Pengaruh Ekstrak Etanol Daun Bangun-Bangun (Plectranthus amboinicus (Lour.) Spreng) Terhadap Penghambatan Karsinogenesis Mammae Mencit Betina Yang Diinduksi Benzo(α)piren

  PENGARUH EKSTRAK ETANOL DAUN BANGUN-BANGUN (Plectranthus amboinicus (Lour.) Spreng) TERHADAP PENGHAMBATAN KARSINOGENESIS MAMMAE MENCIT BETINA YANG DIINDUKSI BENZO(α)PIREN SKRIPSI OLEH: ARNES ANESTESIA SAMOSIR NIM 091501025

  PENGARUH EKSTRAK ETANOL DAUN BANGUN-BANGUN (Plectranthus amboinicus (Lour.) Spreng) TERHADAP PENGHAMBATAN KARSINOGENESIS MAMMAE MENCIT BETINA YANG DIINDUKSI BENZO(α)PIREN SKRIPSI Diajukan untuk Melengkapi Salah Satu Syarat untuk Memperoleh Gelar Sarjana Farmasi pada Fakultas Farmasi Universitas Sumatera Utara OLEH: ARNES ANESTESIA SAMOSIR NIM 091501025 PROGRAM SARJANA FARMASI FAKULTAS FARMASI UNIVERSITAS SUMATERA UTARA MEDAN 2014

PENGESAHAN SKRIPSI PENGARUH EKSTRAK ETANOL DAUN BANGUN-BANGUN (Plectranthus amboinicus (Lour.) Spreng) TERHADAP PENGHAMBATAN KARSINOGENESIS MAMMAE MENCIT BETINA YANG DIINDUKSI BENZO(α)PIREN OLEH: ARNES ANESTESIA SAMOSIR NIM 091501025

  Dipertahankan dihadapan Panitia Penguji Skripsi Fakultas Farmasi Universitas Sumatera Utara Pada Tanggal: 04 Februari 2014

  Pembimbing I, Panitia Penguji, Poppy Anjelisa Z. Hasibuan, M.Si., Apt. Prof. Dr. Rosidah, M.Si., Apt.

  NIP 197506102005012003 NIP 195103261978022001 Pembimbing II, Poppy Anjelisa Z. Hasibuan, M.Si., Apt. NIP 197506102005012003 Marianne, S.Si., M.Si., Apt. NIP 198005202005012006 Dra. Suwarti Aris, M.Si., Apt.

  NIP 195107231982032001 Drs. Rasmadin Mukhtar, M.S., Apt.

  NIP 194909101980031002 Medan, Februari 2014 Fakultas Farmasi Universitas Sumatera Utara Dekan,

Prof. Dr. Sumadio Hadisahputra, Apt.

  NIP 195311281983031002

KATA PENGANTAR

  Puji dan syukur kehadirat Tuhan Yang Maha Esa, karena limpahan rahmat kasih dan karuniaNya, sehingga penulis dapat menyelesaikan skripsi ini yang berjudul “Pengaruh Ekstrak Etanol Daun Bangun-Bangun (Plectranthus amboinicus (Lour.) Spreng) Terhadap Penghambatan Karsinogenesis Mammae

Mencit Betina Yang Diinduksi B enzo(α)piren”. Skripsi ini diajukan sebagai

  salah satu syarat untuk memperoleh gelar sarjana farmasi pada Fakultas Farmasi Universitas Sumatera Utara.

  Pada kesempatan ini penulis juga mengucapkan terima kasih yang tulus dan ikhlas kepada Bapak Prof. Dr. Sumadio Hadisahputra, Apt., selaku Dekan Fakultas Farmasi USU yang telah memberikan fasilitas sehingga penulis dapat menyelesaikan pendidikan. Ibu Poppy Anjelisa Z. Hasibuan, M.Si, Apt., dan Ibu Marianne, S.Si., M.Si., Apt., selaku pembimbing yang telah memberikan waktu, bimbingan dan nasehat selama penelitian hingga selesainya penyusunan skripsi ini. Bapak Drs. Syahrial Yoenoes, S.U., Apt., selaku penasehat akademik yang telah memberikan bimbingan kepada penulis selama perkuliahan. Bapak dan Ibu staf pengajar Fakultas Farmasi Universitas yang telah mendidik penulis selama perkuliahan. Prof. Dr. Rosidah., M.Si., Apt., Ibu Dra. Suwarti Aris., M.Si., Apt., dan Bapak Drs.Rasmadin Mukhtar, M.S., Apt., selaku dosen penguji yang telah memberikan kritik, saran, dan arahan kepada penulis dalam menyelesaikan skripsi ini.

