Corilagin inhibits angiotensin II-induced atrial fibrosis and fibrillation in mice through the PI3K-Akt pathway

Document Type : Original Article

Authors

Cardiovascular Department, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China

Abstract

Objective(s): Corilagin (Cor) is reported as beiing hepatoprotective, anti-inflammatory, antibacterial, and anti-oxidant, while the effect on atrial fibrosis remains unknown. Therefore, we investigated the protective effect of Cor in angiotensin II (Ang II)-induced atrial fibrosis and atrial fibrillation (AF).
Materials and Methods: C57BL/6 mice (male, 8–10 weeks, n = 40) were subcutaneously infused either with saline or Ang II (2.0 mg/kg/day) and Cor (30 mg/kg) intraperitoneally injected 2 hr before Ang II infusion for 4 weeks. Mice were grouped into the control group (n=8), Cor group (n=8), Ang II group (n=8), and Ang II + Cor group (n=8). Morphological, histological, and biochemical examinations were performed. In vivo, transesophageal burst pacing was used to generate AF.
Results: Cor treatment markedly reduced Ang II-induced AF development in mice. Ang II + Cor therapy potentially decreased the atrial fibrotic area. It significantly decreased the increase in smooth muscle alpha-actin (α-SMA), CTGF, Collagen I, and Collagen III expressions brought on by Ang II treatment. Moreover, Ang II + Cor treatment remarkably decreased the malondialdehyde (MDA) content, whereas superoxide dismutase (SOD) and catalase (CAT) activities were potentially increased (all, P<0.001). In addition, Ang II + Cor significantly reduced Ang II-induced interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) concentrations in atrial tissues. Furthermore, Cor significantly inhibited Ang II-induced p-PI3K, p-Akt, and NF-κB p-p65 protein expression in atrial tissues. 
Conclusion: Our data speculated that Cor could have a protective effect against Ang II-induced atrial fibrosis and AF via down-regulation of the PI3K-Akt pathway.

