Composição fitoquímica e propriedades farmacológicas potenciais da Morus nigra L.: uma revisão narrativa

Phytochemical composition and potential pharmacological properties of Morus nigra l.: narrative review

Resumo

Morus nigra L. é uma planta de origem asiática com propriedades terapêuticas conhecidas há séculos e utilizada pelas medicinas tradicionais grega, ayurvédica e chinesa para o tratamento de diversas enfermidades. Tendo em vista o gênero Morus constar da Relação Nacional de Plantas Medicinais do Interesse do SUS, este trabalho objetivou apresentar os principais componentes fitoquímicos das diferentes partes da planta e suas principais atividades farmacológicas potenciais. Realizou-se uma revisão narrativa da literatura científica de estudos publicadas no período de 2009 a 2020 constantes na plataforma Portal de Periódicos Capes que indexa diversas bases de dados científicas. Dos artigos selecionados, constatou-se através das análises fitoquímicas de Morus nigra L., diferentes classes de substâncias tais como flavonoides, alcaloides, cumarinas, triterpenos, entre outras. As atividades farmacológicas potenciais investigadas foram anti-inflamatória, antinociceptiva, anti-hiperglicêmica, antimicrobiana, anti-hiperlipidêmica, anticancerígena, antiaterogênica, função protetora de vários órgãos, entre outras. Nenhuma toxicidade foi revelada nos estudos realizados. Os resultados sugerem fortemente que as diversas atividades de Morus nigra L. têm como base principal a sua atividade antioxidante proveniente da diversidade dos seus compostos fenólicos. Os ensaios realizados ainda não são suficientes para o uso clínico, segundo os critérios científicos válidos atualmente, embora o uso tradicional demonstre justamente o contrário. Dessa forma, faz-se necessário mais estudos e ensaios clínicos para que as evidências permitam o uso de M. nigra em humanos, através das mais diversas formas farmacêuticas fitoterápicas seguras e eficazes, podendo ser utilizada na atenção primária à saúde como um recurso para controlar e prevenir várias doenças crônicas.

Referências

¹WHO, 2002. Traditional Medicine Strategy 2002–2005. World Health Organization, Geneva. Suiza. Disponivel em: https://www.paho.org/. Acesso em: março 2021.

²Brasil. 2006a. Política Nacional de Práticas Integrativas e Complementares no SUS - PNPIC-SUS. Ministério da Saúde, Secretaria de Atenção à Saúde, Departamento de Atenção Básica, Ministério da Saúde, Brasília, Brasil. Disponível em: http://bvsms.saude.gov.br/bvs/publicacoes/politica_nacional_fitoterapicos.pdf.Acesso em: fevereiro 2019.

³Brasil. 2006b. Política Nacional de plantas medicinais e fitoterápicos / Ministério da Saúde, Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Departamento de Assistência Farmacêutica. – Brasília, Brasil. – (Série B. Textos Básicos de Saúde). Disponível em: http://bvsms.saude.gov.br/bvs/publicacoes/politica_nacional_fitoterapicos.pdf.Acesso em:  fevereiro 2019.

⁴da Silva NCB, Regis ACD, Esquibel MA, Santos JES and Almeida MZ. Uso de plantas medicinais na comunidade quilombola da Barra II – Bahia, Brasil. Boletín Latinoamericano y del Caribe de Plantas Medicinales y aromáticas[Internet].2012;11(5):435-453.

⁵Brasil. 2017. Relação Nacional de Medicamentos Essenciais: RENAME 2017. Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Assistência Farmacêutica e Insumos Estratégicos.210 p. Brasília: Ministério da Saúde, 2017. Disponível em:  http://conitec.gov.br/images/Artigos_Publicacoes/Rename/Rename-2017-Agosto2017.pdf. Acesso em: abril 2019.

⁶Oliveira ACB, Oliveira AP, Guimarães AL, Oliveira RA, Silva FS, Reis SAGB, Ribeiro LAA, and Almeida JRGS. Avaliação toxicológica pré-clínica do chá das folhas de Morus nigra L. (Moraceae). Rev. Bras. Pl. Med [Internet]. 2013;15(2):244-249. DOI: https://doi.org/10.1590/S1516-05722013000200012

⁷Rodrigues EL, MarcelinoG, Silva GT, Figueiredo OS, Garcez WS, Corsino J, Guimarães RCA and Freitas KC. Nutraceutical and Medicinal Potential of the Morus Species in Metabolic Dysfunctions. Int. J. Mol. Sci [Internet]. 2019;20:301. DOI: https://doi.org/10.3390/ijms20020301

⁸Corrêa MP. Dicionário das plantas úteis do Brasil e das exóticas cultivadas. Rio de Janeiro: Imprensa Nacional; 1926-1978. Ministério da Agricultura, Instituto Brasileiro de Desenvolvimento Florestal,1984.

