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SKRIPSI
DIANI MEGA SARI
PENGARUH PEMBERIAN EKSTRAK
TEMULAWAK(Curcuma xanthorrhiza Roxb.)
SEBAGAI ADJUVAN TERAPI VALSARTAN
TERHADAP HISTOPATOLOGI JANTUNG
PADA MENCIT JANTAN (Mus musculus)
YANG DIINDUKSI HIPERTENSI
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2015
ii
Lembar Pengesahan
PENGARUH PEMBERIAN EKSTRAK TEMULAWAK
(Curcuma xanthorrhiza Roxb.) SEBAGAI ADJUVAN TERAPI
VALSARTAN TERHADAP HISTOPATOLOGI JANTUNG
PADA MENCIT JANTAN (Mus musculus)
YANG DIINDUKSI HIPERTENSI
SKRIPSI
Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada
Program Studi Farmasi Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang
2015
Oleh :
DIANI MEGA SARI
NIM : 201110410311056
Disetujui oleh :
Pembimbing I Pembimbing II
Dra. Lilik Yusetyani, Apt., Sp. FRS dr. Dian Yuliarta Lestari, Sp.PA
NIP . 11407040450 NIP. 11308090462
iii
Lembar Pengujian
PENGARUH PEMBERIAN EKSTRAK TEMULAWAK
(Curcuma xanthorrhiza Roxb.) SEBAGAI ADJUVAN TERAPI
VALSARTAN TERHADAP HISTOPATOLOGI JANTUNG
PADA MENCIT JANTAN (Mus musculus)
YANG DIINDUKSI HIPERTENSI
SKRIPSI
Telah diuji dan dipertahankan di depan tim penguji
Pada tanggal 29 Juli 2015
Oleh :
DIANI MEGA SARI
NIM : 201110410311056
Tim Penguji :
Penguji I Penguji II
Dra. Lilik Yusetyani, Apt., Sp. FRS dr. Dian Yuliarta Lestari, Sp.PA
NIP . 11407040450 NIP. 11308090462
Penguji III Penguji IV
Siti Rofida, S.Si., M.Farm., Apt. Hidajah Rachmawati, S.Si., Apt., Sp.FRS.
NIP. 11408040453 NIP. 11406090449
iv
KATA PENGANTAR
Bismillahirrohmanirrohim
Assalamualaikum warohmatullahi wabaraokatuh
Puji syukur tercurahkan kepada Allah SWT, Tuhan semesta alam karena
berkat rahmat dan hidayahnya, penulis dapat menyelesaikan skripsi yang berjudul
Pengaruh Pemberian Ekstrak Temulawak (Curcuma xanthorrhiza Roxb.)
Sebagai Adjuvan Terapi Valsartan Terhadap Histopatologi Jantung Pada
Mencit Jantan (Mus musculus) Yang Diinduksi Hipertensi.
Skripsi ini diajukan untuk memenuhi persyaratan dalam mencapai gelar
Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang, dalam penyusunan skripsi ini penulis tidak
terlepas dari peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena
itu, dengan segala kerendahan hati, penulis mengucapkan terima kasih kepada:
1. Allah SWT, Tuhan semesta alam yang memberikan rahmat, nikmat dan
hidayahnya kepada umatnya, Rasulullah SAW, yang sudah menuntun kita
menuju jalan yang lurus.
2. Bapak Yoyok Bekti Prasetyo, S.Kep., M.Kep., Sp.Kom selaku Dekan
Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah
memberikan kesempatan penulis belajar di Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang.
3. Ibu Nailis Syifa’, S.Farm.,M.Sc.,Apt selaku Ketua Program Studi Farmasi
sekaligus Dosen Wali Universitas Muhammadiyah Malang yang telah
memberikan motivasi dan kesempatan penulis belajar di Program Studi
Farmasi Universitas Muhammadiyah Malang.
4. Ibu Dra. Lilik Yusetyani, Apt., Sp. FRS selaku Dosen Pembimbing I, dan
dr. Dian Yuliarta Lestari, Sp.PA selaku Dosen Pembimbing II disela
kesibukan beliau masih bisa meluangkan waktu untuk membimbing dan
memberi pengarahan dan dorongan moril sampai terselesaikannya skripsi
ini.
v
5. Ibu Siti Rofida, S.Si., M.Farm., Apt. dan Ibu Hidajah Rachmawati, S.Si.,
Apt., Sp.FRS selaku Dosen Penguji yang telah banyak memberikan saran
dan masukan serta motivasi demi kesempurnaan skripsi ini.
