EFFECTS OF PALM OIL DERIVED TOCOTRIENOL RICH FRACTION AND VITAMIN E ISOMERS ON BIOMARKERS OF EARLY ATHEROGENESIS IN STIMULATED HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS
Keywords:
Endothelial activation, inflammation, tocopherol, tocotrienols, vitamin EAbstract
This study was conducted to investigate the effects of tocotrienol rich fraction (TRF), α-TOC, and pure TCT isomers (α-. γ- & δ-TCT) on inflammation, endothelial activation, nuclear factor kappa B (NFκB), endothelial nitric oxide synthase (eNOS) and monocyte binding activity (MBA) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of α-TOC, pure TCT isomers and TRF (0.3-10 µM) together with lipopolysaccharides (LPS) for 16 h. Culture medium and cells were collected and measured for the protein and gene expression of IL-6, TNF-α, NFκB, ICAM-1, VCAM-1, e-selectin, and eNOS. Monocyte binding activity (MBA) was measured by Rose Bengal staining. Area under the curve (AUC) analysis revealed that TRF and pure TCT particularly γ- and δ- isomers, showed better inhibition of inflammation and endothelial activation, MBA and greater eNOS increment than α-TOC. These suggest that TRF and pure TCT isomers have potential as preventive anti-atherogenic agents by attenuating the release of early biomarkers of atherogenesis which is better than α-TOC in LPS-stimulated human endothelial cells.
Downloads
Metrics
References
Abner, E.L, Schmitt, F.A, Mendiondo, M.S, Marcum, J.L. & Kryscio, R.J. 2011. Vitamin E and all-cause mortality: A meta-analyses. Current Aging Science, 4(2): 158–70. DOI: https://doi.org/10.2174/1874609811104020158
Aquila, G., Marracino, L., Martino, V., Calabria, D., Campo, G. & Caliceti, C. 2019. The use of nutraceuticals to counteract atherosclerosis: The role of the notch pathway. Oxidative Medicine and Cellular Longevity, 30: 1-30. DOI: https://doi.org/10.1155/2019/5470470
Bienke, S. & Ley, S.C. 2004. Functions of NF-κB1 and NF-κB2 in immune cell biology. Biochemical Journal, 382 (Pt 2): 393–409. DOI: https://doi.org/10.1042/BJ20040544
ČejkováIvana, S., Lesná, K. & Poledne, P. 2016. Monocyte adhesion to the endothelium is an initial stage of atherosclerosis development. Cor et Vasa, 58: e419-e425. DOI: https://doi.org/10.1016/j.crvasa.2015.08.002
Dutta, A. & Dutta. S. 2003. Vitamin E and its Role in the prevention of atherosclerosis and carcinogenesis: A review. Journal of American College of Nutrition, 22(4): 258-268. DOI: https://doi.org/10.1080/07315724.2003.10719302
El-Solh, A.A., Mador, M.J., Sikka, P., Dhillon, R.S., Amsterdam, D. & Grant, B.J.B. 2002. Adhesion molecules in patients with coronary artery disease and moderate-to-severe obstructive sleep apnea. Chest, 121(5): 1541–1547. DOI: https://doi.org/10.1378/chest.121.5.1541
Fish, J.E., Matouk, C.C., Rachlis, A., Lin, S., Tai, S. C., D’Abreo, C. & Marsden, P.A. 2005. The expression of endothelial nitrix-oxide synthase is control by a-cell specific histone code. Journal of Biological Chemistry, 280(26): 24824-24838. DOI: https://doi.org/10.1074/jbc.M502115200
Hickey, M.J. 2001. Role of inducible nitric oxide synthase in the regulation of leukocyte recruitment. Clinical Science, 100 (1): 1-12. DOI: https://doi.org/10.1042/cs1000001
Ikeda, S., Tohyama, T., Yoshimura, H., Hamamura, K., Abe, K. & Yamashita, K. 2003. Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats. Journal of Nutrition, 133: 428-34. DOI: https://doi.org/10.1093/jn/133.2.428
Libby, P., Buring, J.E., Badimon, L., Hansson, G.K., Deanfield, J., Bittencourt, M.C., Tokgozoglu, L. & Lewis, E.F . 2019. Atherosclerosis. Nature Reviews Disease Primers, 5(1): 56. DOI: https://doi.org/10.1038/s41572-019-0106-z
Linton, M.F., Yancey, P.G., Davies. S.S., Jerome, W.G., Linton, E.F., Song, W.L., Doran, A.C., & Vickers, K.C. 2019. The role of lipids and lipoproteins in atherosclerosis [WWW Document]. Endotext. URL https://www.endotext.org/MDText (accessed 15.10.22).
Liu, T., Zhang, L., Joo, D., & Cong-Sun, S. 2017. NF-κB signalling in inflammation. Signal Transduction and Targeted Therapy, 2: 17023. DOI: https://doi.org/10.1038/sigtrans.2017.23
Miyazawa, T , Burdeos, G.C. , Itaya, M., Nakagawa, K.. & Miyazawa, T . 2019. Vitamin E: Regulatory redox interactions. IUBMB Life, 71(4):430-41. DOI: https://doi.org/10.1002/iub.2008
Miyazawa, T., Shibata, A., Nakagawa, K. & Tsuzuki, T. 2008. Anti-angiogenic function of tocotrienol. Asia Pacific Journal of Clinical Nutrition, 17 (Suppl 1): 25.
