Emodin attenuates insulin resistance in the gastrocnemius muscle by modulating the expression of IL-1βTNF-α/NF-kB-mediated signalling in streptozotocin-induced diabetic Rats
DOI:
https://doi.org/10.52783/jns.v14.2329Keywords:
Type 2 diabetes, Emodin, Insulin resistance, Gastrocnemius muscle and IL-1beta/TNF-α/NF-kB signaling pathwayAbstract
Diabetes mellitus, particularly type 2 diabetes (T2DM), is characterized by insulin resistance, oxidative stress, and inflammation, which contribute to metabolic dysfunction. This study aimed to evaluate the effects of emodin on oxidative stress, inflammatory cytokines, and insulin signaling in a Streptozotocin (STZ)-induced diabetic rat model. Type 2 diabetes was induced by an intraperitoneal injection of streptozotocin (35 mg/kg body weight in 0.1 M citrate buffer, pH 4.5). The rats were divided into five groups, each consisting of six animals: Group I (normal rats, vehicle control), Group II (Type 2 diabetic rats), Group III (Type 2 diabetic rats treated with Emodin at 40 mg/kg b.wt/day orally for 45 days), Group IV (Type 2 diabetic rats treated with metformin), and Group V (control with Emodin). Emodin treatment significantly reduced oxidative stress markers (H₂O₂: 32±2.45 µm, OH: 40±2.9 µm), restored antioxidant enzyme activities (CAT: 15±0.84 ng/L, GPX: 27±1.8 pmol/ml), and reduced inflammatory cytokines (TNF-α: 180±11.64 pg/ml, IL-1β: 360±28.63 pg/ml, NF-kB: 140±8.9 ng/L). Additionally, emodin treatment enhanced the expression of insulin signaling molecules, including IR, IRS-1, PI3K, AKT, GLUT4, and AS160, indicating improved insulin sensitivity. These findings suggest that emodin can modulate oxidative stress, inflammation, and insulin resistance, providing a promising therapeutic approach for type 2 diabetes. Further studies are necessary to explore its clinical relevance and underlying molecular mechanisms.
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Forbes, J. M., & Cooper, M. E. (2013). Mechanisms of diabetic complications. Physiological reviews, 93(1), 137-188.
Roy, J. R., Janaki, C. S., Jayaraman, S., Periyasamy, V., Balaji, T., Vijayamalathi, M., & Veeraraghavan, V. P. (2022). Carica papaya reduces muscle insulin resistance via IR/GLUT4 mediated signaling mechanisms in high fat diet and streptozotocin-induced type-2 diabetic rats. Antioxidants, 11(10), 2081.
DeFronzo, R. A., & Tripathy, D. (2009). Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes care, 32(Suppl 2), S157.
Deenadayalan, A., Subramanian, V., Paramasivan, V., Veeraraghavan, V. P., Rengasamy, G., Coiambatore Sadagopan, J., ... & Jayaraman, S. (2021). Stevioside attenuates insulin resistance in skeletal muscle by facilitating IR/IRS-1/Akt/GLUT 4 signaling pathways: An in vivo and in silico approach. Molecules, 26(24), 7689.
Yaribeygi, H., Sathyapalan, T., Atkin, S. L., & Sahebkar, A. (2020). Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxidative medicine and cellular longevity, 2020(1), 8609213.
Zhang, J., Yu, X. H., Yan, Y. G., Wang, C., & Wang, W. J. (2015). PI3K/Akt signaling in osteosarcoma. Clinica chimica acta, 444, 182-192.
Narasimhan, A., Sampath, S., Jayaraman, S., & Karundevi, B. (2013). Estradiol favors glucose oxidation in gastrocnemius muscle through modulation of insulin signaling molecules in adult female rats. Endocrine Research, 38(4), 251-262.
Jayaraman, S., Natarajan, S. R., Veeraraghavan, V. P., & Jasmine, S. (2023). Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). Journal of Oral Biology and Craniofacial Research, 13(6), 704-713.
Song, P., Kim, J. H., Ghim, J., Yoon, J. H., Lee, A., Kwon, Y., ... & Ryu, S. H. (2013). Emodin regulates glucose utilization by activating AMP-activated protein kinase. Journal of Biological Chemistry, 288(8), 5732-5742.
Bing, S., Haoqiang, Z., Chunyu, M., Yali, Y., Jing, W., Yumeng, G., ... & Xuezheng, L. (2018). The effects of emodin on insulin resistance in KKAy mice with diabetes mellitus. Pharmacognosy Magazine, 14(56).
