KARYA TULIS AKHIR
EFEK MINYAK ATSIRI DAUN KAYU MANIS (Cinnamomum Zeylanikum) SEBAGAI ANTI DEPRESAN PADA MENCIT DITINJAU DARI IMMOBILITY TIME DENGAN METODE TAIL SUSPENTION TEST
Oleh: RIZDIANIS DEVI MASYITHOH 201110330311007
FAKULTAS KEDOKTERAN UNIVERSITAS MUHAMMADIYAH MALANG 2015
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EFEK MINYAK ATSIRI DAUN KAYU MANIS (Cinnamomum Zeylanikum) SEBAGAI ANTI DEPRESAN PADA MENCIT DITINJAU DARI IMMOBILITY TIME DENGAN METODE TAIL SUSPENTION TEST
KARYA TULIS AKHIR Diajukan kepada Universitas Muhammadiyah Malang untuk Memenuhi Salah Satu Persyaratan dalam Menyelesaikan Program Sarjana Fakultas Kedokteran
Oleh: RIZDIANIS DEVI MASYITHOH 201110330311007
FAKULTAS KEDOKTERAN UNIVERSITAS MUHAMMADIYAH MALANG 2015
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LEMBAR PENGESAHAN KARYA TULIS AKHIR Telah disetujui sebagai hasil penelitian untuk memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang Tanggal : 12 Juni 2015
Pembimbing I
dr. Fathiyah Safithri, M.Kes.
Pembimbing II
dr. Thontowi Djauhari Nur Subchi, M.Kes.
Mengetahui, Dekan Fakultas Kedokteran Universitas Muhammadiyah Malang
dr. Irma Suswati, M.Kes.
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Karya Tulis Akhir oleh Rizdianis Devi Masyithoh ini Telah diuji dan dipertahankan di depan Tim Penguji Pada hari Jum’at, 12 Juni 2015
Tim Penguji
dr. Fathiyah Safithri, M.Kes.
,Ketua
dr. Thontowi Djauhari Nur Subchi, M.Kes.
,Anggota
dr. Abi Noor Wahyono, M.Kes, SpAn.
,Anggota
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KATA PENGANTAR
Puji syukur ke hadirat Allah SWT yang telah melimpahkan berkat rahmat dan ridho-Nya sehingga penulis dapat menyelesaikan penyusunan skripsi dengan judul “Efek Minyak Atsiri Daun Kayu Manis (Cinnamomum Zeylanikum) Sebagai Anti Depresan Pada Mencit Ditinjau Dari Immobility Time Dengan Metode Tail Suspension Test” Penulisan penelitian ini dilakukan dalam rangka memenuhi salah satu syarat untuk mencapai gelar Sarjana Kedokteran Jurusan Pendidikan Dokter pada Fakultas Kedokteran Universitas Muhammadiyah Malang. Penelitian ini tidaklah dapat terselesaikan tanpa bantuan, bimbingan, saran, dan dukungan dari berbagai pihak. Untuk itu penulis mengucapkan terima kasih kepada : 1. Allah SWT, Rabb Yang Maha Pengasih dan Maha Pemurah, yang senantiasa membukakan jalan dan kemudahan, serta melimpahkan rahmat dan ridho-Nya. 2. Rosullullah SAW yang senantiasa memberikan suri tauladannya. 3. Ayah Effendi Dwi Furwanto, ibu Wati Dwi Kartika, kakak Rizky Ayundha Sari, adik Rizal Akbar Syahroni dan semua saudara yang selalu memberi dukungan, doa, kasih sayang, semangat, kepercayaan, pengorbanan dan kesabaran yang tak terhingga bagi saya. 4. Seluruh jajaran Dekanat Fakultas Kedokteran Universitas Muhammadiyah Malang.
