dx.doi.org/10.1016/0033-0620(84)90012-4] [PMID: 6371896]
[42]
Taboulet P, Baud FJ, Bismuth C. Clinical features and management of digitalis poisoning-rationale for immunotherapy. J Toxicol Clin Toxicol 1993; 31(2): 247-60.
[http://dx.doi.org/10.3109/15563659309000392] [PMID: 8492338]
[43]
Dey P, Roy S, Chaudhuri TK. Stimulation of murine immune response by the tubers of Dioscorea alata L. of North-Eastern region of India. Proc Zool Soc 2014; 67(2): 140-8.
[http://dx.doi.org/10.1007/s12595-013-0082-3]
[44]
Erdemoglu N, Küpeli E. Yeşilada E. Anti-inflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine. J Ethnopharmacol 2003; 89(1): 123-9.
[http://dx.doi.org/10.1016/S0378-8741(03)00282-4] [PMID: 14522443]
[45]
Shafiq Y, Naqvi SBS, Rizwani GH, et al. A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile. BMC Complem Med Therap 2021; 21(1): 135.
[http://dx.doi.org/10.1186/s12906-021-03308-z] [PMID: 33933037]
[46]
Srivastava AN, Ahmad R, Khan MA. Evaluation and comparison of the in vitro cytotoxic activity of Withania somnifera methanolic and ethanolic extracts against MDA-MB-231 and vero cell lines. Sci Pharm 2015; 84(1): 41-59.
[47]
Mohammed EM, Mouhcine M, Amin L, Saaid A, Khalil H, Laila B. Cytotoxic, antioxidant and antimicrobial activities of Nerium oleander collected in Morocco. Asian Pac J Trop Med 2019; 12(1): 32-7.
[http://dx.doi.org/10.4103/1995-7645.250342]
[48]
Calderón-Montaño J, Burgos-Morón E, Orta M, Mateos S, López-Lázaro M. A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells. Planta Med 2013; 79(12): 1017-23.
[http://dx.doi.org/10.1055/s-0032-1328715] [PMID: 23824549]
[49]
Mohapatra S, Biswal AK, Dandapat J, Debata PR. Leaf extract of Nerium oleander L. inhibits cell proliferation, migration and arrest of cell cycle at G2/M phase in hela cervical cancer cell. Anticancer Agents Med Chem 2021; 21(5): 649-57.
[http://dx.doi.org/10.2174/1871520620666200811121400] [PMID: 32781975]
[50]
Ali HFM, El-Ella FMA, Nasr NF. Screening of chemical analysis, antioxidant antimicrobial and antitumor activities of essential oil of oleander flower. Int J Biochem 2010; 4(4): 190-202.
[51]
Raveen R. Larvicidal activity of Nerium Oleander L. (Apocynaceae) flower extracts against Culex quinquefasciatus Say (Diptera: Culicidae). Int. J Med Res 2014; 1(1): 2348-5906.
[52]
Farooqui S, Tyagi T. Nerium oleander it’s application in basic and applied science a review. Int J Pharm Pharm Sci 2018; 10(3): 1-4.
[http://dx.doi.org/10.22159/ijpps.2018v10i3.22505]
[53]
Dey P. The pharmaco-toxicological conundrum of oleander: Potential role of gut microbiome. Biomed Pharmacother 2020; 129: 110422.
[http://dx.doi.org/10.1016/j.biopha.2020.110422] [PMID: 32563990]
[54]
Sikarwar MS, Patil MB, Kokate CK, Sharma S, Bhat V. Antidiabetic activity of Nerium indicum leaf extract in alloxan-induced diabetic rats. J of Young Pharm 2009; 1(4): 330.
[55]
Sinha SN, Biswas K. A concise review on Nerium oleander L.—an important medicinal plant. Trop Plant Res 2016; 3: 408-12.
[56]
Mwafy SN, Yassin MM. Antidiabetic activity evaluation of glimepiride and Nerium oleander extract on insulin, glucose levels and some liver enzymes activities in experimental diabetic rat model. Pak J Biol Sci 2011; 14(21): 984-90.
[http://dx.doi.org/10.3923/pjbs.2011.984.990] [PMID: 22514888]
[57]
Singhal KG, Gupta GD. Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4–induced liver injury in rats. Asian Pac J Trop Med 2012; 5(9): 677-85.