  Penulis menyampaikan terima kasih yang tak terhingga dan perhargaan yang tulus kepada Ayahanda Ir. J. Samosir dan Ibunda S.C. br. Hutabarat, yang tiada hentinya berdoa dan berkorban dengan tulus ikhlas bagi kesuksesan penulis, untuk adik-adikku Otania Hosianna dan Anggi Mareta serta teman- teman yang selalu setia memberi doa, dorongan dan semangat kepada penulis.

  Penulis menyadari bahwa skripsi ini masih banyak kekurangan, oleh karena itu penulis mengharapkan kritik dan saran yang bersifat membangun dari semua pihak guna perbaikan skripsi ini. Akhir kata penulis berharap semoga skripsi ini bermanfaat bagi ilmu pengetahuan khususnya bidang farmasi.

  Medan, April 2014 Penulis, Arnes Anestesia S NIM 091501025

PENGARUH EKSTRAK ETANOL DAUN BANGUN-BANGUN (Plectranthus amboinicus (Lour.) Spreng) TERHADAP PENGHAMBATAN KARSINOGENESIS MAMMAE MENCIT BETINA YANG DIINDUKSI BENZO(α)PIREN ABSTRAK

  

Kanker payudara merupakan salah satu jenis kanker penyebab kematian

di dunia setelah kanker paru-paru, hepar dan kolon. Tujuan penelitian ini adalah untuk mengetahui kemampuan ekstrak etanol daun bangun-bangun dalam penghambatan karsinogenesis mamae mencit betina yang diinduksi dengan benzo(α)piren serta untuk mengetahui dosis ekstrak etanol daun bangun-bangun yang memberikan efek terbaik dalam penghambatan karsinogenesis.

  

Uji antikarsinogenesis ekstrak etanol daun bangun-bangun (Plectranthus

amboinicus, (Lour.) Spreng) dilakukan terhadap mencit betina yang diinduksi benzo(α)piren. Mencit betina dibagi menjadi 5 kelompok yaitu: kelompok normal, benzo(α)piren dan 3 kelompok uji. Semua kelompok kecuali kelompok normal, diinduksi dengan benzo(α)piren (15 mg/kg bb) selama 14 hari. Pada hari ke-15 sampai hari ke-28 kelompok normal diberi suspensi CMC 1% dan kelompok uji diberi ekstrak etanol daun bangun-bangun dosis 250, 500 dan 750 mg/kg bb per hari. Parameter yang diamati selama penelitian adalah berat badan, jumlah nodul dan insidensi kematian. Kemudian mencit dibedah dan diambil tumor payudara yang terbentuk. Gambaran jaringan tumor diamati dengan menggunakan pewarnaan hematoxilin-eosin.

  

Hasil penelitian menunjukkan penurunan berat badan yang paling

signifikan terjadi pada kelompok benzo(α)piren diikuti oleh kelompok ekstrak 250, 500 dan 750 mg/kg bb. Rata-rata jumlah nodul yang paling banyak yaitu pada kelompok benzo(α)piren (2,00 ± 1,225), diikuti kelompok 250 dan 750 mg/kg bb dengan rata-rata jumlah nodul yang sama (0,40 ± 0,548) dan pada kelompok ekstrak 500 mg/kg bb (0,40 ± 0,447). Persen insidensi kematian mencit secara berurut adalah kelompok ekstrak 750 mg/kg bb (40%), kelompok benzo (α)piren (33,33%), kelompok ekstrak 250 dan 500 mg/kg bb dengan persen insidensi kematian yang sama (25%) dan kelompok normal (0%). Gambaran jaringan tumor payudara mencit betina terlihat bahwa pada kelompok benzo(α)piren telah terjadi fibrioadenoma, sedangkan pada kelompok ekstrak 250 dan 500 mg/kg bb terbentuk kista dan pada kelompok ekstrak 750 mg/kg bb terjadi adenokarsinoma.

  

Dapat disimpulkan bahwa ekstrak etanol daun bangun-bangun memiliki

kemampuan untuk menghambat karsinogenesis mamae mencit betina yang diinduksi benzo(α)piren dan dosis 500 mg/kg bb memberikan efek terbaik dalam penghambatan karsinogenesis.