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5. dr. Irma Suswati, M.Kes. selaku Dekan Fakultas Kedokteran Universitas Muhammadiyah Malang. 6. dr. Fathiyah Safithri, M.Kes. selaku pembimbing I, terima kasih atas bimbingan dan kesabarannya serta semangatnya dari awal memasuki FK UMM hingga penulis dapat menyelesaikan penelitian ini dengan baik. 7. dr. Thontowi Djauhari Nur Subchi, M.Kes. selaku pembimbing II, terima kasih atas bimbingan dan kesabarannya sehingga saya dapat menyelesaikan penelitian ini dengan baik. 8. dr. Abi Noor Wahyono, M.Kes, SpAn. selaku penguji, terima kasih atas bimbingan dan masukan-masukannya yang sangat membantu dalam penyelesaian tugas akhir ini selama di FKUMM. 9. Ibu Nailis, yang bersedia mengajari penulis tentang cara penghitungan dan pembagian dosis. 10. Seluruh Staf Tata Usaha dan Staf Lab. Terpadu Fakultas Kedokteran . Terima kasih atas bantuan yang diberikan kepada penulis. 11. Sahabat penulis Putri, Oky, Vindy, Ani, Anggi, Devy, Mas Dimas, Otoy, Sucik serta teman sejawat FK 2011 yang telah banyak memberi doa dan dukungannya. 12. Semua pihak yang turut membantu dalam menyelesaikan karya tulis ini dan juga mendoakan demi suksesnya karya tulis ini yang tidak bisa penulis sebut satu-perstu.
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Penulis menyadari skripsi ini masih jauh dari sempurna, untuk itu saran dan kritik konstruktif sangat penulis harapkan. Semoga skripsi ini dapat memberikan sumbangan yang berharga, bagi kepentingan keilmuan maupun aplikasi di dunia kedokteran. Akhir kata penulis berharap adanya saran dan kritik yang membangun dan semoga penelitian ini dapat menambah wawasan serta bermanfaat bagi semua pihak.
Malang, 12 Juni 2015
Penulis
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DAFTAR ISI
HALAMAN JUDUL ........................................................................................... i LEMBAR PENGESAHAN ................................................................................ iii LEMBAR PENGUJI ........................................................................................... iv KATA PENGANTAR ......................................................................................... v ABSTRAK ........................................................................................................... viii DAFTAR ISI ........................................................................................................ x DAFTAR TABEL ............................................................................................... xiv DAFTAR GAMBAR ........................................................................................... xv DAFTAR SINGKATAN ..................................................................................... xvi DAFTAR LAMPIRAN ....................................................................................... xvii
BAB I PENDAHULUAN .................................................................................... 1 1.1 Latar Belakang ...................................................................................... 1 1.2 Rumusan Masalah................................................................................. 3 1.3 Tujuan Penelitian .................................................................................. 3 1.3.1 Tujuan Umum ............................................................................. 3 1.3.2 Tujuan Khusus ............................................................................ 3 1.4 Manfaat Penelitian ................................................................................ 3 1.4.1 Manfaat Akademis ...................................................................... 3 1.4.2 Manfaat Klinis ............................................................................. 3 1.4.3 Manfaat Masyarakat .................................................................... 4
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BAB II TINJAUAN PUSTAKA......................................................................... 5 2.1 Kayu Manis........................................................................................... 5 2.1.1 Klasifikasi Kayu Manis ............................................................... 5 2.1.2 Morfologi Kayu Manis ................................................................ 6 2.1.3 Jenis – jenis Kayu Manis ............................................................ 7 2.1.4 Budidaya Kayu Manis ................................................................. 8 2.1.5 Kandungan Kimia Kayu Manis................................................... 9 2.1.6 Minyak Atsiri Kayu Manis ......................................................... 11 2.1.7 Minyak Daun Kayu Manis .......................................................... 12 2.1.8 Eugenol ....................................................................................... 