Hepatoprotective Effect of Silymarin Peptide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice
DOI:
https://doi.org/10.24079/cajms.2024.03.005Keywords:
Acute liver injury, Carbon tetrachloride (CCl4), Silymarin, Apoptosis, HepatoprotectiveAbstract
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.
Downloads
185
References
1. Peng J, Li J, Huang J, et al. p300/CBP inhibitor A-485 alleviates acute liver injury by regulating macrophage activation and polarization. Theranostics. 2019;9(26):8344-8361. https://doi.org/10.7150/thno.30707
2. Yang W, Tao K, Zhang P, et al. Maresin 1 protects against lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting macrophage pyroptosis and inflammatory response. Biochem Pharmacol. 2022, 195:114863. https://doi.org/10.1016/j.bcp.2021.114863
3. Li X, Sun R, Liu R. Natural products in licorice for the therapy of liver diseases: Progress and future opportunities. Pharmacol Res. 2019, 144:210-226. https://doi.org/10.1016/j.phrs.2019.04.025
4. Gillessen A, Schmidt HH. Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Adv Ther. 2020, 37(4):1279-1301. https://doi.org/10.1007/s12325-020-01251-y
5. Xie Y, Zhang D, Zhang J, et al. Metabolism, Transport and Drug-Drug Interactions of Silymarin. Molecules. 2019,24(20):3693. https://doi.org/10.3390/molecules24203693
6. Di Costanzo A, Angelico R. Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art. Molecules. 2019,24(11):2155. https://doi.org/10.3390/molecules24112155
7. Ferraz AC, Almeida LT, da Silva Caetano CC, et al. Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection. Antiviral Res. 2021,194:105168. https://doi.org/10.1016/j.antiviral.2021.105168
8. Okda TM, Abd-Alhaseeb MM, Barka K, et al. Ginger potentiates the effects of silymarin on liver fibrosis induced by CCL4: the role of galectin-8. Eur Rev Med Pharmacol Sci. 2019,23(2):885-891. https://doi.org/10.26355/eurrev_201901_16903
9. Jiang YC, Han X, Dou JY, et al. Protective role of Siberian onions against toxin-induced liver dysfunction: an insight into health-promoting effects. Food Funct. 2022,13(8):4678-4690. https://doi.org/10.1039/d1fo04404d
10. Zhang X, Kuang G, Wan J, et al. Salidroside protects mice against CCl4-induced acute liver injury via down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation. Int Immunopharmacol. 2020,85:106662. https://doi.org/10.1016/j.intimp.2020.106662
11. Ullah H, Khan A, Baig MW, et al. Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice. BMC Complement Med Ther. 2020,20(1):115. https://doi.org/10.1186/s12906-020-02906-7
12. Wang B, Li J, Jiao J, et al. Myeloid DJ-1 deficiency protects acetaminophen-induced acute liver injury through decreasing inflammatory response. Aging. 2021,13(14):18879-18893. https://doi.org/10.18632/aging.203340
13. Li Q, Tan Y, Chen S, et al. Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-kappaB signaling. J Recept Signal Transduct Res. 2021,41(3):294-303. https://doi.org/10.1080/10799893.2020.1808675
14. Savio LEB, de Andrade Mello P, Figliuolo VR, et al. CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury. J Hepatol. 2017,67(4):716-726. http://dx.doi.org/10.1016/j.jhep.2017.05.021
15. Cheng R, Billet S, Liu C, et al. Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells. Oncogene. 2020,39(7):1543-1556. https://www.nature.com/articles/s41388-019-1084-z
16. Zheng J, Chen L, Lu T, et al. MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKalpha activation. Cell Death Dis. 2020,11(4):256. https://doi.org/10.1038/s41419-020-2424-1
17. Chen SN, Tan Y, Xiao XC, et al. Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis. Acta Pharmacol Sin. 2021,42(10):1610-1619. https://doi.org/10.1038/s41401-020-00597-x
18. Dai C, Xiao X, Li D, et al. Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis. Cell Death Dis. 2018,9(12):1164. https://doi.org/10.1038/s41419-018-1136-2
19. Jia S, Chen Q, Wu J, Yao X, Shao J, Cheng X, Zhang C, Cen D, Wang Y, Shen Z et al: Danshensu derivative ADTM ameliorates CCl(4)‑induced acute liver injury in mice through inhibiting oxidative stress and apoptosis. Pathol Res Pract. 2021,228:153656. https://doi.org/10.1016/j.prp.2021.153656
20. Huang X, Chu X, Tian Y, et al. Preventive effect of salmon sperm DNA on acute carbon tetrachloride-induced liver injury in mice through Nrf2/ARE and mitochondrial apoptosis pathway. Food Sci. nutr. 2023,11(2):733-742. https://doi.org/10.1002/fsn3.3109
21. Cai J, Kong D, Long Z, et al. Targeting PARK7 Improves Acetaminophen-Induced Acute Liver Injury by Orchestrating Mitochondrial Quality Control and Metabolic Reprogramming. Antioxidants. 2022,11(11):2128. https://doi.org/10.3390/antiox11112128
22. Rostami A, Baluchnejadmojarad T, Roghani M. Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation. Mol Biol Rep. 2022,49(6):4179-4191. https://doi.org/10.1007/s11033-022-07251-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Mongolian National University of Medical Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
