Effect of mulberry leaf extract (Morus nigra L.) on cardiovascular inflammatory process and insulin resistance of dyslipidemic mice

Authors

DOI:

https://doi.org/10.33448/rsd-v11i2.25473

Keywords:

Dyslipidemia; Cardiac inflammation; Aorta; Insulin; Mulberry.

Abstract

Objective: To evaluate the effect of mulberry leaf extract on cardiovascular inflammation, insulin resistance and left ventricular hypertrophy in dyslipidemic mice. Methodology: Knockout mice for the LDL receptor gene were divided into four experimental groups (n=20): group S (Standard), fed a standard diet; group SA (Standard / Mulberry), fed a standard diet and mulberry leaves extract; group HL (Hyperlipidic), fed a hyperlipidic diet and group HLA (Hyperlipidic / Mulberry), fed a hyperlipidic diet and mulberry leaves extract. After 15 days of experiment, plasma was collected and the plasma levels of total cholesterol and its fractions, triglycerides, C-reactive protein, insulin, glucose were quantified and the Homa index calculated. Heart and aortic wall tissues were collected to quantify the expression of CD40L by the western blotting method. Histological slides with heart tissue were prepared and stained with hematoxylin and eosin for general histological evaluation and stained with picrosírius red to evaluate the collagen deposit area. Results: Mulberry leaf extract elevated plasma HDL, moderately prevented hypercholesterolemia and did not reduce hypertriglyceridemia in HLA group mice, prevented insulin resistance and consequently hyperinsulinemia, reduced plasma CRP level and prevented increased CD40L expression. Conclusion: Treatment with mulberry leaves extract prevented cardiovascular inflammation and insulin resistance, thus reducing the development of left ventricular hypertrophy.

References

Abel, L. C., Ferreira, L. R., Cunha Navarro, I., Baron, M. A., Kalil, J., Gazzinelli, R. T., Rizzo, L. V., & Cunha-Neto, E. (2014). Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and potentiated by IFN- γ and CD40-CD40L interactions. Mediators of inflammation, 2014, 345659.

Aghababaee, S. K., Vafa, M., Shidfar, F., Tahavorgar, A., Gohari, M., Katebi, D., & Mohammadi, V. (2015). Effects of blackberry (Morus nigra L.) consumption on serum concentration of lipoproteins, apo A-I, apo B, and high-sensitivity-C-reactive protein and blood pressure in dyslipidemic patients. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 20(7), 684–691.

Albuquerque, M. A. C., & Neri, D. F. M. (2012). Uso do extrato etanólico das folhas da Morus nigra L. (Moraceae) como proposta de tratamento do diabetes Mellitus associado ao alcoolismo crônico. In: JORNADA DE INICIAÇÃO CIENTÍFICA DA EMBRAPA SEMIÁRIDO, 7. JORNADA DE INICIAÇÃO CIENTÍFICA DA FACEPE/UNIVASF, 1., 2012, Petrolina. Anais... Petrolina: Embrapa Semiárido.

Almeida, J. R. G. S., Souza, G. R., Araújo, E. C. C., Silva, F. S., Lima, J. T., Ribeiro, L. A. A., Nunes, X. P., Barbosa Filho, J. M., Quintans-Júnior, L. J., & dos Santos, M. R. V. (2012). Medicinal plants and natural compounds from the genus Morus (Moraceae) with hypoglycemic activity: a review. In: Sureka Chackrewarthy. (Org.). Glucose Tolerance. 1ed.Rijeka - Croatia: InTech. 1, 189-206.

Almeida, J. R. G. S., Guimarães, A. L., Oliveira, A. P., Araújo, E. C. C., Silva, F. S., Neves, L. F., Oliveira, R. A., Sá, P. G. S., & Quintans-Júnior L. J. (2011). Evaluation of Hypoglycemic Potential and Pre-Clinical Toxicology of Morus nigra L. (Moraceae). Lat. Am J Pharm. 30(1):96-100.

Araujo, C. M., de Lúcio, K. de P., Silva, M. E., Isoldi, M. C., Souza, G. H. B. de, Brandão, G. C., Schulz, R., & Costa, D. C. (2015). Morus nigra leaf extract improves glycemic response and redox profile in the liver of diabetic rats. Food & function, 6(11), 3490-3499.

Armstrong, A. T., Binkley, P. F., Baker, P. B., Myerowitz, P. D., & Leier, C. V. (1998). Quantitative investigation of cardiomyocyte hypertrophy and myocardial fibrosis over 6 years after cardiac transplantation. Journal of the American College of Cardiology, 32(3), 704–710.

Barbalho, S. M., Bechara, M. D., Quesada, K., Gabaldi, M. R., Goulart, R. A., Tofano, R. J., & Gasparini, R. G. (2015). Síndrome metabólica, aterosclerose e inflamação: tríade indissociável? Jornal Vascular Brasileiro, 14(4), 319-327.

Cardoso, L. M., Leite, J. P., & Peluzio, M. C. G. (2011). Efeitos biológicos das antocianinas no processo aterosclerótico. Revista Colombiana De Ciencias Químico-Farmacéuticas. 40(1):116-138.