[http://dx.doi.org/10.1016/S1995-7645(12)60106-0] [PMID: 22805717]
[58]
Akhtar T, Sheikh N, Abbasi MH. Alternative therapeutic approaches: Hepatoprotective effect of nerium oleander extract in thioacetamide induced hepatotoxicity. Int J Clin Exp Med 2016; 9(8): 16118-24.
[59]
Rout S, Kar D, Maharana L. Evaluation of antimicrobial, antioxidant and wound healing Activity of different fractions of methanolic Extract of Nerium oleander Linn. Int J of Drug Dev and Res 2014; 6: 241-51.
[60]
Hase GJ, Deshmukh KK, Pokharkar RD, Gaje TR, Phatanagre ND. Phytochemical studies on Nerium oleander L. Using GC-MS. Int J of Pharmacognosy and Phytochem Res 2017; 9(6): 885-91.
[61]
Akgun SG, Aydemir S, Ozkan N, Yuksel M, Sardas S. Evaluation of the wound healing potential of Aloe vera-based extract of Nerium oleander. North Clin Istanb 2017; 4(3): 205-12.
[PMID: 29270567]
[62]
Hussain MA, Gorsi MS. Antimicrobial activity of Nerium oleander Linn. Asian J Plant Sci 2004; 3(2): 177-80.
[http://dx.doi.org/10.3923/ajps.2004.177.180]
[63]
Malik R, Bokhari T, Siddiqui M, Younis U, Hussain M, Khan I. Antimicrobial activity of Nerium oleander L. and Nicotiana tabacum L.: A comparative study. Pak J Bot 2015; 47: 1587-92.
[64]
Saranya S, Archana D, Santhy KS. Antimicrobial and antioxidant effects of Nerium oleander flower extracts. Int J Curr Microbiol Appl Sci 2017; 6(5): 1630-7.
[http://dx.doi.org/10.20546/ijcmas.2017.605.178]
[65]
Zia A, Siddiqui BS, Begum S, Siddiqui S, Suria A. Studies on the constituents of the leaves of Nerium oleander on behavior pattern in mice. J Ethnopharmacol 1995; 49(1): 33-9.
[http://dx.doi.org/10.1016/0378-8741(95)01300-8] [PMID: 8786655]
[66]
Tien VN, Duc LV, Bui Thanh TB. Isolated compounds and cardiotonic effect on the isolated rabbit heart of methanolic flower extract of Nerium oleander L. Res J Phy 2016; 10: 21-9.
[http://dx.doi.org/10.3923/rjphyto.2016.21.29]
[67]
Patel G, Nayak S, Shrivastava S. Antiulcer activity of methanolic leaves of Nerium Indicum mill. Int J Biomed Res 2010; 1(2): 55-61.
[68]
Gayathri V, Ananthi S, Chandronitha C, Ramakrishnan G, Sundaram RL, Vasanthi HR. Cardioprotective effect of Nerium oleander flower against isoproterenol-induced myocardial oxidative stress in experimental rats. J Cardiovasc Pharmacol Ther 2011; 16(1): 96-104.
[http://dx.doi.org/10.1177/1074248410381759] [PMID: 21191138]
[69]
Kumar A, De T, Mishra A, Mishra A. Oleandrin: A cardiac glycosides with potent cytotoxicity. Pharmacogn Rev 2013; 7(14): 131-9.
[http://dx.doi.org/10.4103/0973-7847.120512] [PMID: 24347921]
[70]
Zamani J, Aslani A. Cardiac findings in acute yellow oleander poisoning. J Cardiovasc Dis Res 2010; 1(1): 27-9.
[http://dx.doi.org/10.4103/0975-3583.59982] [PMID: 21188087]
[71]
Karthik G, Iyadurai R, Ralph R, et al. Acute oleander poisoning: A study of clinical profile from a tertiary care center in South India. J Family Med Prim Care 2020; 9(1): 136-40.
[72]
Abdou RH, Basha WA, Khalil WF. Subacute toxicity of Nerium oleander ethanolic extract in mice. Toxicol Res 2019; 35(3): 233-9.