Keywords

Main Subjects

References

1. Li CY, Zhang JR, Hu WN, Li SN. Atrial fibrosis underlying atrial fibrillation. Int J Mol Med 2021; 47: 9-20.
2. Everett TH, Olgin JE. Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm 2007; 4: 24-27.
3. Jalife J, Kaur K. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc Med 2015; 25: 475-484.
4. Lv W, Zhang L, Cheng X, Wang H, Qin W, Zhou X, et al. Apelin inhibits angiotensin ii-induced atrial fibrosis and atrial fibrillation via TGF-β1/Smad2/α-SMA pathway. Front Physiol 2020; 11: 583570-583579.
5. Liu Y, Lv H, Tan R, An X, Niu XH, Liu YJ, et al. Platelets promote Ang II (angiotensin II)-induced atrial fibrillation by releasing TGF-β1 (Transforming Growth Factor-β1) and interacting with fibroblasts. Hypertension 2020; 76: 1856-1867. 
6. He X, Gao X, Peng L, Wang S, Zhu Y, Ma H, et al. Atrial fibrillation induces myocardial fibrosis through angiotensin II type 1 receptor-specific Arkadia-mediated downregulation of Smad7. Circ Res 2011; 108:164-175. 
7. Truong V, Jain A, Anand-Srivastava MB, Srivastava AK. Angiotensin II-induced histone deacetylase 5 phosphorylation, nuclear export, and Egr-1 expression are mediated by Akt pathway in A10 vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2021; 320: 1543-1554.
8. Zhang GH, Miao FA, Xu JG, Zhang Y. Angiotensin II enhances the proliferation of Natural Killer/T-cell lymphoma cells via activating PI3K/Akt signaling pathway. Biosci Rep 2020; 40: BSR20202388.
9. Khan H, Singh A, Thapa K, Garg K, Grewal AK, Singh TG. Therapeutic modulation of the phosphatidylinositol 3-kinases (PI3K) pathway in cerebral ischemic injury. Brain Res 2021; 147399.
10. Oeckinghaus A, Ghosh S. The NF-κB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 2009; 1: a000034.
11. Qin W, Cao L, Massey IY. Role of PI3K/Akt signaling pathway in cardiac fibrosis. Mol Cell Biochem 2021; 476: 4045-4059.
12. He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Sig Transduct Target Ther 2021; 6: 425441.
13. Gupta A, Singh AK, Kumar R, Ganguly R, Rana HK, Pandey PK, et al. Corilagin in cancer: A critical evaluation of anticancer activities and molecular mechanisms. Molecules 2019; 24: 3399-3417.
14. Li X, Deng Y, Zheng Z, Huang W, Chen L, Tong Q, et al. Corilagin, a promising medicinal herbal agent. BioMed Pharmacother 2018; 99: 43-50.
15. Yan F, Cheng D, Wang H, Gao M, Zhang J, Cheng H, et al. Corilagin ameliorates con A-induced hepatic injury by restricting M1 macrophage polarization. Front Immunol 2022; 12: 807509.
16. Du P, Ma Q, Zhu ZD, Li G, Wang Y, Li QQ, et al. Mechanism of corilagin interference with IL-13/STAT6 signaling pathways in hepatic alternative activation macrophages in schistosomiasis-induced liver fibrosis in mouse model. Eur J Pharmacol 2016; 793: 119-126.
17. Li HR, Li G, Li M, Zhang SL, Wang H, Luo T, et al. Corilagin ameliorates schistosomiasis hepatic fibrosis through regulating IL-13 associated signal pathway in vitro and in vivo. Parasitology 2016; 143: 1629-1638.
18. Li YQ, Chen YF, Dang YP, Wang Y, Shang ZZ, Ma Q, et al. Corilagin counteracts IL-13ralpha1 signaling pathway in macrophages to mitigate schistosome egg-induced hepatic fibrosis. Front Cell Infect Microbiol 2017; 7:443.
19.  Zhou X, Xiong J, Lu S, Luo L, Chen ZL, Yang F, et al. Inhibitory effect of corilagin on miR-21-regulated hepatic fibrosis signaling pathway. Am J Chin Med 2019; 47: 1541-1569.
20. Zhan Y, Abe I, Nakagawa M, Ishii Y, Kira S, Miyoshi M, et al. A traditional herbal medicine rikkunshito prevents angiotensin II-induced atrial fibrosis and fibrillation. J Cardiol 2020; 76: 626-635.
21. Li J, Wang S, Zhang YL, Bai J, Lin QY, Liu RS, Yu XH, Li HH. Immunoproteasome subunit β5i promotes Ang II (angiotensin II)-induced atrial fibrillation by targeting ATRAP (Ang II Type I receptor-associated protein) degradation in mice. Hypertension 2019; 73: 92-101.
22. Li L, Hou X, Xu R, Liu C, Tu M. Research review on the pharmacological effects astragaloside IV, Fundam. Clin. Pharmacol 2017; 31: 17-36.
23. Ma JY, Zhang WX, Chen H, Jiang Y, Tu P, Ding H. The protective effects of echinacoside on oxidative stress injury in vascular dementia rats, Chin Pharmacol Bull 2014; 30: 638-642.
24. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 2001; 29: e45.
25. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE Jr, Cleveland JC, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130: 199-267.
26. Jalife J. Mechanisms of persistent atrial fibrillation. Curr Opin Cardiol 2014; 29: 20-27.
27. Clementy N, Benhenda N, Piver E, Pierre B, Bernard A, Fauchier L, et al. Serum galectin-3 levels predict recurrences after ablation of atrial fibrillation. Sci Rep 2016; 6: 34357-34363.
28. Nattel S, Harada M. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol 2014; 63: 2335-2345.
29. Burstein B, Nattel S. Atrial fibrosis: Mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008; 51: 802-809.
30. Mayyas F, Alzoubi KH, Van Wagoner DR. Impact of aldosterone antagonists on the substrate for atrial fibrillation: Aldosterone promotes oxidative stress and atrial structural/electrical remodeling. Int J Cardiol 2013; 168: 5135-5142.
31. Sygitowicz G, Maciejak-Jastrzebska A, Sitkiewicz DA. Review of the Molecular mechanisms underlying cardiac fibrosis and atrial fibrillation. J Clin Med. 2021; 10: 4430.
32. Anderson ME. Oxidant stress promotes disease by activating CaMKII. J Mol Cell Cardiol 2015; 89:160-167.
33. Wang Q, Quick AP, Cao S, Reynolds J, Chiang DY, Beavers D, et al. Oxidized CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) is essential for ventricular arrhythmia in a mouse model of duchenne muscular dystrophy. Circ Arrhythm Electrophysiol 2018; 11: e005682.
34. Rudolph TK, Ravekes T, Klinke A, Friedrichs K, Mollenhauer M, Pekarova M, et al. Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation. Cardiovasc Res 2016; 109: 174-184.
35. Vyas V, Hunter RJ, Longhi MP, Finlay MC. Inflammation and adiposity: New frontiers in atrial fibrillation. Europace 2020; 22: 1609-1618.
36. Guo YJ, Zhao L, Li XF, Mei YW, Zhang SL, Tao JY, et al. Effect of corilagin on anti-inflammation in HSV-1 encephalitis and HSV-1 infected microglias. Eur J Pharmacol 2010; 635: 79-86.
37. Wang J, Fu D, Senouthai S, You Y. Critical roles of PI3K/ Akt/ NF‑κB survival axis in angiotensin II‑induced podocyte injury. Mol Med Rep 2019; 20: 5134-5144.
38. Lu J, Ye C, Huang Y, Huang D, Tang L, Hou W, et al. Corilagin suppresses RANKL‐induced osteoclastogenesis and inhibits oestrogen deficiency‐induced bone loss via the NF‐κB and PI3K/AKT signalling pathways. J Cell Mol Med 2020; 24: 10444-10457.
 
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 6
June 2024
Pages 717-724

Files

Share

How to cite

Statistics