Cardioprotective Activity of Propionic Acid in High-Fat Diet/ Streptozotocin-Induced Cardiotoxicity in Diabetic Rats Model
DOI:
https://doi.org/10.31674/mjmr.2026.v010i01.003Abstract
Background: The healthcare sector is increasingly focusing on the discovery of toxic-free natural medicines to treat diabetes-related complications. The current study investigated the cardioprotective efficacy of propionic acid (PA) in a type 2 diabetic rat model. Methods: Twenty-five Wistar rats (200–300 g) were used. The rats were fed a high-fat diet for 8 weeks, and streptozotocin (30 mg/kg b.wt) was injected intraperitoneally to induce diabetes. The animals were divided into 5 groups (n = 5) and treated for 4 weeks. Group 1: normal control; Group 2: normal control + PA (60 mg/kg b.wt); Group 3: diabetic; Group 4: diabetic + PA (60 mg/kg b.wt); Group 5: diabetic + metformin (200 mg/kg b.wt). Serum and supernatant plasma retrieved from blood samples, along with heart tissue homogenate after centrifugation, were used to determine biochemical parameters. Results: Propionic acid administration significantly (p < 0.05) reduced serum insulin, fasting blood glucose, oral glucose tolerance, cardiac creatine kinase-myoglobin, troponin-I, Lactate dehydrogenase, brain natriuretic peptide, caspase-3, triglycerides, total cholesterol, low-density lipoprotein cholesterol, oxidative malondialdehyde, tumor necrosis factor-α, interleukin-1β, interleukin-6, heart rate, blood pressure, QT and QTc intervals, QRS interval, PR interval, and food and water intake. It also significantly increased cardiac B-cell lymphoma-2, superoxide dismutase, catalase, reduced glutathione, high-density lipoprotein cholesterol, P-wave, and body and heart weight in diabetic rats. Conclusion: Propionic acid lowered hyperglycemia and prevented cardiac injury by suppressing elevated cardiac injury markers, oxidative stress, and inflammation. Propionic acid may be useful as a natural medication for treating cardiac ailments in diabetes.
Keywords:
Cardiac, Diabetes Mellitus, Inflammation, Oxidative Stress, Propionic AcidDownloads
References
Ajao, F.O., Iyedupe, M.O., Oneosinina, A.R., Olaolu, K.N., & Isaac, A.T. (2023). Molecular docking and admet properties of Anacardium occidentale methanolic nut extract against inflammatory, oxidative and apoptotic markers of diabetes. Journal of Medical Sciences, 93(3), e885. https://doi.org/10.20883/medical.e885
Akhtar, M. S., Alavudeen, S. S., Raza, A., Imam, M. T., Almalki, Z. S., Tabassum, F., & Iqbal, M. J. (2023). Current understanding of structural and molecular changes in diabetic cardiomyopathy. Life Sciences, 332, 122087. https://doi.org/10.1016/j.lfs.2023.122087
Almalki, N. A., Al-Abbasi, F. A., Moglad, E., Afzal, M., Al-Qahtani, S. D., Alzarea, S. I., ... & Kazmi, I. (2024). Protective activity of hirsutidin in high-fat intake and streptozotocin-induced diabetic rats: In silico and in vivo study. Heliyon, 10(19). https://doi.org/10.1016/j.heliyon.2024.e38625
Ansari, P., Khan, J. T., Chowdhury, S., Reberio, A. D., Kumar, S., Seidel, V., ... & Flatt, P. R. (2024). Plant-based diets and phytochemicals in the management of diabetes mellitus and prevention of its complications: A review. Nutrients, 16(21), 3709. https://doi.org/10.3390/nu16213709
Attanasio, U., Mercurio, V., & Fazio, S. (2024). Insulin Resistance with Associated Hyperinsulinemia as a Cause of the Development and Worsening of Heart Failure. Biomedicines, 12(12), 2890. https://doi.org/10.3390/biomedicines12122890
Barka, C.E., Bensenane, B., Merzouk, H., Mebarki, A., Haddam, H.Y., Berroukeche, F., & Mokhatri-Soulimane, N. (2024). Antidiabetic Effects of Coffee Silverskin Extract in Streptozotocin-Induced Diabetic Wistar Rats. Waste Biomass Valorization, 15, 5219–5234. https://doi.org/10.1007/s12649-024-02504-5.
