b Efek Pemberian Ekstrak Buah Andaliman (Zanthoxylum acanthopodium) Terhadap Penurunan Kadar Gula Darah pada Mencit Model Diabetes Mellitus Tipe 1

Kruskal-Wallis Test Test Statistics

a,b

hari_3 hari_6 hari_9 hari_12 Chi-Square 15.707 17.110 14.880 15.759 df 4 4 4 4 Asymp. Sig. .003 .002 .005 .003 a. Kruskal Wallis Test b. Grouping Variable: Kelompok Post Hoc Tests Multiple Comparisons Tukey HSD Dependent Variable I Kelompok J Kelompok Mean Difference I- J Std. Error Sig. 95 Confidence Interval Lower Bound Upper Bound hari_3 Aquades 100 -30.27600 11.56668 .105 -64.8878 4.3358 200 -29.86800 11.56668 .112 -64.4798 4.7438 300 10.91000 11.56668 .877 -23.7018 45.5218 Metformin -32.80600 11.56668 .069 -67.4178 1.8058 100 Aquades 30.27600 11.56668 .105 -4.3358 64.8878 200 .40800 11.56668 1.000 -34.2038 35.0198 300 41.18600 11.56668 .015 6.5742 75.7978 Metformin -2.53000 11.56668 .999 -37.1418 32.0818 200 Aquades 29.86800 11.56668 .112 -4.7438 64.4798 100 -.40800 11.56668 1.000 -35.0198 34.2038 300 40.77800 11.56668 .016 6.1662 75.3898 Metformin -2.93800 11.56668 .999 -37.5498 31.6738 300 Aquades -10.91000 11.56668 .877 -45.5218 23.7018 100 -41.18600 11.56668 .015 -75.7978 -6.5742 200 -40.77800 11.56668 .016 -75.3898 -6.1662 Metformin -43.71600 11.56668 .009 -78.3278 -9.1042 Metformin Aquades 32.80600 11.56668 .069 -1.8058 67.4178 Universitas Sumatera Utara 100 2.53000 11.56668 .999 -32.0818 37.1418 200 2.93800 11.56668 .999 -31.6738 37.5498 300 43.71600 11.56668 .009 9.1042 78.3278 hari_6 Aquades 100 -79.15400 16.74127 .001 -129.2502 -29.0578 200 -67.47600 16.74127 .005 -117.5722 -17.3798 300 -44.58800 16.74127 .096 -94.6842 5.5082 Metformin -80.24600 16.74127 .001 -130.3422 -30.1498 100 Aquades 79.15400 16.74127 .001 29.0578 129.2502 200 11.67800 16.74127 .955 -38.4182 61.7742 300 34.56600 16.74127 .273 -15.5302 84.6622 Metformin -1.09200 16.74127 1.000 -51.1882 49.0042 200 Aquades 67.47600 16.74127 .005 17.3798 117.5722 100 -11.67800 16.74127 .955 -61.7742 38.4182 300 22.88800 16.74127 .654 -27.2082 72.9842 Metformin -12.77000 16.74127 .938 -62.8662 37.3262 300 Aquades 44.58800 16.74127 .096 -5.5082 94.6842 100 -34.56600 16.74127 .273 -84.6622 15.5302 200 -22.88800 16.74127 .654 -72.9842 27.2082 Metformin -35.65800 16.74127 .247 -85.7542 14.4382 Metformin Aquades 80.24600 16.74127 .001 30.1498 130.3422 100 1.09200 16.74127 1.000 -49.0042 51.1882 200 12.77000 16.74127 .938 -37.3262 62.8662 300 35.65800 16.74127 .247 -14.4382 85.7542 hari_9 Aquades 100 -89.20200 22.29543 .006 -155.9183 -22.4857 200 -86.24400 22.29543 .008 -152.9603 -19.5277 300 -66.81000 22.29543 .050 -133.5263 -.0937 Metformin -90.62600 22.29543 .005 -157.3423 -23.9097 100 Aquades 89.20200 22.29543 .006 22.4857 155.9183 200 2.95800 22.29543 1.000 -63.7583 69.6743 300 22.39200 22.29543 .850 -44.3243 89.1083 Metformin -1.42400 22.29543 1.000 -68.1403 65.2923 200 Aquades 86.24400 22.29543 .008 19.5277 152.9603 100 -2.95800 22.29543 1.000 -69.6743 63.7583 300 19.43400 22.29543 .904 -47.2823 86.1503 Metformin -4.38200 22.29543 1.000 -71.0983 62.3343 300 Aquades 66.81000 22.29543 .050 .0937 133.5263 100 -22.39200 22.29543 .850 -89.1083 44.3243 200 -19.43400 22.29543 .904 -86.1503 47.2823 Metformin -23.81600 22.29543 .820 -90.5323 42.9003 Universitas Sumatera Utara Metformin Aquades 90.62600 