Influence of safflower oil (Carthamus tinctorius L.) on insulin resistance and ventricular hypertrophy in dyslipidemic mice




Cholesterol; Cardiovascular diseases; Phytotherapic; Glucose; Left ventricular hypertrophy.


The regulation of lipid metabolism through the consumption of herbal medicines is a strategy to reduce the risk of cardiovascular diseases. Therefore, the aim of the study was to evaluate the effect of safflower oil on insulin resistance and left ventricular hypertrophy (LVH) in mice with the LDL receptor (LDLr -/-) with different diets. LDLr -/- mice were divided into four groups: C: standard diet; CCA: standard diet 2mg/kg/day of safflower oil; HL: hyperlipidic diet; HLCA: hyper dietalipid and 2mg/kg/day of safflower oil. After 15 days of experiment, total cholesterol and its fractions, triglycerides, C-reactive protein, insulin, glucose and adaptation to the Homa index were quantified. Histological slides with cardiac tissue were prepared and stained with hematoxylin and eosin, for general histological evaluation; and stained with picrosirius red to assess the collagen deposit area. The results obtained showed that safflower oil prevented the reduction of serum HDL levels and increased levels of CRP, partially prevented insulin resistance and hyperinsulinemia in the HLCA group mice. The use of safflower oil balanced the anti-hypertrophic factors in relation to the hypertrophic factors (hyperinsulinemia and inflammatory process), preventing LVH in the HLCA group mice. In conclusion, safflower oil prevented the development of LVH and partially insulin resistance.


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 American College Cardiology, 32(3), 704–710. / S0735-1097 (98) 00296-4

Bao, L. D., Wang, Y., Ren, X. H., Ma, R. L., Lv, H. J., & Agula, B. (2015). Hypolipidemic effect of safflower yellow and primary mechanism analysis. Genetics and Molecular Research. 14(2), 6270-6278.

Barter, P. J., Nicholls, S., Rye, K. A., Anantharamaiah, G. M., Navab, M., & Fogelman, A. M. (2004). Antiinflammatory Properties of HDL. Circulation Research, 95(8), 764-772.

Beisiegel, U., Weber, W., & Bengtsson-Olivecrona, G. (1991). Lipoprotein lipase increases the binding of chylomicrons to the useful protein to the low density lipoprotein receptor. Proceedings National Academy Sciences United States America, 88(19), 8342-8346.

Campanella, L. C. A., Silva, A. C., Freygang, J., & Dal-Magro, D. D. (2014). Efeito da suplementação de óleo de cártamo sobre o peso corporal, perfil lipídico, glicídico e antioxidante de ratos wistar induzidos à obesidade. Revista Ciências Farmacéuticas Básica Aplicada, 35(1),141-147.

Cho, S. H., Choi, S. W., Choi, Y., & Lee, W. J. (2000). Effects of defatted safflower and perilla seed powders on lipid metabolism in ovariectomized female rats fed high cholesterol diets. Journal-Korean Society of Food Science and Nutrition, 30(1), 112e118.

Faludi, A. A., Izar, C. O. M., Saraiva, J. F. K., Chacra, A. P. M., Bianco, H. T., Afiune Neto, A., et al. (2017). Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. Arquivos Brasileiros de Cardiologia. 109(2), 1-76. Recuperado de

Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of preparatory ultracentrifugation. Clinical Chemistry, 18(6), 499-502.

Giribela, C. R. G., Gengo, R., Hong, V., & Colombo, F. M. C. (2011). Função e disfunção endotelial: da fisiopatologia às perspectivas de uso em pesquisa e na prática clínica. Revista Brasileira Hipertensão,18(1), 27-32.

Garcia, J. A. D., & Incerpi, E. K. (2008). Fatores e mecanismos envolvidos na hipertrofia ventricular esquerda e o papel anti-hipertrófico do óxido nítrico. Arquivos Brasileiros de Cardiologia. 90(6), 443-450.

Garcia, J. A. D., Lima, C. C., Messora, L. B., Cruz, A. F., Marques, A. P. S., Simão, T. P., et al. (2011). Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos. Revista Portuguesa de Cardiologia, 30(10), 763-769.

Holvoet, P. (2008). Relations between metabolic syndrome, oxidative stress and in inflammation and cardiovascular disease. Verhandelingen - Koninklijke Academie voor Geneeskunde van België, 70 (3), 193-219.