Brito, L. B., Leal, B. O., Silva, J. R. D., Barbosa, K. M. P., Silva, V. T. D., Costa, A. S., ... & Araújo, M. F. M. D. (2025). Efecto del consumo de galletas a base de harina de anacardo (Anacardium occidentale l.) en niños con sobrepeso: un ensayo clínico piloto aleatorizado. Nutrición Hospitalaria, 42(1), 19-25. https://doi.org/10.20960/nh.05241
Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., ... & Sasso, F. C. (2023). Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Current Issues in Molecular Biology, 45(8), 6651-6666. https://doi.org/10.3390/cimb45080420
Caturano, A., Rocco, M., Tagliaferri, G., Piacevole, A., Nilo, D., Di Lorenzo, G., ... & Sasso, F. C. (2025). Oxidative stress and cardiovascular complications in type 2 diabetes: from pathophysiology to lifestyle modifications. Antioxidants, 14(1), 72. https://doi.org/10.3390/antiox14010072
Deng, T., Xu, J., Wang, Q., Wang, X., Jiao, Y., Cao, X., ... & Xiao, C. (2024). Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis. Frontiers in Pharmacology, 15, 1369337. https://doi.org/10.3389/fphar.2024.1369337
Dias, T. D. S., Almondes, K. G. D. S., Firmino, M. A., Oliveira, L. F. N. D., Freire, W. B. D. S., Barbosa Jr, F., ... & Maia, C. S. (2024). Effect of Cashew Nut Consumption on Biomarkers of Copper and Zinc Status in Adolescents with Obesity: A Randomized Controlled Trial. Nutrients, 17(1), 163. https://doi.org/10.3390/nu17010163
Diaz, L., & Bielczyk-Maczynska, E. (2025). High-density lipoprotein cholesterol: how studying the ‘good cholesterol’could improve cardiovascular health. Open biology, 15(2), 240372. https://doi.org/10.1098/rsob.240372
El-Nasr, N. M. A., Hussien, Y. A., El-Baset, M. A., Shabana, M. E., & Saleh, D. O. (2025). Astaxanthin mitigates diabetic cardiomyopathy and nephropathyin HF/HFr/STZ diabetic rats via modulating NOX4, fractalkine, Nrf2, and AP-1 pathways. Scientific Reports, 15(1), 20199. https://doi.org/10.1038/s41598-025-06263-8
Emeka, P. M., Badger-Emeka, L. I., Thirugnanasambantham, K., & Alatawi, A. S. (2024). Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice. Pharmaceuticals, 17(11), 1523. https://doi.org/10.3390/ph17111523
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 18(6), 499-502. https://doi.org/10.1093/clinchem/18.6.499
Hashiesh, H. M., Sheikh, A., Meeran, M. F. N., Saraswathiamma, D., Jha, N. K., Sadek, B., ... & Ojha, S. (2023). β-Caryophyllene, a dietary phytocannabinoid, alleviates diabetic cardiomyopathy in mice by inhibiting oxidative stress and inflammation activating cannabinoid type-2 receptors. ACS Pharmacology & Translational Science, 6(8), 1129-1142. https://doi.org/10.1021/acsptsci.3c00027
Horvath, C., Houriet, J., Kellenberger, A., Moser, C., Balazova, L., Balaz, M., ... & Wolfrum, C. (2025). Genkwanin glycosides are major active compounds in Phaleria nisidai extract mediating improved glucose homeostasis by stimulating glucose uptake into adipose tissues. Nature Communications, 16(1), 7648. https://doi.org/10.1038/s41467-025-62689-8
Hurtado-Carneiro, V., LeBaut-Ayuso, Y., Velázquez, E., Flores-Lamas, C., Fernández-de la Rosa, R., García-García, L., ... & Pozo, M. Á. (2024). Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy. Heliyon, 10(15). https://doi.org/10.1016/j.heliyon.2024.e35752
