Post on 19-Mar-2019
KARYA TULIS AKHIR
PENGARUH EKSTRAK BIJI PINANG (Areca catechu) TERHADAP
REGRESI PLAK ENDOTEL VASKULAR PADA TIKUS PUTIH
MODEL ATEROSKLEROTIK
Oleh:
Vihara Dewi Mahendra
(09020071)
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2013
i
HASIL PENELITIAN
PENGARUH EKSTRAK BIJI PINANG (Areca catechu) TERHADAP
REGRESI PLAK ENDOTEL VASKULAR PADA TIKUS PUTIH MODEL
ATEROSKLEROTIK
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
Program Sarjana Fakultas Kedokteran
Oleh:
Vihara Dewi Mahendra
(09020071)
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2013
ii
LEMBAR PENGESAHAN
LAPORAN HASIL PENELITIAN
Telah disetujui sebagai hasil penelitian
Untuk memenuhi persyaratan
Pendidikan Sarjana Fakultas Kedokteran
Universitas Muhammadiyah Malang
Tanggal : 28 Januari 2013
Pembimbing I
Prof.Dr.H.Djoni Djunaedi, dr,Sp.PD.,KPTI.,FINASIM
Pembimbing II
dr. Erdy Kuswandana
Mengetahui,
Fakultas Kedokteran
Dekan,
dr. Irma Suswati, M.Kes
iii
LEMBAR PENGUJIAN
Karya Tulis Akhir ini telah diuji dan dipertahankan di depan Tim Penguji pada tanggal 28
Januari 2013
Tim Penguji
Prof.Dr.H.Djoni Djunaedi, dr,Sp.PD.,KPTI.,FINASIM Ketua
dr. Erdy Kuswandana Anggota
dr.Fathiyah Safitri,Mkes Anggota
iv
KATA PENGANTAR
Assalamu’alaikum warahmatullahi wabarakatuh
Segala puji bagi Allah SWT atas segala rahmat,hidayah serta innayah –
Nya dan serta shalawat serta salam terlimpahkan bagi junjungan kita Nabi
Muhammad SAW. Syukur Alhamdulillah tak terhingga atas limpahan rahmat dan
karunia Allah serta doa dari kerabat dan rekan sehingga penulis dapat
menyelesaikan karya tulis akhir ini.
Dalam kesempatan ini penulis ingin mengucapkan terimakasih yang tak terhingga
kepada pihak- pihak yang turut membantu terselesaikannya tugas akhir ini, yaitu :
1. Ayah dan ibu tercinta, yang selalu tak henti-hentinya mendoakan dan memberi
semangat pada putri tercintanya.
2. Prof.Dr.H.Djoni Djunaedi, dr,Sp.PD.,KPTI.,FINASIM dan dr. Erdy
Kuswandana selaku dosen pembimbing, atas bimbingan dan saran yang telah
diberikan kepada penulis.
3. dr.Fathiyah Safithri,Mkes selaku dosen penguji atas bimbingan dan saran yang
telah diberikan kepada penulis.
4. dr. Thontowi Djauhari NS,Mkes, drg. Prasetyo Adi dan dr Indra Setiawan ,Sp
THT –KL atas bimbingan , saran , semangat serta ilmu – ilmu yang
bermanfaat yang telah diberikan kepada penulis .
5. dr. Soebarkah Basuki, Sp.PA selaku pembimbing Patologi Anatomi atas
bimbingan,semangat sertaa saran yang telah diberikan kepada penulis.
6. Fajar Akhmad Fauzi, seseorang yang dengan penuh kesabaran, perhatian,
kasih sayang serta doa yang tak henti-hentinya untuk penulis.
v
7. Adik- adikku tercinta, Clara Shinta, Seisa, Lyla, terimakasih banyak telah
memberikan warna baru dalam kehidupan penulis.
8. Rekan se – Timku, Fahmy,Erwin,Surya,Ana, terimakasih atas kerjasama,
bantuan dan semangat kalian. Semoga kita dapat menjadi dokter yang baik
kelak. Amin.
9. Mbak Emi, mbak Dilla, dan teman- teman Asisten lab Skill, terimakasih
banyak atas bantuan dan semangat yang selama ini diberikan kepada penulis.
