{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:30:56Z","timestamp":1792701056168,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006378","name":"Universitas Indonesia","doi-asserted-by":"publisher","award":["NKB-1328\/UN2.RST\/HKP.05.00\/2020"],"award-info":[{"award-number":["NKB-1328\/UN2.RST\/HKP.05.00\/2020"]}],"id":[{"id":"10.13039\/501100006378","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague\u2013Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&amp;E)\u2013Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.<\/jats:p>","DOI":"10.3390\/medicina59061044","type":"journal-article","created":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T15:29:52Z","timestamp":1685287792000},"page":"1044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model"],"prefix":"10.3390","volume":"59","author":[{"given":"Irena","family":"Ujianti","sequence":"first","affiliation":[{"name":"Departement of Medical Physiology, Faculty of Medicine, Universitas Muhammadiyah Prof. Dr. Hamka, Jakarta 121130, Indonesia"},{"name":"Graduate Student in Doctoral Program in Medical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imelda Rosalyn","family":"Sianipar","sequence":"additional","affiliation":[{"name":"Departement of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani Retno","family":"Prijanti","sequence":"additional","affiliation":[{"name":"Departement of Biochemistry and Molecular Biology, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irsan","family":"Hasan","sequence":"additional","affiliation":[{"name":"Departement of Internal Medicine, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wawaimuli","family":"Arozal","sequence":"additional","affiliation":[{"name":"Departement of Pharmacology and Therapeutic, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Aulia","family":"Jusuf","sequence":"additional","affiliation":[{"name":"Departement of Histology, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heri","family":"Wibowo","sequence":"additional","affiliation":[{"name":"Departement of Parasitology, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joedo","family":"Prihartono","sequence":"additional","affiliation":[{"name":"Departement of Community Medicine, Universitas Indonesia, Jakarta 10320, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patwa","family":"Amani","sequence":"additional","affiliation":[{"name":"Departement of Medical Physiology, Faculty of Medicine, Universitas Trisakti, Jakarta 11440, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewi Irawati Soeria","family":"Santoso","sequence":"additional","affiliation":[{"name":"Departement of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,28]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"14","author":"Younossi","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kanda, T., Goto, T., Hirotsu, Y., Masuzaki, R., Moriyama, M., and Omata, M. (2020). Molecular mechanisms: Connections between nonalcoholic fatty liver disease, steatohepatitis and hepatocellular carcinoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041525"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.18051\/UnivMed.2019.v38.194-201","article-title":"Low vitamin B12 diet increases liver homocysteine levels and leads to liver steatosis in rats","volume":"38","author":"Sianipar","year":"2019","journal-title":"Universa Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"020004","DOI":"10.1063\/1.5096672","article-title":"Developing vitamin B12 deficient rat model based on duration of restriction diet: Assessment of plasma vitamin B12, homocysteine (Hcy), and blood glucose levels","volume":"2092","author":"Sianipar","year":"2019","journal-title":"AIP Conf. Proc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108415","DOI":"10.1016\/j.jnutbio.2020.108415","article-title":"The deficit in folate and vitamin B12 triggers liver macrovesicular steatosis and inflammation in rats with dextran sodium sulfate-induced colitis","volume":"84","author":"Harb","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.endonu.2013.10.012","article-title":"Therapeutic potential of Hibiscus sabdariffa: A review of the scientific evidence","volume":"61","author":"Guardiola","year":"2014","journal-title":"Endocrinol. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1017\/S0029665115004218","article-title":"Polyphenols and non-alcoholic fatty liver disease: Impact and mechanisms","volume":"75","author":"Vauzour","year":"2016","journal-title":"Proc. Nutr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1039\/C5FO00714C","article-title":"Polyphenolic extract from Hibiscus sabdariffa reduces body fat by inhibiting hepatic lipogenesis and preadipocyte adipogenesis","volume":"7","author":"Kao","year":"2016","journal-title":"Food Funct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.fitote.2013.01.003","article-title":"Fitoterapia Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: A comprehensive review of animal and human studies","volume":"85","author":"Hopkins","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.foodchem.2014.05.002","article-title":"Hibiscus sabdariffa L.\u2014A phytochemical and pharmacological review","volume":"165","author":"Bonnlaender","year":"2014","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/ptr.6592","article-title":"Effect of Hibiscus sabdariffa (Roselle) supplementation in regulating blood lipids among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis","volume":"34","author":"Zhang","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1002\/jsfa.7254","article-title":"Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats","volume":"96","author":"Ajiboye","year":"2016","journal-title":"J. Sci. Food Agric."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ojulari, O.V., Lee, S.G., and Nam, J. (2019). Beneficial Effects of Natural Bioactive Compounds from Hibiscus sabdariffa L. on Obesity. Molecules, 24.","DOI":"10.3390\/molecules24010210"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/13880200590963934","article-title":"Effects of Aqueous Extracts of Petals of Red and Green Hibiscus sabdariffa on Plasma Lipid and Hematological Variables in Rats","volume":"43","author":"Olatunji","year":"2005","journal-title":"Pharm. