Efek Ekstrak Etanol Daun Kipahit (Tithonia diversifolia) terhadap Kadar Gula Darah, Antioksidan (Malondialdehyde), Profil Lipid, HMG-CoA pada Tikus Putih Galur Wistar (Rattus norvegicus) yang Diinduksi Streptozotocin (STZ) dan High Fatty Diet (HFD)
Main Article Content
Diabetes melitus tipe 2 (DMT2) merupakan penyakit metabolik kronis dengan prevalensi global yang terus meningkat. Tithonia diversifolia (kipahit) mengandung senyawa bioaktif yang berpotensi sebagai antidiabetes. Penelitian ini bertujuan menganalisis efek ekstrak etanol daun kipahit terhadap gula darah, antioksidan (MDA), profil lipid, dan HMG-CoA pada tikus Wistar yang diinduksi STZ dan HFD. Penelitian eksperimental laboratorium dengan rancangan post-test only controlled group menggunakan 36 tikus dibagi menjadi 6 kelompok: kontrol normal, kontrol negatif (STZ+HFD), kontrol positif (STZ+HFD+metformin), dan 3 kelompok perlakuan dengan dosis 100, 150, dan 200 mg/kgBB. Parameter yang diukur meliputi berat badan, gula darah, MDA, profil lipid, dan HMG-CoA. Hasil menunjukkan efek signifikan: penurunan MDA (p=0,003) terutama pada dosis 100 mg/kgBB (8,91±3,90 µmol/L) dibanding kontrol diabetes (94,66±35,06 µmol/L); proteksi berat badan (p<0,001); efek hipoglikemik dengan dosis 200 mg/kgBB terbaik (112,17±13,50 mg/dL); perbaikan profil lipid dengan penurunan trigliserida (p=0,028), peningkatan HDL (p=0,042), dan penurunan LDL (p=0,028); tidak ada efek signifikan pada HMG-CoA (p=0,524). Molecular docking menunjukkan senyawa aktif memiliki afinitas pengikatan superior terhadap HMG-CoA dan leptin dibanding metformin. Tidak ada dosis tunggal optimal untuk semua parameter: dosis 100 mg/kgBB untuk antioksidan dan berat badan, 150 mg/kgBB untuk profil lipid, dan 200 mg/kgBB untuk kontrol glikemik. Hasil ini mendukung daun kipahit sebagai terapi komplementer potensial untuk pengelolaan diabetes melitus.
Keywords:
Tithonia Diversifolia, Diabetes Melitus, Antioksidan, Malondialdehyde, Profil Lipid, HMG-CoA, Streptozotocin, Molecular Docking
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Senudin, A. Y. (2016). Efek Hepatoprotektif Jangka Panjang Infusa Daun Insulin (Thitonia diversifolia) pada Tikus Jantan Galur Sprague Dawley Terinduksi Karbon Tetraklorida (Vol. 53).
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Stamler, J., Vaccaro, O., Neaton, J. D., & Wentworth, D. (1993). Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care, 16(2), 434–444.
Su, J., Luo, Y., Hu, S., Tang, L., & Ouyang, S. (2023). Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents. International Journal of Molecular Sciences, 24(17).
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Usti, O. M., F, B., & R, R. (2021). Efek Ekstrak Daun Paitan (Thitonia Diversifolia) Terhadap Penurunan Kadar Glukosa Darah pada Mencit (Mus Musculus) yang Diinduksi Aloksan. BRMJ: Baiturrahmah Medical Journal, 1(2), 1–10.
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Wszola, M., Klak, M., Kosowska, A., Tymicki, G., Berman, A., Adamiok-Ostrowska, A., & al., et. (2021). Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes. Biomedicines, 9(12).
Wu, L., & Parhofer, K. G. (2014). Diabetic dyslipidemia. Metabolism, 63(12), 1469–1479.
Zhang, J., Yakovlieva, L., de Haan, B. J., de Vos, P., Minnaard, A. J., Witte, M. D., & al., et. (2020). Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing ? Cells. Antibiotics (Basel, Switzerland), 9(4).
Zhu, B. T. (2022). Pathogenic Mechanism of Autoimmune Diabetes Mellitus in Humans: Potential Role of Streptozotocin-Induced Selective Autoimmunity against Human Islet ?-Cells. Cells, 11(3).
Bastaki, S. (2005). Diabetes mellitus and its treatment. International Journal of Diabetes and Metabolism, 13, 111–134.
Dilworth, L., Facey, A., & Omoruyi, F. (2021). Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. International Journal of Molecular Sciences, 22(14).
Federation, I. D. (2017). IDF Diabetes Atlas 8th Edition. International Diabetes Federation.
Federation, I. D. (2019). IDF Diabetes Atlas 9th edition. International Diabetes Federation.
Federation, I. D. (2021). IDF Diabetes Atlas (10th ed.). International Diabetes Federation.
González, P., Lozano, P., Ros, G., & Solano, F. (2023). Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. International Journal of Molecular Sciences, 24(11).
Haffner, S. M., Lehto, S., Rönnemaa, T., Pyörälä, K., & Laakso, M. (1998). Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. The New England Journal of Medicine, 339(4), 229–234.
Indonesia, K. K. R. (2013). Riset Kesehatan Dasar (Riskesdas) 2013.
Joseph, J. J., Deedwania, P., Acharya, T., Aguilar, D., Bhatt, D. L., Chyun, D. A., & al., et. (2022). Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation, 145(9), e722–e759.