13 2.1.9 Mekanisme Kerja Eugenol Sebagai Antidepresan ...................... 14 2.2 Depresi .................................................................................................. 16 2.2.1 Definisi Depresi .......................................................................... 16 2.2.2 Epidemiologi Depresi.................................................................. 16 2.2.3 Etiologi Depresi .......................................................................... 17 2.2.4 Klasifikasi Depresi ...................................................................... 18 2.2.5 Faktor Resiko Depresi ................................................................. 19 2.2.6 Gambaran Klinis Depresi ............................................................ 21 2.2.7 Antidepresan ............................................................................... 22 2.2.8 Mekanisme Depresi Akibat Stressor ........................................... 23 2.3 Bahan dan Metode ................................................................................ 25 2.3.1 Hewan percobaan ........................................................................ 25 2.3.2 Uji Penggantungan Ekor (Tail Suspension Test) ........................ 28 2.3.2 Uji Berenang Paksa (Forced SwimmingTtest) ............................ 30
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2.3.3 Uji Roda Putar Celup (Rotarod Test) .......................................... 30
BAB III KERANGKA KONSEPTUAL DAN HIPOTESIS ........................... 32 3.1 Kerangka Konseptual............................................................................ 32 3.2 Hipotesis ............................................................................................... 34 BAB IV METODE PENELITIAN .................................................................... 35 4.1 Jenis Penelitian ..................................................................................... 35 4.2 Lokasi dan Waktu Penelitian ................................................................ 35 4.3 Populasi dan Sampel ............................................................................. 35 4.3.1 Populasi ....................................................................................... 35 4.3.2 Sampel ......................................................................................... 35 4.3.3 Estimasi Besar Sampel ................................................................ 36 4.3.4 Teknik Pengambilan Sampel ....................................................... 36 4.3.5 Karakteristik Sampel Penelitian .................................................. 37 4.3.6 Variabel Penelitian ...................................................................... 37 4.3.7 Definisi Operasional.................................................................... 37 4.4 Alat dan Bahan Penelitian .................................................................... 38 4.4.1 Alat .............................................................................................. 38 4.4.2 Bahan........................................................................................... 38 4.5 Alur Penelitian ...................................................................................... 39 4.6 Prosedur Penelitian ............................................................................... 40 4.6.1 Pembagian Kelompok Mencit ..................................................... 40 4.6.2 Adaptasi Hewan Percobaan......................................................... 40 4.6.3 Penggantungan ekor dengan Tail Suspension Test ..................... 40
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4.6.4 Ekstrak Minyak Atsiri Daun Kayu Manis ................................... 40 4.6.5 Penentuan Dosis .......................................................................... 41 4.6.6 Pengukuran Immobility time ....................................................... 42 4.7 Analisis Data .......................................................................................... 42 BAB V HASIL DAN ANALISIS PENELITIAN .............................................. 43 5.1 . Hasil Penelitian ..................................................................................... 43 5.1.1 Hasil Pengukuran Immobility Time pada Mencit ........................ 43 5.2 Analisis Data......................................................................................... 45 BAB VI PEMBAHASAN.................................................................................... 51 BAB VII KESIMPULAN DAN SARAN ........................................................... 55 7.1 . Kesimpulan ........................................................................................... 55 7.2 . Saran ..................................................................................................... 55 DAFTAR PUSTAKA .......................................................................................... 56
