TY  - JOUR
T1  - The Effect of Carob Aqueous Extract on Oxidative Stress, Proinflammatory Cytokines, Glucose and Lipid Concentrations in the Blood of Diabetic Rats.
TT  - Diyabetik Sıçanların Kanında Keçiboynuzu Sulu Ekstraktının Oksidatif Stres, Proinflamatuar Sitokinler, Glikoz ve Lipid Düzeylerine Etkisi
AU  - Eryavuz, Abdullah
AU  - Avşar, Mehmet Talha
PY  - 2025
DA  - October
Y2  - 2025
DO  - 10.30607/kvj.1591051
JF  - Kocatepe Veterinary Journal
JO  - kvj
PB  - Afyon Kocatepe Üniversitesi
WT  - DergiPark
SN  - 1308-1594
SP  - 192
EP  - 199
VL  - 18
IS  - 3
LA  - en
AB  - Herbal treatments offer potential benefits in controlling blood glucose levels and preventing diabetes-related complications. This study was conducted to determine the effects of the application of carob fruit aqueous extract prepared by ultrasound-assisted extraction (UAE) method on oxidative stress, glycemic level, proinflammatory cytokines and lipid profile levels in the blood of rats with experimental diabetes induced by streptozotocin-nicotinamide (STZ-NA) model. Forty male Wistar Albino (200-250 g live weight) animals used in the study were divided into four groups as normal control, diabetic control, normal group given 200 mg.kg-1 carob aqueous extract and diabetic group given 200 mg.kg-1 carob aqueous extract. At the end of the 21-day study, plasma glucose, hemoglobin A1C (HbA1c), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), malondialdehyde (MDA), reduced glutathione (GSH), proinflammatory cytokines interleukin 1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total cholesterol, triglyceride, leptin and 25-hydroxy vitamin D levels were measured in blood samples taken from all animals. Carob aqueous extract treatment did not cause a significant decrease in high glucose, HbA1c and HOMA-IR values caused by diabetes. The blood insulin levels were not affected by the treatments. Diabetes increased MDA, IL-6 and triglyceride levels (p
KW  - Diabetes
KW  - oxidative stress
KW  - hyperglycemia
KW  - dyslipidemia
KW  - Carob aqueous extract
N2  - Bitkisel tedaviler, kan glikoz seviyelerinin kontrol altına alınması ve diyabetle ilişkili komplikasyonların önlenmesinde potansiyel faydalar sunmaktadır. Bu çalışmada; streptozotosin-nikotinamid (STZ-NA) modelle deneysel diyabet oluşturulan sıçanlara ultrasonik-destekli ekstraksiyon (UAE) yöntemiyle hazırlanmış keçiboynuzu meyvesi sulu ekstraktı uygulamasının kan oksidatif stres, glisemik düzey, proinflamatuar sitokin ve lipit profil düzeylerine etkilerinin belirlenmesi amacıyla yapıldı. Çalışmada 40 adet erkek Wistar Albino (200-250g canlı ağırlık) hayvan kullanıldı. Deneydeki hayvanlar normal kontrol, diyabetik kontrol, 200 mg/kg keçiboynuzu ekstraktı verilen normal ve 200 mg/kg keçiboynuzu ekstraktı verilen diyabetik grup olmak üzere dört gruba ayrıldı. Toplam 21 gün süren çalışmanın sonunda tüm hayvanlardan alınan kan örneklerinde; plazma glikoz, hemoglobin A1C (HbA1c), insülin, insülin direncinin homeostatik model değerlendirmesi (HOMA-IR), malondialdehid (MDA), indirgenmiş glutatyon (GSH), proinflamatuar sitokinler interlökin 1-beta (IL-1β), tümör nekroz faktörü-alfa (TNF-α), interlökin-6 (IL-6), total kolesterol, trigliserit, leptin ve 25-hidroksi vitamin D düzeyleri ölçüldü. Keçiboynuzu ekstraktı uygulaması, diyabetin yol açtığı yüksek glikoz, HbA1c ve HOMA-IR değerlerinde önemli bir düşüşe neden olmadı. Uygulamaların kan insülin düzeylerine etkisi olmadı. Diyabet; MDA, IL-6 ve trigliserit düzeylerini artırırken (p
CR  - Akinlade, O. M., Owoyele, B. V., & Soladoye, A. O. (2021). Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy. African health sciences, 21(2), 719–727. https://doi.org/10.4314/ahs.v21i2.30
CR  - Aloud, A. A., Veeramani, C., Govindasamy, C., Alsaif, M. A., & Al-Numair, K. S. (2018). Galangin, a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats. Redox report : communications in free radical research, 23(1), 29–34. https://doi.org/10.1080/13510002.2017.1365224
CR  - Aly, Y. E., Abdou, A. S., Rashad, M. M., & Nassef, M. M. (2016). Effect of exercise on serum vitamin D and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus. Journal of advanced research, 7(5), 671–679. https://doi.org/10.1016/j.jare.2016.07.001
CR  - Behl, T., Gupta, A., Albratty, M., Najmi, A., Meraya, A. M., Alhazmi, H. A., Anwer, M. K., Bhatia, S., & Bungau, S. G. (2022). Alkaloidal Phytoconstituents for Diabetes Management: Exploring the Unrevealed Potential. Molecules (Basel, Switzerland), 27(18), 5851. https://doi.org/10.3390/molecules27185851
CR  - Beutler, E., Duron, O., & Kelly, B. M. (1963). Improved method for the determination of blood glutathione. The Journal of laboratory and clinical medicine, 61, 882–888.