Levine, J. H. (2006). Managing multiple cardiovascular risk factors: state of the science. Journal of Clinical Hypertension (Greenwich), 8(10 Suppl 3), 12–22.
Mane, K., Chaluvaraju, K., Niranjan, M., Zaranappa, T., & Manjuthej, T. (2012). Review of insulin and its analogues in diabetes mellitus. Journal of Basic and Clinical Pharmacy, 3(2), 283–293.
Mooradian, A. D. (2009). Dyslipidemia in type 2 diabetes mellitus. Nature Clinical Practice Endocrinology & Metabolism, 5(3), 150–159.
Parhofer, K. G. (2015). Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia. Diabetes & Metabolism Journal, 39(5), 353–362.
Pratiwi, D. B., Fitriyanto, R. E., & Utami, M. (2020). Pengaruh Pemberian Ekstrak Etanol Daun Kembang Bulan (Tithonia Diversifolia) Terhadap Kadar SGOT dan SGPT Tikus Galur Wistar yang Diinduksi Diabetes Melitus Dengan Streptozotosin. Prosiding Seminar Nasional Hasil Penelitian Dan Pengabdian Masyarakat, 1, 76–81.
Ramadhani, M. A., Hati, A. K., Lukitasari, N. F., & Jusman, A. H. (2020). Skrining Fitokimia Dan Penetapan Kadar Flavonoid Total Serta Fenolik Total Ekstrak Daun Insulin (Tithonia diversifolia) Dengan Maserasi Menggunakan Pelarut Etanol 96%. Indonesian Journal of Pharmaceutical and Natural Product, 3(1), 8–18.
Ramalho, A., & Petrica, J. (2023). The Quiet Epidemic: An Overview of Emerging Qualitative Research Trends on Sedentary Behavior in Aging Populations. Healthcare (Basel, Switzerland), 11(15).
Roep, B. O., Thomaidou, S., van Tienhoven, R., & Zaldumbide, A. (2021). Type 1 diabetes mellitus as a disease of the ?-cell (do not blame the immune system?). Nature Reviews Endocrinology, 17(3), 150–161.
Sahara, W. (2019). Uji Efek Ekstrak Etanol Daun Afrika (Vernonia Amygdalina Delile) Dan Ekstrak Etanol Daun Insulin (Tithonia Diversifolia (Hemsly) A Gray) Terhadap Penurunan Kadar Gula Darah Pada Tikus Putih Dengan Glibenklamid Sebagai Pembanding.
Sarwar, N., Gao, P., Seshasai, S. R. K., Gobin, R., Kaptoge, S., Di Angelantonio, E., & al., et. (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet (London, England), 375(9733), 2215–2222.
Sasmita, F. W., Susetyarini, E., Husamah, H., & Pantiwati, Y. (2017). Efek ekstrak daun kembang bulan (Tithonia diversifolia) terhadap kadar glukosa darah tikus wistar (Rattus norvegicus) yang diinduksi alloxan. Majalah Ilmiah Biologi Biosfera: A Scientific Journal, 34(1), 22–31.
Schofield, J. D., Liu, Y., Rao-Balakrishna, P., Malik, R. A., & Soran, H. (2016). Diabetes Dyslipidemia. Diabetes Therapy, 7(2), 203–219.
Senudin, A. Y. (2016). Efek Hepatoprotektif Jangka Panjang Infusa Daun Insulin (Thitonia diversifolia) pada Tikus Jantan Galur Sprague Dawley Terinduksi Karbon Tetraklorida (Vol. 53).
Sone, H., Takahashi, A., Shimano, H., Ishibashi, S., Yoshino, G., Morisaki, N., & al., et. (2002). HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes. Life Sciences, 71(20), 2403–2412.
Stamler, J., Vaccaro, O., Neaton, J. D., & Wentworth, D. (1993). Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care, 16(2), 434–444.
Su, J., Luo, Y., Hu, S., Tang, L., & Ouyang, S. (2023). Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents. International Journal of Molecular Sciences, 24(17).
Taskinen, M. R., & Borén, J. (2015). New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis, 239(2), 483–495.
Usti, O. M., F, B., & R, R. (2021). Efek Ekstrak Daun Paitan (Thitonia Diversifolia) Terhadap Penurunan Kadar Glukosa Darah pada Mencit (Mus Musculus) yang Diinduksi Aloksan. BRMJ: Baiturrahmah Medical Journal, 1(2), 1–10.
Utami, N. F., Mbete, F. N., & Effendi, E. M. (2020). Efektivitas Kombinasi Ekstrak Etanol 96% Daun Insulin (Tithonia diversifolia) dan Daun Sirsak (Annona muricata) Sebagai Antihiperglikemik Pada Mencit Putih Jantan. Fitofarmaka: Jurnal Ilmiah Farmasi, 10(2), 170–177.
Wszola, M., Klak, M., Kosowska, A., Tymicki, G., Berman, A., Adamiok-Ostrowska, A., & al., et. (2021). Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes. Biomedicines, 9(12).
Wu, L., & Parhofer, K. G. (2014). Diabetic dyslipidemia. Metabolism, 63(12), 1469–1479.
Zhang, J., Yakovlieva, L., de Haan, B. J., de Vos, P., Minnaard, A. J., Witte, M. D., & al., et. (2020). Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing ? Cells. Antibiotics (Basel, Switzerland), 9(4).
Zhu, B. T. (2022). Pathogenic Mechanism of Autoimmune Diabetes Mellitus in Humans: Potential Role of Streptozotocin-Induced Selective Autoimmunity against Human Islet ?-Cells. Cells, 11(3).