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DAFTAR TABEL
Tabel
Halaman
2.1 Kandungan Minyak Atsiri Kayu Manis .......................................................... 9 2.2 Komposisi Mineral dan Vitamin dalam 100 g Kayu Manis ........................... 10 2.3 Data Biologis Mencit (Mus musculus) ........................................................... 27 5.1 Urutan rata-rata Immobility time Sebagai Efek Dari Pemberian minyak atsiri daun kayu manis (Cinnamomum zeylanicum)........................... 44
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DAFTAR GAMBAR
Gambar
Halaman
2.1 Kayu Manis (Cinnamomum zeylanicum) ........................................................ 6 2.2 Struktur kimia minyak atsiri kayu manis ........................................................ 10 2.3 Mencit (Mus musculus) ................................................................................... 26 2.4 Tail Suspension Test........................................................................................ 29 2.5 Forced Swimming Test .................................................................................... 30 2.6 Rotarod Test .................................................................................................... 31 4.1 Alur penelitian ................................................................................................. 39 4.2 Perangkat Destilasi Uap .................................................................................. 41 5.1 Grafik efek pemberian minyak atsiri daun kayu manis (Cinnamomum zeylanikum) terhadap Immobility time.................................... 43 5.2 Grafik Linieritas antara pemberian dosis minyak atsiri daun kayu manis (Cinnamomum zeylanikum) terhadap Immobility time. ............... 50
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DAFTAR SINGKATAN
ACTH
:Adenocorticotropine hormone
CRH
: Corticotropin Releasing Hormone
DA
: Dopamin
FST
: Forced Swimming Test
GABA
: Gamma Amino Butiric Acid
HPA
: Hypothalamus Pituitary Adrenal
LC
: Locus Ceruleus
MAO
: Monoamine Oxidase
MAOI
: Monoamine Oxidase Inhibitor
NE
: Norepinefrin
PVN
: Paraventricular
SSP
: Susunan Saraf Pusat
SSRI
: Selective Serotonin Reuptake Inhibitors
TCA
: Tricyclic
TH
: Tryrosine Hydroxylase
TST
: Tail Suspension Test
5-HT
: 5-hydroxytryptamine
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DAFTAR LAMPIRAN
Lampiran 1 Perhitungan Immobility Time.......................................................... 62 Lampiran 2 Analisis Data Immobility Time ....................................................... 63 Lampiran 3 Foto Penelitian ................................................................................ 70 Lampiran 4 “ETHICAL CLEARENCE” ............................................................ 72 Lampiran 5 Determinasi Tanaman Kayu Manis ................................................ 73
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DAFTAR PUSTAKA
Abreu, N., Powell, V. B., & Sudak, D. (2012). Cognitive-Behavioral Therapy for Depression. In I. R. D. Oliveira (Ed.), Standard and Innovative Strategies in Cognitive Behavior Therapy: In Tech. Alimul, Aziz A, 2009. Pengantar Kebutuhan Dasar Manusia: Aplikasi Konsep & Proses Keperawatan, Jakarta: Salemba Medika. Amir, N., 2005. Depresi, Aspek Neurobiologi Diagnosis dan Tatalaksana, Jakarta: Balai Penerbit FKUI; hal 133 – 8. Ashwani Arya, Preeti Verma. 2012. A Review on Pathophysiology, Classification and Long term course on depression. International Research Journal of Pharmacy. Aynur Buyukbalci Sedef Nehir EI. Plant Foods Hum Nurt 2008; 63: 27-33. Ball Harriet A, Sumathipala Athula, Siribaddana Sisira H. 2009. Genetic and environmental contributions to depression in Sri Lanka. The British Journal of Psychiatry. Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring the brain. 2005. Berridge C.W., The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Research Reviews 42 (2003) 33–84. Accepted 21 January 2003. Bhagwagar, ZB., Whale, R., Cowen, PJ. 2002. State and trait abnormalities in serotonin function in major depression. Br.J. Psycchiatry. 181:242-247. Bhowmik Debjit, Kumar K.P.S, Srivastava Shweta. 2012. Depression - Symptoms, Causes, Medications and Therapies. The Pharma Innovation. Department of pharmaceutical sciences, Karpagam University, Coimbatore, Tamil Nadu, India. Brooker, Cris. 2008. Ensiklopedia Keperawatan. Jakarta : Buku Kedokteran EGC. Castagne V, Moser P, Porsolt RD. Behavioral assessment of antidepressant activity in rodents. Medical college of Georgia: CRC Press; 2009 [cited 2010 July 10]. Available from:http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=frbehav Crawley, M. J. 2007. The R Book. Wiley. London, United Kingdom.