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ai, Y., Sun, Z., Peng, C., Liu, L., Xiao, X., and Li, J. (2017). Homocysteine induces hepatic steatosis involving ER stress response in high methionine diet-fedmice. Nutrients, 9.","DOI":"10.3390\/nu9040346"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"192","DOI":"10.13181\/mji.v23i4.848","article-title":"Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat","volume":"23","author":"Andraini","year":"2015","journal-title":"Med. J. Indones."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jamrozik, D., Borymska, W., and Kaczmarczyk-\u017bebrowska, I. (2022). Hibiscus sabdariffa in Diabetes Prevention and Treatment\u2014Does It Work? An Evidence-Based Review. Foods, 11.","DOI":"10.3390\/foods11142134"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.55230\/mabjournal.v51i2.2164","article-title":"Consumption of Hibiscus sabdariffa Dried Calyx Ethanol Extract Improved Redox Imbalance and Glucose Plasma in Vitamin B12 Restriction Diet in Rats","volume":"51","author":"Ujianti","year":"2022","journal-title":"Malays. Appl. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/TP.0000000000002484","article-title":"Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver","volume":"103","author":"Younossi","year":"2019","journal-title":"Transplantation"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ueno, A., Hamano, T., Enomoto, S., Shirafuji, N., Nagata, M., Kimura, H., Ikawa, M., Yamamura, O., Yamanaka, D., and Ito, T. (2022). Influences of Vitamin B12 Supplementation on Cognition and Homocysteine in Patients with Vitamin B12 Deficiency and Cognitive Impairment. Nutrients, 14.","DOI":"10.3390\/nu14071494"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/fcp.12220","article-title":"Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms","volume":"30","author":"Souirti","year":"2016","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3945\/jn.114.199711","article-title":"L-serine supplementation attenuates alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats","volume":"145","author":"Sim","year":"2015","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1007\/s11356-020-10674-7","article-title":"Antiapoptotic and antioxidant capacity of phytochemicals from Roselle (Hibiscus sabdariffa) and their potential effects on monosodium glutamate-induced testicular damage in rat","volume":"28","author":"Gad","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1039\/c3fo30270a","article-title":"Hibiscus sabdariffa L. aqueous extract attenuates hepatic steatosis through down-regulation of PPAR-\u03b3 and SREBP-1c in diet-induced obese mice","volume":"4","year":"2013","journal-title":"Food Funct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1039\/c3fo60495k","article-title":"Hibiscus sabdariffa extract inhibits obesity and fat accumulation, and improves liver steatosis in humans","volume":"5","author":"Chang","year":"2014","journal-title":"Food Funct."},{"key":"ref_26","first-page":"6","article-title":"Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)","volume":"12","author":"Muniz","year":"2013","journal-title":"Nutr. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1271\/bbb.110579","article-title":"A polyphenol extract of Hibiscus sabdariffa L. Ameliorates acetaminophen-induced hepatic steatosis by attenuating the mitochondrial dysfunction In Vivo and In Vitro","volume":"76","author":"Lee","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molmed.2019.09.007","article-title":"NRF2: Redox and Metabolic Regulator of Stem Cell State and Function","volume":"26","author":"Dai","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1038\/s41598-022-11027-9","article-title":"Hibiscus sabdariffa extract improves hepatic steatosis, partially through IRS-1\/Akt and NRF2 signaling pathways in rats fed a high fat diet","volume":"12","author":"Prasomthong","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.apsb.2020.02.005","article-title":"NF-\u03baB\/HDAC1\/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis","volume":"10","author":"Guo","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_31","first-page":"395","article-title":"The effect of roselle flower petals extract (Hibiscus sabdariffa Linn.) on reducing inflammation in dextran sodium sulfateinduced colitis","volume":"17","author":"Lubis","year":"2020","journal-title":"Med. Glas."},{"key":"ref_32","first-page":"1","article-title":"Down-regulation of NFkB, Bax,TGF-\u03b2, Smad-2mRNA expression in the livers of carbon tetrachloride treated rats using different natural antioxidants","volume":"59","author":"Fadda","year":"2016","journal-title":"Braz. Arch. Biol. Technol."},{"key":"ref_33","unstructured":"Nurkhasanah (2015). The effect of rosella (Hibiscus sabdariffa L.) treatment on IL-10 and IL-14 secretion on dimethylbenz (A) anthracene (DMBA) induced rat. Int. J. Pharm. Pharm. Sci., 7, 402\u2013404."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.gene.2017.09.051","article-title":"Glucose regulated protein 78 is potentially an important player in the development of nonalcoholic steatohepatitis","volume":"637","author":"Zhou","year":"2017","journal-title":"Gene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2337\/db09-0755","article-title":"Grp78 heterozygosity promotes adaptive unfolded protein response and attenuates diet-induced obesity and insulin resistance","volume":"59","author":"Ye","year":"2010","journal-title":"Diabetes"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1044\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:00Z","timestamp":1760125440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,28]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["medicina59061044"],"URL":"https:\/\/doi.org\/10.3390\/medicina59061044","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,28]]}}}