⁹Souza GR, Silva JC, de Oliveira Júnior RG, Saraiva SRGL, Guimarães AL, de Oliveira AP and Almeida JRGS. Atividade antinociceptiva do extrato etanólico das folhas de Morus nigra L. (Moraceae). Rev Ciênc Farm Básica Apl [Internet]. 2015;36(1):137-142.

¹⁰Guizzo PL, Bredda TCC, Scarpa MVC and Navarro FF. Controle de qualidade e triagem fitoquímica da droga vegetal das folhas de Morus nigra L (Moraceae). Revista de Ciências Farmacêuticas Básica e Aplicada[Internet]. 2015;36(2):259-265.

¹¹Akhlaq A, Mehmood MH, Rehman A, Ashraf Z, Syed S, Bawany AS, Gilani A, Ilyas M and Siddiqui BS. The Prokinetic, Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic, Ca2+ Channel Blocking, and Antimuscarinic Mechanisms. Phytother. Res[Internet]. 2016;30:1362–1376.  DOI: https://doi.org/ 10.1002/ptr.5641

¹²Mazimba O, Majinda RRT and Motlhanka D. Antioxidant and antibacterial constituents from Morus Nigra. African Journal of Pharmacy and Pharmacology . [Internet] 2011;5(6): 751-754. DOI: https://doi.org/ 10.5897/AJPP11.260

¹³Iqbal S, Younas U, Sirajuddin, Chan KW, Sarfraz RA and Uddin MK. Proximate Composition and Antioxidant Potential of Leaves from Three Varieties of Mulberry (Morus sp.): A Comparative Study. Int. J. Mol. Sci [Internet]. 2012;13:6651-6664. DOI: https://doi.org/10.3390/ijms13066651

¹⁴Jiang Y, Dai M, Nie W, Yang X and Zeng X. Effects of the ethanol extract of black mulberry (Morus nigra L.) fruit on experimental atherosclerosis in rats. Journal of Ethnopharmacology  [Internet]. 2017;200:228-235. DOI: https://doi.org/10.1016/j.jep.2017.02.037

¹⁵Figueredo KC, Guex CG, Reginato FZ, da Silva ARH, Cassanego GB, Lhamas CL, Boligon AA, Lopes GHH and Bauermann LF. Safety assessment of Morus nigra L. leaves: Acute and subacute oral toxicity studies in Wistar rats. Journal of Ethnopharmacology [Internet]. 2018; 224:290–296. DOI: https://doi.org/10.1016/j.jep.2018.05.013

¹⁶Farmacopeia Brasileira. 1ª.ed. 1175 p. Rio de Janeiro. 1926. Disponível em: http://portal.anvisa.gov.br/documents/33832/261726/1_edicao.pdf/fef00ec7-a9b3-4fdd-a42d-60f0573b433b. Acesso em julho 2018.

¹⁷Uphof JCT. Dictionary of Economic Plants. New York: Verlag; 1968.

¹⁸Morgan R. Enciclopédia das ervas e plantas medicinais. São Paulo: Hemus; 1979.

¹⁹Cruz GL. Dicionário de plantas úteis do Brasil. Rio de Janeiro: Bertrand; 1993.

²⁰Padilha MM, Vilela FC, da Silva MJD, dos Santos MH, da Silva GA and Paiva AG. Antinociceptive effect of Morus nigra leaves in mice. J med Food . [Internet] 2009;12(6): 1381-1385. DOI: https://doi.org/ 10.1089/jmf.2009.0012

²¹Imran M, Khan H, Shah M, Khan R ans Khan F. Chemical composition and antioxidant activity of certain Morus species. J Zhejiang Univ-Sci B (Biomed & Biotechnol [Internet]. 2010;11(12):973-980. DOI: https://doi.org/10.1631/jzus.B1000173

²²Chen H, Pu J, Liu D, Yu W, Shao Y, Yang G, Xiang Z and He N. Anti-Inflammatory and Antinociceptive Properties of Flavonoids from the Fruits of Black Mulberry (Morus nigra L.). PLoS ONE [Internet]. 2016;11(4):e0153080. DOI: https://doi.org/10.1371/journal.pone.0153080

