eprintid: 56429 rev_number: 8 eprint_status: archive userid: 2314 dir: disk0/00/05/64/29 datestamp: 2026-09-16 09:23:19 lastmod: 2026-09-16 09:23:19 status_changed: 2026-09-16 09:23:19 type: thesis metadata_visibility: show creators_name: RARA NADIKA, RARA title: SKRIPSI-2210015037-RARA NADIKA-REPOSITORY ispublished: pub subjects: R subjects: Skripsi divisions: 11201 abstract: Obesitas merupakan kondisi patologis yang ditandai oleh akumulasi jaringan adiposa berlebih dan dikaitkan dengan peningkatan produksi reactive oxygen species (ROS) yang memicu stres oksidatif dan penurunan kadar glutathione (GSH). Holothuria atra merupakan spesies teripang yang mengandung senyawa bioaktif yang diduga mampu memodulasi kapasitas antioksidan endogen. Penelitian ini bertujuan untuk mengevaluasi efek pemberian ekstrak H. atra terhadap kadar GSH aorta pada tikus obesitas yang diinduksi high fat diet (HFD). Penelitian eksperimental in vivo ini menggunakan tikus jantan Sprague Dawley yang dibagi menjadi tiga kelompok: kelompok Pakan Normal, kelompok Pakan HFD, dan kelompok Pakan HFD+Ekstrak H. atra dengan dosis 300 mg/kgBB selama 6 minggu. Kadar GSH aorta diukur menggunakan metode ELISA. Hasil penelitian menunjukkan bahwa kadar GSH aorta kelompok Pakan HFD+Ekstrak H. atra secara signifikan lebih tinggi dibandingkan kelompok Pakan HFD (3,36 ± 0,15 μg/mL vs 1,70 ± 0,02 μg/mL; p < 0,001), meskipun belum mencapai kadar kelompok Pakan Normal (10,38 ± 1,08 μg/mL). Temuan ini mengindikasikan bahwa ekstrak H. atra berpotensi meningkatkan kapasitas antioksidan endogen pada jaringan aorta tikus obesitas. Kata kunci: glutathione, high fat diet, Holothuria atra, obesitas, Sprague Dawley date: 2026 date_type: published full_text_status: restricted institution: Universitas Muhammadiyah Prof. DR. Hamka department: PROGRAM STUDI PENDIDIKAN DOKTER thesis_type: bachelor thesis_name: bphil referencetext: Agoston, D. V. (2017). How to Translate Time? The Temporal Aspect of Human and Rodent Biology. Frontiers in Neurology, 8. https://doi.org/10.3389/fneur.2017.00092 Ahmed, B., Sultana, R., & Greene, M. W. (2021). Adipose tissue and insulin resistance in obese. Biomedicine & Pharmacotherapy, 137, 111315. https://doi.org/10.1016/j.biopha.2021.111315 Al’asyi, A., Ujianti, I., Nadika, R., Zahirah, Z., Faizin, B. J., Afifah, D. A., Farhan, R., Rahmadina, S. P., Lubis, R. ZN., Ghaisani, S., Arkananta, K., Lakshmi, B. S., & Pangestu, M. (2025). Exploring the potential of Holothuria atra extract in modulating fasting triglyceride index and obesity: In silico, in vitro and in vivo studies. Narra J, 5(3). https://doi.org/10.52225/narra.v5i3.2839 Aoyama, K. (2021). Glutathione in the Brain. International Journal of Molecular Sciences, 22(9), 5010. https://doi.org/10.3390/ijms22095010 Chai, Y. C., & Mieyal, J. J. (2023). Glutathione and Glutaredoxin—Key Players in Cellular Redox Homeostasis and Signaling. Antioxidants, 12(8), 1553. https://doi.org/10.3390/ANTIOX12081553 Chełchowska, M., Jurczewska, J., Gajewska, J., Mazur, J., Szostak-Węgierek, D., Rudnicka, E., & Ambroszkiewicz, J. (2023). Antioxidant Defense Expressed as Glutathione Status and Keap1-Nrf2 System Action in Relation to Anthropometric Parameters and Body Composition in Young Women with Polycystic Ovary Syndrome. Antioxidants, 12(3),730. https://doi.org/10.3390/antiox12030730 Cheng, H. S., Ton, S. H., Phang, S. C. W., Tan, J. B. L., & Abdul Kadir, K. (2017). Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome. Journal of Advanced Research, 8(6), 743– 752. https://doi.org/10.1016/j.jare.2017.10.002 Delwatta, S. L., Gunatilake, M., Baumans, V., Seneviratne, M. D., Dissanayaka, M. L. B., Batagoda, S. S., Udagedara, A. H., & Walpola, P. B. (2018). Reference values for selected hematological, biochemical and physiological parameters of Sprague‐Dawley rats at the Animal House, Faculty of Medicine, University of Colombo, Sri Lanka. Animal Models and Experimental Medicine, 1(4), 250–254. https://doi.org/10.1002/ame2.12041 Ejigu, B. A., & Tiruneh, F. N. (2023). The Link between Overweight/Obesity and Noncommunicable Diseases in Ethiopia: Evidences from Nationwide WHO STEPS Survey 2015. International Journal of Hypertension, 2023, 1–11. https://doi.org/10.1155/2023/2199853 Engin, A. (2017). Endothelial Dysfunction in Obesity (pp. 345– 379). https://doi.org/10.1007/978-3-319-48382-5_15 Fan, C., Ling-Hu, A., Sun, D., Gao, W., Zhang, C., Duan, X., Li, H., Tian, W., Yu, Q., & Ke, Z. (2023). Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease. Journal of Agricultural and Food Chemistry, 71(50), 20105 20117. https://doi.org/10.1021/acs.jafc.3c06498 Fu, M., Yoon, K.-S., Ha, J., Kang, I., & Choe, W. (2025). Crosstalk Between Antioxidants and Adipogenesis: Mechanistic Pathways and Their Roles in Metabolic Health. Antioxidants, 14(2), 203. https://doi.org/10.3390/antiox14020203 Haam, J.-H., Kim, B. T., Kim, E. M., Kwon, H., Kang, J.-H., Park, J. H., Kim, K.- K., Rhee, S. Y., Kim, Y.-H., & Lee, K. Y. (2023). Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity. Journal of Obesity & Metabolic Syndrome, 32(2), 121– 129. https://doi.org/10.7570/jomes23031 Han, X., Liu, P., Zheng, B., Zhang, M., Zhang, Y., Xue, Y., Liu, C., Chu, X., Wang, X., Sun, S., & Chu, L. (2022). 6-Gingerol exerts a protective effect against hypoxic injury through the p38/Nrf2/HO-1 and p38/NF-κB pathway in H9c2 cells. The Journal of Nutritional Biochemistry, 104, 108975. https://doi.org/10.1016/j.jnutbio.2022.108975 Han, X., Yang, Y., Zhang, M., Chu, X., Zheng, B., Liu, C., Xue, Y., Guan, S., Sun, S., & Jia, Q. (2022). Protective Effects of 6-Gingerol on Cardiotoxicity Induced by Arsenic Trioxide Through AMPK/SIRT1/PGC-1α Signaling Pathway. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.868393 He, J., & Hewett, S. J. (2025). Nrf2 Regulates Basal Glutathione Production in Astrocytes. International Journal of Molecular Sciences, 26(2), 687. https://doi.org/10.3390/ijms26020687 Hernandez-Quiles, M., Broekema, M. F., & Kalkhoven, E. (2021). PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action. Frontiers in Endocrinology, 12, 624112. https://doi.org/10.3389/fendo.2021.624112 Hoang, T. H., Liang, Q., Luo, X., Tang, Y., Qin, J. G., & Zhang, W. (2022). Bioactives From Marine Animals: Potential Benefits for Human Reproductive Health. Frontiers in Marine Science, 9. https://doi.org/10.3389/fmars.2022.872775 Hong, K. H., Um, M. Y., Ahn, J., & Ha, T. Y. (2023). 6-Gingerol Ameliorates Adiposity and Inflammation in Adipose Tissue in High Fat Diet-Induced Obese Mice: Association with Regulating of Adipokines. Nutrients, 15(15), 3457. https://doi.org/10.3390/nu15153457 Horwitz, A., & Birk, R. (2023). Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity—The Case of BBS Obesity. Nutrients, 15(15), 3445. https://doi.org/10.3390/NU15153445 IHME. (2024). Global Burden of Disease – Risk Factors: Age-standardized deaths from all causes attributed to high body-mass index per 100,000 people. IHME, Global Burden of Disease. https://ourworldindata.org/obesity Istiqomah, A., Istiqomah, A., Suryanti, S., Muskananfola, M. R., & Nisak, Y. K. (2025). Identifikasi Holothuria atra pada Ekosistem Lamun di Pulau Cemara Kecil Taman Nasional Karimunjawa. Jurnal Kelautan: Indonesian Journal of Marine Science and Technology, 18(2), 67– 77. https://doi.org/10.21107/jk.v18i2.22492 Jaganjac, M., Milkovic, L., Sunjic, S. B., & Zarkovic, N. (2020). The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies. Antioxidants, 9(11), 1151. https://doi.org/10.3390/ANTIOX9111151 Kalinina, E. (2024). Glutathione-Dependent Pathways in Cancer Cells. International Journal of Molecular Sciences, 25(15), 8423. https://doi.org/10.3390/ijms25158423 Kemenkes. (2025). Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/Menkes/509/2025 Tentang Pedoman Nasional Pelayanan Klinis Tata Laksana Obesitas Dewasa. Kementrian Kesehatan Repoblik Indonesia. https://keslan.kemkes.go.id/unduhan/KMK%20No.%20HK.01.07-MENKES- 509-2025.pdf Lee, Y.-H., Kim, S., Lee, S., Kim, K.-M., Jung, J.-C., Son, T., Ki, S., Seo, W.-D., Kwak, J.-H., Hong, J., & Jung, Y.-S. (2017). Antioxidant Effect of Barley Sprout Extract via Enhancement of Nuclear Factor-Erythroid 2 Related Factor 2 Activity and Glutathione Synthesis. Nutrients, 9(11), 1252. https://doi.org/10.3390/nu9111252 Li, W., Zeng, H., Xu, M., Huang, C., Tao, L., Li, J., Zhang, T., Chen, H., Xia, J., Li, C., & Li, X. (2021). Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.697483 Li, X., Ren, Y., Chang, K., Wu, W., Griffiths, H. R., Lu, S., & Gao, D. (2023). Adipose tissue macrophages as potential targets for obesity and metabolic diseases. Frontiers in Immunology, 14, 1153915. https://doi.org/10.3389/fimmu.2023.1153915 Li, Y., Cifuentes-Pagano, E., DeVallance, E. R., de Jesus, D. S., Sahoo, S., Meijles, D. N., Koes, D., Camacho, C. J., Ross, M., St Croix, C., & Pagano, P. J. (2019). NADPH oxidase 2 inhibitors CPP11G and CPP11H attenuate endothelial cell inflammation & vessel dysfunction and restore mouse hind-limb flow. Redox Biology, 22, 101143. https://doi.org/10.1016/j.redox.2019.101143 Lin, X., & Li, H. (2021). Obesity: Epidemiology, Pathophysiology, and Therapeutics. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.706978 Madla, C. M., Qin, Y., Gavins, F. K. H., Liu, J., Dou, L., Orlu, M., Murdan, S., Mai, Y., & Basit, A. W. (2022). Sex Differences in Intestinal P-Glycoprotein Expression in Wistar versus Sprague Dawley Rats. Pharmaceutics, 14(5), 1030. https://doi.org/10.3390/pharmaceutics14051030 Megawati, G., Syahruddin, S. S., Tjandra, W., Kusumawati, M., Herawati, D. M. D., Gurnida, D. A., & Musfiroh, I. (2023). Effects of Indonesian Shortfin Eel (Anguilla bicolor) By-Product Oil Supplementation on HOMA-IR and Lipid Profile in Obese Male Wistar Rats. Nutrients, 15(18), 3904. https://doi.org/10.3390/nu15183904 Mi, R., Fu, Z., Jiang, J., Gao, S., Guan, X., Wang, X., & Zhou, Z. (2024). Sea Cucumber Viscera Processed by Protease Hydrolysis Combined with Cordyceps militaris Fermentation Protect Caco-2 Cells against Oxidative Damage via Enhancing Antioxidant Capacity, Activating Nrf2/HO-1 Pathway and Improving Cell Metabolism. Antioxidants, 13(8), 988. https://doi.org/10.3390/antiox13080988 