UJI AKTIVITAS HIPOGLIKEMIK FRAKSI ETANOL DAN RESIDU DEKOKTA HERBA SAMBILOTO (Andrographis paniculata (Burm.f.) Ness) MELALUI AKSI ANTIOKSIDAN DAN PENINGKATAN TRANSLOKASI PROTEIN GLUT-4 PADA TIKUS RESISTEN INSULIN

HADI KURNIAWAN, Prof. Dr. Agung Endro Nugroho, M.Si., Apt.

2014 | Tesis | S2 Ilmu Farmasi

Gaya hidup tidak sehat dapat meningkatkan risiko terjadinya diabetes mellitus (DM) tipe 2 resisten insulin. Kondisi obesitas (hiperlipidemia) dapat mengakibatkan gangguan sinyal translokasi protein GLUT-4 pada membran sel otot sehingga memacu hiperglikemia dan hiperinsulinemia. Hiperglikemik yang berkepanjangan menyebabkan terjadinya peningkatan stres oksidatif dan produksi radikal bebas berlebih. Penelitian ini bertujuan mengevaluasi pengaruh fraksi etanol dan residu dekokta herba sambiloto (Andrographis paniculata (Burm.f.) Nees.) yang diduga mengandung flavonoid sebagai antioksidan dan antiDM tipe 2 pada tikus resisten insulin. Hewan uji DM tipe 2 resisten insulin diinduksi dengan diet kaya lemak dan fruktosa peroral selama 120 hari. Kondisi resisten insulin ditetapkan dengan membandingkan nilai parameter resisten insulin hewan uji normal dan hewan uji induksi kaya lemak-fruktosa. Dari hasil analisis statistik menggunakan Independent Sample-t Test pada seluruh parameter resisten insulin menunjukkan bahwa tikus terinduksi diet kaya lemak-fruktosa terindikasi DM tipe 2 resisten insulin. Setelah hewan uji dinyatakan resisten insulin, hewan uji diberi perlakuan fraksi etanol dan residu dekokta herba sambiloto selama 14 hari lalu dilakukan analisis data dan statistik. Penurunan kadar glukosa kelompok kontrol positif, fraksi etanol dosis 225 dan 675 mg/kgBB serta fraksi residu dekokta dosis 675 mg/kgBB berbeda signifikan antara hari ke-120 dengan hari ke-127 dan 134. Persen daya hipoglikemik menunjukkan fraksi etanol dekokta dosis 225 mg/kgBB (63,45±0,67%) memiliki daya hipoglikemik preprandial terbaik sedangkan daya hipoglikemik postprandial dimiliki oleh fraksi etanol dekokta dosis 225 mg/kgBB (68,29±0,63%) dan fraksi etanol dekokta dosis 675 mg/kgBB (64,61±0,41%) setelah perlakuan 14 hari. Sementara hasil kuantifikasi translokasi protein GLUT- 4 menunjukkan bahwa kelompok fraksi etanol dekokta dosis 225 mg/kgBB mampu meningkatkan translokasi protein GLUT-4 secara signifikan. Fraksi etanol dan fraksi residu dekokta memiliki aktivitas antioksidan lemah dengan IC50 berturut-turut 632,08±15,92 dan 3.870,88±177,12 ppm dengan kadar flavonoid total masing-masing 5,13±0,07 dan 2,05±0,02%.

Unhealthy lifestyle can increase the risk of diabetes mellitus (DM) type 2 insulin resistance. Obesity (hiperlipidemia) conditions which can lead signals disorder of GLUT-4 protein translocation to the membrane of the muscle cells that can stimulate hyperglycemia and hyperinsulinemia. The protracted hyperglycemic causes increased oxidative stress and excessive production of free radicals. This research aimed to evaluate the effect of ethanol fraction and decocta residual of herbaceous sambiloto (Andrographis paniculata (Burm.f.) Nees) which was suspected contain flavonoid as antioxidants and anti- DM type 2 in insulin resistance rats. Animal of DM type 2 insulin resistances were induced by a high fat diet and fructose for 120 days. Insulin resistance conditions were determined by comparing the parameters value of normal animal experiment of insulin resistance and induction of animal experiment with high fat fructose diet. From the results of statistical analyzes by using independent sample t-test on all parameters of insulin resistance showed that a diet of high fat-fructose of rats induction was indicated the insulin-resistant of diabetes mellitus type 2. After experimental animals were clarified as insulin resistant, the animals were treated with fractions of ethanol and decocta residual of herbaceous sambiloto for 14 days, than data and statistic were analyzed. The decreasing of glucose levels of positive control, ethanol fraction with dose 225 and 675 mg/kgBW and decocta residual fraction groups was differed significantly between day 120 to day 127 and 134. Percentage of power hypoglycemic showed decocta ethanol fraction with dose 225 mg/kgBB (63.45±0.67%) had the best pre-prandial of power hypoglycemic whereas postprandial of power hypoglycemic was possessed by decocta ethanol fraction with dose 225 mg/kgBB (68.29±0.63%) and fraction of ethanol decocta with dose 675 mg/kgBB (64.61±0.41%) after 14 days of treatment. While the results of quantification of the protein translocation of GLUT-4 showed that the fraction of the decocta ethanol group with dose 225 mg/kg was able to increase the translocation of GLUT-4 protein significantly. Ethanol fraction and residual decocta fraction have weak antioxidant activity with IC50 successively 632.08±15.92 and 3,870.88±177.12 ppm with total flavonoid levels of each 5.13±0.07 and 2.05±0.02%.

Kata Kunci : A. paniculata, flavonoid, resisten insulin, protein GLUT-4, antioksidan