xvi
Crowley J, Edward Brodkin. Pharmacogenomic Evaluation of the Antidepressant Citalopram in the Mouse Tail Suspension Test. Neuropsychopharmacology 31(2006): 2433-2442 Cucci T, Vigne J-D and Auffray J-C (2005). "First occurrence of the house mouse (Mus musculus domesticus Schwarz & Schwarz, 1943) in the Western Mediterranean: a zooarchaeological revision of subfossil occurrences". Biological Journal of the Linnean Society 84: 429–445. doi: 10.1111/j.10958312.2005.00445.x (http://dx.doi.org/10.1111/j.1095-8312.2005.00445.x). Dalimartha, S. 2005. Atlas Tumbuhan Obat Indonesia Jilid 3. Trubus Agriwidya. Jakarta. 198 hlm. Departemen Kesehatan Republik Indonesia. 2004. Data Prevalensi Depresi di Dunia dan ndonesia. Available at: www.depkes.go.id. Acessed: November 7, 2010. Do Amaral JF, Silva MI, De Aquino Neto MR. Antidepressant-like effect of biseugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system. National Institute of Health Journal [serial on the Internet]. 2013 Oct;27(5):471-82. doi: 10.1111/j.14728206.2012.01058.x. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22827775 Federer W. Statistics and society: data collectionand interpretation. 2nd ed. New York: Marcel Dekker;1991. Galambos Nancy L, Leadbeater Bonnie J, Barker Erin T. 2005. Gender differences in and risk factors for depression in adolescence: A 4-year longitudinal study. International Journal of Behavioral Development. Guenther, E. 2006. Minyak Atsiri. Jilid 1, Penerjemah Ketaren S., Penerbit UI Press, Jakarta. Gunawan, D, Mulyani, S., (2004), Ilmu Obat Alam (Farmakognosi) Jilid I, Penerbit Penebar Swadaya, Jakarta. Gunawan, 2009. Farmakologi dan Terapi. Edisi ke-5 Jakarta: Balai Penerbit Fakultas Kedokteran UI. Hariana A. Tumbuhan obat & khasiatnya seri 2. Jakarta: Penebar Swadaya, 2008: 14-15. Hawari, D. 2011. Manajemen Stres, Cemas, dan Depresi. Jakarta: Fakultas Kedokteran Universitas Indonesia.
xvii
Jakhetia V, Patel R, Khatri P. 2010. Cinnamon: A Pharmacological Review. Journal of Advanced Scientific Research. Kaplan HI, Sadock BJ, Grebb JA. Sinopsis psikiatri : ilmu pengetahuan perilaku psikiatri klinis.7 ed. Jakarta: Binarupa Aksara: 2010 p. 777-89. Keliat, dkk. (2011). Manajemen Kasus Gangguan Jiwa (intermediate Course). (K. d. Monica Ester S, Ed.) Jakarta: Buku Kedokteran EGC. Khare. C. P. 2007. Indian Medical Plant – an illustrated Dictionary. India: Springer. Kong Xiaojun, Liu Xiawang Li Jianyong. 2014. Advances in Pharmacological Research of Eugenol. Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture/Key Laboratory of New Animal Drug Project, Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China. Krinke, G. J. 2000. The Laboratory Rat. San Diego, CA: Academic Press. Hal: 150152. Laurence L, Raymond M, Salmon C.C. 2008. Corticosteroid-serotonin interaction in the neurobiological mechanism of stress-related disorders. Neuroscience and Biobehavioral Reviews 32(2008) 1174-1184. Journal homepage: www.elsevier.com/locate/neubiorev Maity TK, Mandal SC, Saha BP, Pal M. Effect of Ocimum sanctum roots