Miranda, J., Eseberri, I., Lasa, A., & Portillo, M. P. (2018). Lipid metabolism in adipose tissue and liver from diet-induced obese rats: a comparison between Wistar and Sprague-Dawley strains. Journal of Physiology and Biochemistry, 74(4), 655–666. https://doi.org/10.1007/s13105-018-0654-9 Morawietz, H., Brendel, H., Diaba-Nuhoho, P., Catar, R., Perakakis, N., Wolfrum, C., & Bornstein, S. R. (2023). Cross-Talk of NADPH Oxidases and Inflammation in Obesity. Antioxidants, 12(8), 1589. https://doi.org/10.3390/antiox12081589 Naomi, R., Teoh, S. H., Embong, H., Balan, S. S., Othman, F., Bahari, H., & Yazid, M. D. (2023). The Role of Oxidative Stress and Inflammation in Obesity and Its Impact on Cognitive Impairments—A Narrative Review. Antioxidants, 12(5), 1071. https://doi.org/10.3390/antiox12051071 Ngo, V., & Duennwald, M. L. (2022). Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants, 11(12), 2345. https://doi.org/10.3390/antiox11122345 Oh, S. S., & Narver, H. L. (2024). Mouse and Rat Anesthesia and Analgesia. Current Protocols, 4(2). https://doi.org/10.1002/cpz1.995 Pan, H., Guo, R., Zhu, J., Wang, Q., Ju, Y., Xie, Y., Zheng, Y., Wang, Z., Li, T., Liu, Z., Lu, L., Li, F., Tong, B., Xiao, L., Xu, X., Li, R., Yuan, Z., Yang, H., Wang, J., … Liu, L. (2018). A gene catalogue of the Sprague-Dawley rat gut metagenome. GigaScience, 7(5). https://doi.org/10.1093/gigascience/giy055 Pangestuti, R., & Arifin, Z. (2017). Medicinal and health benefit effects of functional sea cucumbers. Journal of Traditional and Complementary Medicine, 8(3), 341. https://doi.org/10.1016/J.JTCME.2017.06.007 Peng, Z., Zeng, Y., Zeng, X., Tan, Q., He, Q., Wang, S., & Wang, J. (2024). 6-Gingerol improves lipid metabolism disorders in skeletal muscle by regulating AdipoR1/AMPK signaling pathway. Biomedicine & Pharmacotherapy, 180, 117462. https://doi.org/10.1016/j.biopha.2024.117462 Permata, P., Suryono, S., Lokollo, F. F., Widianingsih, W., Endrawati, H., Zainuri, M., & Hartati, R. (2021). Hubungan Panjang Berat Teripang Holothuria atra di Pulau Panjang, Jepara. Buletin Oseanografi Marina, 10(2), 123–132. https://doi.org/10.14710/BULOMA.V10I2.36380 Ritchie, H., & Rose, M. (2024, January). Obesity. Our World in Data. https://ourworldindata. org/obesity Santacroce, G., Gentile, A., Soriano, S., Novelli, A., Lenti, M. V., & Di Sabatino, A. (2023). Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease. Frontiers in Medicine, 10, 1124275. https://doi.org/10.3389/FMED.2023.1124275 Scirè, A., Casari, G., Romaldi, B., de Bari, L., Antognelli, C., & Armeni, T. (2023). Glutathionyl Hemoglobin and Its Emerging Role as a Clinical Biomarker of Chronic Oxidative Stress. Antioxidants 2023, Vol. 12, Page 1976, 12(11), 1976. https://doi.org/10.3390/ANTIOX12111976 Setyastuti, A., Wirawati, I., & Iswari, M. Y. (2018). Identification and distribution of sea cucumber exploited in Lampung, Indonesia. Biodiversitas Journal of Biological Diversity, 19(2), 676– 682. https://doi.org/10.13057/biodiv/ d190247 Setyastuti, A., Wirawati, I., Permadi, S., & Vimono, I. B. (2019). Jenis, Sebaran, dan Status Nilai Ekonomi TERIPANG INDONESIA. PT. Media Sains Nasional. Ujianti, I., Lakhsmi, B. S., Nurusshofa, Z., & Stujanna, E. N. (2023). Bioactive Compound of Holothoroidea. Widina Media Utama. Ujianti, I., Lakshmi, B. S., Nurushoffa, Z., & Stujanna, E. N. (2023). Bioactive Compound of Holothoroidea. Environmental Science, Biology. Ujianti, I., Semara