Volume 15, Issue 1 (April 2021)
Qom Univ Med Sci J 2021, 15(1): 2-9 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Moslehi A, Komeili-Movahed T. The Effects of Rosmarinic Acid on the Liver Fibrosis Induced by Non-alcoholic Steatohepatitis in Male Mice. Qom Univ Med Sci J 2021; 15 (1) :2-9
URL: http://journal.muq.ac.ir/article-1-3091-en.html
URL: http://journal.muq.ac.ir/article-1-3091-en.html
1- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran. , moslehi2000@gmail.com
2- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
2- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Abstract: (1594 Views)
Background and Objectives: Non-Alcoholic Steatohepatitis (NASH) is a serious and increasing liver disease, which develops into cirrhosis, fibrosis, and hepatocellular carcinoma. Rosmarinic Acid (RA) is a powerful antioxidant and anti-inflammatory compound. Therefore, this study aimed to assess the role of RA on a mouse model of NASH-induced liver fibrosis.
Methods In this research, C57/BL6 mice were divided into 4 equal groups, as follows: the control, RA, NASH, and NASH+RA groups. In the third and fourth groups, NASH was induced by Methionine-Choline Deficient (MCD) diet for 8 weeks. In the RA and NASH+RA group, RA was intraperitoneally injected daily for 8 weeks in mice. After 8 weeks, the explored animals were sacrificed and the blood and liver samples were obtained. Then, Trichrome-Masson staining, serum, and molecular analyses were performed.
Results After RA administration, the plasma levels of ALT and AST decreased. RA administration also reduced TGFβ and α-SMA genes expression. Finally, the histopathological evaluation revealed that RA administration decreased NASH-induced liver fibrosis.
Conclusion It seems that RA administration improves NASH-induced liver fibrosis through the inhibition of the α-SMA/ TGF-β signaling pathway.
Methods In this research, C57/BL6 mice were divided into 4 equal groups, as follows: the control, RA, NASH, and NASH+RA groups. In the third and fourth groups, NASH was induced by Methionine-Choline Deficient (MCD) diet for 8 weeks. In the RA and NASH+RA group, RA was intraperitoneally injected daily for 8 weeks in mice. After 8 weeks, the explored animals were sacrificed and the blood and liver samples were obtained. Then, Trichrome-Masson staining, serum, and molecular analyses were performed.
Results After RA administration, the plasma levels of ALT and AST decreased. RA administration also reduced TGFβ and α-SMA genes expression. Finally, the histopathological evaluation revealed that RA administration decreased NASH-induced liver fibrosis.
Conclusion It seems that RA administration improves NASH-induced liver fibrosis through the inhibition of the α-SMA/ TGF-β signaling pathway.
Type of Study: Original Article |
Subject:
فیزیولوژی
Received: 2021/03/13 | Accepted: 2021/04/20 | Published: 2021/03/30
Received: 2021/03/13 | Accepted: 2021/04/20 | Published: 2021/03/30
References
1. Gottlieb A, Mosthael W, Sowa JP, Canbay A. Nonalcoholic-fatty-liver-disease and nonalcoholic steatohepatitis: Successful development of pharmacological treatment will depend on translational research. Digestion. 2019; 100(2):79-85. [DOI:10.1159/000493259] [PMID] [DOI:10.1159/000493259]
2. Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol. 2013; 10(11):627-36. [DOI:10.1038/nrgastro.2013.149] [PMID] [DOI:10.1038/nrgastro.2013.149]