²³Yazdankhah S, Hojjati M and Azizi MH. The Antidiabetic Potential of Black Mulberry Extract-Enriched Pasta through Inhibition of Enzymes and Glycemic.  Plant Foods for Human Nutrition [Internet]. 2019;74:149–155. DOI: https://doi.org/10.1007/s11130-018-0711-0

²⁴Mallhi TH, Qadir MI, Khan YH and Ali M. Hepatoprotective activity of aqueous methanolic extract of Morus nigra against paracetamol-induced hepatotoxicity in mice. Bangladesh J Pharmacol [Internet]. 2014;9:60-66. DOI: https://doi.org/10.3329/bjp.v9i1.17337

²⁵Iqbal K, Iqbal J, Umair M, Farooq U, Iqbal MM, Qamar S and Bashir M. Anti-leishmanial and cytotoxic activities of extracts from three Pakistani plants. Tropical Journal of Pharmaceutical Research [Internet]. Outubro 2016;15(10):2113-2119. DOI:https://doi.org/10.4314/tjpr.v15i10.9

²⁶Dalmagro AP, Camargo A and Zeni ALB. Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice. Metab Brain Dis [Internet]. 2017;32:1963–1973. DOI: https://doi.org/10.1007/s11011-017-0089-y

²⁷Abouzed TK, Sadek KM, Ghazy EW, Abdo W, Kassab MA, Hago S, Abdel-Wahab S, Mahrous EA, Abdel-Sattar E and Assar DH.Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway. Journal of Pharmacy and Pharmacology [Internet]. 2020;72:1615-1628. DOI: https://doi.org/10.1111/jphp.13338

²⁸Turan I, Demir S, Kilinc K, Burnaz NA, Yaman SO, Akbulut K, Mentese A, Aliyazicioglu Y and Deger O. Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells. Saudi Pharmaceutical Journal [Internet]. 2017;25:241–248. DOI: https://doi.org/ 10.1016/j.jsps.2016.06.002

²⁹De Freitas MM, Fontes PR, Souza PM, Fagg CW, Guerra ENS, Nóbrega YKM, Silveira D, Bazzo YF, Simeoni LA, de Mello MH and Magalhães PO. Extracts of Morus nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity. PLoS ONE [Internet]. 2016; 11(9):e0163130. DOI: https://doi.org/10.1371/journal.pone.0163130

³⁰Diab KA, Fahmy MA, Hassan EM, Hassan ZM, Omara EA and Abdel-Samie NS.  Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice. Mol Biol Rep [Internet]. 2020;47(3):1733-1749. DOI: https://doi.org/10.1007/s11033-020-05265-1

³¹Turgut NH, Mert DG, Egilmez HR, Arslanbas E, Tepe B, Gungor H, Yilmaz and Tuncel NB. Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice, Pharmaceutical Biology [Internet].2016;54(6):1052-1064, DOI: https://doi.org/ 10.3109/13880209.2015.1101476

³²Zeni ALB, Moreira TD, Dalmagro AP, Camargo A, Bini LA, Simionatto EL and Scharf DR. Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra leaves extract. Anais da Academia Brasileira de Ciências[Internet]. 2017;89(4):2805-2815. DOI: https://doi.org/ 10.1590/0001-3765201720160660

³³Dalmagro AP, Camargo A, Pedron NB, Garcia SAM and Zeni ALB. Morus nigra leaves extract revokes the depressive-like behavior, oxidative stress, and hippocampal damage induced by corticosterone: a pivotal role of the phenolic syringic acid. Behavioural Pharmacology [Internet]. 2020;31:397–406. DOI:https://doi.org/10.1097/FBP.0000000000000549.

³⁴Padilha MM, Vilela FC, Rocha CQ, Dias MJ, Soncini R, dos Santos M, da Silva GQ and Paiva AG. Antiinflammatory Properties of Morus nigra Leaves. Phytother. Res [Internet]. 2010;24:1496–1500. DOI: https://doi.org/10.1002/ptr.3134

³⁵Mallhi TH, Qadir MI and Khan YH. Determination of phytoconstituents of n-hexane extract of leaves of Morus nigra and evaluation of their effects on biochemical and histopathological parameters in paracetamol intoxicated mice liver. Braz. J. Pharm. Sci [Internet]. 2018; 54(3):e18101. DOI: https://doi.org/10.1590/s2175-97902018000318101

³⁶Wang L, Yang Y, Liu C and Chen R. Three new compounds from Morus nigra L. Journal of Asian Natural Products Research [Internet]. 2010;12(6):431–437. DOI: https://doi.org/ 10.1080/10286020.2010.489824

