Dose-dependent anticholesterol effects of Fuji apple simplicia in a rat model of metabolic syndrome
Abstract
Background: Metabolic syndrome-associated dyslipidemia increases cardiovascular disease risk. Fuji apples (Malus domestica) contain bioactive compounds that may modulate cholesterol metabolism.
Objective: To evaluate dose-dependent anticholesterol effects of Fuji apple simplicia in metabolic syndrome rats.
Methods: Thirty male Wistar rats were allocated into five groups (n=6): negative control, positive control (metabolic syndrome without treatment), and three treatment groups receiving simplicia at 150, 300, or 450 mg/200 g body weight/day for 28 days. Metabolic syndrome was induced using high-fat diet and streptozotocin-nicotinamide injection. Total cholesterol was measured using enzymatic colorimetric assay and analyzed using mixed ANOVA.
Results: Simplicia produced significant dose-dependent cholesterol reductions compared to positive control (p<0.001). Reductions were 71.77 mg/dL (34.09%), 100.53 mg/dL (47.78%), and 112.02 mg/dL (52.75%) at doses of 150, 300, and 450 mg/200 g body weight/day, respectively.
Conclusion: Fuji apple simplicia exhibits significant anticholesterol activity in metabolic syndrome rats through a dose-dependent mechanism, supporting its potential as a complementary intervention for hypercholesterolemia management in metabolic syndrome.
References
Islam MS, Wei P, Suzauddula M, Nime I, Feroz F, Acharjee M, et al. (2024) The interplay of factors in metabolic syndrome: Understanding its roots and complexity. Mol Med 30(1): 279. https://doi.org/10.1186/s10020-024-01019-y
Krishnamoorthy Y, Rajaa S, Murali S, Sahoo J, Kar SS (2022) Association between anthropometric risk factors and metabolic syndrome among adults in India: A systematic review and meta-analysis of observational studies. Prev Chronic Dis 19: e1. https://doi.org/10.5888/pcd19.210231
Mohamed SM, Shalaby MA, El-Shiekh RA, El-Banna HA, Emam SR, Bakr AF (2023) Metabolic syndrome: Risk factors, diagnosis, pathogenesis, and management with natural approaches. Food Chem Adv 3: 100268. https://doi.org/10.1016/j.focha.2023.100335
Kementerian Kesehatan Republik Indonesia (2023) Survei Kesehatan Indonesia 2023. Jakarta: Kementerian Kesehatan Republik Indonesia.
Kementerian Kesehatan Republik Indonesia (2013) Laporan Nasional RISKESDAS 2013. Jakarta: Kementerian Kesehatan Republik Indonesia.
Kementerian Kesehatan Republik Indonesia (2018) Laporan Nasional RISKESDAS 2018. Jakarta: Kementerian Kesehatan Republik Indonesia.
Sigit FS, Tahapary DL, Trompet S, Sartono E, Willems Van Dijk K, Rosendaal FR, et al. (2020) The prevalence of metabolic syndrome and its association with body fat distribution in middle-aged individuals from Indonesia and the Netherlands: A cross-sectional analysis of two population-based studies. Diabetol Metab Syndr 12(1): 101. https://doi.org/10.1186/s13098-019-0503-1
Chu SY, Jung JH, Park MJ, Kim SH (2019) Risk assessment of metabolic syndrome in adolescents using the triglyceride/high-density lipoprotein cholesterol ratio and the total cholesterol/high-density lipoprotein cholesterol ratio. Ann Pediatr Endocrinol Metab 24(1): 41-48. https://doi.org/10.6065/apem.2019.24.1.41
Huang G, Xu J, Zhang Z, Cai L, Liu H, Yu X (2022) Total cholesterol and high density lipoprotein cholesterol ratio is associated with metabolic syndrome in a very elderly Chinese population. Sci Rep 12(1): 15541. https://doi.org/10.1038/s41598-022-19445-5
Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, et al. (2024) A systematic review of metabolic syndrome: Key correlated pathologies and non-invasive diagnostic approaches. J Clin Med 13(21): 6368. https://doi.org/10.3390/jcm13195880