3. Liu W, Baker RD, Bhatia T, Bhatia T, Zhu L, Baker SS. Pathogenesis of nonalcoholic steatohepatitis. Cell Mol Liff Sci. 2016; 73(10):1969-87. [DOI:10.1007/s00018-016-2161-x] [PMID] [DOI:10.1007/s00018-016-2161-x]
4. Noureddin M, Mato JM, Lu SC. Nonalcoholic fatty liver disease: update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp Biol Med (Maywood). 2015; 240(6):809-20. [DOI:10.1177/1535370215579161] [PMID] [PMCID] [DOI:10.1177/1535370215579161]
5. Anty R, Gual P. [Physiopathologie des stéatoses hépatiques métaboliques [Pathogenesis of non-alcoholic fatty liver disease (French)]. Presse Med. 2019; 48(12):1468-83. [DOI:10.1016/j.lpm.2019.09.051] [PMID] [DOI:10.1016/j.lpm.2019.09.051]
6. Takatani N, Kono Y, Beppu F, Okamatsu-Ogura Y, Yamano Y, Miyashita K, et al. Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice. Biochem Biophys Res Commun. 2020; 528(2):305-10. [DOI:10.1016/j.bbrc.2020.05.050] [PMID] [DOI:10.1016/j.bbrc.2020.05.050]
7. Peverill W, Powell LW, Skoien R. Evolving concepts in the pathogenesis of NASH: Beyond steatosis and inflammation. Int J Mol Sci. 2014; 15(5):8591-638. [DOI:10.3390/ijms15058591] [PMID] [PMCID] [DOI:10.3390/ijms15058591]
8. Zhang CY, Yuan WG, He P, Lei JH, Wang CX. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol. 2016; 22(48):10512-22. [DOI:10.3748/wjg.v22.i48.10512] [PMID] [PMCID] [DOI:10.3748/wjg.v22.i48.10512]
9. Basaranoglu M, Basaranoglu G, Sentürk H. From fatty liver to fibrosis: A tale of "second hit". World J Gastroenterol 2013; 19(8):1158-65. [DOI:10.3748/wjg.v19.i8.1158] [PMID] [PMCID] [DOI:10.3748/wjg.v19.i8.1158]
10. Xu F, Liu C, Zhou D, Zhang L. TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis. J Histochem Cytochem. 2016; 64(3):157-67. [DOI:10.1369/0022155415627681] [PMID] [PMCID] [DOI:10.1369/0022155415627681]
11. Zhang L, Zhou F, ten Dijke P. Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer. Trends Biochem Sci. 2013; 38(12):612-20. [DOI:10.1016/j.tibs.2013.10.001] [PMID] [DOI:10.1016/j.tibs.2013.10.001]
12. Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol. 2018; 24(16):1679-707. [DOI:10.3748/wjg.v24.i16.1679] [PMID] [PMCID] [DOI:10.3748/wjg.v24.i16.1679]
13. Dai J, Xu M, Zhang X, Niu Q, Hu Y, Li Y, et al. Bi-directional regulation of TGF-β/Smad pathway by arsenic: A systemic review and meta-analysis of in vivo and in vitro studies. Life Sci. 2019; 220:92-105. [DOI:10.1016/j.lfs.2019.01.042] [PMID] [DOI:10.1016/j.lfs.2019.01.042]
14. Hasanein P, Seifi R. Beneficial effects of rosmarinic acid against alcohol-induced hepatotoxicity in rats. Can J Physiol Pharmacol. 2018; 96(1):32-7. [DOI:10.1139/cjpp-2017-0135] [PMID] [DOI:10.1139/cjpp-2017-0135]
15. Diao J, Wei J, Yan R, Liu X, Li Q, Li L, et al. Rosmarinic Acid suppressed high glucose-induced apoptosis in H9c2 cells by ameliorating the mitochondrial function and activating STAT3. Biochem Biophys Res Commun. 2016; 477(4):1024-30. [DOI:10.1016/j.bbrc.2016.07.024] [PMID] [DOI:10.1016/j.bbrc.2016.07.024]
16. Zhang Y, Chen X, Yang L, Zu Y, Lu Q. Effects of rosmarinic acid on liver and kidney antioxidant enzymes, lipid peroxidation and tissue ultrastructure in aging mice. Food Funct. 2015; 6(3):927-31. [DOI:10.1039/C4FO01051E] [PMID] [DOI:10.1039/C4FO01051E]
17. Prasannarong M, Saengsirisuwan V, Surapongchai J, Buniam J, Chukijrungroat N, Rattanavichit Y. Rosmarinic acid improves hypertension and skeletal muscle glucose transport in angiotensin II-treated rats. BMC Complement Altern Med. 2019; 19(1):165. [DOI:10.1186/s12906-019-2579-4] [PMID] [PMCID] [DOI:10.1186/s12906-019-2579-4]