22.29543 .005 23.9097 157.3423 100 1.42400 22.29543 1.000 -65.2923 68.1403 200 4.38200 22.29543 1.000 -62.3343 71.0983 300 23.81600 22.29543 .820 -42.9003 90.5323 hari_12 Aquades 100 -56.12200 10.47329 .000 -87.4620 -24.7820 200 -49.94200 10.47329 .001 -81.2820 -18.6020 300 -27.63200 10.47329 .101 -58.9720 3.7080 Metformin -55.62600 10.47329 .000 -86.9660 -24.2860 100 Aquades 56.12200 10.47329 .000 24.7820 87.4620 200 6.18000 10.47329 .975 -25.1600 37.5200 300 28.49000 10.47329 .086 -2.8500 59.8300 Metformin .49600 10.47329 1.000 -30.8440 31.8360 200 Aquades 49.94200 10.47329 .001 18.6020 81.2820 100 -6.18000 10.47329 .975 -37.5200 25.1600 300 22.31000 10.47329 .246 -9.0300 53.6500 Metformin -5.68400 10.47329 .982 -37.0240 25.6560 300 Aquades 27.63200 10.47329 .101 -3.7080 58.9720 100 -28.49000 10.47329 .086 -59.8300 2.8500 200 -22.31000 10.47329 .246 -53.6500 9.0300 Metformin -27.99400 10.47329 .094 -59.3340 3.3460 Metformin Aquades 55.62600 10.47329 .000 24.2860 86.9660 100 -.49600 10.47329 1.000 -31.8360 30.8440 200 5.68400 10.47329 .982 -25.6560 37.0240 300 27.99400 10.47329 .094 -3.3460 59.3340 hari_15 Aquades 100 -49.75800 9.29904 .000 -77.5842 -21.9318 200 -48.33000 9.29904 .000 -76.1562 -20.5038 300 -21.51200 9.29904 .182 -49.3382 6.3142 Metformin -49.24600 9.29904 .000 -77.0722 -21.4198 100 Aquades 49.75800 9.29904 .000 21.9318 77.5842 200 1.42800 9.29904 1.000 -26.3982 29.2542 300 28.24600 9.29904 .046 .4198 56.0722 Metformin .51200 9.29904 1.000 -27.3142 28.3382 200 Aquades 48.33000 9.29904 .000 20.5038 76.1562 100 -1.42800 9.29904 1.000 -29.2542 26.3982 300 26.81800 9.29904 .062 -1.0082 54.6442 Metformin -.91600 9.29904 1.000 -28.7422 26.9102 300 Aquades 21.51200 9.29904 .182 -6.3142 49.3382 Universitas Sumatera Utara 100 -28.24600 9.29904 .046 -56.0722 -.4198 200 -26.81800 9.29904 .062 -54.6442 1.0082 Metformin -27.73400 9.29904 .051 -55.5602 .0922 Metformin Aquades 49.24600 9.29904 .000 21.4198 77.0722 100 -.51200 9.29904 1.000 -28.3382 27.3142 200 .91600 9.29904 1.000 -26.9102 28.7422 300 27.73400 9.29904 .051 -.0922 55.5602 . The mean difference is significant at the 0.05 level. Homogeneous Subsets hari_3 Tukey HSD a Kelompok N Subset for alpha = 0.05 1 2 300 5 -27.3860 Aquades 5 -16.4760 -16.4760 200 5 13.3920 100 5 13.8000 Metformin 5 16.3300 Sig. .877 .069 Means for groups in homogeneous subsets are displayed. a. Uses Harmonic Mean Sample Size = 5.000. hari_6 Tukey HSD a Kelompok N Subset for alpha = 0.05 1 2 Aquades 5 -44.1540 300 5 .4340 .4340 200 5 23.3220 100 5 35.0000 Metformin 5 36.0920 Sig. .096 .247 Universitas Sumatera Utara Means for groups in homogeneous subsets are displayed. a. Uses Harmonic Mean Sample Size = 5.000. hari_9 Tukey HSD a Kelompok N Subset for alpha = 0.05 1 2 Aquades 5 -43.8100 300 5 23.0000 200 5 42.4340 100 5 45.3920 Metformin 5 46.8160 Sig. 1.000 .820 Means for groups in homogeneous subsets are displayed. a. Uses Harmonic Mean Sample Size = 5.000. hari_12 Tukey HSD a Kelompok N Subset for alpha = 0.05 1 2 Aquades 5 3.6520 300 5 31.2840 31.2840 200 5 53.5940 Metformin 5 59.2780 100 5 59.7740 Sig. .101 .086 Means for groups in homogeneous subsets are displayed. a. Uses Harmonic Mean Sample Size = 5.000. Universitas Sumatera Utara hari_15 Tukey HSD a Kelompok N Subset for alpha = 0.05 1 2 3 Aquades 5 21.1160 300 5 42.6280 42.6280 200 5 69.4460 69.4460 Metformin 5 70.3620 70.3620 100 5 70.8740 Sig. .182 .051 1.000 Means for groups in homogeneous subsets are displayed. a. Uses Harmonic Mean Sample Size = 5.000. Universitas Sumatera Utara Daftar Pustaka 1. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. American Diabetes Association; 2012 2. Piero M.N, Nzaro, G.M, Njagi J.M. Diabetes mellitus – a devastating metabolic disorder. Asian Journal of Biomedical and Pharmaceutical Sciences 2014; 0440: 7-1. 3. Subroto MA. Ramuan herbal untuk diabetes mellitus. Jakarta: Penebar Swadaya; 2006. p. 16-19. 4. Adibe, M. O. Prevalence of Concurrent Use Of Herbal And Synthetic Medicines Among Outpatients In A Mission Hospital In Nigeria. International Journal of Drug Development and Research 2009; 11: 66- 60. 5. Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiati S. Buku Ajar Ilmu Penyakit Dalam Jilid III edisi V. Jakarta: Interna Publishing; 2009. 6. Siregar B.L. Andaliman Zanthoxylum acanthopodium DC. di Sumatera Utara: deskripsi dan perkecambahan. Hayati 2002;101: 40-38. 7. Suarsana I.N, Priosoeryanto B.P, Wresdiyati T, Bintang M. Aktivitas Daya Hambat Enzim α−Glukosidase dan Efek Hipoglikemik Ekstrak Tempe pada Tikus Diabetes. Jurnal Veteriner 2010;113: 195-190. 8. Ozougwu J.C, Obimba K.C, Belonwu C.D, Unakalamba, C.B. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. Academic journals 2013;44: 57-46. 9. Wijaya C.H, Triyanti I, Apriyantono A. Identification of volatile compounds and key aroma compounds of andaliman fruit Zanthoxylum acanthopodium. J. Food Sci. Biotechnol 2002;116: 683-680. 10. Kristanty R.E, Mun’im A, Katrin. Isolation of antioxidant and xanthine oxidase inhibitor from n-butanol extract of andaliman fruit Zanthoxylum acanthopodium. Int. j. Med. Arom 2012;23: 376-389. 11. Parhusip, A. J. N.,Sibuea. P, dan Tarigan. A. Studi Tentang Aktivitas Antimikroba Alami Pada Andaliman. Seminar Nasional Teknologi Pangan. Jakarta;1999.p.190-193. 12. Robinson, T. Kandungan Organik Tumbuhan Tinggi. Bandung: Penerbit ITB;1995.p.57-59. 13. Waheed A, Mahmud S, Akhtar M, Nazir T. Studies on the components of essential oil of Zanthoxylum armatum by GC-MS. American Journal Of Analytical Chemistry 2011;2: 258-261. 14. Campbell NA and Jane B. Reece. Biology. 10 th ed. USA: Pearson education, inc; 2014.p. 9. 15. Guyton, A.C. and Hall, J.E. Textbook of Medical Physiology. 11 th ed. USA; Elsevier Inc; 2006.p. 831-836. 16. Himawan I.W, Pulungan A.B, Tridjaja B, Batubara R.L. Komplikasi jangka pendek dan jangka panjang diabetes mellitus tipe 1. Sari pediatri 2009;106: 372-367. Universitas Sumatera Utara 17. Ditjen Bina Farmasi dan Alkes. Pharmaceutical Care untuk penyakit Diabetes Mellitus. Jakarta: Departemen Kesehatan RI; 2005.p. 9, 29, 30, 32, 39, 43 18. PERKENI. Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia. Perkumpulan Endokrinologi Indonesia; 2011. 19. Yanling W, Yanping D, Yoshimasa T, Wen Z. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int. J. Med. Sci 2014;1111: 1200-1185. 20. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res 2001; 50: 546-536. 21. Gupta D.D, Mandi S.S. Species Specific AFLP Markers for authentication of Zanthoxylum acanthopodium Zanthoxylum oxyphyllum. Journal of Medicinal Plants Studies 2013;16: 1-9. 