extract on swimming performance in mice. Phytotherapy research [homepage on the internet]. c2000 [cited 2009 Dec 20]; 14(2):120-21. Available from: http://www3.interscience.wiley.com/journal/70001433/abstract Mansari M. El, Guiard B.P, Chernoloz O. 2010. Relevance of Norepinephrine– Dopamine Interactions in the Treatment of Major Depressive Disorder. CNS Neuroscience & Therapeutics 16 (2010) e1–e17. Available from: http://www.neuropharmacologie.u-psud.fr/Bruno_Guiard_files/20406250.pdf Maramis A., S. Darmono., M. Maramis. 2003. Depresi. Dalam: Penanganan Depresi dan Anxietas di Pelayanan Primer. Surabaya: Indopsy. Hal 20-2. Maslim. R., 2002. Diagnosa Gangguan Jiwa Rujukan Ringkas Dari PPDGJ-III. Jakarta : Bagian Ilmu Kedokteran Jiwa FK-Unika Atmajaya, 58-65 Mathiazhagan S, Anand S, Parthiban R. 2013. Antidepressant-like effect of ethanolic extract from Caryophyllus aromaticus in albino rats. IOSR Journal of Dental and Medical Sciences. Available from: http://www.iosrjournals.org/iosr-jdms/papers/Vol4-issue2/G0423740.pdf
xviii
Mehta Ashish K, Halder Sumita, Khanna Naresh. The effect of the essential oil of Eugenia caryophyllata in animal models of depression and locomotor activity. National Institute of Health Journal [serial on the Internet]. 2013 Sep;16(5):233-8. doi: 10.1179/1476830512Y.0000000051. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23462195 Melgar Natalia, Rossi Maximo. 2010. A Cross-Country Analysis of the Risk Factors for Depression at the Micro and Macro Level. Inter-American Development Bank. Moro D and Morris K (2000). "Movements and refugia of Lakeland Downs shorttailed mice, Leggadina lakedownensis, and house mice, Mus domesticus, on Thevenard Island, Western Australia". Wildlife Research 27: 11–20. doi: 10.1071/WR99016 (http://dx.doi.org/10.1071/WR99016). Mosmann, T. (2000). "Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays," Journal of Immunological Methods, 65:55-63. Mossner Rainald, Mikova Olya, Kountsilieri Eleni. 2007. Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression. The World Journal of Biological Psychiatry, 8(3): 141174. Musser G, Amori G, Hutterer R, Kryštufek B, Yigit N & Mitsain G (2008). Mus musculus (http://www. iucnredlist.org/details/13972). 2008 IUCN Red List of Threatened Species. IUCN 2008. Retrieved on 10 October 2008. National Institute of Mental Health (NIMH). 2010. Depression and College Students, available from http://www.nimh.nih.gov/health/publications/depression-and-collegestudents/index.shtml Nevid, J. S., Rathus, S. A., & Greene, B. (2005). Psikologi abnormal (5th ed., Vol. 1). Jakarta: Erlangga. Opmeer E.M., Depression and the role of genes involved in dopamine metabolism and signaling. Progress in Neurobiology 92 (2010) 112–133. P.A. Paranagama, S. Wimalasena, G.S. Jayatilake, A.L. Jayawardena, U.M. Senanayake and M. Mubarak (2011), A Comparison of Essential Oil Constituents of Bark, Leaf, Root and Fruit of Cinnamon (Cinnamomum zeylanicum Blum) Grown in Sri Lanka, J. Natn. Sci. Foundation Sri Lanka, 29, 147-153.
