Comparative Analysis of Hematological Profiles in Diabetic Mice Treated with D-Allulose and Neoagaro-Oligosaccharides

Authors

  • Salsabila Faradisa Nuris Universitas Gadjah Mada
  • Wiwin Ariesti Universitas Gadjah Mada
  • Tri Rini Nuringtyas Universitas Gadjah Mada
  • Budi Saksono Badan Riset dan Inovasi Nasional
  • Rahadian Yudo Hartantyo Universitas Gadjah Mada
  • Fajar Sofyantoro Universitas Gadjah Mada
  • Nastiti Wijayanti Universitas Gadjah Mada

DOI:

https://doi.org/10.25134/quagga.v18i2.504

Keywords:

BALB/c mice, Diabetes Mellitus, D-allulose, Hematological profile, Neoagaro-oligosaccharides

Abstract

Diabetes mellitus is characterized by chronic hyperglycemia that induces oxidative stress and inflammation, contributing to hematological dysfunction and increased systemic risk. This study comparatively evaluated the effects of D-allulose and neoagarooligosaccharides (NAOS) on hematological parameters in BALB/c mice with type 2 diabetes induced by streptozotocin. Experimental groups consisted of control, negative control, positive control (metformin), and treatment groups receiving D-allulose (0.05, 0.1, 0.2 g/kg BW) or NAOS (100, 200, 400 mg/kg BW) orally for 28 days. Hematological assessments included red blood cell (RBC) count, erythrocyte indices (hemoglobin, hematocrit, mean corpuscular hemoglobin), leukocyte count, and lymphocyte levels. Negative controls displayed decreased RBC parameters and lymphocytes, with elevated leukocytes, indicating hematological impairment associated with hyperglycemia. D-allulose improved RBC count, hemoglobin, and MCH, while reducing leukocyte count and elevating lymphocytes, especially at lower doses. NAOS primarily enhanced erythrocyte quality by improving hemoglobin, hematocrit, and MCH, while also modulating leukocyte and lymphocyte profiles. Overall, D-allulose was more effective in restoring erythrocyte quantity, whereas NAOS contributed more prominently to erythrocyte index improvement. Both agents show potential in reducing hematological disorders associated with inflammation in diabetes cases.

References

Ahmed, S. M. U., Luo, L., Namani, A., Wang, X. J., & Tang, X. (2017). Nrf2 signaling pathway: Pivotal roles in inflammation. In Biochimica et Biophysica Acta - Molecular Basis of Disease, 1863 (2): 585-597. Elsevier B.V. https://doi.org/10.1016/j.bbadis.2016.11.005

Al-Dewachi, A. B., & AL-Dewachi, S. O. (2024). Association between hematological indices and blood glucose level among patients with type 2 diabetes. Irish Journal of Medical Science, 193(5): 2307–2312. https://doi.org/10.1007/s11845-024-03754-x

Alekseeva, G. S., Erofeeva, M. N., Hernandez-Blanco, J. A., Litvinov, M. N., Chistopolova, M. D., Kim, M. D., ... & Naidenko, S. V. (2024). Hematological analysis as a method of monitoring physiological status of medium carnivorous mammals in the russian far east. Nature Conservation Research. Заповедная наука, 9(4): 93-104. https://dx.doi.org/10.24189/ncr.2024.034

Ayodele, O. O., Onajobi, F. D., & Osoniyi, O. R. (2020). Modulation of Blood Coagulation and Hematological Parameters by Crassocephalum crepidioides Leaf Methanol Extract and Fractions in STZ-Induced Diabetes in the Rat. Scientific World Journal, 2020 (1): 1-11. https://doi.org/10.1155/2020/1036364

Bambo, G. M., Asmelash, D., Alemayehu, E., Gedefie, A., Duguma, T., & Kebede, S. S. (2024). Changes in selected hematological parameters in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis. Frontier in Medicine, 11: 1294290. https://doi.org/10.3389/fmed.2024.1294290

Bella, L. M., Fieri, I., Tessaro, F. H. G., Nolasco, E. L., Nunes, F. P. B., Ferreira, S. S., Azevedo, C. B., & Martins, J. O. (2017). Vitamin D modulates hematological parameters and cell migration into peritoneal and pulmonary cavities in alloxan-diabetic mice. BioMed Research International, 2017 (2017): 7651815. https://doi.org/10.1155/2017/7651815

