Reducing of Ethanol-Induced Liver Injury by Camellia sinensis Extract in Rats through Immunological and Oxidative Stress Pathways

Hashim  Abass

doi:10.17605/cajmns.v6i3.2816

Hashim Abass Department of Pathology, College of Medicine, University of Diyala, Diyala, Iraq

DOI: https://doi.org/10.17605/cajmns.v6i3.2816

Keywords: Camellia Sinensis, Inflammation, TNF-Α, IL-6, Malondialdehyde

Abstract

Camellia sinensis exhibits potential hepatoprotective properties attributed to its high polyphenolic content, especially catechins. This study sought to assess the efficacy of C. sinensis extract in mitigating ethanol-induced hepatic injury in a rat model, with particular emphasis on biomarkers associated with oxidative stress and inflammatory responses. Adult male of Wistar rats were allocated into four experimental groups , control, ethanol-treated (ETOH), ethanol plus low-dose C. sinensis (ETOH + CSL) and ethanol plus high-dose C. sinensis (ETOH + CSH). Hepatic damage induced by ethanol was evaluated by quantifying serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) as a key of oxidative stress biomarker. Ethanol exposure markedly increased TNF-α, IL-6, and MDA levels relative to the control group, indicating pronounced hepatic inflammation and oxidative stress. However, supplementation with C. sinensis extract dose-dependently reduced TNF-α and IL-6. Particularly, the high-dose C. sinensis group (ETOH + CSH) exhibited a significant reduction in both pro-inflammatory cytokines and MDA levels, emphasizing its strong role as anti-inflammatory and antioxidant. The conclusion show that C. sinensis extract, particularly at higher doses, can mitigate ethanol-induced hepatic damage by modulating inflammation and oxidative stress and these results support the potential therapeutic use of C. sinensis in treating alcoholic liver diseases.

References

B. N. Singh, S. Shankar, and R. K. Srivastava, “Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications,” Biochem. Pharmacol., vol. 82, no. 12, pp. 1807–1821, 2011.

P. Lam, F. Cheung, H. Y. Tan, N. Wang, M. F. Yuen, and Y. Feng, “Hepatoprotective effects of Chinese medicinal herbs: a focus on anti-inflammatory and anti-oxidative activities,” Int. J. Mol. Sci., vol. 17, no. 4, p. 465, 2016.

S. Li et al., “The role of oxidative stress and antioxidants in liver diseases,” Int. J. Mol. Sci., vol. 16, no. 11, pp. 26087–26124, 2015.

S. Samanta, “Potential bioactive components and health promotional benefits of tea (Camellia sinensis),” J. Am. Nutr. Assoc., vol. 41, no. 1, pp. 65–93, 2022.

M. Nikoo, J. M. Regenstein, and H. Ahmadi Gavlighi, “Antioxidant and antimicrobial activities of (‐)‐epigallocatechin‐3‐gallate (EGCG) and its potential to preserve the quality and safety of foods,” Compr. Rev. Food Sci. Food Saf., vol. 17, no. 3, pp. 732–753, 2018.

J. Kruszka, J. Martyński, K. Szewczyk-Golec, A. Woźniak, and J. Nuszkiewicz, “The Role of Selected Flavonoids in Modulating Neuroinflammation in Alzheimer’s Disease: Mechanisms and Therapeutic Potential,” Brain Sci., vol. 15, no. 5, p. 485, 2025.

H. Y. Zhang, H. L. Wang, G. Y. Zhong, and J. X. Zhu, “Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury,” Pharm. Biol., vol. 56, no. 1, pp. 594–611, 2018.

S. Li, M. Hong, H.-Y. Tan, N. Wang, and Y. Feng, “Insights into the role and interdependence of oxidative stress and inflammation in liver diseases,” Oxid. Med. Cell. Longev., vol. 2016, no. 1, p. 4234061, 2016.

