Hepatoprotective Effect of Silymarin Peptide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Authors

  • Ananda International School of Mongolian Traditional Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
  • Tsend-Ayush Damba International School of Mongolian Traditional Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
  • Xiulan Su Clinical Medical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Tong Dao Street 1, Huimin District, 010050 Hohhot, Inner Mongolia, China
  • Khurelbaatar Nyamdavaa Department of Physiology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

DOI:

https://doi.org/10.24079/cajms.2024.03.005

Keywords:

Acute liver injury, Carbon tetrachloride (CCl4), Silymarin, Apoptosis, Hepatoprotective

Abstract

Objective: Liver diseases and injuries are significant global health concerns; in particular, acute liver injury (ALI) is a prominent cause of liver diseases and is associated with high morbidity and mortality. The application of natural products in preventing and treating liver diseases is consid­erable. Silymarin and silymarin peptides derive from the Milk thistle (Silybum marianum). Still, they differ in their composition and effects: Silymarin is a complex mixture of flavonoids, primarily made up of silybinin, silybinin, and silychristin. Silymarin is well-known for its antioxidant, an­ti-inflammatory, and hepatoprotective properties. It is often a dietary supplement to support liver health. Silymarin Peptide refers to specific peptides derived from silymarin. These peptides have more enhanced bioavailability and activity of effect compared to the whole silymarin compound. Therefore, this study aimed to investigate the hepatoprotective effects of silymarin peptide on acute liver injury (ALI) in mice induced by carbon tetrachloride (CCl4) compared with Silymarin. Methods: Forty-eight male C57BL/6J mice were randomly divided into six groups (n=8 per group): Control group: regular saline+olive oil, Negative control group: 10% CCl4 solution (10 μl/g), Treatment group 1: CCl4+50 mg/kg silymarin peptide, Treatment group 2: CCl4+100 mg/ kg silymarin peptide, Treatment group 3: CCl4+200 mg/kg silymarin peptide, and Positive control group: CCl4+100 mg/kg silymarin. The treatment of silymarin was used as a positive control. At the end of the experiments, mice were euthanized, and the blood and liver samples were collect­ed. Results: The results showed that silymarin peptide ameliorated the histopathological dam­age of liver tissues caused by CCl4 and decreased the CCl4-induced serum AST and ALT levels, among which the 200 mg/kg dose demonstrated the most notable protective effect. Additionally, silymarin peptide showed no significant influence on CCL2 levels but markedly reduced TNF-α and CXCL5 levels, with the most apparent impact at 100 mg/kg. Finally, the terminal deoxynu­cleotidyl transferase‐mediated dUTP‐nick end labeling (TUNEL) staining indicated that the 200 mg/kg dose of silymarin peptide restrained CCl4-induced hepatocytic apoptosis. Conclusion: Silymarin peptide alleviated CCl4-induced ALI in mice by inhibiting inflammatory cytokines release and decreasing hepatocyte apoptosis.

 

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References

1. Kim MJ, Suh DJ. Profiles of serum bile acids in liver diseases. Korean J Intern Med. 1986;1:37-42. https://doi.org/10.3904/kjim.1986.1.1.37

2. Xun Z. Yao X, Ou Q. Emerging roles of bile acids in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Cell Mol Immunol. 2023;20:1087–1089. https://doi.org/10.1038/s41423-023-01026-9

3. Shao JW, Ge TT, Chen SZ, et al. Role of bile acids in liver diseases mediated by the gut microbiome. World J Gastroenterol. 2021;14:3010-3021. https://doi.org/10.3748/wjg.v27.i22.3010

4. Chiang JYL. Bile acid metabolism and signaling in liver disease and therapy. Liver Res. 2017; 1:3-9. https://doi.org/10.1016/j.livres.2017.05.001

5. Cai J, Rimal B, Jiang C, et al. Patterson AD. Bile acid metabolism and signaling, the microbiota, and metabolic disease. Pharmacol Ther. 2022;237:108-113. https://doi.org/10.1016/j.pharmthera.2022.108238

6. Wang X, Xie G, Zhao A, et al. Serum bile acids are associated with pathological progression of hepatitis B-induced cirrhosis. J Proteome Res. 2016;1:1126-1134. https://doi.org/10.1021/acs.jproteome.5b00217

7. Allen K, Jaeschke H, Copple BL. Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol. 2011;178:175-186. https://doi.org/10.1016/j.ajpath.2010.11.026

8. Mouzaki M, Wang AY, Bandsma R, et al. Bile acids and dysbiosis in non-alcoholic fatty liver disease. PLoS One. 2016;20:e0151829. https://doi.org/10.1371/journal.pone.0151829

