Volume 16, Issue 11 (February 2023)
Qom Univ Med Sci J 2023, 16(11): 868-879 |
Back to browse issues page
Ethics code: IR.MUQ.AEC.1400.002
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Komeili-Movahhed T, Moslehi A. Protective Effect of Rosmarinic Acid on Inflammatory Changes of Hepatic Cells in Non-alcoholic Steatohepatitis in Mice: Cyclooxygenase 2/ Prostaglandin E2 Pathway. Qom Univ Med Sci J 2023; 16 (11) :868-879
URL: http://journal.muq.ac.ir/article-1-3582-en.html
URL: http://journal.muq.ac.ir/article-1-3582-en.html
1- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
2- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran ,amoslehi@muq.ac.ir
2- Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran ,
Abstract: (730 Views)
Background and Objectives: Nonalcoholic Steatohepatitis (NASH) is one of the common liver diseases, characterized by excessive lipid accumulation (steatosis) and inflammation in the liver. Inflammation is one of main reasons for this disease which takes place from different pathways. Rosmarinic Acid (RA) is an antioxidant and anti-inflammatory product with positive effects on the improvement of liver injuries. This study aims to evaluate protective effect of RA against liver inflammation caused by NASH in male mice through affecting cyclooxygenase-2/ Prostaglandin E2 (COX-2/PEG2) pathway and Matrix Metalloproteinase-9 (MMP-9).
Methods: In this study, 24 C57/BL6 male mice were used. They were divided into four groups of 6 including; Control, RA, NASH, and NASH+RA. The NASH was induced by a methionine/choline-deficient diet for 8 weeks. The RA was administrated intraperitoneally and daily for 8 weeks. After 8 weeks, the animals were sacrificed and their liver was removed. hematoxylin and eosin staining was preformed for histological evaluation and real-time PCR and ELISA assays were used for molecular studies.
Results: The RA significantly reduced hepatic steatosis and inflammation as well as the expression of MMP-9 and COX-2 which led to the significant reduction of PEG2 level.
Conclusion: It seems that RA can reduce liver inflammation and thereby attenuate NASH in male mice by reducing the expression of COX-2 enzyme and MMP-9 and the concentration of PEG2.
Methods: In this study, 24 C57/BL6 male mice were used. They were divided into four groups of 6 including; Control, RA, NASH, and NASH+RA. The NASH was induced by a methionine/choline-deficient diet for 8 weeks. The RA was administrated intraperitoneally and daily for 8 weeks. After 8 weeks, the animals were sacrificed and their liver was removed. hematoxylin and eosin staining was preformed for histological evaluation and real-time PCR and ELISA assays were used for molecular studies.
Results: The RA significantly reduced hepatic steatosis and inflammation as well as the expression of MMP-9 and COX-2 which led to the significant reduction of PEG2 level.
Conclusion: It seems that RA can reduce liver inflammation and thereby attenuate NASH in male mice by reducing the expression of COX-2 enzyme and MMP-9 and the concentration of PEG2.
Keywords: Liver, Nonalcoholic fatty liver disease, Matrix Metalloproteinase-9, Prostaglandin E2, Rosmarinic acid
Type of Study: Original Article |
Subject:
فیزیولوژی
Received: 2022/10/2 | Accepted: 2022/12/19 | Published: 2023/01/1
Received: 2022/10/2 | Accepted: 2022/12/19 | Published: 2023/01/1
References
1. Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021; 397(10290):2212-24. [DOI:10.1016/S0140-6736(20)32511-3] [PMID] [DOI:10.1016/S0140-6736(20)32511-3]
2. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019; 92:82-97. [DOI:10.1016/j.metabol.2018.11.014] [PMID] [DOI:10.1016/j.metabol.2018.11.014]
3. Manne V, Handa P, Kowdley KV. Pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Clin Liver Dis. 2018; 22(1):23-37. [DOI:10.1016/j.cld.2017.08.007] [PMID] [DOI:10.1016/j.cld.2017.08.007]
4. Cao Y, Mai W, Li R, Deng S, Li L, Zhou Y, et al. Macrophages evoke autophagy of hepatic stellate cells to promote liver fibrosis in NAFLD mice via the PGE2/EP4 pathway. Cell Mol Life Sci. 2022; 79(6):303. [PMID] [DOI:10.1007/s00018-022-04319-w]
5. Komeili-Movahhed T, Bassirian M, Changizi Z, Moslehi A. SIRT1/NFkappaB pathway mediates anti-inflammatory and anti-apoptotic effects of rosmarinic acid on in a mouse model of nonalcoholic steatohepatitis (NASH). J Recept Signal Transduct Res. 2022; 42(3):241-50. [DOI:10.1080/10799893.2021.1905665] [PMID] [DOI:10.1080/10799893.2021.1905665]
6. Dai W, Sun Y, Jiang Z, Du K, Xia N, Zhong G. Key genes associated with non-alcoholic fatty liver disease and acute myocardial infarction. Med Sci Monit. 2020; 26:e922492. [DOI:10.12659/MSM.922492] [DOI:10.12659/MSM.922492]