Mohd Ariff, A., Abu Bakar, N.A., Abd. Muid, S. Omar, E. Ismail, N.H., Ali, A.M., Mohd Kasim, N.A. & Nawawi, H. 2020. Ficus deltoidea suppresses endothelial activation, inflammation, monocytes adhesion and oxidative stress via NF-κB and eNOS pathways in stimulated human coronary artery endothelial cells. BMC Complementary Medicine and Therapies, 20: 56. DOI: https://doi.org/10.1186/s12906-020-2844-6
Mu, W., Chen, M., Gong, Z., Zheng, F. & Xing, Q. 2015. Expression of vascular cell adhesion molecule-1 in the aortic tissues of atherosclerotic patients and the associated clinical implications. Experimental and Therapeutic Medicine, 10(2): 423-428. DOI: https://doi.org/10.3892/etm.2015.2540
Muid, S., Ali, A.M, Yusoff, K. & Nawawi, H. 2013. Optimal antioxidant activity with moderate concentrations of tocotrienol of tocotrienol in in vitro assays. International Food and Research Journal, 20(2): 687-94.
Muid, S., Froemming, G.R.A., Rahman, T.H, Ali, A.M. & Nawawi H. 2017. Tocotrienols reduce monocytes adhesion to stimulated human endothelial cells. International Food and Research Journal, 24(6): 2580-2585.
Mussbacher, M., Salzmann, M., Brostjan, C., Hoesel, B., Schoergenhofer, C., Datler, H. et al. 2019. Cell type-specific roles of NF-kB linking inflammation and thrombosis. Frontiers in Immunology, 10: 85. DOI: https://doi.org/10.3389/fimmu.2019.00085
Naito, Y., Shimozawa, M., Kuroda, M., Nakabe, N., Manabe, H., Katada, K., Kokura, S., Ichikawa, H., Yoshida, N., Noguchi, N. & Yoshikawa, T. 2005. Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules. Atherosclerosis, 180: 19-25. DOI: https://doi.org/10.1016/j.atherosclerosis.2004.11.017
Niki, E. & Abe, K. 2019. Vitamin E: Structure, properties and functions. In: Vitamin E: Chemistry and nutrional benefits. Royal Society of Chemistry. pp.1-11. DOI: https://doi.org/10.1039/9781788016216-00001
Peng, H.B., Libby, P. & Liao, J.K. 1995. Induction and stabilization of IκBα by nitric oxide mediates inhibition of NFκB. Journal of Biological Chemistry, 270: 14214-14219. DOI: https://doi.org/10.1074/jbc.270.23.14214
Qureshi, A.A. , Reis, J.C., Papasian, J.C., Morrison, D.C. & Qureshi, N. 2010. Tocotrienols inhibit lipopolysaccharide-induced pro-inflammatory cytokines in macrophages of female mice. Lipids in Health and Disease, 9: 143. DOI: https://doi.org/10.1186/1476-511X-9-143
Qureshi, A.A., Pearce, C., Nor, R.M., Gapor, A., Peterson. D.M. & Elson, CE. 1996. Dietary d-tocopherol attenuates the impact of d-tocotrienol on hepatic 3-hydroxy-3- methylglutaryl coenzyme A reductase activity in chickens. Journal of Nutrition, 126: 389-94. DOI: https://doi.org/10.1093/jn/126.2.389
Qureshi, A.A., Reis, J.C., Qureshi, N., Papasian, C.J, Morrison, D.C & Schaefer, D.M. 2011. δ-Tocotrienol and quercetin reduce serum levels of nitric oxide and lipid parameters in female chickens. Lipids in Health and Disease, 10(39): 1-22. DOI: https://doi.org/10.1186/1476-511X-10-39
Rimm, E.B., Stampfer, M.J & Ascherio, A. 1993. Vitamin E consumption and the risk of coronary heart disease in men. New England Journal of Medicine, 328: 1450-56. DOI: https://doi.org/10.1056/NEJM199305203282004
Selvaduray, K.R, Radhakrishnan, A.K., Kutty, M.K. & Nesaretnam, K. 2012. Palm tocotrienols decrease levels of pro-angiogenic markers in human umbilical vein endothelial cells (HUVEC) and murine mammary cancer cells. Genes Nutrition, 7: 53–61. DOI: https://doi.org/10.1007/s12263-011-0223-0
Sue-Mian, T., Wan Ngah, W.Z., Mat Top, G. & Mazlan, M. 2010. Comparison of the effects of α-Tocopherol and γ-Tocotrienol against oxidative stress in two different neuronal cultures. Sains Malaysiana, 39(1): 145–156.
Szewczyk, K., Chojnacka, A. & Górnicka, M. 2021. Tocopherols and Tocotrienols-Bioactive dietary compounds; What is certain, what is doubt?. International Journal of Molecular Sciences, 22: 6222. DOI: https://doi.org/10.3390/ijms22126222
Theriault, A., Choa, J.T. & Gapor, A. 2002. Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes. Atherosclerosis, 160: 21-30. DOI: https://doi.org/10.1016/S0021-9150(01)00540-8
Upadhyay, R.K. 2015. Emerging risk biomarkers in cardiovascular diseases and disorders. Journal of Lipids, 2015: 971453. DOI: https://doi.org/10.1155/2015/971453
Vallance, P. & Chan, N. 2001. Endothelial function and nitric oxide: Clinical relevance. Heart, 85: 342-50. DOI: https://doi.org/10.1136/heart.85.3.342
Wu, S.J., Liu, P.L. & Lean-Teik N. 2008. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells. Molecular Nutrition and Food Research, 52:921-29. DOI: https://doi.org/10.1002/mnfr.200700418
Ziegler, M., Wallert, M., Lorkowski, S. & Peter K. 2020. Cardiovascular and metabolic protection by vitamin E: A matter of treatment strategy? Antioxidants, 9: 935. DOI: https://doi.org/10.3390/antiox9100935
Published
How to Cite
Issue
Section
Any reproduction of figures, tables and illustrations must obtain written permission from the Chief Editor (wicki@ukm.edu.my). No part of the journal may be reproduced without the editor’s permission