Song, Y. P., Fan, X. F., Guo, Z. Y., Fan, Y. J., & Yang, J. L. (2017). Therapeutic effects of emodin in type 2 diabetes mellitus in KKAy mouse model. Int J Clin Exp Med, 10(10), 14408-14413.
Wu, Z., Chen, Q., Ke, D., Li, G., & Deng, W. (2014). Emodin protects against diabetic cardiomyopathy by regulating the AKT/GSK-3β signaling pathway in the rat model. Molecules, 19(9), 14782-14793.
Pazhani, J., Chanthu, K., Jayaraman, S., & Varun, B. R. (2023). Evaluation of salivary MMP-9 in oral squamous cell carcinoma and oral leukoplakia using ELISA. Journal of Oral and Maxillofacial Pathology, 27(4), 649-654.
Cao, Y., Chang, S., Dong, J., Zhu, S., Zheng, X., Li, J., ... & Zhang, Y. (2016). Emodin ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle. European Journal of Pharmacology, 780, 194-201.
Xue, J., Ding, W., & Liu, Y. (2010). Anti-diabetic effects of emodin involved in the activation of PPARγ on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice. Fitoterapia, 81(3), 173-177.
Sagar, S., Ramani, P., Moses, S., Gheena, S., & Selvaraj, J. (2024). Correlation of salivary cytokine IL-17A and 1, 25 dihydroxycholecalciferol in patients undergoing orthodontic treatment. Odontology, 1-10.
Bortolon, J. R., Murata, G. M., Borges, L., Weimann, E., Silva, M. B. B., Dermargos, A., & Hatanaka, E. (2020). Recovery of diabetic rats after physical exhaustion: kinetic alterations in muscle inflammation and muscle-signaling proteins to atrophy and hypertrophy. Frontiers in Physiology, 11, 573416.
Lima Leite, A., Gualiume Vaz Madureira Lobo, J., Barbosa da Silva Pereira, H. A., Silva Fernandes, M., Martini, T., Zucki, F., ... & Buzalaf, M. A. R. (2014). Proteomic analysis of gastrocnemius muscle in rats with streptozotocin-induced diabetes and chronically exposed to fluoride. PloS one, 9(9), e106646.
Devasagayam, T. P., & Tarachand, U. (1987). Decreased lipid peroxidation in the rat kidney during gestation. Biochemical and biophysical research communications, 145(1), 134-138.
Pick, E., & Keisari, Y. (1981). Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages—induction by multiple nonphagocytic stimuli. Cellular immunology, 59(2), 301-318.
Puntarulo, S., & Cederbaum, A. I. (1988). Effect of oxygen concentration on microsomal oxidation of ethanol and generation of oxygen radicals. Biochemical Journal, 251(3), 787-794.
Fourney, R. M., (1988). Northern blotting: efficient RNA staining and transfer. Focus, 10, 1.
Kharroubi, A. T., & Darwish, H. M. (2015). Diabetes mellitus: The epidemic of the century. World journal of diabetes, 6(6), 850.
Mason, S., & Wadley, G. D. (2014). Skeletal muscle reactive oxygen species: a target of good cop/bad cop for exercise and disease. Redox Report, 19(3), 97-106.
Selvaraj, J., Sathish, S., Mayilvanan, C., & Balasubramanian, K. (2013). Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat. Molecular and cellular biochemistry, 372, 113-126.
Sruthi, M. A., Mani, G., Ramakrishnan, M., & Selvaraj, J. (2023). Dental caries as a source of Helicobacter pylori infection in children: An RT‐PCR study. International Journal of Paediatric Dentistry, 33(1), 82-88.
Yasothkumar, D., Ramani, P., Jayaraman, S., Ramalingam, K., & Tilakaratne, W. M. (2024). Expression Profile of Circulating Exosomal microRNAs in Leukoplakia, Oral Submucous Fibrosis, and Combined Lesions of Leukoplakia and Oral Submucous Fibrosis. Head and Neck Pathology, 18(1), 28.
Zhang, R., Zhu, R., & Xu, J. (2010). Molecular mechanisms of emodin in inhibiting insulinresist. Shanghai J Tradit Chin Med, 44(8), 71-73.
Fathima, J. S., Jayaraman, S., Sekar, R., & Syed, N. H. (2024). The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders. Odontology, 1-10.
Song, B., & Liu, X. Z. (2011). Emodin improves insulin sensitivity in KKAy diabetic mice. Chinese PLA Postgrad Med, 32, 1274-1276.
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