10. Mbak siti, Mbak Vina,Mbak laela,mbak Iin,Mbak desy,mbak Rahma,Mas
heru dan seluruh staf dan karyawan UMC terimakasih banyak atas bantuan
dan semangat serta hari- hari yang sangat menyenangkan selama 2,5 tahun ini.
11. Teman – teman FK 09 , terimakasih atas bantuan dan hari- hari yang
menyenangkan selama 3,5 tahun ini.
12. Bapak Sujono dan seluruh Staf TU dan karyawan FK UMM atas bantuannya
selama masa kuliah hingga terselesaikannya tugas akhir ini.
13. Pak Aris Sandy terimakasih banyak atas bantuan selama penelitian yang
diberikan kepada penulis.
Karya tulis ini masih jauh dari kesempurnaan, dengan segala kerendahan
hati penulis memohon maaf yang sebesar-besarnya dan mengharapkan saran
kritik yang membangun. Semoga karya tulis ini dapat menambah wawasan dan
khasanah ilmu pengetahuan bagi semua pihak
Malang 11 Oktober 2012
Penulis
vi
ABSTRAK
Mahendra,Vihara Dewi.2013.Pengaruh Ekstrak Biji Pinang (Areca catechu)
terhadap Regresi Plak Endotel Vaskular Tikus Putih Model Aterosklerotik. Tugas
Akhir Fakultas Kedokteran Universitas Muhammadiyah Malang. Pembimbing :
(1) Djoni Djunaedi* (2) Erdy Kuswandana**.
Latar Belakang : Plak Ateroma merupakan salah satu indikasi adanya
aterosklerosis yang ditandai dengan penebalan dinding endotel vaskular dimana
salah satu penyebabnya adalah adanya respon inflamasi dan oksidan bebas dalam
darah serta kondisi hiperkolesterolemia. Biji pinang mempunyai komposisi
Proantosianidin yang berfungsi sebagai antioksidan dan anti inflamasi untuk
meregresi plak ateroma.
Tujuan : Untuk membuktikan pengaruh biji pinang (Areca Catechu ) terhadap
regresi plak endotel vaskular pada tikus putih model aterosklerotik
Metode : Penelitian ini merupakan penelitian eksperimental dengan menggunakan
metode The post test control group design. Masing-masing diberikan dengan
dosis 1,8 mg/200 g BB tikus /hari, 2,25 mg/200 g BB tikus /hari, dan 2,7 mg/200
g BB tikus /hari.
Hasil :Dari hasil uji anova menunjukkan bahwa nilai sig = 0,000 lebih kecil dari
pada p (0,01) yang berarti terdapat pengaruh perlakuan dosis yang sangat
bermakna pada ketebalan endotel arkus aorta tikus putih 3 bulan perlakuan. Uji
korelasi menunjukkan bahwa nilai sig (2-tailed) = 0,000 < p (0,01) yang berarti
terdapat hubungan yang berbanding lurus sangat bermakna yang berarti kenaikan
dosis ekstrak biji pinang menyebabkan kenaikan regresi plak aorta pada tikus
putih 3 bulan perlakuan. Hal ini ditunjukkan dengan nilai pearson correlation =
0,963.Dari hasil uji regresi menunjukkan bahwa Y = 22,961 (X) – 21,721 dimana
Y adalah besarnya regresi plak dan X adalah besarnya dosis. Terlihat ada
pengaruh yang sangat signifikan (sig 0,00 < p 0,01) . besar pengaruh dosis
ekstrak biji buah pinang terhadap penurunan plak endotel arkus aorta sebesar 92,8
% yang dapat dilihat dari R2= 0,928
Kesimpulan : Biji Pinang (Areca catechu ) dapat meregresi plak endotel vaskular
tikus putih model aterosklerotik.
Kata Kunci : Biji Pinang , Proantosianidin, Regresi plak ateroma
* Guru Besar Ilmu Penyakit Dalam konsultan Penyakit Tropis dan Infeksi FK
UMM
** Staf Ahli dan Dosen FK UMM
vii
ABSTRACT
Mahendra,Vihara Dewi.2013.The Effect of Betel Nut Seed Extract (Areca
catechu) as a Plaque Regression of Vascular Endothelium in Atherosclerotic Rat
Model. Final Project in medical Faculty of Muhammadiyah Malang . Advisors :
(1) Djoni Djunaedi *(2) Erdy Kuswandana**
Background : Atherosclerosis plaque is characterized by thickening of vascular
endothelial wall. The pathogenesis of atherosclerosis is inflammatory response to
endothelial injury and free oxidants in hypercholesterolemic condition. The main
composition of betel nut seed is proanthocyanidin has an antioxidant and anti
inflammatory effect to atherosclerotic plaque regression.