  Kata kunci : bangun- bangun, karsinogenesis, benzo(α)piren

EFFECT OF ETHANOLIC LEAVES EXTRACT OF BANGUN-BANGUN (Plectranthus amboinicus (Lour.) Spreng) AGAINST MAMMARY CARCINOGENESIS OF FEMALE MICE INDUCED BY BENZO(α)PIREN ABSTRACT

  Breast cancer is one of the causes of cancer death worldwide after lung cancer, stomach, liver and colon. One of medicinal plants traditionally used to treat cancer is bangun-bangun leaves (Plectranthus amboinicus, (Lour.) Spreng). The purpose of this study was to determine the ability of ethanolic leaves extract of bangun-bangun in the inhibition of mammary carcinogenesis induced by benzo(α)piren in female mice and to investigate the dose of ethanolic leaves extract of bangun-bangun that gives the best effect in the inhibition of carcinogenesis.

  Anticarcinogenesis test of ethanolic leaves extract of bangun-bangun (Plectranthus amboinicus, (Lour.) Spreng) conducted on female mice that induced by benzo(α)piren. Female mice were divided into 5 groups: the normal group, benzo(α)piren and 3 test groups. Except for the normal group, all groups induced by benzo(α)piren (15 mg/kg bw) for 14 days. On the 15th to the 28th day, the normal group were given 1% CMC suspension and the test groups were given ethanolic leaves extract of bangun-bangun dose of 250, 500 and 750 mg/kg bw per day. Parameters were observed during the study were body weight, number of nodules and the incidence of death. Then the mice were dissected and taken breast tumors are formed. Picture of tumor tissue was observed using hematoxiline-eosine staining.

  The results showed that weight loss the most significant is in the grou

p of benzo(α)piren followed by the extract group 250, 500 and 750 mg/kg

bw. The average number of nodules that has the most nodules is benzo(α) piren group (2.00 ± 1.225), followed by extract groups of 250 and 750 mg/kg ( 0.40 ± 0.548) and in the group of 500 mg extract/kg body weight (0.40 ± 0.447).

  Percent incidence of mice death sequentially were extract 750 mg/kg (40%), groups of benzo(α)piren (33.33%), extract groups of 250 and 500 mg/kg bw (25%) and normal group (0%). The image of breast tumor tissue of female mice shows that the group of benzo(α)piren fibrioadenoma has occurred, while in the extract of 250 and 500 mg/kg in the form of cysts and the group of extract 750 mg/kg bw occurred adenocarcinoma.

  It can be concluded that the ethanolic leaves extract of bangun-bangun has the ability to inhibit mammary carcinogenesis in female mice induced by benzo(α)piren and a dose of 500 mg/kg bw gave the best effect in the inhibition of carcinogenesis.

  Keywords : bangun-bangun, carcinogenesis, benzo(α)piren

  DAFTAR ISI

  Halaman JUDUL ............................................................................................................. i LEMBAR PENGESAHAN ............................................................................. iii KATA PENGANTAR ..................................................................................... iv ABSTRAK ....................................................................................................... vi ABSTRACT ..................................................................................................... vii DAFTAR ISI .................................................................................................... viii DAFTAR TABEL ............................................................................................ x DAFTAR GAMBAR ....................................................................................... xi DAFTAR LAMPIRAN .................................................................................... xii BAB I PENDAHULUAN ................................................................................

  1

  1.1 _{................................................................................................. L} atar Belakang ...............................................................................

  1

  1.2 _{................................................................................................. P} erumusan Masalah .......................................................................

  4

  1.3 _{................................................................................................. H} ipotesis .........................................................................................

  4

  1.4 _{................................................................................................. T} ujuan Penelitian ...........................................................................

  5

  1.5 _{................................................................................................. M} anfaat penelitian ..........................................................................

  9

  2.3 _{................................................................................................. E} kstraksi ........................................................................................

  22

  2.2.5 _{.......................................................................................} F itoestrogen .........................................................................

  19

  2.2.3 _{.......................................................................................} B enzo(α)piren ...................................................................... 17 2.2.4 _{.......................................................................................} K anker payudara ..................................................................

  15

  Siklus sel ...........................................................................

  2.2.2 _{.......................................................................................}

  12

  2.2.1 _{.......................................................................................} K arsinogenesis .....................................................................

  2.2 _{................................................................................................. K} anker ............................................................................................

