Effectiveness of Celastrol in Reducing Inflammatory Cell Infiltration via H&E in the Liver of High-Fat Diet-Fed ApoE-Knockout Mice

Authors

  • Arifah Ahmad Damahuri Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia; Laboratory Animal Care Unit, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia
  • Thuhairah Hasrah Abdul Rahman Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia
  • Yakoh Karemdabeh Department of Chemistry, Faculty of Education, Fatoni University, Yala, Thailand
  • Nasibah Azme Laboratory Animal Care Unit, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia ; Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia

DOI:

https://doi.org/10.21834/e-bpj.v10iSI35.7505

Keywords:

Celastrol, Inflammatory cell, H&E staining, ApoE-knockout mice

Abstract

High-fat diet (HFD) promotes liver inflammation by increasing infiltration of inflammatory cells. This study analyzed the effect of celastrol on hepatic inflammation in ApoE-knockout mice on HFD. Treatment with celastrol (1.5, 2, or 2.5 mg/kg/day) for 4 weeks, followed by liver tissue staining with H&E. Quantification of infiltration areas was obtained with NDP.view 2 software and analyzed with the Kruskal-Wallis test. At the maximum dose (2.5 mg/kg), the inflammatory cell infiltration of the liver was significantly decreased in comparison with untreated HFD controls. These results justify the potential use of celastrol as an anti-inflammatory in diet-induced liver inflammation.

References

Allison, A. C., Cacabelos, R., Lombardi, V. R., Alvarez, X. A., & Vigo, C. (2001). Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease. Progress in neuro-psychopharmacology & biological psychiatry, 25(7), 1341–1357.

Bergwik, J., Liu, J., Padra, M., Bhongir, R. K. V., Tanner, L., Xiang, Y., Lundblad, M., Egesten, A., & Adner, M. (2024). A novel quinoline with airway relaxant effects and anti-inflammatory properties. Respiratory Research, 25.

Camargo, F. N., Matos, S. L., Araujo, L. C. C., Carvalho, C. R. O., Amaral, A. G., & Camporez, J. P. (2022). Western Diet-Fed ApoE Knockout Male Mice as an Experimental Model of Non-Alcoholic Steatohepatitis. Current Issues in Molecular Biology, 44(10), 4692–4703.

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204.

Duan, Y., Zeng, L., Zheng, C., Song, B., Li, F., Kong, X., & Xu, K. (2018). Inflammatory Links Between High Fat Diets and Diseases. Frontiers in Immunology, 9, 2649.

Elrazik, N. A. A., El-Mesery, M., & El-Shishtawy, M. M. (2022). Sesamol protects against liver fibrosis induced in rats by modulating lysophosphatidic acid receptor expression and TGF-β/Smad3 signaling pathway. Naunyn-schmiedeberg's Archives of Pharmacology, 395(8), 1003-1016.

Fischer, A. H., Jacobson, K. A., Rose, J., & Zeller, R. (2008). Hematoxylin and eosin staining of tissue and cell sections. Cold spring harbor protocols, 2008(5), pdb-prot4986.

Hammerich, L., & Tacke, F. (2023). Hepatic inflammatory responses in liver fibrosis. Nature Reviews Gastroenterology & Hepatology, 20(10), 633-646.

Liu, Y., Hua, X., Zhu, S., Wang, C., Chen, X., Shi, Y., Song, J., & Zhou, W. (2023). Automated identification and quantification of myocardial inflammatory infiltration in digital histological images to diagnose myocarditis. arXiv preprint arXiv:2307.01098.

Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454(7203), 428-435.

Pahwa, R., Goyal, A., & Jialal, I. (2018). Chronic inflammation. StatPearls Publishing LLC.

Schierwagen, R., Maybüchen, L., Zimmer, S., Hittatiya, K., Bäck, C., Klein, S., Uschner, F. E., Reul, W., Boor, P., Nickenig, G., Strassburg, C. P., Trautwein, C., Plat, J., Lütjohann, D., Sauerbruch, T., Tacke, F., & Trebicka, J. (2015). Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis. Scientific Reports, 5.

Schneider, L. J., Santiago, I., Johnson, B., Stanley, A. H., Penaredondo, B., & Lund, A. K. (2023). Histological features of non-alcoholic fatty liver disease revealed in response to mixed vehicle emission exposure and consumption of a high-fat diet in wildtype C57Bl/6 male mice. Ecotoxicology and Environmental Safety, 261, 115094.

Sjölin, H., Tomasello, E., Mousavi-Jazi, M., Bartolazzi, A., Kärre, K., Vivier, E., & Cerboni, C. (2002). Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell–mediated resistance to murine cytomegalovirus infection. Journal of Experimental Medicine, 195(7), 825-834.

Stanton, M. C., Chen, S. C., Jackson, J. V., Rojas-Triana, A., Kinsley, D., Cui, L., ... & Jenh, C. H. (2011). Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice. Journal of inflammation, 8, 1-14.

Wang, Y., Li, C., Gu, J., Chen, C., Duanmu, J., Miao, J., Yao, W., Tao, J., Tu, M., Xiong, B., Zhao, L., & Liu, Z. (2020). Celastrol exerts anti-inflammatory effect in liver fibrosis via activation of AMPK-SIRT3 signalling. Journal of Cellular and Molecular Medicine, 24(1), 941–953.

Wree, A., McGeough, M. D., Inzaugarat, M. E., Eguchi, A., Schuster, S., Johnson, C. D., ... & Feldstein, A. E. (2018). NLRP3 inflammasome driven liver injury and fibrosis: roles of IL‐17 and TNF in mice. Hepatology, 67(2), 736-749.

Zhang, Y., Geng, C., Liu, X., Li, M., Gao, M., Liu, X., Fang, F., & Chang, Y. (2017). Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1. Molecular Metabolism, 6(1), 138–147.

Zhu, Y., Wan, N., Shan, X., Deng, G., Xu, Q., Ye, H., & Sun, Y. (2021). Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice. Acta Pharmaceutica Sinica B, 11(5), 1200–1212.

Published

2025-11-30

How to Cite

Ahmad Damahuri, A., Abdul Rahman, T. H., Karemdabeh, Y., & Azme, N. (2025). Effectiveness of Celastrol in Reducing Inflammatory Cell Infiltration via H&E in the Liver of High-Fat Diet-Fed ApoE-Knockout Mice . Environment-Behaviour Proceedings Journal, 10(SI35). https://doi.org/10.21834/e-bpj.v10iSI35.7505