22. Gultom S. Flavonoid Buah Andaliman Zanthoxylum acanthopodium DC sebagai antioksidan dan inhibitor α-glukosidase. Thesis. Bogor: Program Pascasarjana IPB; 2011. 23. Lenzen S. The mechanisms of alloxan and streptozotocin-induced diabetes. Diabetologia 2008;51: 226-216. 24. Hayati F, Widyarini, S, Helminawati. Efek antihiperglikemia infusa kangkung darat Ipomoea reptans Poir terhadap kadar glukosa darah mencit jantan yang diinduksi streptozotocin. Jurnal Ilmiah Farmasi 2010;71: 22-13. 25. Depkes RI. Cara Pembuatan Simplisia. Jakarta: Departemen Kesehatan Republik Indonesia;1985.p.2-24. 26. Ditjen POM.Parameter Standar Umum Ekstrak Tumbuhan Obat. Jakarta: Departemen Kesehatan RI;2000.p. 3-5, 10-11 27. World Health Organization. General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. Geneva: WHO; 2001 28. Tensiska. Aktivitas Antioksidan Ekstrak Buah Andaliman Zanthoxylum acannhopodium DC dalam Beberapa Sistem Pangan dan Kesetabilan Aktivitasnya Terhadap Kondisi Suhu dan pH. Thesis. Bogor: Program Pascasarjana IPB;2001. 29. Andayani. Kajian Daya Insektisida Alami Nabati Kulit Buah Manggis Garcinia mangostan, Buah Andaliman Zanthoxylum acanthopodium DC, Getah Gambir Uncaria gambir Roxb dan Daun Teh Camellia sinensis L Terhadap Perkembangan Hama Gudang Sitophilus zeamays otsh. Skripsi. Bogor: Fakultas Teknologi pertanian IPB; 2000. 30 Robinson, T. Kandungan Organik Tumbuhan Tinggi. 6 th ed. Bandung: Institut Teknologi Bandung;1995.p.191 31. Golbidi S, Ebadi A, Laher I. Antioxidants in the treatment of diabetes. Current Diabetes Reviews 2011;7: 125-106. 32. Setiawan B, Suhartono E. Stres oksidatif dan peran antioksidan pada diabetes mellitus. Maj Kedokt Indon 2005;552: 91-86. 33. Kristanty RE, Suriawati J. Cytotoxic and antioxidant activity of petroleum extract of andaliman fruits Zanthoxylum acanthopodium DC.. International Journal of PharmTech Research 2014;63: 1069-1064. Universitas Sumatera Utara 34. Jiang Y, Huang W, Wang J, Xu Z, He J. Metformin plays a dual role in MIN6 pancreatic β cell function trough AMPK-dependent autophagy. Int. J. Biol. Sci 2014;103: 277-268. 35. Hur KY, Lee M. New mechanisms of metformin action: Focusing on mitochondria and the gut. J Diabetes Investig 2015;6: 609-600. 36. Klip A, Leiter LA. Cellular mechanism of action of metformin. Diabetes care 2013;136: 704-694. 37. Rohilla A, Ali S. Alloxan induced diabetes : mehchanisms and effects. International journal of research in pharmaceutical and biomedical sciences 2012;32:823-819. 38. Diandra. Pengaruh Pemberian Infusa Herba Sambiloto Andrographis paniculata Nees Terhadap Glibenklamid Dalam Menurunkan Kadar Glukosa Darah Tikus Putih Jantan Yang Dibuat Diabetes. Depok: Fakultas Matematika da Ilmu Pengetahuan Alam UI; 2011. 39. Katzung BG. Farmakologi dasar dan klinik. Jakarta: Salemba Medika; 2002. p 677-678. 40. Raju SB, Rao, GB, Latha MY. Anti-hyperglycemic activity of Hygrophila spinosa roots in alloxan-induced diabetic rats. Int. J. Pharm Ind. Res 2011;14: 317-315. 41. Ramaiah A. Antidiabetic activity of methanolic extract of Memecylon Malabrium Cogn Melastomataceae Leaves. International Journal of Phytopharmacy 2013;21:12-9. Universitas Sumatera Utara 19 BAB 3 KERANGKA TEORI, KERANGKA KONSEP DAN HIPOTESIS

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