Lakshmi, B., Nurusshofa, Z., Sukarya, W., & Indriyanti, L. (2023). Network Pharmacology Analysis Reveals Bioactive Compounds and Potential Targets of Sea cucumber for Cervical Cancer Therapy. F1000Research, 12, 1358. https://doi.org/10.12688/f1000research.138298.1 Utomo, H. S., Effendi, A., Simangunsong, S. P., Staf, S., Komando, D., & Laut, A. (2025). Potensi dan Tantangan Indonesia sebagai Negara Maritim dalam Mewujudkan Poros Maritim Dunia. Journal of Knowledge and Collaboration, 12230(2), 3. https://ojs.arbain.co.id/index.php/jkc/index Vilchis-Landeros, M. M., Vázquez-Meza, H., Vázquez-Carrada, M., Uribe-Ramírez, D., & Matuz-Mares, D. (2024). Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment. International Journal of Molecular Sciences, 25(11), 5675. https://doi.org/10.3390/IJMS25115675/S1 Wang, J., Li, D., Wang, P., Hu, X., & Chen, F. (2019). Ginger prevents obesity through regulation of energy metabolism and activation of browning in highfat diet-induced obese mice. The Journal of Nutritional Biochemistry, 70, 105– 115. https://doi.org/10.1016/j.jnutbio.2019.05.001 Wang, S., Song, X., Gao, H., Zhang, Y., Zhou, X., & Wang, F. (2025). 6-Gingerol Inhibits Ferroptosis in Endothelial Cells in Atherosclerosis by Activating the NRF2/HO-1 Pathway. Applied Biochemistry and Biotechnology, 197(6), 3890–3906. https://doi.org/10.1007/s12010-025-05214-3 Wang, T., Zheng, L., Liu, X., & Zhao, M. (2023). Sea cucumber (Holothuria nobilis) hydrolysates improve diabetic nephropathy via suppression of oxidative stress in high-fat diet/streptozotocin-induced diabetic rats. Journal of Functional Foods, 106, 105589. https://doi.org/10.1016/j.jff.2023.105589 Wargasetia, T. L., Ratnawati, H., Widodo, N., & Widyananda, M. H. (2023a). Antioxidant and Anti-inflammatory Activity of Sea Cucumber ( Holothuria scabra) Active Compounds against KEAP1 and iNOS Protein. Bioinformatics and Biology Insights, 17. https://doi.org/10.1177/11779322221149613 Wen, L., Li, R., Zhao, Y. C., Yang, J. Y., X. Y, Xue, C. H., & Wang, Y. M. (2022). comparative study of the anti-obesity effects of dietary sea cucumber saponins and energy restriction in response to weight loss and weight regain in mice. Marine Drugs, 20(10), 629. WHO. (2025, May 7). Obesity and overweight. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight Xiao, W., & Loscalzo, J. (2020). Metabolic Responses to Reductive Stress. Antioxidants & Redox Signaling, 32(18), 1330– 1347. https://doi.org/10.1089/ars.2019.7803 Yang, K., Lu, Y., Yue, Z., Jin, S., Wang, P., Liu, C., Wang, L., Yin, Q., Dang, X., Guo, H., & Chang, J. (2024). 6-Gingerol activates the Nrf2 signaling pathway to alleviate hydrogen peroxide induced oxidative stress on primary chicken embryo hepatocytes. Journal of Functional Foods, 122, 106535. https://doi.org/10.1016/j.jff.2024.106535 Yao, J., Wu, D., & Qiu, Y. (2022). Adipose tissue macrophage in obesity-associated metabolic diseases. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.977485 Zhao, Y., Wang, H., Zhou, J., & Shao, Q. (2022). Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer. Cancers 2022, Vol. 14, Page 2560, 14(10), 2560. https://doi.org/10.3390/CANCERS14102560 citation: RARA NADIKA, RARA (2026) SKRIPSI-2210015037-RARA NADIKA-REPOSITORY. Bachelor thesis, Universitas Muhammadiyah Prof. DR. Hamka. document_url: http://repository.uhamka.ac.id/id/eprint/56429/1/SKRIPSI-2210015037-RARA%20NADIKA-REPOSITORY.pdf