Sains Malaysiana 49(6)(2020): 1313-1322

http://dx.doi.org/10.17576/jsm-2020-4906-09

 

Trihoney Suppresses Soluble Adhesion Molecules (ICAM-1 and VCAM-1) in Hypercholesterolemic Atherosclerotic Rabbits: A Comparative Study with Atorvastatin

(Trihoney Menekan Molekul Pelekatan Larut (ICAM-1 dan VCAM-1) pada Arnab Aterosklerotik Hiperkolesterolemik: Kajian Perbandingan dengan Atorvastatin)

Hamad Abdul Salam Hamad Alfarisi1, Muhammad Ibrahim*1, Zenab B. Hamad Mohamed1, Asmah Hanim Hamdan2 & Che Anuar Che Mohamad3

 

1Department of Nutrition Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

 

2Department of Pathology & Laboratory Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

 

3Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

 

Received: 21 December 2019/Accepted: 9 March 2020

 

ABSTRACT

Atherosclerosis is a chronic inflammatory disease and high serum cholesterol proven as the main trigger of its pathogenesis. Development of atherosclerotic lesions is closely related to the level of serum cholesterol. Expression of adhesion molecules has been correlated with the extent of aortic lesions. Serum circulating forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been detected in high levels in vascular inflammatory diseases. Honey has been shown to diminish the expression of VCAM-1 in vascular endothelium. Thirty-six male New Zealand white (NZW) rabbits were grouped into: normal diet (C), normal diet with 0.6 g/kg/day of Trihoney (C+H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of Trihoney (HCD+H1), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD+H2) and 1% cholesterol diet with 2 mg/kg/day of atorvastatin (HCD+At). Animals were sacrificed after 12 weeks of treatment. Serum was analysed for lipids, ICAM-1 and VCAM-1. Atherosclerotic plaques in the aorta were quantified. Serum ICAM-1 and VCAM-1 were significantly elevated in the HCD group when compared to the control groups. Groups Supplemented with Trihoney showed a significant suppression of serum ICAM-1 and VCAM-1 in comparison to the HCD group. Serum ICAM-1 and VCAM-1 exhibited a significant positive correlation with serum cholesterol. Serum VCAM-1 showed a significant positive correlation with the percentage of aortic lesions. Results of this study showed that Trihoney has anti-atherosclerotic potential through suppression of adhesion molecules. Trihoney was comparable to atorvastatin and may be suggested as an adjuvant remedy for protection against atherosclerosis.

Keywords: Adhesion molecules; atorvastatin; cholesterol; Trihoney  


ABSTRAK


Aterosklerosis adalah penyakit keradangan kronik dan kolesterol serum yang tinggi terbukti sebagai pencetus utama patogenesisnya. Perkembangan lesi aterosklerotik berkait rapat dengan tahap kolesterol serum. Ekspresi molekul lekatan telah berkorelasi dengan sejauh mana lesi aorta. Bentuk peredaran serum molekul lekatan antara sel (1 ICAM-1) dan molekul lekatan sel vaskular-1 (VCAM-1) telah dikesan pada tahap tinggi dalam penyakit radang vaskular. Madu terbukti dapat mengurangkan ekspresi VCAM-1 pada endotelium vaskular. Tiga puluh enam ekor arnab putih New Zealand (NZW) dikelompokkan kepada: diet normal (C), diet normal dengan 0.6 g/kg/day Trihoney (C+H), 1% diet kolesterol  (HCD), 1% kolesterol diet dengan 0.3 g/kg/day Trihoney (HCD+ H1), 1% diet kolesterol dengan 0.6 g/kg/day Trihoney (HCD+H2) dan 1%diet kolesterol  dengan 2 mg/kg/day atorvastatin (HCD + At). Haiwan dikorbankan setelah 12 minggu rawatan. Serum dianalisis untuk lipid, ICAM-1 dan VCAM-1. Plak aterosklerotik di aorta diukur. Serum ICAM-1 dan VCAM-1 meningkat secara signifikan dalam kumpulan HCD jika dibandingkan dengan kumpulan kawalan. Kumpulan yang diberi Trihoney menunjukkan penekanan serum ICAM-1 dan VCAM-1 yang signifikan berbanding dengan kumpulan HCD. Serum ICAM-1 dan VCAM-1 menunjukkan korelasi positif yang signifikan dengan kolesterol serum. Serum VCAM-1 menunjukkan korelasi positif yang signifikan dengan peratusan lesi aorta. Hasil kajian ini menunjukkan bahawa Trihoney mempunyai potensi anti-aterosklerotik melalui penekanan molekul lekatan. Trihoney setanding dengan atorvastatin dan boleh disarankan sebagai ubat tambahan untuk perlindungan terhadap aterosklerosis.

Kata kunci: Atorvastatin; kolesterol; molekul lekatan; Trihoney

 

REFERENCES

 

AEPC 2012. Kuantan: International Islamic University Malaysia Animal Ethics Policy.