Objective : To demonstrate the effect of betel nut seed extract (Areca catechu) as
a plaque regression of vascular endothelium in atherosclerotic rat model.
Methods : This experimental research was using the post test control group
design. The doses in each group in this experiment were given by 1,8 mg/200g
/day, 2,25 mg/200 g/day, and 2,7 mg/200 g /day.
Results :The anova test showed that significancy value = 0,000 < p (0,01) which
means that there was a significant effect in vascular endothelial wall thickening
during 3 months experiments. Correlation test showed that significancy value (2-
tailed) = 0,000 < p (0,01) which means that there was a strong relationship
between increasing dose of betel nut seed extract versus plaque regression, it
showed in pearson correlation test = 0,963. The equation in regression test was Y
= 22,961 (X) – 21,721 where Y was vascular endothelial wall and X was the
dose of betel nut extract, and there’s a significant relationship (sig 0,00 < p 0,01) .
the percentage of the regression in vascular endothelial wall was 92,8 % , (it
showed in R2= 0,928 )
Conclusion : Betel nut seed (Areca catechu) could regress the endothelial
vascular plaque in Atherosclerosis Rat Model.
Keywords : Betel nut seed, Proanthocyanidin, Plaque regression,Vascular
atherosclerosis
*Lecturer and Professor in Internal Medicine,Tropical Infection Consultant in FK
UMM
* Staff and Lecturer in FK UMM
viii
DAFTAR ISI
HALAMAN JUDUL ........................................................................................ i
LEMBAR PENGESAHAN ............................................................................ ii
LEMBAR PENGUJIAN ................................................................................. iii
KATA PENGANTAR ..................................................................................... iv
ABSTRAK ....................................................................................................... vi
ABSTRACT ..................................................................................................... vii
DAFTAR ISI .................................................................................................... viii
DAFTAR TABEL ............................................................................................ xii
DAFTAR GAMBAR ....................................................................................... xiii
DAFTAR GRAFIK .......................................................................................... xiv
DAFTAR LAMPIRAN .................................................................................... xv
DAFTAR SINGKATAN ................................................................................. xvi
BAB 1 PENDAHULUAN .............................................................................. 1
1.1 Latar Belakang ............................................................................... 1
1.2 Rumusan Masalah .......................................................................... 4
1.3 Tujuan Penelitian ............................................................................ 4
1.3.1 Tujuan Umum ...................................................................... 4
1.3.2 Tujuan Khusus...................................................................... 4
1.4 Manfaat Penelitian .......................................................................... 5
1.5 Batasan Penelitian .......................................................................... 5
BAB 2 TINJAUAN PUSTAKA ..................................................................... 6
2.1 Pinang (A.catechu) ......................................................................... 6
2.1.1 Kandungan Kimia ................................................................ 8
ix
2.1.2 Proantosianidin ..................................................................... 8
2.1.3 Proantosianidin sebagai Antioksidan ................................... 10
2.1.4 Proantosianidin sebagai Anti Inflamasi................................ 14
2.1.4.1 Peranan HDL sebagai Anti Inflamasi ...................... 15
2.2 Pembuluh Darah ............................................................................. 18
2.2.1 Fisiologi Pembuluh Darah .................................................... 18
2.2.2 Histopatologi Pembuluh Darah ............................................ 19
2.2.3 Dinding Sel Pembuluh Darah dan Respon terhadap Jejas ... 21
2.2.3.1 Sel Endotel Pembuluh Darah ................................... 21
2.2.3.2 Sel Otot Polos Pembuluh Darah .............................. 24
2.2.3.3 Angiogenesis ............................................................ 25
2.3 Aterosklerosis ................................................................................. 27
2.3.1 Definisi Aterosklerosis ......................................................... 27