CR  - Brassesco, M. E., Brandão, T. R., Silva, C. L., & Pintado, M. (2021). Carob bean (Ceratonia siliqua L.): A new perspective for functional food. Trends in Food Science & Technology, 114, 310-322. https://doi.org/10.1016/j.tifs.2021.05.037
CR  - Cloete L. (2022). Diabetes mellitus: an overview of the types, symptoms, complications and management. Nursing standard (Royal College of Nursing (Great Britain) : 1987), 37(1), 61–66. https://doi.org/10.7748/ns.2021.e11709
CR  - Demesa, A. G., Saavala, S., Pöysä, M., & Koiranen, T. (2024). Overview and Toxicity Assessment of Ultrasound-Assisted Extraction of Natural Ingredients from Plants. Foods, 13(19), 3066. https://doi.org/10.3390/foods13193066
CR  - Dludla, P. V., Mabhida, S. E., Ziqubu, K., Nkambule, B. B., Mazibuko-Mbeje, S. E., Hanser, S., Basson, A. K., Pheiffer, C., & Kengne, A. P. (2023). Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World journal of diabetes, 14(3), 130–146. https://doi.org/10.4239/wjd.v14.i3.130
CR  - Draper, H. H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods in enzymology, 186, 421–431. https://doi.org/10.1016/0076-6879(90)86135-i
CR  - El-Beih, N. M., Ramadan, G., El-Husseiny, E. A., & Hussein, A. M. (2019). Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats. Molecular biology reports, 46(4), 3701–3711. https://doi.org/10.1007/s11033-019-04813-8
CR  - Eleazu, C. O., Eleazu, K. C., Chukwuma, S., & Essien, U. N. (2013). Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. Journal of diabetes and metabolic disorders, 12(1), 60. https://doi.org/10.1186/2251-6581-12-60
CR  - Fatani, S. H., Babakr, A. T., NourEldin, E. M., & Almarzouki, A. A. (2016). Lipid peroxidation is associated with poor control of type-2 diabetes mellitus. Diabetes & metabolic syndrome, 10(2 Suppl 1), S64–S67. https://doi.org/10.1016/j.dsx.2016.01.028
CR  - Federiuk, I. F., Casey, H. M., Quinn, M. J., Wood, M. D., & Ward, W. K. (2004). Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment. Comparative medicine, 54(3), 252–257.