Li, J., Feng, Z., Lu, B., Fang, X., Huang, D., & Wang, B. (2023). Resveratrol alleviates high glucose-induced oxidative stress and apoptosis in rat cardiac microvascular endothelial cell through AMPK/Sirt1 activation. Biochemistry and Biophysics Reports, 34, 101444. https://doi.org/10.1016/j.bbrep.2023.101444
Li, Y., Chen, Y., Shao, B., Liu, J., Hu, R., Zhao, F., ... & Wang, Y. (2023). Evaluation of creatine kinase (CK)-MB to total CK ratio as a diagnostic biomarker for primary tumors and metastasis screening. Practical Laboratory Medicine, 37, e00336. https://doi.org/10.1016/j.plabm.2023.e00336
Liao, X., Wang, Q., Yang, X., Yao, Y., Zhu, D., Feng, J., & Wang, K. (2025). Bisacurone ameliorates myocardial ischemia/reperfusion injury in rats: regulation of inflammatory and apoptosis pathways via CHOP/GRP78 proteins. BMC Pharmacology and Toxicology, 26(1), 115. https://doi.org/10.1186/s40360-025-00949-5
Marassi, M., & Fadini, G. P. (2023). The cardio-renal-metabolic connection: a review of the evidence. Cardiovascular Diabetology, 22(1), 195. https://doi.org/10.1186/s12933-023-01937-x
Masenga, S. K., Kabwe, L. S., Chakulya, M., & Kirabo, A. (2023). Mechanisms of Oxidative Stress in Metabolic Syndrome. International Journal of Molecular Sciences, 24(9), 7898. https://doi.org/10.3390/ijms24097898
Migdalis, I. N. (2024). Chronic Complications of Diabetes: Prevalence, Prevention, and Management. Journal of Clinical Medicine, 13(23), 7001. https://doi.org/10.3390/jcm13237001
Netala, V. R., Hou, T., Wang, Y., Zhang, Z., & Teertam, S. K. (2025). Cardiovascular Biomarkers: Tools for Precision Diagnosis and Prognosis. International journal of molecular sciences, 26(7), 3218. https://doi.org/10.3390/ijms26073218
Ong, K. L., Stafford, L. K., McLaughlin, S. A., Boyko, E. J., Vollset, S. E., Smith, A. E., ... & Brauer, M. (2023). Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet, 402(10397), 203-234. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2823%2901301-6
Ozorowski, M., Wiciński, M., Kuźmiński, O., Wojciechowski, P., Siedlecki, Z., Śniegocki, M., & Włodarczyk, E. (2025). The Effects of Quercetin on Vascular Endothelium, Inflammation, Cardiovascular Disease and Lipid Metabolism—A Review. Nutrients, 17(9), 1579. https://doi.org/10.3390/nu17091579
Patsoukaki, V., Lind, L., Lampa, E., Radhi, S., Eeg-Olofsson, K., Eliasson, B., & Eriksson, J. W. (2025). Risk differences and underlying factors of cardiovascular events and mortality in patients with type 2 diabetes versus type 1 diabetes: a longitudinal cohort study of Swedish nationwide register data. The Lancet Diabetes & Endocrinology, 13(10), 848-862. https://doi.org/10.1016/S2213-8587(25)00165-2
Racine, K. C., Iglesias-Carres, L., Herring, J. A., Wieland, K. L., Ellsworth, P. N., Tessem, J. S., Ferruzzi, M. G., Kay, C. D., & Neilson, A. P. (2024). The high-fat diet and low-dose streptozotocin type-2 diabetes model induces hyperinsulinemia and insulin resistance in male but not female C57BL/6J mice. Nutrition research, 131, 135–146. https://doi.org/10.1016/j.nutres.2024.09.008
Rao, B. M., Vedavijaya, T., Ramani, Y. R., Sayana, S. B., & Vedavijaya, T. (2025). Protective Role of Methanol Leaf Extract of Catharanthus Roseus in Lipid Profile Modulation in Diabetic Wistar Rats. Cureus, 17(1). https://doi.org/10.7759/cureus.77420.