2.3.2 Faktor Resiko Aterosklerosis ............................................... 27
2.3.3 Hipotesis Terjadinya Aterosklerosis .................................... 28
2.3.4 Klasifikasi mekanisme Aterosklerosis ................................. 29
2.3.4.1 Cedera Endotel ......................................................... 29
2.3.4.2 Akumulasi Leukosit ................................................. 30
2.3.4.3 Pembentukan Foam Cell .......................................... 31
2.3.4.4 Regresi Plak Aterosklerosis ..................................... 33
BAB 3 KERANGKA KONSEP DAN HIPOTESIS .................................... 35
3.1 Kerangka Konsep ........................................................................... 35
3.2 Hipotesis ......................................................................................... 36
x
BAB 4 METODE PENELITIAN .................................................................. 37
4.1 Rancangan Penelitian ..................................................................... 37
4.2 Tempat dan Waktu Penelitian ........................................................ 37
4.3 Populasi dan Sampel ...................................................................... 37
4.3.1 Populasi.. .............................................................................. 37
4.3.2 Sampel .................................................................................. 37
4.3.3 Estimasi Besar Sampel ......................................................... 37
4.3.4 Teknik Sampling .................................................................. 39
4.3.5 Karakteristik Sampel Penelitian ........................................... 39
4.3.6 Variabel Penelitian ............................................................... 39
4.3.6.1 Variabel Bebas ......................................................... 39
4.3.6.2 Variabel Tergantung ................................................ 39
4.3.7 Definisi Operasional ............................................................. 39
4.4 Diet Aterosklerotik ......................................................................... 40
4.5 Dasar Penentuan Dosis Buah Pinang ............................................. 40
4.6 Bahan dan Instrumen Penelitian ..................................................... 41
4.7 Alur Penelitian ............................................................................... 43
4.8 Prosedur Penelitian ......................................................................... 44
4.8.1 Pembagian Kelompok Tikus ................................................ 44
4.8.2 Adaptasi ................................................................................ 45
4.8.3 Pemberian Diet Aterogenik .................................................. 45
4.8.4 Pemberian Ekstrak Buah Pinang .......................................... 45
4.9 Proses anestesi dan Pembedahan Hewan Coba .............................. 46
4.9.1 Proses Anestesi ..................................................................... 46
xi
4.9.2 Proses Pembedahan .............................................................. 46
4.10 Pembuatan Sediaan Histologi ....................................................... 46
4.11 Analisis Data ................................................................................ 47
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA ............................. 48
5.1 Gambar sediaan histopatologis dinding arkus aorta ....................... 48
5.2 Pengaruh Dosis Ekstrak Biji Pinang Terhadap Ketebalan
Dinding Arkus Aorta.............................................................. ....... 52
5.3 Pengaruh dosis ekstrak biji pinang terhadap regresi plak endotel
vaskular pada tikus model aterosklerotik ...................................... 56
BAB 6 PEMBAHASAN ................................................................................ 58
BAB 7 KESIMPULAN DAN SARAN .......................................................... 64
7.1 Kesimpulan............................................................... ...................... 64
7.2 Saran ............................................................................................. 64
DAFTAR PUSTAKA ..................................................................................... 65
LAMPIRAN .................................................................................................... 69
xii
DAFTAR TABEL
Tabel 5.1 Pengaruh ekstrak biji pinang terhadap ketebalan dinding endotel
arkus aorta setelah 3 bulan perlakuan ............................................. 53
Tabel 5.2 Tebal plak endotel pada dinding arkus aorta ................................... 56
Tabel 5.3 Tabel hasil regresi plak dinding arkus aorta ................................. 57
xiii
DAFTAR GAMBAR
Gambar 2.1 Pohon pinang ................................................................................ 4