CR  - German, J. P., Wisse, B. E., Thaler, J. P., Oh-I, S., Sarruf, D. A., Ogimoto, K., Kaiyala, K. J., Fischer, J. D., Matsen, M. E., Taborsky, G. J., Jr, Schwartz, M. W., & Morton, G. J. (2010). Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes, 59(7), 1626–1634. https://doi.org/10.2337/db09-1918
CR  - Hazra, P., Istiak, A. S. M. E., Koly, K. N., Akter, F., Ferdous, M. F., Das, S. R., Hasan, M.I., Haque, A., Hayat, S., Sultana, N., & Rafiq, K. (2023). Comparative Efficacy of Combined Formulation of Andrographis paniculata, Lagerstroemia speciosa and Tribulus terrestris with Glimepiride on Renal and Pancreatic Injury in Alloxan Induced Type-1 Diabetic Mice. European Journal of Veterinary Medicine, 3(3), 14-20. https://doi.org/10.24018/ejvetmed.2023.3.3.97
CR  - Ighodaro, O. M., Adeosun, A. M., & Akinloye, O. A. (2017). Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas, Lithuania), 53(6), 365–374. https://doi.org/10.1016/j.medici.2018.02.001
CR  - Kado, S., Nagase, T., & Nagata, N. (1999). Circulating levels of interleukin-6, its soluble receptor and interleukin-6/interleukin-6 receptor complexes in patients with type 2 diabetes mellitus. Acta diabetologica, 36(1-2), 67–72. https://doi.org/10.1007/s005920050147
CR  - Kane, J. P., Pullinger, C. R., Goldfine, I. D., & Malloy, M. J. (2021). Dyslipidemia and diabetes mellitus: Role of lipoprotein species and interrelated pathways of lipid metabolism in diabetes mellitus. Current opinion in pharmacology, 61, 21–27. https://doi.org/10.1016/j.coph.2021.08.013
CR  - King G. L. (2008). The role of inflammatory cytokines in diabetes and its complications. Journal of periodontology, 79(8 Suppl), 1527–1534. https://doi.org/10.1902/jop.2008.080246
CR  - Kottaisamy, C. P. D., Raj, D. S., Prasanth Kumar, V., & Sankaran, U. (2021). Experimental animal models for diabetes and its related complications-a review. Laboratory animal research, 37(1), 23. https://doi.org/10.1186/s42826-021-00101-4
CR  - Kuchmerovska, Т.М., Donchenko, G.V., Tychonenko, T.M., Guzyk, M.M., Yanitska, L.V., Stepanenko, S.P., & Klimenko, А.P. (2012). Nicotinamide influence on functional state of pancreatic cells. Ukrainian Biochemical Journal, 84, 81–88.
CR  - Kumar, S., Narwal, S., Kumar, V., & Prakash, O. (2011). α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacognosy reviews, 5(9), 19–29. https://doi.org/10.4103/0973-7847.79096
CR  - Laaraj, S., Hussain, A., Mouhaddach, A., Noutfia, Y., Gorsi, F. I., Yaqub, S., Hussain, I., Nisar, R., Salmaoui, S., & Elfazazi, K. (2024). Benefits and Antihyperglycemic Potential of Carob Fruit (Ceratonia siliqua L.) - An Overview. Ecological Engineering & Environmental Technology, 25(3), 124-132. https://doi.org/10.12912/27197050/178456
CR  - Laaraj, S., Salmaoui, S., Addi, M., El-Rhouttais, C., Tikent, A., Elbouzidi, A., Taibi, M., Hano, C., Noutfia, Y., & Elfazazi, K. (2023). Carob (Ceratonia siliqua L.) seed constituents: A comprehensive review of composition, chemical profile, and diverse applications. Journal of Food Quality, 2023(1), 3438179. https://doi.org/10.1155/2023/3438179
CR  - Lv, Q. Z., Long, J. T., Gong, Z. F., Nong, K. Y., Liang, X. M., Qin, T., Huang, W., & Yang, L. (2021). Current state of knowledge on the antioxidant Nutritional effects and mechanisms of action of polyphenolic compounds. Natural Product Communications, 16(7), 1934578X211027745. https://doi.org/10.1177/1934578X211027745
CR  - Macho-González, A., Garcimartín, A., López-Oliva, M. E., Ruiz-Roso, B., Martín de la Torre, I., Bastida, S., Benedí, J., & Sánchez-Muniz, F. J. (2019). Can Carob-Fruit-Extract-Enriched Meat Improve the Lipoprotein Profile, VLDL-Oxidation, and LDL Receptor Levels Induced by an Atherogenic Diet in STZ-NAD-Diabetic Rats?. Nutrients, 11(2), 332. https://doi.org/10.3390/nu11020332
CR  - Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28(7), 412–419. https://doi.org/10.1007/BF00280883
CR  - Moumou, M., Mokhtari, I., Milenkovic, D., Amrani, S., & Harnafi, H. (2023). Carob (Ceratonia siliqua L.): A comprehensive review on traditional uses, chemical composition, pharmacological effects and toxicology (2002-2022). Journal of Biologically Active Products from Nature, 13(3), 179-223. https://doi.org/10.1080/22311866.2023.2237481
CR  - Mughni, A., Ekasaputra, V. M., Susanto, R. T., Prasetya, A. T., Putranto, I., & Erlangga, D. (2023). HOMA-IR level in obese type 2 diabetic rat model treated by Sleeve gastrectomy and pancreatic omentoplasty. Journal of Experimental and Clinical Medicine, 40(1), 27-30. https://doi.org/10.52142/omujecm.40.1.6
CR  - Nakamura, T., Terajima, T., Ogata, T., Ueno, K., Hashimoto, N., Ono, K., & Yano, S. (2006). Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. Biological & pharmaceutical bulletin, 29(6), 1167–1174. https://doi.org/10.1248/bpb.29.1167
CR  - Nemet, M., Vasilić, M., & Tomas, A. (2022). Lipid-Lowering Effects of Carob Extracts (Ceratonia siliqua): Proposed Mechanisms and Clinical Importance. Frontiers in pharmacology,13,921123. https://doi.org/10.3389/fphar.2022.921123
CR  - Nzekwe, S., Morakinyo, A., Oguntibeju, O., & Ayeleso, A. (2020). Effect of taraxacum officinale leaf extract on liver antioxidant status in streptozotocin-induced diabetic male wistar rats. African Journal of Biomedical Research, 23(3), 421-428.