S. K. Asrani, H. Devarbhavi, J. Eaton, and P. S. Kamath, “Burden of liver diseases in the world,” J. Hepatol., vol. 70, no. 1, pp. 151–171, 2019.

Y. M. Yang, Y. E. Cho, and S. Hwang, “Crosstalk between oxidative stress and inflammatory liver injury in the pathogenesis of alcoholic liver disease,” Int. J. Mol. Sci., vol. 23, no. 2, p. 774, 2022.

D. Grotto et al., “Importance of the lipid peroxidation biomarkers and methodological aspects for malondialdehyde quantification,” Quim. Nova, vol. 32, pp. 169–174, 2009.

T. Zhao, C. Li, S. Wang, and X. Song, “Green tea (Camellia sinensis): A review of its phytochemistry, pharmacology, and toxicology,” Molecules, vol. 27, no. 12, p. 3909, 2022.

A. M. Ali, N. A. Hussein, D. Jawad, H. H. Abed, and S. M. Mekkey, “Hepatotoxic effects of Stevia rebaudiana leaf extract and commercial stevia on rats: a comparative study,” Rev. Clin. Pharmacol. Pharmacokinet., vol. 38, no. 2, pp. 69–72, 2024.

A. G. Al-Ziaydi, H. H. Abed, A. M. Ali, E. M. Nayif, and A. H. Fadhel, “Evaluate toxic effect of bisphenol a on kidney of male mice and mitigation its effect by green tea extract,” J. Glob. Pharma Technol., vol. 12, no. 2, pp. 664–670, 2020.

H. H. Abed, E. Alwasiti, and A. T. Tawfeeq, “Titanium nanoparticles conjugated with streptokinase as a modified thrombolytic agent,” Int. J. Curr. Pharm. Res, vol. 112, pp. 18–25, 2020.

H. H. Abed, A. M. Ali, and A. G. Al-Ziaydi, “Evaluation level of serum vitamin B12 in Iraqi patients with diabetes mellitus type 2, who used the metformin drug as a hypoglycemic agent,” Pak. J. Pharm. Sci, vol. 36, no. 2, pp. 425–429, 2023.

A. G. Al-Ziaydi, H. H. Abed, A. M. Ali, E. Mobder, and A. H. F. Nayif, “Evaluate Toxic Effect of Bisphenol A on Kidney of Male Mice and Mitigation Its Effect by Green Tea Extract,” 2009.

R. F. de Araújo Júnior et al., “Carvedilol improves inflammatory response, oxidative stress and fibrosis in the alcohol-induced liver injury in rats by regulating Kuppfer cells and hepatic stellate cells,” PLoS One, vol. 11, no. 2, p. e0148868, 2016.

M. Menegazzi, R. Campagnari, M. Bertoldi, R. Crupi, R. Di Paola, and S. Cuzzocrea, “Protective effect of epigallocatechin-3-gallate (EGCG) in diseases with uncontrolled immune activation: could such a scenario be helpful to counteract COVID-19?,” Int. J. Mol. Sci., vol. 21, no. 14, p. 5171, 2020.

D. Mokra, M. Joskova, and J. Mokry, “Therapeutic effects of green tea polyphenol (‒)-Epigallocatechin-3-Gallate (EGCG) in relation to molecular pathways controlling inflammation, oxidative stress, and apoptosis,” Int. J. Mol. Sci., vol. 24, no. 1, p. 340, 2022.

G. Tang, Y. Xu, C. Zhang, N. Wang, H. Li, and Y. Feng, “Green tea and epigallocatechin gallate (EGCG) for the management of nonalcoholic fatty liver diseases (NAFLD): Insights into the role of oxidative stress and antioxidant mechanism,” Antioxidants, vol. 10, no. 7, p. 1076, 2021.

C. Martins-Gomes, F. M. Nunes, and A. M. Silva, “Natural products as dietary agents for the prevention and mitigation of oxidative damage and inflammation in the intestinal barrier,” Antioxidants, vol. 13, no. 1, p. 65, 2024.