Gambar 2.2 Buah pinang.................................................................................. 6
Gambar 2.3 Mekanisme prontosianidin sebagai antioksidan .......................... 14
Gambar 2.4 Hambatan HDL terhadap sintesis adhesi protein ......................... 16
Gambar 2.5 Mekanisme HDL sebagai anti inflamasi ...................................... 17
Gambar 2.6 Arteriol,Venul,dan kapiler............................................................ 19
Gambar 2.7 Lapisan vaskular ........................................................................... 20
Gambar 2.8 Histologi penampag arteri ............................................................ 21
Gambar 2.9 Respon dinding pembuluh darah terhadap adanya jejas .............. 24
Gambar 2.10 Fatty streaks dan fibrous cap ..................................................... 29
Gambar 2.11 Proses terjadinya plak ateroma ................................................... 29
Gambar 2.12 Patogenesis terjadinya aterosklerosis ......................................... 30
Gambar 2.13 Proses terjadinya aterosklerosis ................................................. 32
Gambar 2.14 Gambaran histologi fibrous plak pada dinding pembuluh
Darah ........................................................................................... 32
Gambar 2.15 Patologi anatomi plak ateroma ................................................... 33
Gambar 2.16 Mekanisme regresi plak aterosklerosis pada sel endotel ............ 34
Gambar 5.1 Gambaran Mikroskopis ketebalan dinding arkus aorta tiap
Perlakuan .................................................................................... 49
xiv
DAFTAR GRAFIK
Grafik 5.1 Grafik persamaan regresi hubungan antara dosis ekstrak biji
pinang dengan ketebalan dinding arkus aorta ............................... 52
Grafik 5.2 Grafik persamaan regresi hubungan antara dosis ekstrak biji
pinang dengan regresi plak dinding arkus aorta ............................ 55
Grafik 5.3 Grafik gambaran regresi plak endotel arkus aorta ........................ 57
xv
DAFTAR LAMPIRAN
Lampiran 1 Ketebalan plak pada dinding endotel arkus aorta setelah
3 bulan perlakuan ........................................................................ 69
Lampiran 2 Regresi Plak 3 bulan perlakuan .................................................. 74
Lampiran 3 Diet Aterogenik ........................................................................... 79
Lampiran 4 Pelaksanaan Penelitian ................................................................ 80
Lampiran 5 Dokumentasi ............................................................................... 82
Lampiran 6 Surat Keterangan Penelitian ....................................................... 83
Lampiran 7 Surat Keterangan Konsultasi PA ............................................... 84
xvi
DAFTAR SINGKATAN
ABCA1 : ATP binding cassette transporter 1
AP – 1 : Activator protein 1
apoA-1 : Apolipoprotein A 1
CD -31 : Cluster disease 31
CERP : Cholesterol efflux regulatory protein
CSF : Colony stimulating factor
ECM : Extracellular matrix
FGF : Fibroblast growth factor
GPCR : G protein coupled receptor
HDL : High density lipoprotein
HUVECs : Human umbilical vein endothelial cells
ICAM – 1 : Intercellular adhesion molecule - 1
IHD : Ischaemic heart disease
IL-1 : Interleukin -1
IL-6 : Interleukin - 2
LDL : Low density lipoprotein
LPS : Lipopolysacharide
MCP – 1 : Monocyte chemoatractant protein 1
NF-κβ : Nuclear factor kappa β
NO : Nitric oxide
OPCs : Oligomeric Proantocyanidins
Ox LDL : Oxydized LDL
PAF : Platelet activating factor
PAI : Plasminogen activator inhibitor
PDGF : Platelet derived growth factor
PECAM – 1 : Platelet endothelial cell adhesion molecule - 1
PGI2 : Prostacyclin
rHDL : Reconstitued high density lipoprotein
ROS : Reactive oxygen spesies
S1P : Spingosine 1 phosphate
xvii
SMase : Sphingomyelinase
SMC : Smooth muscle cell
TF : Tissue factor
TGF β : Transforming growth factor β
TNF α : Tumor necrosis factor
UV : Ultraviolet
VCAM – 1 : Vascular cell adhesion molecule - 1
VE cadherin : Vascular endothelial cadherin
VLDL : Very low density lipoprotein
vWF : von Willebrand Factors
xviii
DAFTAR PUSTAKA
Anonim. 2011.Cardiovascular diseases (CVDs). diakses 27 Juli 2011.
http://www.who.int/mediacentre/factsheets/fs317/en/index.html
Backer, C.A., and Van Den Brink, R.C., 1968, Flora of Java (Spermatophytes
Only), Noordhoff NV, Groningen, Netherlands, Vol III, p.164-194.
Bagchi D, Krohn RL, Bagchi M, et al. 1997. Oxygen free radical scavenging
abilities of vitamins C and E, and a grape seed proanthocyanidin extract
in vitro. Res Commun Mol Pathol Pharmacol;95:179-189.
Bagchi, Stohs,Das et al. 2000. Free radicals and grape sed proanthocyanidin
extract: importance in human health and disease prevention. Toxicology.
148 (2000), 187-197.