Alfarisi, H.A.H., Ibrahim, M.B., Mohamed, Z.B.H., Hamdan, A.H.B. & Mohamad, C.A.C.     2019. Trihoney Ameliorates Oxidative Stress in Atherosclerotic Aorta. International Journal of Allied Health Sciences 3(3): 767-767.

Al-Waili, N., Salom, K., Al-Ghamdi, A., Ansari, M.J., Al-Waili, A. & Al-Waili, T. 2013. Honey and cardiovascular risk factors, in normal individuals and in patients with diabetes mellitus or dyslipidemia. Journal of Medicinal Food 16(12): 1063-1078.

Bergheanu, S.C., Bodde, M.C. & Jukema, J.W. 2017. Pathophysiology and treatment of atherosclerosis: Current view and future perspective on lipoprotein modification treatment. Netherlands Heart Journal 25(4): 231-242.

Boesten, L.S.M., Zadelaar, A.S.M., van Nieuwkoop, A., Gijbels, M.J., De Winther, M.P., Havekes, L.M. & van Vlijmen, B.J. 2005. Tumor necrosis factor-α promotes atherosclerotic lesion progression in APOE*3-leiden transgenic mice. Cardiovascular Research 66(1): 179-185.

Bolayirli, I.M., Aslan, M., Balci, H., Altug, T., Hacibekiroglu, M. & Seven, A. 2007. Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine. Life Sciences 81(2): 121-127.

Brevetti, G., Schiano, V. & Chiariello, M. 2006. Cellular adhesion molecules and peripheral arterial disease. Vascular Medicine 11(1): 39-47.

Brown, S. 2016. Taking Blood Sample from Rabbit. IDEXX Laboratory. pp. 1-11.

Catapano, A.L., Graham, I., De Backer, G., Wiklund, O., Chapman, M.J., Drexel, H., Hoes, A.W., Jennings, C.S., Landmesser, U., Pedersen, T.R. & Reiner, Ž. 2016. 2016 ESC/EAS guidelines for the management of dyslipidaemias: The task force for the management of dyslipidaemias of the european society of cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 253(2016): 281-344.

de Almeida Torres, R.J., Noronha, L.D., de Almeida Torres, R.D.R., Nagashima, S., de Almeida Torres, C.L., Luchini, A., de Almeida Torres, R.A., Précoma, L.B. & Précoma, D.B. 2014. Increased intercellular adhesion molecule-1 immunoreactivity in the sclera-choroid complex in hypercholesterolemia experimental model. Revista Brasileira de Oftalmologia 73(4): 210-215.

Du, B., Xu, G., Cao, H., Cui, W., Lin, S., Liu, Y. & Qin, L. 2013. Effects of atorvastatin on expression of ICAM-1 in atherosclerotic rabbits. Journal of Cardiovascular Medicine 14(2): 120-126.

Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Honda, K. & Watanabe, T. 2001. Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet. Arteriosclerosis, Thrombosis, and Vascular Biology 21(1): 88-94.

Fotis, L., Agrogiannis, G., Vlachos, I.S., Pantopoulou, A., Margoni, A., Kostaki, M., Verikokos, C., Tzivras, D., Mikhailidis, D.P. & Perrea, D. 2012. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 at the early stages of atherosclerosis in a rat model. In vivo 26(2): 243-250.

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

Hansson, G.K. 2005. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine 352(16): 1685-1695.

Hope, S.A. & Meredith, I.T. 2003. Cellular adhesion molecules and cardiovascular disease. Part I. Their expression and role in atherogenesis. Internal Medicine Journal 33(8): 380-386.

Ibrahim, M., Ahmed, I.A., Mikail, M.A., Ishola, A.A., Draman, S., Isa, M.L.M. & Yusof, A.M. 2017. Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced hypercholesterolemic rabbits. Lipids in Health and Disease 16(1): 1-8.

Jellinger, P.S., Handelsman, Y., Rosenblit, P.D., Bloomgarden, Z.T., Fonseca, V.A., Garber, A.J., Grunberger, G., Guerin, C.K., Bell, D.S., Mechanick, J.I. & Pessah-Pollack, R. 2017. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocrine Practice 23(2): 1-87.

Jorge, P.A.R., Almeida, E.A.D., Ozaki, M.R., Jorge, M. & Carneiro, A. 2005. Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits. Arquivos Brasileiros de Cardiologia 84(4): 314-319.

Kong, L., Luo, C., Li, X., Zhou, Y. & He, H. 2013. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipids in Health and Disease 12(1): 1-12.

Li, H., Cybulsky, M.I., Gimbrone Jr., M.A. & Libby, P. 1993. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology 13(2): 197-204.

Lorkowski, S. & Cullen, P. 2007. Atherosclerosis: Pathogenesis, clinical features & treatment. Encyclopedia of Life Sciences. pp. 1-11.