A. M. Posadino et al., “Medicinal and mechanistic overview of artemisinin in the treatment of human diseases,” Biomed. Pharmacother., vol. 163, p. 114866, 2023.

Y. Yang et al., “Exploring the potential of treating chronic liver disease targeting the PI3K/Akt pathway and polarization mechanism of macrophages,” Heliyon, vol. 9, no. 6, 2023.

H. Han et al., “Danger signals in liver injury and restoration of homeostasis,” J. Hepatol., vol. 73, no. 4, pp. 933–951, 2020.

E. Karatayli, R. A. Hall, S. N. Weber, S. Dooley, and F. Lammert, “Effect of alcohol on the interleukin 6-mediated inflammatory response in a new mouse model of acute-on-chronic liver injury,” Biochim. Biophys. Acta (BBA)-Molecular Basis Dis., vol. 1865, no. 2, pp. 298–307, 2019.

E. Slevin et al., “Kupffer cells: inflammation pathways and cell-cell interactions in alcohol-associated liver disease,” Am. J. Pathol., vol. 190, no. 11, pp. 2185–2193, 2020.

M. Pae and D. Wu, “Immunomodulating effects of epigallocatechin-3-gallate from green tea: mechanisms and applications,” Food Funct., vol. 4, no. 9, pp. 1287–1303, 2013.

A. Payne, S. Nahashon, E. Taka, G. M. Adinew, and K. F. A. Soliman, “Epigallocatechin-3-Gallate (EGCG): New therapeutic perspectives for neuroprotection, aging, and neuroinflammation for the modern age,” Biomolecules, vol. 12, no. 3, p. 371, 2022.

H. Khan et al., “Targeting NF-κB signaling pathway in cancer by dietary polyphenols,” Crit. Rev. Food Sci. Nutr., vol. 60, no. 16, pp. 2790–2800, 2020.

H. S. Youn et al., “Suppression of MyD88-and TRIF-dependent signaling pathways of Toll-like receptor by (−)-epigallocatechin-3-gallate, a polyphenol component of green tea,” Biochem. Pharmacol., vol. 72, no. 7, pp. 850–859, 2006.

S. K. Das and D. M. Vasudevan, “Alcohol-induced oxidative stress,” Life Sci., vol. 81, no. 3, pp. 177–187, 2007.

G. L. Tipoe, T.-M. Leung, M.-W. Hung, and M.-L. Fung, “Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection,” Cardiovasc. Haematol. Disord. Targetsrug Targets-Cardiovascular Hematol. Disord., vol. 7, no. 2, pp. 135–144, 2007.

C. Chen, Q. Liu, L. Liu, Y. Hu, and Q. Feng, “Potential biological effects of (‐)‐epigallocatechin‐3‐gallate on the treatment of nonalcoholic fatty liver disease,” Mol. Nutr. Food Res., vol. 62, no. 1, p. 1700483, 2018.

A. E. Bulboaca et al., “The effect of nano-epigallocatechin-gallate on oxidative stress and matrix metalloproteinases in experimental diabetes mellitus,” Antioxidants, vol. 9, no. 2, p. 172, 2020.

R. Domitrović and I. Potočnjak, “A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives,” Arch. Toxicol., vol. 90, no. 1, pp. 39–79, 2016.

P. Cao et al., “Angelica sinensis polysaccharide protects against acetaminophen-induced acute liver injury and cell death by suppressing oxidative stress and hepatic apoptosis in vivo and in vitro,” Int. J. Biol. Macromol., vol. 111, pp. 1133–1139, 2018.

S. Sengottuvelu, S. Duraisami, J. Nandhakumar, R. Duraisami, and M. Vasudevan, “Hepatoprotective activity of Camellia sinensis and its possible mechanism of action,” 2008.