³⁷Zoofishan Z, Hohmann J and Hunyadi A. Phenolic antioxidants of Morus nigra roots, and antitumor potential of morusin. Phytochemistry Reviews [Internet]. 2018;17:1031–1045. DOI: https://doi.org/10.1007/s11101-018-9565-1

³⁸Mascarello A, Menegatti ACO, Calcaterra A, Martins PGA, Chiaradia-Delatorre LD, DÁquarica I, Ferrari F, Pau V, Sanna A, De Logu A, Botta M, Botta B, Terenzi H and Mori M. Naturally occurring Diels-Alder-type adducts from Morus nigra as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B. European Journal of Medicinal Chemistry [Internet]. 2018;144:277-288. DOI: https://doi.org/10.1016/j.ejmech.2017.11.087

³⁹Xiao Hu, Mei-Hua Yu, Gui-Rui Yan, He-Yao Wang, Ai-Jun Hou and Chun Lei. Isoprenylated phenolic compounds with tyrosinase inhibition from Morus nigra. Journal of Asian Natural Products Research [Internet]. 2017; DOI: https://doi.org/10.1080/10286020.2017.1350653

⁴⁰Chen H, Yu W, Chen G, Meng S, Xiang Z and He N. Antinociceptive and Antibacterial Properties of Anthocyanins and Flavonols from Fruits of Black and Non-Black Mulberries. Molecules [Internet]. 2018;23(4). DOI: https://doi.org/10.3390/molecules23010004

⁴¹Stefãnut MN, Cãta A, Pop R, Tãnasie C, Boc D, Ienascu I and Ordodi V. Anti-hyperglycemic Effect of Bilberry, Blackberry and Mulberry Ultrasonic Extracts on Diabetic Rats. Plant Foods Hum Nutr [Internet]. 2013;68:378-384 DOI: https://doi.org/ 10.1007/s11130-013-0380-y

⁴²El-Mawala AMAA, Mohamed KM and Mostafa AM. Induction of Biologically Active Flavonoids in Cell Cultures of Morus nigra and Testing their Hypoglycemic Efficacy. Sci Pharm [Internet]. 2011;79:951–961. DOI: https://doi.org/10.3797/scipharm.1101-15

⁴³Xu L, Yu M, Huang C, Niu L, Wang Y, Wu C, Yang P and Hu X. Isoprenylated flavonoids from Morus nigra and their PPAR γ agonistic activities. Fitoterapia [Internet]. 2018;127:109–114. DOI: https://doi.org/ 10.1016/j.fitote.2018.02.004

⁴⁴Júnior IIS, Barbosa HM, Carvalho DCR, Barros RA, Albuquerque FP, da Silva DHA, Souza GR, Souza NAC, Rolim LA, Silva FMM, Duarte GIBP, Almeida JRGS, Júnior FMO, Gomes DA and Lira EC. Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats. The Scientific World Journal[Internet]. 2017;2017:5275813. DOI: https://doi.org/10.1155/2017/5275813

⁴⁵Sánchez-Salcedo EM, Mena P, García-Viguera C, Martínez JJ and Hernandéz F. Phytochemical evaluation of white (Morus alba L.) and black (Morus nigra L.) mulberry fruits, a starting point for the assessment of their beneficial properties. J. Funct. Foods [Internet]. 2015;12:399–408. DOI: https://doi.org/10.1016/j.jff.2014.12.010

⁴⁶Sánchez-Salcedo EM, Amorós A, Hernandéz F and Martínez JJ. Physicochemical Properties of White (Morus alba) and Black (Morus nigra) Mulberry Leaves, a New Food Supplement. Journal of Food and Nutrition Research [Internet]. 2017;5(4):253-261. DOI: https://doi.org/10.12691/jfnr-5-4-7

⁴⁷Ercisli S, Tosun M, Duralija B, Voca S, Sengul M and Turan M. Phytochemical Content of Some Black (Morus nigra L.) and Purple (Morus rubra L.) Mulberry Genotypes. Food Technol. Biotechnol [Internet]. 2010;48(1):102–106. ISSN 1330-9862.

⁴⁸Minhas MA, Begum A, Hamid S, Babar M, Ilyas R, Ali S, Latif F and Andleeb S. Evaluation of Antibiotic and Antioxidant Activity of Morus nigra (Black Mulberry) Extracts Against Soil Borne, Food Borne and Clinical Human Pathogens. J. Zool[Internet].2016;48(5):1381-1388.