7. Fei J, Liang B, Jiang C, Ni H, Wang L. Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model. Biomed Pharmacother. 2019; 109:1586-92. [DOI:10.1016/j.biopha.2018.09.161] [PMID] [DOI:10.1016/j.biopha.2018.09.161]
8. Yuan Y, Naito H, Kitamori K, Hashimoto S, Asano T, Nakajima T. The antihypertensive agent hydralazine reduced extracellular matrix synthesis and liver fibrosis in nonalcoholic steatohepatitis exacerbated by hypertension. PLoS One. 2020; 15(12):e0243846. [PMID] [DOI:10.1371/journal.pone.0243846]
9. Coilly A, Desterke C, Guettier C, Samuel D, Chiappini F. FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis. Sci Rep. 2019; 9(1):19785. [PMID] [PMCID] [DOI:10.1038/s41598-019-56235-y]
10. Wong CT, Bestard-Lorigados I, Crawford DA. Autism-related behaviors in the cyclooxygenase-2-deficient mouse model. Genes Brain Behav. 2019; 18(1):e12506. [DOI:10.1111/gbb.12506] [PMID] [DOI:10.1111/gbb.12506]
11. Chung MY, Mah E, Masterjohn C, Noh SK, Park HJ, Clark RM, et al. Green Tea lowers hepatic COX-2 and prostaglandin E2 in rats with dietary fat-induced nonalcoholic steatohepatitis. J Med Food. 2015; 18(6):648-55. [DOI:10.1089/jmf.2014.0048] [PMID] [DOI:10.1089/jmf.2014.0048]
12. Zhao JS, Zhu FS, Liu S, Yang CQ, Chen XM. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. Chin Med J (Engl). 2012; 125(13):2316-21. [PMID]
13. 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]
14. Diao J, Wei J, Yan R, Liu X, Li Q, Lin 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]
15. Domitrovic R, Potocnjak I, Crncevic-Orlic Z, Skoda M. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food Chem Toxicol. 2014; 66:321-8. [DOI:10.1016/j.fct.2014.02.002] [PMID] [DOI:10.1016/j.fct.2014.02.002]
16. Heidari F, Komeili-Movahhed T, Hamidizad Z, Moslehi A. The protective effects of rosmarinic acid on ethanol-induced gastritis in male rats: Antioxidant defense enhancement. Res Pharm Sci. 2021; 16(3):305-14. [DOI:10.4103/1735-5362.314829] [PMID] [PMCID] [DOI:10.4103/1735-5362.314829]
17. Wen YJ, Yin MC. The anti-inflammatory and anti-glycative effects of rosmarinic acid in the livers of type 1 diabetic mice. Biomedicine (Taipei). 2017; 7(3):19. [PMID] [PMCID] [DOI:10.1051/bmdcn/2017070319]
18. Fan YT, Yin GJ, Xiao WQ, Qiu L, Yu G, Hu YL, et al. Rosmarinic acid attenuates sodium taurocholate-induced acute pancreatitis in rats by inhibiting nuclear factor-kappaB activation. Am J Chin Med. 2015; 43(6):1117-35. [DOI:10.1142/S0192415X15500640] [PMID] [DOI:10.1142/S0192415X15500640]
19. An Y, Zhao J, Zhang Y, Wu W, Hu J, Hao H, et al. Rosmarinic acid induces proliferation suppression of hepatoma cells associated with NF-kappaB signaling pathway. Asian Pac J Cancer Prev. 2021; 22(5):1623-32. [DOI:10.31557/APJCP.2021.22.5.1623] [PMID] [PMCID] [DOI:10.31557/APJCP.2021.22.5.1623]
20. Komeili Movahhed T, Moslehi A, Golchoob M, Ababzadeh 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. [PMID]
21. Eo SH, Kim SJ. Rosmarinic acid induces rabbit articular chondrocyte differentiation by decreases matrix metalloproteinase-13 and inflammation by upregulating cyclooxygenase-2 expression. J Biomed Sci. 2017; 24(1):75. [DOI:10.1186/s12929-017-0381-5] [PMID] [PMCID] [DOI:10.1186/s12929-017-0381-5]
22. 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]
23. Huang L, Chen J, Quan J, Xiang D. Rosmarinic acid inhibits proliferation and migration, promotes apoptosis and enhances cisplatin sensitivity of melanoma cells through inhibiting ADAM17/EGFR/AKT/GSK3β axis. Bioengineered. 2021; 12(1):3065-76. [DOI:10.1080/21655979.2021.1941699] [PMID] [PMCID] [DOI:10.1080/21655979.2021.1941699]
24. 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]
25. Thingore C, Kshirsagar V, Juvekar A. Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice. Metab Brain Dis. 2021; 36(2):299-313. [DOI:10.1007/s11011-020-00629-9] [PMID] [DOI:10.1007/s11011-020-00629-9]
26. 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]
27. Chen WP, Jin GJ, Xiong Y, Hu PF, Bao JP, Wu LD. Rosmarinic acid down-regulates NO and PGE2 expression via MAPK pathway in rat chondrocytes. J Cell Mol Med. 2018; 22(1):346-53. [DOI:10.1111/jcmm.13322] [PMID] [PMCID] [DOI:10.1111/jcmm.13322]
28. Yen JH, Khayrullina T, Ganea D. PGE2-induced metalloproteinase-9 is essential for dendritic cell migration. Blood. 2008; 111(1):260-70. [DOI:10.1182/blood-2007-05-090613] [PMID] [PMCID] [DOI:10.1182/blood-2007-05-090613]
29. Kothari P, Pestana R, Mesraoua R, Elchaki R, Khan KM, Dannenberg AJ, et al. IL-6-mediated induction of matrix metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages. J Immunol. 2014; 192(1):349-57. [DOI:10.4049/jimmunol.1301906] [PMID] [PMCID] [DOI:10.4049/jimmunol.1301906]
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