6. Untuk semua para bapak dan ibu dosen Program Studi Farmasi
Universitas Muhammadiyah Malang, yang telah memberikan waktunya
untuk mengajarkan ilmu-ilmu yang sangat bermanfaat.
7. Ibu Sendy Lia Yunita, S.Farm., Apt yang telah bersusah payah membantu
jalannya ujian skripsi sehingga kami dapat melaksanakan ujian skripsi
dengan baik beserta Staff Tata Usaha Program Studi Farmasi Universitas
Muhammadiyah Malang terima kasih karena telah banyak membantu
dalam hal administrasi.
8. Orang tua tercinta Bapak Budi Irianto,S.H dan Ibu Murlini, S.Pd yang
tiada hentinya memotivasi dalam segala hal, dengan sabar mendoakan
untuk kesuksesan putrinya. Terima kasih banyak atas didikan, kerja keras,
dan kasih sayang yang diberikan.
9. Buat kakak dan adik tersayang (Jarwo Permana Putra, S.E.,Ak. dan Drana
Salsabila) yang memotivasi penulis untuk jadi yang lebih baik lagi.
10. Teman-teman seperjuangan team skripsi ―CURCUMIN‖ Vita, Bela, Putri,
Reny, Opik, Priyadi, Ilham, ka Wawan, ka Mutia, dan anggota lainnya,
terimakasih banyak buat semangat, saran, masukan, bantuan dan
kerjasamanya selama ini. Kalian luar biasa, sedih aja tetap bahagia apalagi
saat bahagia.
11. Buat teman piknik dan seperjuangan Eya, Aisyah, Wildan, Yolla, Lina,
yang selalu senang sedih bersama selama 4 tahun perkuliahan.
12. Teman-teman Farmasi B dan Teman-teman Farmasi 2011 terima kasih
atas kebersamaannya selama 4 tahun terakhir ini.
13. Teman sekamar tersayang Risma Yulita terimakasih atas bantuan saran
dan semangatnya selama 4 tahun.
14. Terimakasih untuk Erik Agashi yang selalu membantu penulis selama di
Malang, tempat untuk cerita senang, sedih, dll. Terimakasih selalu
memberikan semangat dan motivasi selama ini.
vi
15. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf
dan terima kasih yang sebesar-besarnya. Semua keberhasilan ini tak luput
dari bantuan, doa yang telah kalian semua berikan.
Jasa dari semua pihak yang telah membantu dalam penelitian ini, penulis
tidak mampu membalas dengan apapun. Semoga amal baik semua pihak
mendapat imbalan dari Allah SWT. Akhir kata penulis berharap semoga
penelitian ini bermanfaat bagi berbagai pihak dan menambah wawasan serta
memperluas pola pikir sebagai seorang farmasis.
Malang,
Peneliti,
Diani Mega Sari
vii
DAFTAR ISI
Halaman
HALAMAN JUDUL .................................................................................. i
LEMBAR PENGESAHAN ....................................................................... ii
LEMBAR PENGUJIAN ............................................................................ iii
KATA PENGANTAR ............................................................................... iv
RINGKASAN ............................................................................................ vii
ABSTRAK ................................................................................................. ix
ABSTRACK .............................................................................................. x
DAFTAR ISI .............................................................................................. xi
DAFTAR TABEL ...................................................................................... xiv
DAFTAR GAMBAR ................................................................................. xv
DAFTAR LAMPIRAN .............................................................................. xvi
DAFTAR SINGKATAN ........................................................................... xvii
BAB I PENDAHULUAN ...................................................................... 1
1.1 Latar belakang ........................................................................ 1
1.2 Rumusan Masalah .................................................................. 4
1.3 Tujuan Penelitian ................................................................... 4
1.4 Manfaat Penelitian ................................................................. 4
BAB II TINJAUAN PUSTAKA ............................................................. 5
2.1 Tinjauan Hipertensi ................................................................ 5
2.1.1 Definisi Hipertensi ......................................................... 5
2.1.2 Epidemiologi Hipertensi ................................................. 5
2.1.3 Etiologi Hipertensi ......................................................... 6
2.1.3.1 Hipertensi Essensial ........................................... 6
2.1.3.2 Hipertensi Sekunder ........................................... 6
2.1.4 Manifestasi Klinik Hipertensi ......................................... 7
2.1.5 Klasifikasi dan Kriteria Hipertensi .................................. 7
2.1.6 Patofisiologi Hipertensi ................................................... 8
2.1.7 Komplikasi Hipertensi .................................................... 11
2.2 Tinjauan Jantung ..................................................................... 12
2.2.1 Anatomi dan Fisiologi Jantung ....................................... 12
viii
2.3 Hubungan antara Hipertrofi dengan Histologi Jantung ......... 14
2.3.1 Patofisiologi ................................................................... 14