  5

  9

  8 2.1.5 Khasiat tumbuhan .............................................................

  8 2.1.4 Kandungan kimia tumbuhan .............................................

  7 2.1.3 Morfologi tumbuhan .........................................................

  7 2.1.2 Nama daerah .....................................................................

  7 2.1.1 Sistematika tumbuhan .......................................................

  2.1 _{................................................................................................. U} raian Tumbuhan ...........................................................................

  7

  6 BAB II TINJAUAN PUSTAKA ......................................................................

  1.6 _{................................................................................................. K} erangka Pikir Penelitian ...............................................................

  24

  BAB II METODE PENELITIAN ....................................................................

  27

  3.1 _{................................................................................................. A} lat dan Bahan ..............................................................................

  27

  3.1.1 _{.......................................................................................} A lat .......................................................................................

  27

  3.1.2 _{.......................................................................................} B ahan ...................................................................................

  27 3.2 Hewan Percobaan .............................................................................

  28

  3.3 _{................................................................................................. P} embuatan Pereaksi .......................................................................

  28

  3.3.1 _{.......................................................................................} P ereaksi Bouchardat .............................................................

  28

  3.3.2 _{.......................................................................................}

  Pereaksi Dragendorff ........................................................

  29

  3.3.3 _{.......................................................................................} P ereaksi Mayer ....................................................................

  29

  3.3.4 _{.......................................................................................} P ereaksi besi (III) klorida 1% b/v ........................................

  29

  3.3.5 _{.......................................................................................} P ereaksi Molisch .................................................................

  29

  3.3.6 _{.......................................................................................} P ereaksi timbal (II) asetat 0,4 M .........................................

  29

  3.3.7 _{.......................................................................................} P ereaksi klorakhidrat ...........................................................

  29

  3.3.8 _{.......................................................................................} P ereaksi asam klorida 0,2 N ................................................

  30

  3.3.9 _{.......................................................................................} P ereaksi asam klorida 2 N ...................................................

  3.5.1 _{.......................................................................................} P emeriksaan makroskopik ...................................................

  33

  3.5.4 _{.......................................................................................} P enetapan kadar sari larut dalam air .................................... 32 3.5.5 _{.......................................................................................} P enetapan kadar sari larut dalam etanol ..............................

  31

  3.5.3 _{.......................................................................................} P enetapan kadar air .............................................................

  31

  3.5.2 _{.......................................................................................} P emeriksaan miksroskopik ..................................................

  31

  31

  30

  3.5 _{................................................................................................. P} emeriksaan Karakteristik Simplisia .............................................

  31

  30 3.4.3 Pembuatan simplisia .........................................................

  30 3.4.2 Identifikasi tumbuhan ........................................................

  30 3.4.1 Pengumpulan bahan tumbuhan .........................................

  3.3.11 _{.....................................................................................} P ereaksi Liebermann-Burchard ........................................... 30 3.4 _{................................................................................................. P} engumpulan dan Pengolahan Tumbuhan .....................................

  30

  3.3.10 _{.....................................................................................} P ereaksi natrium hidroksida 2 N .........................................

  3.5.6 _{.......................................................................................} P enetapan kadar abu total .................................................... 33

  3.5.7 _{.......................................................................................} P enetapan kadar abu tidak larut asam ................................. 33 3.6 _{................................................................................................. S} krining Fitokimia Simplisia .........................................................

  33

  3.6.1 _{.......................................................................................} P emeriksaan alkaloid ...........................................................

  34

  3.6.2 _{.......................................................................................} P emeriksaan flavanoid ........................................................

  34

  3.6.3 _{.......................................................................................} P emeriksaan glikosida .........................................................

  34

  3.6.4 _{.......................................................................................} P emeriksaan steroid/triterpenoid .........................................

  35

  3.6.5 _{.......................................................................................} P emeriksaan saponin ...........................................................

  35

  3.6.6 _{.......................................................................................} P emeriksaan tanin ...............................................................

  35

  3.7 _{................................................................................................. P} embuatan Ekstrak Etanol Daun Bangun-Bangun ........................

  36

  3.8 _{................................................................................................. K} arakterisasi Ekstrak Etanol Daun Bangun-bangun ......................

  36

  3.9 _{................................................................................................. P} emeriksaan Skrining Fitokimia Ekstrak Etanol Daun Bangun- Bangun ........................................................................................