Barter PJ, Rye KA,Nicholls S. 2004. Antiinflammatory Properties of HDL. J
Circulation Research. 95: 764-772.
Barter,Philip.2005. The role of HDL –cholesterol in preventing atherosclerotic
disease. European Heart Journal Supplements,F4-F8.
Cominacini L,Rigoni A,Pasini AF et al. 2001.The binding of oxidized low density
lipoprotein (ox LDL) to ox LDLmreceptor – 1 reduces the intracellular
concentration of nitric oxide in endothelial cells through an increased
production of superoxide. J Biol Chem 276 : 13750 -13755.
D. English, Z. Welch, A.T. Kovala et al., (2000). Sphingosine 1-phosphate
released from platelets during clotting accounts for the potent
endothelial cell chemotactic activity of blood serum and provides a novel
link between hemostasis and angiogenesis. FASEB Journal, 14(14),
2255–65.
Duke,.2011.Chemical and their Biological activities in : Areca catechu
L.Phytochemical and Ethnobotanical Databases. Hawai.
Faunci, Braunwald, Kasper et al.2008. The Pathogenesis, Prevention, and
Treatment of Atherosclerosis in Harrison’s Princples of Internal
Medicine 17th edition ch:235: 1425-1433. USA : McGraw-Hill
Companies.
Fine, A.M., 2000, Oligomeric Proanthocyanidin Complexes: History, Structure,
and Phytopharmaceutical Applications, Altern Med Rev, 5(2):144-151.
Guyton AC, Hall JE. 2006.Sirkulasi dalam Buku Ajar Fisiologi Kedokteran.
Jakarta : Penerbit Buku Kedokteran EGC.
xix
Habatul H. 2006. Pengaruh Pemberian VCO (Virgin Coconut Oil) terhadap
Gambaran Histologi Tiroid Tikus Putih (Rattus norvegicus). Skripsi.
UMY. Yogyakarta. (Unpublished)
Halliwell, B., Gutteridge, J.M.C., Cross, C.E., 1992. Free radicals,antioxidants,
and human disease: where we are now? J. Lab. Clin. Med. 199, 598-620.
Holvoet P,Collen D. 1998. Oxidation of low density lipoproteins in pathogenesis
of atherosclerosis. Elsevier atherosclerosis 137 : S33-S38.
Holvoet,Mertens.2001.Oxidized LDL and HDL : antagonist in atherothrombosis.
The FASEB journal vol 15:2073-2084.
Karsch, K.R. (1992). Atherosclerosis—Where are we heading? Herz 17: 309-319.
Kuehnel W. 2003. Color Atlas of Cytology, Histology, and Microscopic Anatomy
4 ed . New York: Thieme.
Kumar et al. 2007. Robbins Basic Pathology 8th edition. Elsevier Inc
Kumazawa,S.,Taniguchi,M.,Suzuki,Y.,& Shimura,M. (2002). Antioxidant activity
of polyphenols in Carob Pods. Journal of Agricultural and Food
Chemistry,50,373-377.
Lee, K.K., and Choi, J.D., 1999, The Effects of Areca Catechu L Extract on
Anti-Inflammation and Anti-Melanogenesis, Intern.J. Cosmetic Sci
21(4):275-284.
Libby et al. 2009. Inflammation in Atherosclerosis From Pathophysiology to
Practice. Journal of the American College of Cardiology Vol. 54, No.
23.
Matsuda Y,Hirata K,Inoue N et al. 1993. High density lipoprotein reverses
inhibitory effect of oxidized low density lipoprotein on endothelium
dependent relaxation. Circ Res 72:1103-1109.
Mc Creery,Andrea.2002. The miracle of OPC -165. Life sources,inc.
Meiyanto,Edi.,Handayani,Sri,.Rahmi,Fitria.2008.Ekstrak bii buah pinang (Areca
catechu L) mampu menghambat proliferasi dan memacu apoptosis sel
MCF – 7. Majalah Farmasi Indonesia,19(1),12-19.
Michael P.2000. Atherosclerosis What Matters Most in Its Etiology ?.
MetroHealth Medical Center Case Western Reserve University
Murray M, Pizzorno J. Procyanidolic oligomers. In: Murray M, Pizzorno J, eds.