Masenga SK, Kabwe LS, Chakulya M, Kirabo A (2023) Mechanisms of oxidative stress in metabolic syndrome. Int J Mol Sci 24(21): 15873. https://doi.org/10.3390/ijms24097898
Javor E, Šarčevéč D, Rešić A (2024) Metabolic syndrome and pharmacological interventions in clinical development. Diabetology 5(4): 300-320. https://doi.org/10.3390/diabetology5030023
Islam SU, Ahmed MB, Ahsan H, Lee YS (2021) Recent molecular mechanisms and beneficial effects of phytochemicals and plant-based whole foods in reducing LDL-C and preventing cardiovascular disease. Antioxidants 10(7): 1036. https://doi.org/10.3390/antiox10050784
Rodríguez-Negrete EV, Morales-González Á, Madrigal-Santillán EO, Sánchez-Reyes K, Álvarez-González I, Madrigal-Bujaidar E, et al. (2024) Phytochemicals and their usefulness in the maintenance of health. Plants 13(2): 286. https://doi.org/10.3390/plants13040523
Koutsos A, Riccadonna S, Ulaszewska MM, Franceschi P, Trošt K, Galvin A, et al. (2020) Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: A randomized, controlled, crossover trial. Am J Clin Nutr 111(2): 307-318. https://doi.org/10.1093/ajcn/nqz282
Kim SJ, Anh NH, Jung CW, Long NP, Park S, Cho YH, et al. (2022) Metabolic and cardiovascular benefits of apple and apple-derived products: A systematic review and meta-analysis of randomized controlled trials. Front Nutr 9: 890677. https://doi.org/10.3389/fnut.2022.766155
Harsono RDA, Dewi YLR, Lestari A (2022) Effects of Fuji apple juice on total cholesterol levels in hypercholesterolemic elderly people. Nutr Food Sci Res 9(1): 15-18. https://doi.org/10.52547/nfsr.9.1.15
Elshaafi IM, Musa KH, Abdullah Sani N (2020) Effect of oven and freeze drying on antioxidant activity, total phenolic and total flavonoid contents of fig (Ficus carica L.) leaves. Food Res 4(6): 2114-2121. https://doi.org/10.26656/fr.2017.4(6).072
Cozzolino R, Palumbo M, Cefola M, Capotorto I, Linsalata V, Forte G, et al. (2022) Biochemical characterization of apple slices dried using low temperature and stored in modified atmosphere packaging. J Food Compos Anal 112: 104924. https://doi.org/10.1016/j.jfca.2022.104694
Wahyuni TS, Khoiriyah N, Tumewu L, Ekasari W, Fuad A, Widyawaruyanti A. Microscopic and physicochemical evaluation of Ruta angustifolia leaves. J Public Health Afr. 2023 Mar 16;14(Suppl 1):2520. https://doi.org/10.4081/jphia.2023.2520
Debnath A, Ali MA, Newmai K, Madhuri P, Azyu RZ (2024) Effective management of Wistar rats in laboratory research: A brief review. Int J Adv Biochem Res 8(12S): 654-659. https://doi.org/10.33545/26174693.2024.v8.i12Si.3182
de Farias LM, da Silva LAA, de Azevedo MAF, Monteiro NV do N, Maiía Guimarães Silva MGS, Mendes VR, et al. (2023) Effect of chronic apple consumption (Malus domestica Borkh.) on the lipid profile of adults with dyslipidemia: A systematic review. Explor Foods Foodomics 5: 288-299. https://doi.org/10.37349/eff.2023.00022
Aprikian O, Duclos V, Guyot S, Besson C, Manach C, Bernalier A, et al. (2003) Apple pectin and a polyphenol-rich apple concentrate are more effective together than separately on cecal fermentations and plasma lipids in rats. J Nutr 133(10): 3057-3064. https://doi.org/10.1093/jn/133.6.1860
Laurence DR, Bacharach AL (1964) Evaluation of drug activities: Pharmacometrics. London: Academic Press.
Shoji T, Akazome Y, Kanda T, Ikeda M (2004) The toxicology and safety of apple polyphenol extract. Food Chem Toxicol 42(6): 959-967. https://doi.org/10.1016/j.fct.2004.02.008
Ritschel WA (1974) Laboratory manual of biopharmaceutics and pharmacokinetics. Ridgeway: Drug Intelligence Publications.