Biro, K., Feher, G., Vekasi, J., Kenyeres, P., Toth, K., & Koltai, K. (2021). Hemorheological parameters in diabetic patients: Role of glucose lowering therapies. Metabolites, 11(12): 806. https://doi.org/10.3390/metabo11120806

Canfora, E. E., Jocken, J. W. and Blaak, E. E. 2015. Short-chain Fatty Acids in Control of Body Weight and Insulin Sensitivity. Nature Reviews Endocrinology, 11(10): 577-591. https://doi.org/10.1038/nrendo.2015.128.

Cardoso, C. R. L., Leite, N. C., & Salles, G. F. (2021). Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study. Cardiovascular Diabetology, 20(1): 133. https://doi.org/10.1186/s12933-021-01324-4

Chan, H. C., Zhu, Y., Hu, Y., Ko, T. P., Huang, C. H., Ren, F., Chen, C. C., Ma, Y., Guo, R. T., & Sun, Y. (2012). Crystal structures of d-psicose 3-epimerase from Clostridium cellulolyticum H10 and its complex with ketohexose sugars. Protein and Cell, 3(2): 123–131. https://doi.org/10.1007/s13238-012-2026-5

Chen, A., Leith, M., Tu, R., Tahim, G., Sudra, A., & Bhargava, S. (2017). Effects of diluents on cell culture viability measured by automated cell counter. PLoS ONE, 2(3): e0173375. https://doi.org/10.1371/journal.pone.0173375

Cheong, K. L., Qiu, H. M., Du, H., Liu, Y. and Khan, B. M. 2018. Oligosaccharides Derived from Red Seaweed: Production, Properties, and Potential Health and Cosmetic Applications. Molecules, 23(10): 2451. https://doi.org/10.3390/molecules23102451

Delesderrier, E., Curioni, C., Omena, J., Macedo, C. R., Cople-Rodrigues, C., & Citelli, M. (2020). Antioxidant nutrients and hemolysis in sickle cell disease. Clinica Chimica Acta, 510: 381–390.

https://doi.org/10.1016/j.cca.2020.07.020

Ebrahim, H., Fiseha, T., Ebrahim, Y., & Bisetegn, H. (2022). Comparison of hematological parameters between type 2 diabetes mellitus patients and healthy controls at Dessie comprehensive specialized hospital, Northeast Ethiopia: Comparative cross-sectional study. PLoS ONE, 217(7): e0272145. https://doi.org/10.1371/journal.pone.0272145

Ebrahimi, R., Mohammadpour, A., Medoro, A., Davinelli, S., Saso, L., & Miroliaei, M. (2025). Exploring the links between polyphenols, Nrf2, and diabetes: A review. Biomedicine & Pharmacotherapy, 186, 118020. https://doi.org/10.1016/j.biopha.2025.118020

Hajiaghaalipour, F., Khalilpourfarshbafi, M. & Arya, A. 2015. Modulation of Glucose Transporter Protein by Dietary Flavonoids in Type 2 Diabetes Mellitus. International Journal of Biological Sciences, 11(5), 508-524. https://doi.org/10.7150/ijbs.11241

Hong S.J., Lee J.H., Kim E.J., Yang H.J., Park J.S., Hong S.K. 2017. Anti-obesity and Anti-diabetic Effect of Neoagarooligosaccharides on High-Fat Diet Induced Obesity in Mice. Marine Drugs, 15(4): 90. https://doi.org/10.3390/md15040090

Hossain, A., Yamaguchi, F., Matsuo, T., Tsukamoto, I., Toyoda, Y., Ogawa, M., Nagata, Y., & Tokuda, M. (2015). Rare sugar d-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus. Pharmacology & Therapeutics, 155: 49–59. https://doi.org/10.1016/j.pharmthera.2015.08.004