The Textbook of Natural Medicine. 2nd ed. London: Churchill
Livingston; 1999:899-902.
xx
Murray, C.J., and Lopez, A.D. (1997). Global mortality, disability, and the
contribution of risk factors: Global Burden of Disease Study. Lancet
349: 1436-1442.
Nonaka, G., 1989. Isolation and structure elucidation of tannins, Pure & Appl.
Chem, 61 (3): 357-360
O’Connel.,Genest,Jacques.,Brian J. 2001. High density Lipoproteins and
Endothelial Function. J Circulation 104 : 1978-1983.
Robbins and Cotran, 2007. Pathologic Basis of Disease, 8th Edition : Saunders
Robert F,Mathew T.2002. The vascular endothelium: structure and function.
Cambridge University Press
Robinson T. 1995. Kandungan Organik Tumbuhan Tinggi. Bandung: ITB Press.
Shahidi, F., Wanasundara, P.K.J., 1992. Phenolic antioxidants. Crit. Rev. Food Sci.
Nutr. 32, 67 – 103
Shih D.M., Xia Y. -R., Wang X-P., et al. 2000. Combined serum
paraoxonase/apolipoprotein E knockout mice exhibit increased
lipoprotein oxidation and atherosclerosis. J Biol Chem. 275: 17527–
17535
Stannard,Khan,Graham et al.2001. Inability of plasma high density lipoproteins to
inhibit cell adhesion molecule expression in human coronary artery
endothelial cells. Elsevier atherosclerosis 154 :31-38.
Staples GW, Bevacqua RF. 2006. Areca catechu (betel nut palm). Species Profiles
for Pacific Island Agroforestry. Permanent Agriculture Resources (PAR),
Hawai..diakses 19 Juni 2011.
Sugatani J, Miwa M, komiyama Y,et al.1996. High density lipoprotein inhibits the
synthesis of platelet-activating factor in human vascular endothelial
cells. J lipid Mediat Cell Signal 13 :73-88.
Supranto J. 2007. Teknik Sampling untuk Survei & Eksperimen. Jakarta : PT
Rineka Cipta
Suvianto H.2008. Aterosclerosis.anonim
Syamsuhidayat, S.S., Hutapea, J.R., 1991, Inventaris Tanaman Obat Indonesia,
Balitbang Departemen Kesehatan, Vol I: 64-65.
Tabet,Rye,Anne et al.2009. High-density lipoproteins, inflammation and oxidative
stress. Clinical Science (2009) 116, (87–98).
xxi
Tebib K, Bessanicon P, Rouanet J.1994. Dietary grape seed tannins affect
lipoproteins, lipoproteinlipases, and tissue lipids in rats fed
hypercholesterolemic diets. J Nutr 1994;124:2452-2457.
Turk,J.R.,Laughlin,M.H.2004. Physical activity and atherosclerosis:which animal
model?.Can J.appl.Physiol. 29(5) :657-683.
Wadham C,Albanese N,Roberts Jane,et al. 2004. High density lipoproteins
neutralize C –reactive protein proinflammatory activity. J Circulation
109:2116-2122.
Wang, C.K., and Lee, W.H., 1996, Separation, Characteristics, and Biological
Activities of Phenolics in Areca Fruit, J. Agric. Food Chem., 44(8):
2014 -2019.
Weissberg. 2000. Atherosclerosis. Heart March 2000; 83:247-252
Wetwitayaklung,Phaechamud,Limmatvapirat,et al.2005. The study of antioxidant
capacity in various part of Areca catechu L.Naresuan University Journal
2006;14(1):1-14.
Williams KJ, Feig JE, Fisher EA. Rapid regression of atherosclerosis: insights
from the clinical and experimental literature. Nat Clin Pract Cardiovasc
Med. 2008 Feb;5(2):91-102. Cited in Pubmed; PMID 18223541.
Xia, P., Vadas, M. A., Rye, K. A., Barter, P. J. and Gamble, J. R. (1999) High
density lipoproteins (HDL) interrupt the sphingosine kinase signaling
pathway. A possible mechanism for protection against atherosclerosis by
HDL. J. Biol. Chem. 274, 33143–33147.
Yan Ru Su,2000. ACAT Atherosclerosis. Atherosclerosis researcher
unit,Vanderbilt University Mediacal faculty
http://www.ars-grin.gov/cgi-bin/duke/farmacy2.pl
http://www.traditional- tree.org
http://www.nature.com/clinicalpractice