Majtanova, N., Cernak, M. & Majtan, J. 2016. Honey: A natural remedy for eye diseases. Forschende Komplementarmed 23(6): 1-6.

Mikail, M.A. 2015. In vivo antioxidant potential and cardioprotective activities of Baccaurea angulata fruit in relation to suppressed inflammatory response. Doctoral dissertation, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (Unpublished).

Mohanta, S., Yin, C., Weber, C., Hu, D. & Habenicht, A. 2016. aorta atherosclerosis lesion analysis in hyperlipidemic mice. Bio-Protocol 6(11): 1-15.

Moore, K.J. & Tabas, I. 2011. The cellular biology of macrophages in atherosclerosis. Cell 145(3): 341-355.

Ohta, H., Wada, H., Niwa, T., Kirii, H., Iwamoto, N., Fujii, H., Saito, K., Sekikawa, K. & Seishima, M., 2005. Disruption of tumor necrosis factor-α gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis 180(1): 11-17.

Oikonomou, E., Latsios, G., Vogiatzi, G. & Tousoulis, D., 2017. Atherosclerotic plaque. In Coronary Artery Disease: From Biology to Clinical Practice. Massachusetts: Academic Press. pp. 31-41.

Patel, K.M., Strong, A., Tohyama, J., Jin, X., Morales, C.R., Billheimer, J., Millar, J., Kruth, H. & Rader, D.J. 2015. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circulation Research 116(5): 789-796.

Rahman, A.R.A., Suhaimi, A., Meow, C.K., Mustapha, F.I., Mohamad, M., Salleh, N.A. & Ahmad, W.A.W. 2017. Clinical Practice Guideline: Primary & Secondary Prevention of Cardiovascular Disease 2017. Putrajaya: Ministry of Health, Malaysia.

Randolph, G.J. 2014. Mechanisms that regulate macrophage burden in atherosclerosis. Circulation Research 114(11): 1757-1771.

Ray, K.K. & Cannon, C.P. 2005. The potential relevance of the multiple lipid-independent (Pleiotropic) effects of statins in the management of acute coronary syndromes. Journal of the American College of Cardiology 46(8): 1425-1433.

Reagan-Shaw, S., Nihal, M. & Ahmad, N. 2007. Dose translation from animal to human studies revisited. The FASEB Journal 22(3): 659-661.

Song, X., Liu, H., Wang, X., Li, Z. & Huang, C. 2014. Atorvastatin combined with poly-unsaturated fatty acid confers better improvement of dyslipidemia and endothelium function. Lipids in Health and Disease 13(1): 1-5.

Spilioti, E., Jaakkola, M., Tolonen, T., Lipponen, M., Virtanen, V., Chinou, I., Kassi, E., Karabournioti, S. & Moutsatsou, P. 2014. Phenolic acid composition, antiatherogenic and anticancer potential of honeys derived from various regions in Greece. PloS ONE 9(4): e94860.

Sukardi, S., Yaakub, H., Ganabadi, S. & Poon, M.S. 2005. Serum testosterone levels and body weight gain of male rabbits fed with Morinda citrifolia fruit juice. Malaysian Journal of Nutrition 11(1): 59-68.

Thon, C.C., Yein, L.P. & Lian, C.W. 2012. The prevalence of cardiovascular risk factors in the young and middle-aged rural population in Sarawak, Malaysia. The Malaysian Journal of Medical Sciences 19(2): 27-34.

Tousoulis, D., Oikonomou, E., Economou, E.K., Crea, F. & Kaski, J.C. 2016. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. European Heart Journal 37(22): 1723-1732.

Tousoulis, D., Daves, G.J., Asimakopoulos, G., Homaei, H., Zouridakis, E., Ahmed, N. & Kaski, J.C. 2001. Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X). Clinical Cardiology 24(4): 301-304.

Wu, M.Y., Li, C.J., Hou, M.F. & Chu, P.Y. 2017. New insights into the role of inflammation in the pathogenesis of atherosclerosis. International Journal of Molecular Sciences 18(10): 2034-2052.

Yu, Q., Li, Y., Waqar, A.B., Wang, Y., Huang, B., Chen, Y., Zhao, S., Yang, P., Fan, J. & Liu, E. 2012. Temporal and quantitative analysis of atherosclerotic lesions in diet-induced hypercholesterolemic rabbits. BioMed Research International 2012: Article ID. 506159.

Zhou, G., Ge, S., Liu, D., Xu, G., Zhang, R., Yin, Q., Zhu, W., Chen, J. & Liu, X. 2010. Atorvastatin reduces plaque vulnerability in an atherosclerotic rabbit model by altering the 5-lipoxygenase pathway. Cardiology 115(3): 221-228.

 

*Corresponding author; email: abumaisarah@iium.edu.my

 

 

 

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