Amriani A, Fitrya, Novita RP, Caniago D (2021) Uji aktivitas antidiabetes ekstrak etanol akar kabau (Archidendron bubalinum (Jack) I.C. Nielsen) terhadap tikus putih jantan yang diinduksi diet tinggi lemak dan fruktosa. J Penelit Sains 23(2): 102-109. https://doi.org/10.56064/jps.v23i2.635
Pepi S, Talarico L, Leone G, Bonechi C, Tamasi G, Consumi M, et al. (2023) Effect of Annurca apple extract on anti-hyper cholesterol action of a RYR based formulation. Int J Drug Deliv Technol 13(4): 1145-1150. https://doi.org/10.25258/ijddt.13.4.03
Tamura Y, Tomiya S, Takegaki J, Kouzaki K, Tsutaki A, Nakazato K (2020) Apple polyphenols induce browning of white adipose tissue. J Nutr Biochem 77: 108195. https://doi.org/10.1016/j.jnutbio.2019.108299
Skinner RC, Warren DC, Lateef SN, Benedito VA, Tou JC (2018) Apple pomace consumption favorably alters hepatic lipid metabolism in young female Sprague-Dawley rats fed a western diet. Nutrients 10(12): 1807. https://doi.org/10.3390/nu10121882
Fu R, Tang W, Zhang H, Chang H, Chen W (2021) Effects of apple polyphenol on fat metabolism in mice. E3S Web Confer 275: 01038. https://doi.org/10.1051/e3sconf/202126702025
Chambers KF, Day PE, Aboufarrag HT, Kroon PA (2019) Polyphenol effects on cholesterol metabolism via bile acid biosynthesis, CYP7A1: A review. Nutrients 11(12): 2873. https://doi.org/10.3390/nu11112588
Alqarni S, Alsebai M, Alsaigh BA, Alrashedy AS, Albahrani IT, Aljohar AY, et al. (2024) Do polyphenols affect body fat and/or glucose metabolism? Front Nutr 11: 1321891. https://doi.org/10.3389/fnut.2024.1376508
Iqbal I, Wilairatana P, Saqib F, Nasir B, Wahid M, Latif MF, et al. (2023) Plant polyphenols and their potential benefits on cardiovascular health: A review. Molecules 28(14): 5649. https://doi.org/10.3390/molecules28176403
Suman RK, Ray Mohanty I, Borde MK, Maheshwari U, Deshmukh YA (2016) Development of an experimental model of diabetes co-existing with metabolic syndrome in rats. Adv Pharmacol Sci 2016: 3568129. https://doi.org/10.1155/2016/9463476
Hernández-Díazcouder A, Romero-Nava R, Carbó R, Sánchez-Lozada LG, Sánchez-Muñoz F (2019) High fructose intake and adipogenesis. Int J Mol Sci 20(18): 4456. https://doi.org/10.3390/ijms20112787
Moughaizel M, Dagher E, Jablaoui A, Thorin C, Rhimi M, Desfontis JC, et al. (2022) Long-term high-fructose high-fat diet feeding elicits insulin resistance, exacerbates dyslipidemia and induces gut microbiota dysbiosis in WHHL rabbits. PLoS One 17(2): e0263184. https://doi.org/10.1371/journal.pone.0264215
Dutta B, Tripathy A, Archana PR, Kamath SU (2025) Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome. Diabetol Metab Syndr 17(1): 32. https://doi.org/10.1186/s13098-025-01837-y
Gunawan S, Aulia A, Soetikno V (2021) Development of rat metabolic syndrome models: A review. Vet World 14(7): 1774-1783. https://doi.org/10.14202/vetworld.2021.1774-1783
Wang DX, Qing SL, Miao ZW, Luo HY, Tian JS, Zhang XP, et al. (2023) Hepatic Nampt deficiency aggravates dyslipidemia and fatty liver in high fat diet fed mice. Cells 12(4): 586. https://doi.org/10.3390/cells12040568
Yu CHJ, Kienesberger PC, Pulinilkunnil T, Rupasinghe HPV (2023) Effect of (poly)phenol-rich 'Daux Belan' apple supplementation on diet-induced obesity and glucose intolerance in C57BL/6NCrl mice. Sci Rep 13(1): 4519. https://doi.org/10.1038/s41598-023-43687-6
Duan Y, Gong K, Xu S, Zhang F, Meng X, Han J (2022) Regulation of cholesterol homeostasis in health and diseases: From mechanisms to targeted therapeutics. Signal Transduct Target Ther 7(1): 265. https://doi.org/10.1038/s41392-022-01125-5
Copyright (c) 2026 Authors

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