Sarker, M., Chowdhury, N., Bristy, A. T., Emran, T., Karim, R., Ahmed, R., ... & Reza, H. M. (2024). Astaxanthin protects fludrocortisone acetate-induced cardiac injury by attenuating oxidative stress, fibrosis, and inflammation through TGF-β/Smad signaling pathway. Biomedicine & Pharmacotherapy, 181, 117703. https://doi.org/10.1016/j.biopha.2024.117703
Scarpa, E. S., Antonelli, A., Balercia, G., Sabatelli, S., Maggi, F., Caprioli, G., ... & Micucci, M. (2024). Antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic activities of polyphenols for the treatment of two different chronic diseases: type 2 diabetes mellitus and osteoporosis. Biomolecules, 14(7), 836. https://doi.org/10.3390/biom14070836
Shah, M. U., Roebuck, A., Srinivasan, B., Ward, J. K., Squires, P. E., Hills, C. E., & Lee, K. (2025). Diagnosis and management of type 2 diabetes mellitus in patients with ischaemic heart disease and acute coronary syndromes-a review of evidence and recommendations. Frontiers in Endocrinology, 15, 1499681. https://doi.org/10.3389/fendo.2024.1499681
Singh, A., Shadangi, S., Gupta, P. K., & Rana, S. (2025). Type 2 diabetes mellitus: A comprehensive review of pathophysiology, comorbidities, and emerging therapies. Comprehensive Physiology, 15(1), e70003. https://doi.org/10.1002/cph4.70003
Sini, M., Dongmo, F., Mvongo, C., Fokam Tagne, M. A., Jidibe, P., Foyet Fondjo, A., ... & Kamgang, R. (2025). Antihyperglycemic and Antioxidative Stress Effects of Erythrophleum africanum (Fabaceae) Trunk Bark Powder Fractions on High‐Calorie Diet‐Induced Type 2 Diabetes in Rats. Food Science & Nutrition, 13(5), e70290. https://doi.org/10.1002/fsn3.70290
Sukhikh, S., Babich, O., Prosekov, A., Kalashnikova, O., Noskova, S., Bakhtiyarova, A., ... & Ivanova, S. (2023). Antidiabetic properties of plant secondary metabolites. Metabolites, 13(4), 513. https://doi.org/10.3390/metabo13040513
Suzuki, T., Sawada, S., Ishigaki, Y., Tsukita, S., Kodama, S., Sugisawa, T., ... & Katagiri, H. (2016). Lipoprotein lipase deficiency (R243H) in a type 2 diabetes patient with multiple arterial aneurysms. Internal Medicine, 55(9), 1131-1136. https://doi.org/10.2169/internalmedicine.55.5239
Tegegne, B. A., Adugna, A., Yenet, A., Yihunie Belay, W., Yibeltal, Y., Dagne, A., ... & Zeleke, T. K. (2024). A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. Frontiers in Endocrinology, 15, 1440456. https://doi.org/10.3389/fendo.2024.1440456
Wang, L., Bai, Y., Cao, Z., Guo, Z., Lian, Y., Liu, P., ... & Chen, Q. (2024). Histone deacetylases and inhibitors in diabetes mellitus and its complications. Biomedicine & Pharmacotherapy, 177, 117010. https://doi.org/10.1016/j.biopha.2024.117010
Wang, Y., Sun, H., Zhang, J., Xia, Z., & Chen, W. (2020). Streptozotocin-induced diabetic cardiomyopathy in rats: ameliorative effect of PIPERINE via Bcl2, Bax/Bcl2, and caspase-3 pathways. Bioscience, Biotechnology, and Biochemistry, 84(12), 2533-2544. https://doi.org/10.1080/09168451.2020.1815170
Welten, S. J., Elders, P. J., Remmelzwaal, S., Doekhie, R., Kee, K. W., Nijpels, G., & van der Heijden, A. A. (2023). Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: systematic review and meta-analysis. Archives of Cardiovascular Diseases, 116(2), 69-78. https://doi.org/10.1016/j.acvd.2022.11.007
Yedjou, C. G., Grigsby, J., Mbemi, A., Nelson, D., Mildort, B., Latinwo, L., & Tchounwou, P. B. (2023). The Management of Diabetes Mellitus Using Medicinal Plants and Vitamins. International Journal of Molecular Sciences, 24(10), 9085.https://doi.org/10.3390/ijms24109085
Zhang, H., & Dhalla, N. S. (2024). The role of pro-inflammatory cytokines in the pathogenesis of cardiovascular disease. International Journal of Molecular Sciences, 25(2), 1082. https://doi.org/10.3390/ijms25021082
Zhang, H., Kang, K., Chen, S., Su, Q., Zhang, W., Zeng, L., Lin, X., Peng, F., Lin, J., & Chai, D. (2024). High serum lactate dehydrogenase as a predictor of cardiac insufficiency at follow-up in elderly patients with acute myocardial infarction. Archives of gerontology and geriatrics, 117, 105253. https://doi.org/10.1016/j.archger.2023.105253
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