Sains Malaysiana 44(10)(2015): 1501–1510
Anticholesterol
Activity of Anacardium occidentale Linn. Does it Involve in Reverse Cholesterol Transport?
(Aktiviti
Antikolesterol Anacardium occidentale Linn: Adakah Pengangkutan
Kolesterol Berbalik Terlibat)
MOHD KAMAL NIK HASAN1*, IHSAN SAFWAN KAMARAZAMAN1, DARYL JESUS ARAPOC3, NUR
ZALIKHA MOHD TAZA1, ZULKHAIRI HJ. AMOM2, RASADAH MAT ALI1, MOHD SHAHIDAN MOHD ARSHAD1, ZAMREE MD SHAH1 & KHAIRUL KAMILAH ABDUL KADIR1
1Natural Products Division,
Forest Research Institute of Malaysia, 52109 Kepong, Selangor Darul Ehsan, Malaysia
2Department of Basic Sciences,
Faculty of Health Sciences, Universiti Teknologi MARA (UiTM)
43200 Puncak Alam, Selangor Darul
Ehsan, Malaysia
3Agensi Nuklear Malaysia,
43000 Bangi, Selangor Darul Ehsan, Malaysia
Received: 29 January
2015/Accepted: 4 June 2015
ABSTRACT
Anacardium occidentale belongs to
the Anacardiaceae family. It had been scientifically proven to have
anti-hypercholesterolemia effect in high cholesterol diet induced
animal laboratory study. However there is no study regarding the
mechanisms involves in cholesterol reducing effect by A. occidentale
leaves extract. In this study, cytotoxic assessment and anti-cholesterol
activity of A. occidentale leaves aqueous extract (AOE) were investigated. Cytotoxic
study was performed by exposing hepatoma cell (Hep G2) towards AOE
with concentration ranging from 0.002 to 20 mg/mL
for 24 h. Anacardium occidentale extract was found to be
not toxic to the cell. Then, the highest and not toxic AOE concentrations (20, 10, 5 and 2.5 mg/mL) were selected
for anti-cholesterol study. The ability of AOE to
reduce cholesterol in cell culture experiment was carried out by
pretreating Hep G2 with selected concentrations of AOE in 6-well plate before the
cell was exposed to low density lipoprotein (LDL).
The concentration of farnesyl-diphosphate farnesyltransferase (FDFT1),
apolipoprotein A1 (Apo A1), lecithin-cholesterol acyltransferase
(LCAT),
low density lipoprotein receptor (LDL R), scavenger receptor B1
(SR-B1),
ATP
binding cassette transporter A1 (ABCA-1)
and hepatic lipase (HL) were determined from the 6-well plate
media. The results showed that AOE did
not significantly increase the concentration of LDLR.
However, AOE significantly increased the concentration of FDFT1,
APO
A1, LCAT, SRB-1,
ABCA-1 and HL. The HMGR activity experiment showed
that all selected AOE concentrations cannot significantly
reduce the HMGR enzyme activity. These findings
suggested that AOE may involve in reverse cholesterol
transport process to reduce cholesterol metabolism in Hep G2 cell.
Keywords: Anacardium
occidentale; cholesterol metabolism; cytotoxic; Hep G2; reverse cholesterol
transport
ABSTRAK
A. occidentale
adalah daripada keluarga Anacardiaceae. Ia
telah terbukti secara saintifik mempunyai kesan antihiperkolesterolemia
terhadap haiwan eksperimen makmal yang diberikan diet berkolesterol
tinggi. Walau bagaimanapun, mekanisme
yang terlibat dalam menurunkan kolesterol oleh ekstrak daun A.
occidentale masih belum dikaji. Dalam
penyelidikan ini, penilaian sitotoksik dan aktiviti antikolesterol
oleh ekstrak akuas daun A. occidentale (AOE)
telah dikaji. Kajian sitotoksik telah dilakukan dengan mendedahkan
sel hepatoma (Hep G2) kepada AOE berkepekatan daripada 0.002 hingga
20 mg/mL selama 24 jam. Ekstrak
A. occidentale didapati tidak toksik kepada sel.
Kemudian, kepekatan AOE tertinggi dan tidak toksik (20, 10,
5 dan 2.5 mg/mL) telah dipilih untuk kajian antikolesterol.