[http://dx.doi.org/10.5487/TR.2019.35.3.233] [PMID: 31341552]
[73]
Roberts DM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol 2016; 81(3): 488-95.
[http://dx.doi.org/10.1111/bcp.12814] [PMID: 26505271]
[74]
Seigler DS, Spencer KC, Statler WS, Conn EE, Dunn JE. Tetraphyllin B and epitetraphyillin B sulphates: Novel cyanogenic glucosides from Passiflora caerulea and P. alato-caerulea. Phytochemistry 1982; 21(9): 2277-85.
[http://dx.doi.org/10.1016/0031-9422(82)85191-1]
[75]
(a) Poulsen SB, Fenton RA, Rieg T. Sodium-glucose cotransport. Curr Opin Nephrol Hypertens 2015; 24(5): 463-9.
[http://dx.doi.org/10.1097/MNH.0000000000000152] [PMID: 26125647];
(b) Amend N, Worek F, Thiermann H, Wille T. Investigation of cardiac glycosides from oleander in a human induced pluripotent stem cells derived cardiomyocyte model. Toxicol Lett 2021; 350: 261-6.
[76]
(a) Rajapakse S. Management of yellow oleander poisoning. Clin Toxicol 2009; 47(3): 206-12.
[http://dx.doi.org/10.1080/15563650902824001] [PMID: 19306191];
(b) Shridhar NB. Nerium oleander toxicity: a review. Int J Adv Acad Stud 2022; 4(3): 23-32.
[77]
Bao Z, Tian B, Wang X, et al. Oleandrin induces DNA damage responses in cancer cells by suppressing the expression of Rad51. Oncotarget 2016; 7(37): 59572-9.
[http://dx.doi.org/10.18632/oncotarget.10726] [PMID: 27449097]
[78]
Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB. Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res 2000; 60(14): 3838-47.
[PMID: 10919658]
[79]
El-Mallakh RS, Brar KS, Yeruva RR. Cardiac glycosides in human physiology and disease: Update for entomologists. Insects 2019; 10(4): 102.
[http://dx.doi.org/10.3390/insects10040102] [PMID: 30974764]
[80]
Agrawal AA, Petschenka G, Bingham RA, Weber MG, Rasmann S. Toxic cardenolides: Chemical ecology and coevolution of specialized plant–herbivore interactions. New Phytol 2012; 194(1): 28-45.
[http://dx.doi.org/10.1111/j.1469-8137.2011.04049.x] [PMID: 22292897]
[81]
Kovacikova E, Kovacik A, Halenar M, et al. Potential toxicity of cyanogenic glycoside amygdalin and bitter apricot seed in rabbits-Health status evaluation. J Anim Physiol Anim Nutr 2019; 103(2): 695-703.
[http://dx.doi.org/10.1111/jpn.13055] [PMID: 30698299]
[82]
Gomez G, Valdivieso M. The effect of variety and plant age on cyanide content, chemical composition and quality of cassava roots. Nutr Rep Int 1983; 27(4): 857-65.
[83]
Riis L, Bellotti AC, Bonierbale M, O’brien GM. Cyanogenic potential in cassava and its influence on a generalist insect herbivore Cyrtomenus bergi (Hemiptera: Cydnidae). J Econ Entomol 2003; 96(6): 1905-14.
[http://dx.doi.org/10.1603/0022-0493-96.6.1905] [PMID: 14977132]
[84]
Nambisan B. Strategies for elimination of cyanogens from cassava for reducing toxicity and improving food safety. Food Chem Toxicol 2011; 49(3): 690-3.
[http://dx.doi.org/10.1016/j.fct.2010.10.035] [PMID: 21074593]
[85]
Siritunga D, Sayre RT. Generation of cyanogen-free transgenic cassava. Planta 2003; 217(3): 367-73.
[http://dx.doi.org/10.1007/s00425-003-1005-8] [PMID: 14520563]
[86]
Wobeto C, Corrêa AD, Abreu CMP, Santos CD, Pereira HV. Antinutrients in the cassava (Manihot esculenta Crantz) leaf powder at three ages of the plant. Food Sci Technol 2007; 27(1): 108-12.
[http://dx.doi.org/10.1590/S0101-20612007000100019]

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