⁴⁹Lúcio KP, Rabelo ACS, Araújo CM, Brandão GC, de Souza GHB, da Silva RG, Calsavara AJC and Costa DC. Anti-Inflammatory and Antioxidant Properties of Black Mulberry (Morus nigra L.) in a Model of LPS-Induced Sepsis. Oxidative Medicine and Cellular Longevity [Internet]. 2018;2018:5048031. DOI: https://doi.org/10.1155/2018/5048031

⁵⁰Souza, GRS, Oliveira-Junior RG, Diniz TC, Branco A, Lima-Saraiva SRG, Guimarães AL, Oliveira, AP, Pacheco AGM, Silva MG, Moraes-Filho MO, Costa MP, Pessoa CÓ and Almeida JRGS. Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae). Braz. J. Biol [Internet]. 2018;78(2):248-254. DOI: https://doi.org/10.1590/1519-6984.05316

⁵¹Montenote MC, Wajsman VZ, Konno YT, Ferreira PC, Silva RGM, Therezo ALS, Silva LP and Martins LPA. Antioxidant effect of Morus nigra on Chagas disease progression. Rev Inst Med Trop [Internet]. 2017;59:e73. DOI: https://doi.org/10.1590/S1678-9946201759073

⁵²Nesello LAN, Beleza MLML, Mariot M, Mariano LNB, de Souza P, Campos A, Cechinel-Filho V, Andrade SF and da Silva LM. Gastroprotective Value of Berries: Evidences from Methanolic Extracts of Morus nigra and Rubus niveus Fruits. Gastroenterology Research and Practice [Internet]. 2017;2107:7089697. DOI: https://doi.org/ 10.1155/2017/7089697

⁵³Ahangarpour A, Ghanbari H, Hashemitabar M and Moghaddam HF. Effects of Morus Nigra Leaves Extract on Insulin Secretion from Isolated Islets of Langerhans in Male Mouse. Indian J Physiol Pharmacol [Internet]. 2016; 60(4):386-391.

⁵⁴Shahani S, Salehi M, Khoshsirat N and Akbari J. Evaluation of the effect of mouthwash containing black mulberry (Morus nigra L.) fruit juice for treatment of gingivitis. Research Journal of Pharmacognosy [Internet]. 2017;4 (Supplement):35.

⁵⁵Shukla RK, Painuly D, Shukla A, Kumar V, Singh J, Porval A and Vats S. Physical evaluation, proximate analysis and antimicrobial activity of Morus nigra seeds. Int J Pharm Pharm Sci [Internet]. 2015;7(1):191-197. ISSN- 0975-1491

⁵⁶Liu Y, Yan J, Ji Y, Nie W and Jiang Y. Black mulberry ethanol extract attenuates atherosclerosis-related inflammatory factors and downregulates PPARγ and CD36 genes in experimental atherosclerotic rats. Food Funct [Internet]. 2020;11:2997. DOI: https://doi.org/ 10.1039/c9fo02736j

⁵⁷Qadir MI, Ali M and Ibrahim Z. Anticancer activity of Morus nigra leaves extract. Bangladesh J Pharmacol [Internet]. 2014;9:496-497. DOI: https://doi.org/10.3329/bjp.v9i4.19783

⁵⁸Tag HM. Hepatoprotective effect of mulberry (Morus nigra) leaves extract against methotrexate induced hepatotoxicity in male albino rat. BMC Complementary and Alternative Medicine [Internet]. 2015;15:252. DOI: https://doi.org/10.1186/s12906-015-0744-y

⁵⁹Fahimi Z and Jahromy MH. Effects of blackberry (Morus nigra) fruit juice on levodopa-induced dyskinesia in a mice model of Parkinson's disease. J Exp Pharmacol [Internet]. 2018;4(10):29-35. DOI: https://doi.org/ 10.2147/JEP.S161782

⁶⁰Malik MNH, Alamgeer, Salma U, Qayyum A and Samreen S. Phytochemical Analysis and Cardiac Depressant Activity of Aqueous Methanolic Extract of Morus nigra L. Fruit.  Journal of Applied Pharmaceutical Science[Internet]. 2012;2(12):039-041. DOI: https://doi.org/ 10.7324/JAPS.2012.21207

⁶¹Fan L, Peng Y, Wu D, Hu J, Shi X, Yang G and Li X. Dietary supplementation of Morus nigra L. leaves decrease fat mass partially through elevating leptin-stimulated lipolysis in pig model.Journal of Ethnopharmacology [Internet]. 2020; 249:112416. DOI: https://doi.org/10.1016/j.jep.2019.112416.