  36

  3.10 _{...............................................................................................} U ji Efek Karsinogenesis .................................................................

  37

  3.10.1 _{.....................................................................................} P enyiapan hewan percobaan ...............................................

  37

  3.10.2 _{.....................................................................................} P enyiapan sediaan uji ..........................................................

  3.10.2.7 _{.......................................................................} P emeriksaan gambaran jaringan kelenjar payudara dengan pewarnaan hematoxylin dan eosin ................................................................

  4.4 _{Hasil Karakterisasi dan Skrining Ekstrak Etanol Daun Bangun-} Bangun ...........................................................................................

  47

  4.3 _{................................................................................................. H} asil Skrining Fitokimia Simplisia Daun Bangun-Bangun ...........

  45

  4.2 _{................................................................................................. H} asil Karakterisasi Tumbuhan dan Serbuk Simplisia ....................

  45

  4.1 _{................................................................................................. H} asil Identifikasi Tumbuhan ..........................................................

  43 BAB IV HASIL DAN PEMBAHASAN ....................................................... 45

  41 3.11 Analisis Data ..........................................................................

  40

  37

  3.10.2.6 _{.......................................................................} P engambilan jaringan ........................................

  39

  3.10.2.5 _{.......................................................................} U ji antikarsinogenesis ........................................

  38

  3.10.2.4 _{.......................................................................} P enyiapan larutan formalin 10% .......................

  38

  3.10.2.2 _{.......................................................................} P enyiapan larutan benzo(α)piren 15 mg/kg BB 38 3.10.2.3 _{.......................................................................} P enyiapan suspensi ekstrak etanol daun bangun-bangun (SEDBB) ...............................

  37

  3.10.2.1 _{.......................................................................} P enyiapan CMC 1% ..........................................

  48

  4.5 _{Hasil Ekstraksi ...............................................................................}

  50

  4.6 Hasil Uji Antikarsinogenesis Ekstrak Etanol Daun Bangun-Bangun ...........................................................................

  50

  4.6.1 _{.......................................................................................} T umor multiplicity ...............................................................

  50

  4.6.2 _{.......................................................................................} P ersen insidensi ...................................................................

  54

  4.6.3 _{.......................................................................................} P erubahan berat badan mencit .............................................

  55

  4.6.4 _{.......................................................................................} G ambaran jaringan payudara mencit dengan pewarnaan hematoxylin dan eosin .......................................................

  57 BAB V KESIMPULAN DAN SARAN ...........................................................

  60

  5.1 _{................................................................................................. K} esimpulan ..................................................................................... 60 5.2 _{................................................................................................. S} aran ..............................................................................................

  60 DAFTAR PUSTAKA ......................................................................................

  61 LAMPIRAN .....................................................................................................

  66

  DAFTAR TABEL

  Tabel Halaman 4.1 Hasil karakterisasi simplisia daun bangun-bangun .............................

  46 4.2 Hasil skrining fitokimia simplisia daun bangun-bangun .....................

  47 4.3 Hasil karakterisasi ekstrak etanol daun bangun-bangun .....................

  49 4.4 Hasil skrining fitokimia ekstrak etanol daun bangun-bangun .............

  50

  4.5 Jumlah nodul sebelum dan sesudah pemberian ekstrak etanol daun bangun-bangun ...........................................................................

  52

  4.6 Hasil uji one way ANOVA jumlah nodul sesudah pemberian ekstrak etanol daun bangun-bangun .................................................................

  53 4.7 Hasil persen insidensi kematian mencit pada uji karsinogenesis ........

  54 4.8 Perubahan berat badan rata-rata mencit selama 4 minggu ..................

  55

  DAFTAR GAMBAR

  Gambar Halaman

  1.1 _{....................................................................................................} Diagram kerangka pikir penelitian .....................................................................

  6

  2.1 _{....................................................................................................} Struktur benzo(α)piren ...................................................................................... 17 2.2 _{....................................................................................................} Struktur benzo(α)piren-7,8-dihidrodiol-9,10-epoksida ..................................... 18 4.1 _{....................................................................................................} Nodul pada daerah sekitar payudara sesudah perlakuan .................................

  51

  4.2 _{....................................................................................................} Grafik perubahan berat badan rata-rata mencit ..............................................

  56

  4.3 _{....................................................................................................} Gambara n jaringan payudara mencit dengan pewarnaan Hematoxilin dan eosin ........................................................................

  59