9. Perumpail BJ, Li AA, Iqbal U, et al. Potential therapeutic benefits of herbs and supplements in patients with NAFLD. Diseases. 2018;6:80-89. https://doi.org/10.3390/diseases6030080

10. Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med. 2013;10:210-229. https://doi.org/10.4314/ajtcam.v10i5.2

11. Wang L, Li S, Yao Y, et al. The role of natural products in the prevention and treatment of pulmonary fibrosis: A review. Food funct. 2021;12:990-1007. https://doi.org/10.1039/D0FO03001E

12. Langhi C, Vallier M, Bron A, et al. A polyphenol-rich plant extract prevents hypercholesterolemia and modulates gut microbiota in western diet-fed mice. Front Cardiovasc Med. 2024;11:134-138. https://doi.org/10.3389/fcvm.2024.1342388

13. Kim W, Baek WH, Yun SH, et al. Platycodi radix extract prevents hepatic steatosis by enhancing bile acid synthesis in a high-fat diet-induced fatty liver mouse model. Nutrients. 2024;16:893-899. https://doi.org/10.3390/nu16060893

14. Atanasov AG, Zotchev SB, Dirsch VM, et al. International natural product sciences taskforce; supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20:200-216.

15. Ekiert HM, Szopa A. Biological activities of natural products. Molecules. 2020;25:57-69. https://doi.org/10.3390/molecules25235769

16. Azab A, Nassar A, Azab AN. Anti-inflammatory activity of natural products. Molecules. 2016; 21:13-21. https://doi.org/10.3390/molecules21101321

17. Zhang L, Song J, Kong L, et al. The strategies and techniques of drug discovery from natural products. Pharmacol Ther. 2020;216:107-109. https://doi.org/10.1016/j.pharmthera.2020.107686

18. Nuzzo G, Senese G, Gallo C, et al. Antitumor potential of immunomodulatory natural products. Mar Drugs. 2022;20:386-91. https://doi.org/10.3390/md20060386

19. Duarte AP, Luís Â, Gallardo E. Natural products: therapeutic properties and beyond II. Molecules. 2022;27:61-68. https://doi.org/10.3390/molecules27196140

20. Yang JM, Sun Y, Wang M, et al. Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease. World J Gastroenterol. 2019;25:5105-5119. https://doi.org/10.3748/wjg.v25.i34.5105

21. Wang R, Kong J, Wang D, et al. A survey of Chinese herbal ingredients with liver protection activities. Chi Med. 2007;10:51-71. https://doi.org/10.1186/1749-8546-2-5

22. Dai X, Feng J, Chen Y, et al. Traditional Chinese medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Chi Med. 2021;16:68-71. https://doi.org/10.1186/s13020-021-00469-4

23. Kayani S, Ahmad M, Zafar M, et al. Ethnobotanical uses of medicinal plants for respiratory disorders among the inhabitants of Gallies - Abbottabad, Northern Pakistan. J Ethnopharmacol. 2014;156:47-60. https://doi.org/10.1016/j.jep.2014.08.005

24. Zhao X, Guo Y, Zhang Y, et al. Monoterpene derivatives from the flowers of the Hemerocallis minor Mill. Phytochemistry Letters. 2017;21:134-138. https://doi.org/10.1016/j.phytol.2017.06.006

25. Lin YL, Lu CK, Huang YJ, et al. Antioxidative caffeoylquinic acids and flavonoids from Hemerocallis fulva flowers. J Agric Food Chem. 2011;59:8789-8795. https://doi.org/10.1021/jf201166b

26. Glasl S, Tsendayush D, Batchimeg U, et al. Choleretic effects of the Mongolian medicinal plant Saussurea amara in the isolated perfused rat liver. Planta Med. 2007;73:59-66. https://doi.org/10.1055/s-2006-957063

27. Accatino L, Pizarro M, Solís N, et al. Effects of diosgenin, a plant-derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat. Hepatology. 1998;28:129-40. https://doi.org/10.1002/hep.510280118

28. Obmann A, Tsendayush D, Thalhammer T, et al. Extracts from the Mongolian traditional medicinal plants Dianthus versicolorFisch. and Lilium pumilum Delile stimulate bile flow in an isolated perfused rat liver model. J Ethnopharmacol. 2010;131:555-561. https://doi.org/10.1016/j.jep.2010.07.029

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Published

2024-09-27

How to Cite

Ananda, Damba, T.-A., Su, X., & Nyamdavaa, K. (2024). Hepatoprotective Effect of Silymarin Peptide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice. Central Asian Journal of Medical Sciences, 10(3), 123–129. https://doi.org/10.24079/cajms.2024.03.005

Issue

Vol. 10 No. 3 (2024)

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Articles

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