xix
Pedro L.Delgado, MD. 2009. Neurobiology of Serotonin Norepinephrine Reuptake Inhibitors. Primary Psychiatry. 2009;16:5 (Suppl 4):8-15. Available from: http://primarypsychiatry.com/wpcontent/import/0509PP_SNRI_Delgado.pdf Philippine Medicinal Plants. Tan-ag/Kleinhovia hospita Linn. Guest tree. Alternative Medicine in the Philippines. (Online) (http://www.stuartxchange.com/Tan-ag.html. Diakses Tanggal 20 Agustus 2010). Pittenger C, Duman RS. 2008. Stress, depression and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology, 33: 88-109. Porsolt, RD. (2000) Animal models of depression: utility for transgenic research. Rev. Neurosci., 11, 53-58. Rabadia J, S.Satish, Ramanjaneyulu J. 2013. An Investigation of Anti-Depressant Activity of Cinnamomum Camphora Oil in Experimental Mice. Asian Journal of Biomedical & Pharmaceutical Sciences. Rajput MS, Sinha S, Mathur V. Herbal Antidepressants. International Journal of Pharmaceutical Frontier Research (IJPFR), April-June 2011; 1(1):159-169. Reus, V.I, and Osborne S.F. 2000. Psychoneuroendocrinology. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Seventh Edition. Lippincott Williams and Wilkins Publishers. Philadelphia. Richards, D. 2011. Prevalence and clinical course of depression: A Review, Clinical Psychology Review. Richard J. Porter, et al. corticosteroid-serotonin interactions in depression: a review of the human evidence. 2004. Journal psycopharmacology (2004) 173: 1-17. Rismunandar, Ferry B. Paimin.2009.Kayu manis: Budi Daya dan Pengolahan Edisi Revisi, Cetakan ke 8.Jakarta. Penebar Swadaya. Sastrohamidjojo, H., (2004), Kimia Minyak Atsiri, Penerbit Gadjah Mada University Press, Yogyakarta. Sangita Saini, 2012. Recent Therapies in Depression, Clinical, Research and Treatment Approaches to Affective Disorders. Singh G, Maurya S, Cesar MP, Catalan AM. Food and Chemical Toxicology, 2007; 45:1650–1661.
xx
Steiger H, Bruce KR, Groleau P. Neural circuits, neurotransmitters, and behavior: serotonin and temperament in bulimic syndromes. Curr Top Behav Neurosci. 2011;6:125-38. Sundari, E., (2001), Pengambilan minyak atsiri dan oleoresin dari kulit kayu manis, ITB Central Library, Ganesha, Bandung. Tao G, Irie Y, Li DJ. Eugenol and its structural analogs inhibit Monoamin Oxidase A and exhibit antidepressant-like activity. National Institute of Health Journal [serial on the Internet]. 2005 [cited 2009 Dec 10]; 13(15): 4777-88. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC15936201/ Tarbiyati, A. K., Soewandi, dan Sumarni. 2004. Hubungan Antara Insomnia Dan Depresi Lanjut Usia Di Kecamatan Margangsan Yogyakarta. Yogyakarta: FK UGM. Tjitrosoepomo, G. 2005. Taksonomi Tumbuhan Obat-Obatan. Gajah Mada University Press. Yogyakarta. 447 hlm. Trajano Vinicius N, Lima Edeltrudes de O, Souza Evandro L. 2010. Inhibitory effect of the essential oil from Cinnamomum zeylanicum Blume leaves on some food-related bacteria. 30(3): 771-775. Vangalapati M, N Sree S, DV Surya P. 2012. A Review on Pharmacological Activities and Clinical effects of Cinnamon Species. Research Journal of Pharmaceutical, Biological and Chemical Sciences. W. Lucia E, 2007. Aksi Obat. Basis Farmakologi Klinik, Surabaya. W. Lucia E, 2013. Eksperimen Farmakologik orientasi preklinik, Sandira: Surabaya. Zomkowski, A.D.E., Rosa, A.O., Lin, J., Santos, A.R.S., Calixto, J.B., Rodrigues, A.L.S., 2004. Evidence for serotonin receptor subtypes involvement in agmatine antidepressant-like effect in the mouse forced swimming test. Brain Research 1023. 253–263.
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