Ifada, A. S., Kusadi, A. M., & Mulyaningsih, K. (2020). Profil Kadar Kolesterol Darah Mencit Putih (Mus musculus) Yang Diberi Ekstrak Etanol 70% Daun Sirsak (Annona muricata L.) Sebelum dan Bersamaan dengan Induksi High Fat Diet. Jurnal Ilmu Kesehatan dan Farmasi, 8(1), 31-34. https://doi.org/10.51673/jikf.v8i1.531

Jacob, S., Nair, A. B., & Morsy, M. A. (2022). Dose Conversion Between Animals and Humans: A Practical Solution. Indian Journal of Pharmaceutical Education and Research, 56 (3): 600-606. https://doi.org/10.5530/ijper.56.3.108

Jiang, S., Xiao, W., Zhu, X., Yang, P., Zheng, Z., Lu, S., Jiang, S., Zhang, G., & Liu, J. (2020). Review on D-Allulose: In vivo Metabolism, Catalytic Mechanism, Engineering Strain Construction, Bio-Production Technology. Frontiers in Bioengineering and Biotechnology, 8: 26. https://doi.org/10.3389/fbioe.2020.00026

Kannan, G., Paul, B. M., & Thangaraj, P. (2025). Stimulation, regulation, and inflammaging interventions of natural compounds on nuclear factor kappa B (NF-kB) pathway: a comprehensive review. Inflammopharmacology, 33(1): 145–162. https://doi.org/10.1007/s10787-024-01635-4

Li, Y., Liu, Y., Liu, S., Gao, M., Wang, W., Chen, K., Huang, L., & Liu, Y. 2023. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduction and Targeted Therapy, 8(1):152. https://doi.org/10.1038/s41392-023-1400-z

Lin, F., Yang, D., Huang, Y., Zhao, Y., Ye, J., & Xiao, M. (2019a). The potential of neoagaro-oligosaccharides as a treatment of type II diabetes in mice. Marine Drugs, 17(10), 541. https://doi.org/10.3390/md17100541

Lin, F., Ye, J., Huang, Y., Yang, Y., & Xiao, M. (2019b). Simple preparation of diverse neoagaro-oligosaccharides. Processes, 7(5), 267. https://doi.org/10.3390/pr7050267

Liu, F., Wang, T., Wang, S., Zhao, X., & Hua, Y. (2024). The association of platelet to white blood cell ratio with diabetes: a nationwide survey in China. Frontiers in Endocrinology, 15: 1418583. https://doi.org/10.3389/fendo.2024.1418583

Liu, Q., Lei, Z., Huang, A., Wu, Q., Xie, S., Awais, I., ... & Yuan, Z. (2017). Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox. Scientific Reports, 7(1): 41854. https://doi.org/10.1038/srep41854

Milosevic, D., & Panin, V. L. (2019). Relationship between hematological parameters and glycemic control in type 2 diabetes mellitus patients. Journal of Medical Biochemistry, 38(2): 164–171. https://doi.org/10.2478/jomb-2018-0021

Molonia, M. S., Salamone, F. L., Speciale, A., Saija, A., & Cimino, F. (2024). D-Allulose Reduces Hypertrophy and Endoplasmic Reticulum Stress Induced by Palmitic Acid in Murine 3T3-L1 Adipocytes. International Journal of Molecular Sciences, 25(7): 4059. https://doi.org/ 10.3390/ijms25074059

Obeagu, E. I. (2024). Red blood cells as biomarkers and mediators in complications of diabetes mellitus: A review. Medicine, 103(8): e37265. https://doi.org/10.1097/MD.0000000000037265

Ochiai, M., Onishi, K., Yamada, T., Iida, T., & Matsuo, T. (2014). D-Psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet. International Journal of Food Sciences and Nutrition, 65(2): 245–250. https://doi.org/10.3109/09637486.2013.845653

Rehman, U. H., Ullah, K., Rasool, A., Manzoor, R., Yuan, Y., Tareen, A. M., Kaleem, I., Riaz, N., Hameed, S., & Bashir, S. (2023). Comparative impact of streptozotocin on altering normal glucose homeostasis in diabetic rats compared to normoglycemic rats. Scientific Reports, 13(1):7921. https://doi.org/10.1038/s41598-023-29445-8

Sampath, C., Rashid, M. R., Sang, S., & Ahmedna, M. 2017. Green tea epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity. Biomedicine & Pharmacotherapy, 87: 73-81. https://doi.org/10.1016/j.biopha.2016.12.082

