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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