Keupayaan AOE untuk mengurangkan kolesterol dalam eksperimen kultur sel dilakukan dengan merawat Hep G2 menggunakan AOE
berkepekatan terpilih dalam plat 6-telaga sebelum
sel didedahkan dengan lipoprotein ketumpatan rendah (LDL). Kepekatan farnesil-difosfat
farnesiltransferase (FDFT1), apolipoprotin A1 (Apo
A1), lesitin-kolesterol asiltransferase (LCAT), reseptor ketumpatan rendah
lipoprotein (LDLR), reseptor pembangkai -B1 (SR-B1),
kaset pengangkut pengikat ATP A1 (ABCA-1)
dan lipase hepatik (HL) telah ditentukan dalam media daripada
plat 6-telaga. Hasil kajian menunjukkan
bahawa AOE tidak meningkatkan kepekatan LDLR secara
signifikan. Walau bagaimanapun, AOE meningkatkan
kepekatan FDFT1, APO A1, LCAT,
SRB-1
dan ABCA-1 secara signifikan. Ujian
aktiviti HMGR menunjukkan bahawa semua kepekatan AOE terpilih
tidak boleh mengurangkan aktiviti enzim HMGR. Penemuan ini menunjukkan
bahawa AOE mungkin terlibat dalam proses pengangkutan
kolesterol berbalik untuk mengurangkan metabolisme kolesterol dalam
sel Hep G2.
Kata kunci: Anacardium occidentale; Hep G2; metabolisme kolesterol;
pengangkutan kolesterol berbalik; sitotoksik
REFERENCES
Abas, F., Lajis, N.H.,
Israf, D.A., Khozirah, S. & Umi, K.Y. 2006. Antioxidant
and nitric oxide inhibition activities of selected Malay traditional
vegetables. Food Chemistry 95(4): 566-573.
Acton, S., Rigotti, A.,
Landschulz, K.T., Xu, S., Hobbs, H.H. & Krieger, M. 1996. Identification of
scavenger receptor SR-BI as a high density lipoprotein
receptor. Science 271(5248): 518-520.
Brown,
R.J., Lagor, W.R., Sankaranaravanan, S., Yasuda, T., Quertermous, T., Rothblat,
G.H. & Rader, D.J. 2010. Impact of combined deficiency of hepatic lipase
and endothelial lipase on the metabolism of both high-density lipoproteins and
apolipoprotein B-containing lipoproteins. Circulation Research 107(3):
357-364.
Carneiro,
M.M., Miname, M.H., Gagliardi, A.C., Pereira, A.C., Krieger, J.E., Maranhão,
R.C. & Santos, R.D. 2012. The removal from plasma of chylomicrons and
remnants is reduced in heterozygous familial hypercholesterolemia subjects with
identified LDL receptor mutations: Study with artificial emulsions. Atherosclerosis 221(1): 268-274.
Cruz, J.A. 2000. Dietary habits and nutritional status in adolescents over
Europe--Southern Europe. European Journal of Clinical Nutrition 54(1):
S29-S35.
Dansette, P.M., Jaoen,
M. & Pons, C. 2000. HMG-CoA reductase activity in human liver microsomes:
Comparative inhibition by statins. Experimental and Toxicologic Pathology 52(2):
145-148.
Dashti,
N. 1992. The effects of low density lipoproreins, cholesterol,
and 25-hydroxycholesterol on apolipoprotein B gene expression in HepG2 cells. J.
Biol. Chem. 267: 7160-7169.
Dhingra, S. & Ban,
M.P. 2006. Modulation of hypercholesterolemia-induced
alterations in apolipoprotein B and HMG-CoA reductase expression by selenium
supplementation. Chemico- Biological Interaction 161(1): 49-56.
Faridah,
A., Nordin, H.L., Israf, D.A., Khozirah, S. & Umi, K.Y. 2006. Antioxidant
and nitric oxide inhibition activities of selected Malay traditional
vegetables. Food Chemistry 95(4): 566-573.
Fazali,
F., Zulkhairi, A, Nurhaizan, M.E., Kamal, N.H., Zamree, M.S. & Shahidan,
M.A. 2011. Phytochemical screening, in vitro and in vivo antioxidant
activities of aqueous extract of Anacardium occidentale Linn. and its effects on endogenous antioxidant enzymes in
hypercholesterolemic induced rabbits, Research Journal of Biological Sciences 6(2): 69-74.
Frohlich, J., McLeod, R.
& Hon, K. 1982. Lecithin: Cholesterol acyl transferase (LCAT). Clinical
Biochemistry 15(6): 269- 278.
Funatsu, T., Suzuki, K.,
Goto, M., Arai, Y., Kakuta, H., Tanaka, H., Yasuda, S., Ida, M., Nishijima, S.
& Miyata, K. 2001. Prolonged inhibition of cholesterol synthesis by
atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells. Atherosclerosis 157(1): 107-115.