18. Ding Y, Zhang Z, Yue Z, Ding L, Zhou Y, Huanh Z, et al. Rosmarinic Acid Ameliorates H2O2-Induced Oxidative Stress in L02 Cells Through MAPK and Nrf2 Pathways. Rejuvenation Res. 2019; 22(4):289-98. [DOI:10.1089/rej.2018.2107] [PMID] [DOI:10.1089/rej.2018.2107]
19. Lu C, Zou Y, Liu Y, Niu Y. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system. Toxicol Appl Pharmacol. 2017; 318:69-78. [DOI:10.1016/j.taap.2017.01.008] [PMID] [DOI:10.1016/j.taap.2017.01.008]
20. Joardar S, Dewanjee S, Bhowmick S, Dua TK, Das S, Saha A, et al. Rosmarinic Acid Attenuates Cadmium-Induced Nephrotoxicity via Inhibition of Oxidative Stress, Apoptosis, Inflammation and Fibrosis. Int J Mol Sci. 2019; 20(8):2027. [DOI:10.3390/ijms20082027] [PMID] [PMCID] [DOI:10.3390/ijms20082027]
21. Li GS, Jiang WL, Tian JW, Qu GW, Zhu HB, Fu FH. In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis. Phytomedicine. 2010; 17(3-4):282-8. [DOI:10.1016/j.phymed.2009.05.002] [PMID] [DOI:10.1016/j.phymed.2009.05.002]
22. Zhang X, Ma ZG, Yuan YP, Xu SC, Wei WY, Song P, et al. Rosmarinic acid attenuates cardiac fibrosis following long-term pressure overload via AMPKα/Smad3 signaling. Cell Death Dis. 2018; 9(2):102. [DOI:10.1038/s41419-017-0123-3] [PMID] [PMCID] [DOI:10.1038/s41419-017-0123-3]
23. Komeili Movahhed T, Moslehi A, Golchoob M, Abadzadeh S. Allantoin improves methionine-choline deficient diet-induced nonalcoholic steatohepatitis in mice through involvement in endoplasmic reticulum stress and hepatocytes apoptosis-related genes expressions. Iran J Basic Med Sci. 2019; 22(7):736-44. [DOI:10.22038/IJBMS.2019.33553.8012]
24. Nikoukar LR, Nabavizadeh F, Mohamadi SM, Moslehi A, Hassanzadeh G, Nahrevanian H, et al. Protective effect of ghrelin in a rat model of celiac disease. Acta Physiol Hung. 2014; 101(4):438-47. [DOI:10.1556/APhysiol.101.2014.4.5] [PMID] [DOI:10.1556/APhysiol.101.2014.4.5]
25. Kim M, Yoo G, Randy A, Son YJ, Hong CR, Kim SM, et al. Lemon balm and its constituent, Rosmarinic Acid, alleviate liver damage in an animal model of nonalcoholic steatohepatitis. Nutrients. 2020; 12(4):1166. [DOI:10.3390/nu12041166] [PMID] [PMCID] [DOI:10.3390/nu12041166]
26. Hasanein P, Sharifi M. Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats. Pharm Biol. 2017; 55(1):1809-16. [DOI:10.1080/13880209.2017.1331248] [PMID] [PMCID] [DOI:10.1080/13880209.2017.1331248]
27. Zhang T, Ma S, Liu C, Hu K, Xu M, Wang R. Rosmarinic acid prevents radiation-induced pulmonary fibrosis through attenuation of ROS/MYPT1/TGFβ1 signaling via miR-19b-3p. Dose Res. 2020; 18(4):1559325820968413. [DOI:10.1177/1559325820968413] [PMID] [PMCID] [DOI:10.1177/1559325820968413]
28. Chen YY, Tsai CF, Tsai MC, Chen WK, Hsu YW, Lu FJ. Anti-fibrotic effect of rosmarinic acid on inhibition of pterygium epithelial cells. Int J Ophthalmol. 2018; 11(2):189-95. [DOI:10.1177/1559325820968413] [PMID] [PMCID] [DOI:10.1177/1559325820968413]
29. Lin SY, Wang YY, Chen WY, Liao SL, Chou ST, Yang CP, et al. Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats. Food Chem Toxicol 2017; 108(Pt A):214-23. [DOI:10.1016/j.fct.2017.08.005] [PMID] [DOI:10.1016/j.fct.2017.08.005]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Owned by Qom University of Medical Sciences
Published by Qom University of Medical Sciences Press
eISSN: 2008-1375
pISSN: 1735-7799
Email: journal[at]muq.ac.ir
j.mua.ac[at]gmail.com