CR  - Pellegrini, V., La Grotta, R., Carreras, F., Giuliani, A., Sabbatinelli, J., Olivieri, F., Berra, C. C., Ceriello, A., & Prattichizzo, F. (2024). Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment. Cells, 13(19), 1662. https://doi.org/10.3390/cells13191662
CR  - Qasem, M. A., Noordin, M. I., Arya, A., Alsalahi, A., & Jayash, S. N. (2018). Evaluation of the glycemic effect of Ceratonia siliqua pods (Carob) on a streptozotocin-nicotinamide induced diabetic rat model. PeerJ, 6, e4788. https://doi.org/10.7717/peerj.4788
CR  - Riaz, R., Parveen, S., Shafiq, N., Ali, A., & Rashid, M. (2024). Virtual screening, ADME prediction, drug-likeness, and molecular docking analysis of Fagonia indica chemical constituents against antidiabetic targets. Molecular diversity, 10.1007/s11030-024-10897-7. Advance online publication. https://doi.org/10.1007/s11030-024-10897-7
CR  - Ridker, P. M., & Rane, M. (2021). Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease. Circulation research, 128(11), 1728–1746. https://doi.org/10.1161/CIRCRESAHA.121.319077
CR  - Rodríguez, I. A., Serafini, M., Alves, I. A., Lang, K. L., Silva, F. R. M. B., & Aragón, D. M. (2022). Natural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review. Pharmaceutics, 15(1), 85. https://doi.org/10.3390/pharmaceutics15010085
CR  - Roseiro, L.B., Duarte, L.C., Oliveira, D.L., Roque, R., Bernardo-Gil, M.G., Martins, A.I., Sepúlveda, C., Almeida, J., Meireles, M., Gírio, F.M., & Rauter, A. P. (2013). Supercritical, ultrasound and conventional extracts from carob (Ceratonia siliqua L.) biomass: Effect on the phenolic profile and antiproliferative activity. Industrial Crops and Products, 47, 132-138. https://doi.org/10.1016/j.indcrop.2013.02.026
CR  - Rtibi, K., Selmi, S., Grami, D., Saidani, K., Sebai, H., Amri, M., Eto, B., & Marzouki, L. (2017). Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat. Journal of the science of food and agriculture, 97(8), 2664–2670. https://doi.org/10.1002/jsfa.8091
CR  - Schwartz, M. W., & Porte Jr, D. (2005). Diabetes, obesity, and the brain. Science, 307(5708), 375-379. https://doi.org/10.1126/science.1104344
CR  - Shrivastav, D., Kumbhakar, S. K., Srivastava, S., & Singh, D. D. (2024). Natural product-based treatment potential for type 2 diabetes mellitus and cardiovascular disease. World journal of diabetes, 15(7), 1603–1614. https://doi.org/10.4239/wjd.v15.i7.1603
CR  - Singh, R., Gholipourmalekabadi, M., & Shafikhani, S. H. (2024). Animal models for type 1 and type 2 diabetes: advantages and limitations. Frontiers in endocrinology, 15, 1359685. https://doi.org/10.3389/fendo.2024.1359685
CR  - Soliman, N. A. (2001). Effect of experimentally induced diabetes mellitus on serum leptin level and the role of insulin replacement therapy. The Egyptian Journal of Hospital Medicine, 3(1), 190-208. https://doi.org/10.21608/ejhm.2001.18912
CR  - Sugden, M., & Holness, M. (2011). Pathophysiology of diabetic dyslipidemia:implications for atherogenesis and treatment. Clinical Lipidology, 6(4), 401–411. https://doi.org/10.2217/clp.11.32
CR  - Szkudelski T. (2012). Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Experimental biology and medicine (Maywood, N.J.), 237(5), 481–490. https://doi.org/10.1258/ebm.2012.011372
CR  - Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023). Insulin Regulation of Hepatic Lipid Homeostasis. Comprehensive Physiology, 13(3), 4785–4809. https://doi.org/10.1002/cphy.c220015
UR  - https://doi.org/10.30607/kvj.1591051
L1  - https://dergipark.org.tr/tr/download/article-file/4392560
ER  -