Carvalho K. M., Marinho Filho J. D., Melo T. S. de, Araújo A. J., Quetz, J. da S, da Cunha, M. do P., Melo, K. M. de, Silva, A. A. da, Tomé, A. R., Havt, A, Fonseca, S. G., Brito, G. A., Chaves, M. H., Rao, V. S., & Santos, F. A. (2015). The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms. Evidence-based complementary and alternative medicine, 2015:106157.

Casarin, F., Mendes, C. E., Lopes, T. J. (2016) Planejamento experimental do processo de secagem da amora-preta (Rubus sp.) para a produção de farinha enriquecida com compostos bioativos. Braz. J. Food Tecnol, 19:01-08.

Castillo-Hernandez J, Maldonado-Cervantes MI, Reyes JP, Patiño-Marin N, Maldonado-Cervantes E, Solorzano-Rodriguez Claudia et al. (2017). A obesidade é um determinante da resistência à insulina mais importante do que os níveis circulantes de citocinas pró-inflamatórias em pacientes com artrite reumatoide. Rev. Bras. Reumatol, 57(4):320-329.

Chen, H., Pu, J., Liu, D., Yu, W., Shao, Y., Yang G., Xiang, Z., & He, N. (2016). Anti-Inflammatory and antinociceptive properties of flavonoids from the fruits of black mulberry (Morus nigra L.). PLoS One, 11(4):e0153080.

Christison J, Karjalainen A, Brauman J, Bygrave F, Stocker R. (1996). Rapid reduction and removal of HDL- but not LDL-associated cholesteryl ester hydroperoxides by rat liver perfused in situ. Biochem J, 314(Pt3) (Pt3):739-742.

Corica, D., Aversa, T., Ruggeri, R. M., Cristani, M., Alibrandi, A., Pepe, G., De Luca, F., & Wasniewska, M. (2019). Could AGE/RAGE-Related Oxidative Homeostasis Dysregulation Enhance Susceptibility to Pathogenesis of Cardio-Metabolic Complications in Childhood Obesity?. Frontiers in endocrinology, 10, 426.

Costa, G. R. (2017). Efeito de extratos ricos em antocianinas ou elagitaninos de amora silvestre (Morus nigra L.), amora preta (Rubus spp), e grumixama (Eugenia brasiliensis Lam) no crescimento e na expressão de genes e miRNAs de diferentes linhagens de céluas humanas de câncer de mama. (Tese). Universidade de São Paulo: São Paulo, SP. 100 p.

Dalmagro, A. P., Camargo, A., Zeni, A. L. B. (2017). Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice. Metab. Brain Dis, 32(6):1963-73

Faludi, A. A. (Ed.). n/a et al. (2017). Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Ateroclerose. Arq Bras Cardiol, 109(2 supl.1):1-76.

Friedewald, WT, Levi RI, Fredrickson DS. (1972). Estimation of the concentration of low density lipoproteins cholesterol in plasma without use of the ultracentrifuge. Clin. Chem, 18(6):499-502.

Garcia, J. A. D., Incerpi, E. K. (2008). Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico. Arq. Bras. Cardiol, 90(6):443-50.

Garcia, J. A. D. (Ed.). n/a et al. (2011). Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos. Rev Port Cardiol, 30(3):763-9.

Gayoso-Diz, P., Otero-González, A., Rodriguez-Alvarez, M. X., Gude, F., García, F., Francisco, A., & Quintela, A. G. (2013). Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study. BMC Endocr Disord, 13:47.

Hedrick, C. C., Castellani, L. W., Wong, H., Lusis, A. J. (2001). In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL structure and antiatherogenic functions. J. Lipid Res, 42(4):563‐70.

Holvoet, P. (2008). Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg, 70(3):193-219.

INSTITUTO ADOLFO LUTZ. (2008). Métodos físico-químicos para análise de alimentos. São Paulo: Instituto Adolfo Lutz.

Júnior, I. I. D. S., Barbosa, H. M., Carvalho, D. C. R., Barros, R. A., Albuquerque, F. P., Silva, D. H. A. da., Souza, G. R., Souza, N. A. C., Rolim, L. A., Silva, F. M. M., Duarte, G. I. B. P., Almeida, J. R. G. D. S., Oliveira Júnior, F. M. de., Gomes, D. A., & Lira, E. C. Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats. Scientific World Journal. 2017:5275813.

Junqueira, L. C., Bignolas, G., Brentani. R. R. (1979). Picrosirius red staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J, 11(4):447–55.

Lima, J. C. C., Moreira, A., Lima, D., Correia, L. C. L. (2005). Validação da medida de proteína c reativa de alta sensibilidade por quimioluminescência para estimativa de risco cardiovascular em indivíduos ambulatoriais - análise comparativa com nefelometria. Jornal Brasileiro de Patologia Médica laboratorial, 41(1):15-19.