Hwang, E. Y., Yu, M. H., Jung, Y. S., Lee, S. P., Shon, J. H., & Lee, S. O. (2016). Defatted safflower seed extract inhibits adipogenesis in 3T3-L1 preadipocytes and improves lipid profiles in C57BL/6J ob/ob mice fed a high-fat diet. Nutrition Research, 36(9), 995-1003.

Kawashima, S., Hayashi, M., Takii, T., Kimura, H., Zhang, H. L., Nagatsu, A., et al. (1998). Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 by endotoxin-stimulated human blood monocytes. Journal Interferon Cytokine Research, 18(6), 423-428.

Khalid, N., Khan, R. S., Hussain, M. I., Farooq., Ahmad, A., & Ahmed, I. (2017). A comprehensive characterisation of safflower oil for its potential applications as a bioactive food ingredient - A review. Trends in Food Science & Technology, 66, 176-186.

Koyama, N., Kuribayashi, K., Seki, T., Kobayashi, K., Furuhata, Y., Suzuki, K., et al. (2006). Serotonin derivatives, major safflower (Carthamus tinctorius L.) seed antioxidants, inhibit low-density lipoprotein (LDL) oxidation and atherosclerosis in apolipoprotein E-deficient mice. Journal of Agricultural and Food Chemistry. 54(14), 4970-4976.

Lázaro, M. L. (2009). Distribution and biological activities of the flavonoid luteolin. Mini-Reviews in Medicinal Chemistry. 9(1), 31-59. doi:

Moon, K.-D., Back, S.-S., Kim, J.-H., Jeon, S.-M., Lee, M.-K., & Choi, M.-S. (2001). Safflower seed extract lowers plasma and hepatic lipids in rats fed highcholesterol diet. Nutrition Research, 21(6), 895e904.

Olszewer, E., & Júnior L. M. A. (2012). Manual de Fitoterápicos em Obesidade. São Paulo: Ícone.

Organização Mundial da Saúde. (2019). Doenças Cardiovasculares. Recuperado de

Sarto, D. A. Q. S., Siqueira, A. H. M., Almeida, F. M., Caproni, K. P., Martins, A. M., Santos, G. B., 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. 2018.

Seo, T., Ai-Haideri, M., Treskova, E., Worgall, T. S., Kako, Y., Goldberg, I. J., et al. (2000). Lipoprotein lipase-mediated selective uptake from low density lipoprotein requires cell surface proteoglycans and is independent of scavenger receptor class B type 1. Journal Biological Chemistry, 275 (39), 30355–30362.

Serrato, M., & Marian, A. J. (1995). A variant of human paraoxonase/ arylesterase (HUMPONA) gene is a risk factor for coronary artery disease. Journal of Clinical Investigation. 96(6), 3005-3008.

Silva, D. B., Miranda, A. P., Silva, D. B., Angelo, L. R., Rosa, B. B., Soares E. A., et al. (2015). Própolis e natação na prevenção da aterogênese e hipertrofia ventricular esquerda em camundongos hipercolesterolêmicos. Brazilian Journal of Biology, 75 (2), 414-422.

Shin, S., & Ajuwon, K. M. (2018). Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets. Nutrientes, 10(2), 256.

Shirani, J., Pick, R., Roberts, W. C., & Maron, B. J. (2000). Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. Journal American College Cardiology, 35(1), 36–44. / s0735-1097 (99) 00492-1.

Sociedade Brasileira de Cardiologia. (2020). Mortes por doenças cardiovasculares no Brasil em 2020. Recuperado de em

Tian, J., Pei, H., Sanders, J. M., Angle, J. F., Sarembock, I. J., Matsumoto, A. H., et al. (2006). Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice. Biochemical Biophysical Research Communications, 345(3),1004-1009.

Zhao, G., Zheng, X. W., Gai, Y., Chu, W. J., Qin, G. W., & Guo, L. H. (2009). Safflower extracts functionally regulate monoamine transporters. Journal Ethnopharmacoly, 124(1), 116-124. / j.jep.2009.04.002.



How to Cite

Caproni, K. de P. ., Martins, Ângela M. ., Boas, B. M. V. ., Sarto, D. A. Q. S. ., Nachtigall, A. M. ., Santos, L. dos, Soares, E. A. ., Garcia, E. K. I. ., Carvalho, M. das G. de S. ., Cardoso, A. M., & Garcia, J. A. D. . (2020). Influence of safflower oil (Carthamus tinctorius L.) on insulin resistance and ventricular hypertrophy in dyslipidemic mice. Research, Society and Development, 9(9), e243997141.



Health Sciences