2.3.2 Histologi Jantung ............................................................ 16
2.4. Penatalaksanaan Terapi pada Hipertensi .............................. 18
2.4.1Terapi Non Farmakologi ................................................. 18
2.4.2 Terapi Farmakologi ........................................................ 18
2.4.3 Tinjauan Valsartan ......................................................... 21
2.5 Obat Tradisional ..................................................................... 23
2.6 Tinjauan Temulawak .............................................................. 25
2.6.1 Klasifikasi........................................................................ 26
2.6.2 Kandungan Kimia .......................................................... 26
2.6.3 Curcumin ........................................................................ 26
2.6.3.1 Sifat Kimia dan Stabilitas .................................. 27
2.6.3.2 Khasiat dan Manfaat Curcumin ......................... 28
2.7 Metode Ekstraksi ................................................................... 29
2.7.1 Pelarut ............................................................................. 30
2.7.2 Etanol ............................................................................. 31
2.7.3 Kromatografi .................................................................. 31
2.8 Penginduksi L-NAME ............................................................ 31
2.9 Hewan Coba Mencit .............................................................. 33
2.9.1 Klasifikasi Hewan Coba ................................................. 33
2.9.2 Karakteristik ................................................................... 34
BAB III KERANGKA KONSEPTUAL ................................................ 36
3.1 Kerangka Konseptual .............................................................. 36
3.2 Penjelasan Kerangka Konseptual ........................................... 37
3.3 Hipotesis ................................................................................ 38
BAB IV METODE PENELITIAN ........................................................... 39
4.1 Rancangan Penelitian .............................................................. 39
4.1.1 Jenis Penelitian ................................................................ 39
4.1.2 Jumlah Sampel ................................................................ 39
4.2 Variabel Penelitian .................................................................. 40
4.2.1 Klasifikasi Variabel ......................................................... 40
ix
4.2.2 Definisi Operasional Variabel ......................................... 40
4.3 Tempat dan Waktu Penelitian ................................................. 42
4.4 Subyek Penelitian.................................................................... 42
4.4.1 Kriteria Inklusi ................................................................ 43
4.4.2 Kriteria Eksklusi .............................................................. 43
4.5 Prosedur Penelitian ................................................................ 43
4.5.1 Pembuatan Ekstrak Temulawak ..................................... 43
4.5.2 Penginduksi Hipertensi ................................................... 45
4.5.3 Pemberian Terapi ........................................................... 45
4.5.4 Pembuatan Preparat Histopatologi Organ Jantung ......... 45
4.5.5 Pengamatan Preparat Histopatologi Organ Jantung ....... 45
4.6 Alat dan Bahan ........................................................................ 46
4.6.1 Alat ................................................................................. 46
4.6.2 Bahan .............................................................................. 46
4.7 Alur Penelitian ........................................................................ 47
4.8 Analisis Data .......................................................................... 47
BAB V HASIL PENELITIAN ................................................................ 49
5.1 Hasil Penelitian ...................................................................... 49
5.1.1 Massa Otot Jantung Mencit Jantan (Mus musculus) ...... 49
5.1.2 Ketebalan Ventrikel Kiri ................................................ 50
5.2 Analisis Data .......................................................................... 52
5.2.1 Uji Normalitas ................................................................ 52
5.2.2 Uji Homogenitas ............................................................ 53
5.2.3 Uji One Way Anova ........................................................ 53
5.2.4 Uji Post Hoc LSD .......................................................... 54
5.2.5 Uji Pearson Correlation ................................................ 54
BAB VI PEMBAHASAN HASIL PENELITIAN ................................. 55
BAB VII KESIMPULAN DAN SARAN ................................................ 60
7.1 Kesimpulan ............................................................................ 60