Oishi, J. C., Castro, C. A., Silva, K. A., Fabricio, V., Cárni,o E. C., Phillips, S. A. (2018). Disfunção Endotelial e Inflamação Precedem a Elevação da Pressão Arterial Induzida por Dieta Hiperlipídica. Arquivos Brasileiros de Cardiologia, 110( 6):558-67.

Oliveira, F. P. A., Freitas, L. S., Vieira, G. G., Ribeiro, M. F., Freitas, A. R., Correa CR. (2016). Vitamina D associada à resistência insulínica. hu ver, 42(2).

Prakash, D., Suri, S., Upadhyay, G., Singh, B. N. (2007). Total phenol, antioxidant and free radical scavenging activities of some medicinal plants. Int J Food Sci Nutr, 58(1):18-28.

Santos, L. (Ed.). n/a et al. (2017). Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice. Braz J Med Biol Res, 50(3):e5854.

Sarto, D. A. Q. S. (Ed.). n/a et al. (2018). Dry Extract of Passiflora incarnata L. leaves as a Cardiac and Hepatic Oxidative Stress Protector in LDLr-/- Mice Fed High-Fat Diet. Brazilian Archives of Biology and Technology, 61, e18180147.

Schafranski, K., Postigo, P., Vitali, L., Micke, G. A., Richter WE, Chaves ES. (2019). Avaliação de compostos bioativos e atividade antioxidante de extratos de folhas de amoreira preta (Morus nigra L.) utilizando planejamento experimental. Quim. Nova, 42:736-4.

Silva, P. C. da., Torres, F. (2015). Hipercolesterolemia e o desenvolvimento da aterosclerose: revisão de literatura. Revista Científica Da Faculdade De Educação e Meio Ambiente, 6(1):48-58.

Silva, R. A. H. (2012). Estudo da ação do extrato bruto de Morus nigra L. (Moreaceae) e frações fenólicas sobre a atividade antimicrobiana e geração de espécies reativas do oxigênio e nitrogênio: in vitro com ensaios químicos, enzimáticos e celular. (Tese). Universidade Estadual Paulista: Araraquara, SP. 178 p.

Silverman, M. G., Ference, B. A., Im, K., Wiviott, S. D., Giugliano, R. P., Grundy, S. M., Braunwald, E., & Sabatine, M. S. (2016). Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA, 316(12):1289-97.

Simko, F., Luptak, I., Matuskova, J., Babal, P., Pechanova, O., Bernatova, I., & Hulin, I. (2002). Heart remodeling in the hereditary hypertriglyceridemic rat: effect of captopril and nitric oxide deficiency. Ann N Y Acad Sci, 967(1):454-62.

Souza, G. R. (Ed.). n/a et al. (2015). Atividade anticonceptiva do extrato etanólico das folhas de Morus nigra L. Rev. ciênc. farm. básica apl, 36(1):137-42.

Storch, A. A., Mattos, J. D. de., Alves, R., Galdino, I. S., Rocha, H. N. M. (2017). Métodos de Investigação da Função Endotelial: Descrição e suas Aplicações. Int. J. Cardiovasc. Sci, (3(30):262-73.

Tian, J. (Ed.). n/a et al. (2006). Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice. Biochem Biophys Res Commun, 345(3):1004-9.

Trinder, P. (1969). Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem, 6(1):24-7.

Turgut NH, Mert DG, Kara H, Egilmez HR, Arslanbas E, Tepe B, et al. (2016). Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice. Pharmaceutical Biology, 54(6):1052-64.

Xia, P., Vadas, M. A., Rye, K. A., Barter, P. J., Gamble, J. R. (1992). High density lipoproteins (HDL) interrupt the sphingosine kinase signaling pathway. A possible mechanism for protection against atherosclerosis by HDL. J Biol Chem, 274(46):33143-147.

Zeni, A. L. B., Moreira, T. D., Dalmagro, A. P., Camargo, A., Bini, L. A., Simionatto, E. L., & Scharf, D. R. (2017). Evaluation of phenolic compounds and lipid-lowering effect of Morus nigra L leaves extract. An. Acad. Bras. Ciênc, 89(4):2805-15.

Zhang, Y., Wu, L., Ma, Z., Cheng, J., Liu, J. (2015). Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice. Molecules, 23;21(1):E7.

Published

18/01/2022

How to Cite

PEREIRA, C. R.; FARIA, A. L. C. de .; CARVALHO, M. das G. de S. .; VILAS BOAS , B. M. .; GARCIA, E. K. I. .; OLIVEIRA, F. L. de .; SANTOS, L. dos .; ALVES, L. R. de C.; NACHTIGALL, A. M. .; PEREIRA, F. H. .; GARCIA, J. A. D. . Effect of mulberry leaf extract (Morus nigra L.) on cardiovascular inflammatory process and insulin resistance of dyslipidemic mice. Research, Society and Development, [S. l.], v. 11, n. 2, p. e4611225473, 2022. DOI: 10.33448/rsd-v11i2.25473. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/25473. Acesso em: 22 feb. 2024.

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Section

Agrarian and Biological Sciences