Getz, G.S. &
Reardon, C.A. 2011. Apolipoprotein A-I and A-I mimetic peptides: A role in
atherosclerosis. Journal of Inflammation Research 4: 83-92.
Ghanya, A.N., Maznah,
I., Gururaj, B. & Hadiza, A.A. 2010. Vanillin rich fraction regulates LDLR
and HMGCR gene expression in HepG2 cells. Food Research International 43(10):
2437-2443.
Ghosh, S. 2012. Early
steps in reverse cholesterol transport: Cholesteryl ester hydrolase and other
hydrolases. Current Opinion in Endocrinology, Diabetes and Obesity 19(2):
136-141.
Hiromitsu, Y., Yoshiaki,
H., Shigeo, O., Masato, Y., Fumiko, M., Mitsunobu, K., Kazuo, K., Yasuteru, U.,
Sachiyo, S., Kiyoshi, K. & Kazuhiko, N. 2002. Apolipoprotein
A-I deficiency with accumulated risk for CHD but no symptoms of CHD. Atherosclerosis 162(2): 399-407.
Horvat,
S., McWhir, J. & Rozman, D. 2011. Defects in cholesterol synthesis genes in mouse
and in humans: Lessons for drug development and safer treatments. Drug
Metabolism Review 43(1): 69-90.
Kevin, C.M. 2007.
Pathophysiology and management of dyslipidemias associated with obesity, type 2
diabetes and other insulin-resistant states. In Therapeutic Lipidology, edited
by Michael, H.D., Peter, P.T. & Kevin, C.M. New
York: Humana Press Inc. pp 55-68.
Kinoshita,
M., Fujita, M., Usui, S., Maeda, Y., Kudo, M., Hirota, D., Suda, T., Taki, M.,
Okazaki, M. & Teramoto, T. 2004. Scavenger receptor type BI potentiates reverse
cholesterol transport system by removing cholesterol ester from HDL. Atherosclerosis 173(2): 197-202.
Laurence,
D., Emmanuel, F., Gerard, L., Jean-Michel, P., Francoise, G., Serge, M.,
Philippe, G. & Bruno, V. 2003. Cell surface expression of LDL receptor is
decreased in type 2 diabetic
patients and is normalized by insulin therapy. Diabetes Care 26(5):
1540-1544.
Laurens, A. & Paris, R.R.
1977. Sur les polyphénols d’Anacardiacées Africaines et Malgaches: Poupartia
birrea Aub., Poupartia caffra H. Perr. et Anacardium occidentale L.. Plantes Médicinales et Phytothérapie 11: 16-24.
Liu, Y. & Tang, C. 2012.
Regulation of ABCA1 functions by signaling pathways. Biochimica et Biophysica Acta 1821: 522-529.
Mackay, D. & Jones, P.J.
2011. Evaluation of methods for the determination of
cholesterol absorption and synthesis in humans. Atherosclerosis 18(2):
253-262.
Masayoshi, Y., Toru, S.,
Taesik, P., Hiroaki, Y., Yunying, H., Ni, H.S., Ayanna, S.A., Reeba, K.V.,
Rajasekhar, R., Leslie, K.P., Robert, H.E. & Ira, J.G. 2007. Effects of lipoprotein lipase and statins on cholesterol uptake
into heart and skeletal muscle. The Journal of Lipid Research 48(3):
646-655.
Mensah, G.A. 2003. A
heart-healthy and ‘stroke-free’ world through policy development, systems
change, and environmental supports: A 2020 vision for sub-Saharan Africa.
Ethn. Dis. 13(2): 4-12.
Milada, D. & Jiri, J.F.
1999. Advances in understanding of the role of lecithin cholesterol
acyltransferase (LCAT) in cholesterol transport. Clinica Chimica Acta 286(1-2):
257-271.
Ministry of
Health (MOH). 2011. Portal Rasmi Kementrian Kesihatan Malaysia
http://www.moh.gov.my/images/gallery/
stats/heal_fact/health_facts_2010_hor.pdf.
Myoungsook, L., Jin, Q.K.,
Jongwon, K., Hyunhee, O. & Miyoung, P. 2001. Studies on
the plasma lipid profiles, and LCAT and CETP activities according to
hyperlipoproteinemia phenotypes (HLP) Atherosclerosis 159(2): 381-389.
Ness, G.C. & Chambers,
C.M. 2000. Feedback and hormonal regulation of hepatic
3-hydroxy-3-methylglutaryl coenzyme A reductase: The concept of cholesterol
buffering capacity. Proceedings of the Society for Experimental Biology and
Medicine 224(1): 8-19.