Sari, F. R. (2023). The Potential Effect of Honey-derived D-Allulose in Counteracting Hyperglycemia by Time and Dose Dependent Manner in Diabetes Mellitus. Jurnal Kimia Valensi, 9(2): 313–320. https://doi.org/10.15408/jkv.v9i2.34881

Shintani, T., Sakoguchi, H., Yoshihara, A., Izumori, K., & Sato, M. (2017). d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic. Biochemical and Biophysical Research Communications, 493(4), 1528–1533. https://doi.org/10.1016/J.BBRC.2017.09.147

Sibony, W., R., Segev, O., Dor, S., & Raz, I. (2024). Overview of oxidative stress and inflammation in diabetes. Journal Diabetes, 16(10): e70014. https://doi.org/10.1111/1753-0407.70014

Struck, M. B., Andrutis, K. A., Ramirez, H. E., & Battles, A. H. (2011). Effect of a short-term fast on ketamine–xylazine anesthesia in rats. Journal of the American Association for Laboratory Animal Science, 50(3): 344-348.

Tak, J., Bok, M., Rho, H., Park, J. H., Lim, Y., Chon, S., & Lim, H. (2023). Effect of diabetes-specific oral nutritional supplements with allulose on weight and glycemic profiles in overweight or obese type 2 diabetic patients. Nutrition Research and Practice, 17(2): 241–256. https://doi.org/10.4162/nrp.2023.17.2.241

Tanaka, M., Hayashi, N., & Iida, T. (2019). Safety evaluation of 12-week continuous ingestion of D-allulose in borderline diabetes and type 2 diabetes. Fundamental Toxicological Sciences, 6(6): 225–234. https://doi.org/10.2131/fts.6.225

Verdile, G., Keane, K. N., Cruzat, V. F., Medic, S., Sabale, M., Rowles, J., Wijesekara, N., Martins, R. N., Fraser, P. E., & Newsholme, P. (2015). Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease. Mediators of Inflammation, 2015: 105828. https://doi.org/10.1155/2015/105828

Wang, W., Liu, P., Hao, C., Wu, L., Wan, W., & Mao, X. (2017). Neoagaro-oligosaccharide monomers inhibit inflammation in LPS-stimulated macrophages through suppression of MAPK and NF-κB pathways. Scientific reports, 7(1): 44252.

https://doi.org/10.1038/srep44252

Yang, D. K., & Kang, H. S. (2018). Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomolecules and Therapeutics, 26(2): 130–138. https://doi.org/10.4062/biomolther.2017.254

Yuma, T., Tokuda, M., Nishimoto, N., Yokoi, H., & Izumori, K. (2023). Allulose for the attenuation of postprandial blood glucose levels in healthy humans: A systematic review and meta-analysis. PLoS ONE, 18(4): e0281150. https://doi.org/10.1371/journal.pone.0281150

Zhang, W., Yu, S., Zhang, T., Jiang, B., & Mu, W. (2016). Recent advances in d-allulose: Physiological functionalities, applications, and biological production. Trends in Food Science & Technology, 54: 127–137. https://doi.org/10.1016/J.TIFS.2016.06.004

Zhao, T., Zhao, G., Gao, F., Zhang, Q., Shang, S., & Lu, X. (2024). D-allulose attenuated metaflammation by calming adipose tissue macrophages, boosting intestinal barrier, and modulating gut microbiota in HFD mice. Journal of Functional Foods, 121, 106417. https://doi.org/10.1016/J.JFF.2024.106417

Downloads

Published

01-07-2026

How to Cite

Salsabila Faradisa Nuris, Wiwin Ariesti, Tri Rini Nuringtyas, Budi Saksono, Rahadian Yudo Hartantyo, Fajar Sofyantoro, & Nastiti Wijayanti. (2026). Comparative Analysis of Hematological Profiles in Diabetic Mice Treated with D-Allulose and Neoagaro-Oligosaccharides. Quagga: Jurnal Pendidikan Dan Biologi, 18(2), 135–144. https://doi.org/10.25134/quagga.v18i2.504

Similar Articles

You may also start an advanced similarity search for this article.