7.2 Saran ...................................................................................... 60
DAFTAR PUSTAKA ................................................................................. 61
LAMPIRAN ................................................................................................ 68
x
DAFTAR TABEL
Tabel II.1 Klasifikasi Tekanan Darah ......................................................... 8
Tabel II.2 Profil farmakokinetik golongan obat ARB ............................... 20
Tabel II.3 Karakteristik Mus musculus ....................................................... 34
Tabel V.1 Hasil Penimbangan .................................................................... 49
Tabel V.2 Hasil Ketebalan Ventrikel Kiri .................................................. 50
Tabel V.3 Uji Normalitas Shapiro-Wilk ..................................................... 53
Tabel V.4 Uji Homogenitas Levene Test ................................................... 53
Tabel V.5 Uji Pearson Correlation ........................................................... 54
xi
DAFTAR GAMBAR
Gambar 2.1 Perbedaan efek stimulasi reseptor AT1dan AT2 ................... 9
Gambar 2.2 Renin-angiotensin-aldosterone system .................................. 11
Gambar 2.3 Struktur jantung dan Sirkulasi Darah pada Jantung ............... 13
Gambar 2.4 Sinyal utama dan mediator umum renovasi kardiomiosit .... 16
Gambar 2.5 Patologi hypertrophic cardiomyopathy ................................ 17
Gambar 2.6 Ketebalan Otot Jantung Bagian Ventrikel Kiri ..................... 18
Gambar 2.7 Kerja obat pada sistem renin-angiotensin-aldosteron ........... 22
Gambar 2.8 Struktur Kimia Valsartan ...................................................... 22
Gambar 2.9 Tanaman Temulawak ............................................................ 25
Gambar 2.10 Struktur kimia Curcuminoid ................................................ 27
Gambar 2.11 Curcumin menghambat aktivitas p300 HAT ....................... 29
Gambar 2.12 Mekanisme L-NAME induksi Hipertensi ............................ 32
Gambar 2.13 Mus musculus ....................................................................... 33
Gambar 3.1 Kerangka Konsep .................................................................. 36
Gambar 4.1 Rancangan Penelitian ............................................................ 39
Gambar 4.2 Diagram alir ekstraksi kurkumin .......................................... 44
Gambar 4.3 Alur Skema Penelitian .......................................................... 47
Gambar 5.1 Grafik Rata-Rata Massa Otot Jantung .................................. 50
Gambar 5.2 Grafik Rata-Rata Ketebalan Ventrikel Kiri .......................... 51
Gambar 5.3 Ketebalan Ventrikel Kiri ....................................................... 52
xii
DAFTAR LAMPIRAN
Lampiran Halaman
1. Daftar Riwayat Hidup ............................................................................. 68
2. Perhitungan Dosis dan Preparasi Sediaan ............................................... 69
3. Surat Determinasi Temulawak ............................................................... 71
4. Surat Keterangan Kelaikan Etik ............................................................. 72
5. Surat Keterangan Pembacaan Patologi Anatomi .................................... 73
6. Surat Pernyataan ..................................................................................... 74
7. Analisis Statistika ................................................................................... 75
8. Dokumentasi Penelitian ......................................................................... 77
xiii
DAFTAR SINGKATAN
ACE = Angiotensin Converting Enzim
ANG II = Angiotensin II
ARB = Angiotensin Renin Blocker
AT1-R = Angiotensin II Receptor Type 1
AT2-R = Angiotensin II Receptor Type 2
BP = Blood Pressure
cAMP = Cyclic Adenosine Monophosphate
CHF = Chronic heart failure
CO = Cardoac Output
CVD = Cardiovarcular Disease
DASH = Dietary Approaches to Stop Hypertension ERK = Extracellular Regulated Kinase
ESH = European Society of Hypertension
HAT = Histone Asetyltransferase
HCM = Hypertrophyc Cardiomyophaty
HE = Hematoxylin Eosin HF = Heart Failure
HHD = Hypertension Heart Disease
IGF-1 = Insulin Growth Factor type 1
IL-1 = Interleukin-1
IL-6 = Interleukin-2
JNC = Joint National Comittee
JNK = c-Jun N-terminal kinase
L-Name = Nω-nitro-L-arginine methyl ester
LV = Left Ventricle
LVH = Left Ventricle Hypertrophy
MAPK = Mitogen Activated Protein Kinases
M-TOR = Mammalian Target of Rapamycin
NADH = Nicotinamida Adenin Dinukleotida Hydrogen
NADPH = Nicotinamida Adenin Dinukleotida Phosphate
NFAT = Nuclear Factor of Activated T cell
Nf-kB = Nuclear factor-kappaB
NO = Nitric Oxide
NOS = Nitrous Oxide System
P13-akt/PKB = Phosphatidylinositol 3 kinase-aktivasi PKC = Protein Kinase C
RAAS = Renin-Angiotensin Aldosterone System
ROS = Reactive Oxygen Species
SV = Stroke Volume
SVR = Systemic Vascular Resisten
TGF-β = Transforming Growth Factor-β
TNF-α = Tumor Necrosis Factor- α
WHO = World Health Organization
xiv
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