Nurhanani,
R., Rasyidah, R., Sarni, M.J. & Azlina, A.A. 2008. Radical
scavenging and reducing properties of extracts of cashew shoots (Anacardium
occidentale). Food Chemistry 111(1): 38-44.
Ott, D.B. & Lachance,
P.A. 1981. Biochemical controls of liver cholesterol biosynthesis. The
American Journal of Clinical Nutrition 34(10): 2295-306.
Paul, N., Leon, S., Phillip,
B., Peter, C., David, C., Ian, H.C., Ken, S. & David, S. 1997. A
comparative study of the efficacy of AOE and gemfibrozil in combined
hyperlipoproteinemia: Prediction of response by baseline lipids, apo E
genotype, lipoprotein(a) and insulin. Atherosclerosis 129(2): 231-239.
Pearson, T.A. 1999.
Cardiovascular disease in developing countries: Myths, realities, and
opportunities. Cardiovascular Drugs and Therapy 13(2): 95-104.
Polisecki, E., Muallem, H.,
Maeda, N., Peter, I., Robertson, M., McMahon, A.D., Ford, I., Packard, C.,
Shepherd, J., Jukema, J.W., Westendorp, R.G., de Craen, A.J., Buckley, B.M.,
Ordovas, J.M. & Schaefer, E.J. 2008. Prospective study of
pravastatin in the elderly at risk (PROSPER) investigators. Genetic
variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels,
statin response, and cardiovascular disease incidence in PROSPER. Atherosclerosis 200(1): 109-114.
Radhakrishnan, A.R., Helena,
G. & Tatu, A.M. 2001. Cholesterol absorption, synthesis,
and fecal output in postmenopausal women with and without coronary artery
disease. Arteriosclerosis, Thrombosis, and Vascular Biology 21:
1650-1655.
Reinhart, K.M & Woods,
J.A. 2012. Strategies to preserve the use of statins in
patients with previous muscular adverse effects. American Journal of
Healthy-System Pharmacy 69(4): 291-300.
Runnie, I., Salleh, M.N.,
Mohamed, S., Head, R.J. & Abeywardena, M.Y. 2004. Vasorelaxation induced by
common edible tropical plant extracts in isolated rat aorta and mesenteric
vascular bed. Journal of Ethnopharmacology 92(2-3): 311-316.
Sander,
J.R., Joan, M.F., Raymond, L. & George, M.P. 1989. The transport of lipoprotein
cholesterol into bile: A reassessment of kinetic studies in the experimental
animal. Biochimica et Biophysica Acta (BBA) -
Lipids and Lipid Metabolism 1004(3): 327-331.
Sasaki, J., Otonari, T.,
Sawayama, Y., Hata, S., Oshima, Y., Saikawa, T., Biro, S. & Kono, S. 2012.
Double-dose pravastatin versus add-on ezetimibe with low-dose pravastatin
-effects on LDL cholesterol, cholesterol absorption, and cholesterol synthesis
in japanese patients with hypercholesterolemia (PEAS
study). Journal of Atherosclerosis and Thrombosis 19(5): 485-493.
Scharnagl,
H., Schinker, R., Gierens, H., Nauck, M., Wieland, H. & Ma¨rz, W. 2001. Effect of
atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and
triacylglycerides in HepG2 cells. Biochemical Pharmacology 62:
1545-1555.
Stephen, A.H. & Matthew,
J.M. 1997. Reverse cholesterol transport - A review of the process and its
clinical implications. Clinical Biochemistry 30(7): 517-525.
van der Velde, A.E., Brufau, G.
& Groen, A.K. 2010. Transintestinal cholesterol efflux. Current Opinion in Lipidology 21(3): 167-171.
Wilding,
P.M. 2012. Cardiovascular disease, statins and vitamin D. British Journal of Nursing 21(4):
214-220.
Wu, M.P., Wu, S.F., Wang,
T.C., Kao, M.J. & Yang, W.L. 2012. Effectiveness of a
community-based health promotion program targeting people with hypertension and
high cholesterol. Nursing and Health Science 14(2): 173-181.
Yanagita, T., Yamamoto, K.,
Ishida, S., Sonda, K., Morito, F., Saku, K. & Sakai, T. 1994. Effects of simvastatin, a cholesterol synthesis inhibitor, on
phosphatidylcholine synthesis in HepG2 cells. Clin. Ther. 16:
200-208.
Zannis,
V.I., Chroni, A. & Krieger, M. 2006. Role of apoA-I, ABCA1, LCAT,
and SR-BI in the biogenesis of HDL. Journal of Molecular Medicine 84(4):
276-294.
*Corresponding author; email: mohdkamal@frim.gov.my
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