Rosmarinic acid ameliorates the complications of monocrotaline-induced right ventricular hypertrophy on the left ventricle: Investigating the signaling pathway of Wnt/β-catenin in the heart

Document Type : Original Article

Authors

1 Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Persian Gulf Physiology Research Center, Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective(s): Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly found in Boraginaceae species and some species of ferns and hornworts. This study looked at how RA affects oxidative stress and left ventricular hemodynamic functions as well as RVH in monocrotaline (MCT) induced RVH model rats.
Materials and Methods: To cause RVH, MCT (60 mg/kg) was intraperitoneally (IP) injected. Rats were given saline or RA (10, 15, and 30 mg/kg, gavage, over 21 days). In anesthetized rats, the lead II electrocardiogram was recorded. The hemodynamic functions of the isolated heart were measured using the Langendorff apparatus (at constant pressure). Investigations were made into the right ventricular hypertrophy index (RVHI), the activities of superoxide dismutase, catalase, glutathione, and Wnt and β-catenin gene expressions in the left ventricle. H&E staining was used.
Results: A significant decline in electrocardiogram parameters and anti-oxidant enzyme activities, an increase in QTc (Q-T corrected) intervals, MDA (Malondialdehyde), RVHI, and Wnt/β-catenin gene expression, and also significant changes in the hemodynamic parameters were demonstrated in the MCT group.  RA improved the above-mentioned factors.
Conclusion: According to the findings, RA may act as a cardioprotective agent against cardiovascular complications brought on by RVH due to its capacity to boost the activity of cardiac anti-oxidant enzymes and decrease the expression of genes involved in vascular calcification.

Keywords

Main Subjects


1. Hirschhäuser C, Sydykov A, Wolf A, Esfandiary A, Bornbaum J, Kutsche HS, et al. Lack of contribution of p66shc to pressure overload-induced right heart hypertrophy. Int J Mol Sci 2020; 21: 9339-9353.
2. Sanders JL, Koestenberger M, Rosenkranz S, Maron BA. Right ventricular dysfunction and long-term risk of death. Cardiovasc Diagn Ther 2020; 10: 1646-1658.
3. Yang DL, Zhang HG, Xu YL, Gao YH, Yang XJ, Hao XQ, et al. Resveratrol inhibits right ventricular hypertrophy induced by monocrotaline in rats. Clin Exp Pharmacol Physiol 2010; 37: 150-155.
4. Bueno-Beti C, Sassi Y, Hajjar RJ, Hadri L. Pulmonary artery hypertension model in rats by monocrotaline administration. Experimental Models of Cardiovascular Diseases: Methods Protoc 2018: 233-241.
5. Huggins CE, Domenighetti AA, Pedrazzini T, Pepe S, Delbridge LM. Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice. J Renin Angiotensin Aldosterone Syst 2003; 4: 186-190.
6. Fulton DJ, Li X, Bordan Z, Haigh S, Bentley A, Chen F, et al.  Reactive oxygen and nitrogen species in the development of pulmonary hypertension. Antioxidants (Basel) 2017; 6: 54.
7. Byrne NJ, Rajasekaran NS, Abel ED, Bugger H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radic Biol Med 2021; 169: 317-342.
8. Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci 2007; 52: 2015-2021.
9. Phadwal K, Koo E, Jones RA, Forsythe RO, Tang K, Tang Q, et al. Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor. J Cell Physiol 2022; 237: 4303-4316.
10. Willems BA, Furmanik M, Caron MM, Chatrou ML, Kusters DH, Welting TJ, et al. Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signaling. Sci Rep 2018; 8: 4961.
11. Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness. Cardiovasc Res 2018; 114: 590-600.
12. Byon CH, Heath JM, Chen Y. Redox signaling in cardiovascular pathophysiology: a focus on hydrogen peroxide and vascular smooth muscle cells. Redox Biol 2016; 9: 244-253.
13. Zhang H, Chen J, Shen Z, Gu Y, Xu L, Hu J, et al. Indoxyl sulfate accelerates vascular smooth muscle cell calcification via microRNA-29 b-dependent regulation of Wnt/β-catenin signaling. Toxicol Lett 2018; 284: 29-36.
14. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933-956.
15. Litvinenko VI, Popova TP, Simonjan AV, Zoz IG, Sokolov VS. „Gerbstoffe” und Oxyzimtsäureabkömmlinge in Labiaten. Planta Med 1975; 27: 372-380.
16. Osakabe N, Yasuda A, Natsume M, Yoshikawa T. Rosmarinic acid inhibits epidermal inflammatory responses: anticarcinogenic effect of Perilla frutescens extract in the murine two-stage skin model. Carcinogenesis 2004; 25: 549-557.
17. Brosková Z, Drábiková K, Sotníková R, Fialova S, Knezl V. Effect of plant polyphenols on ischemia‐reperfusion injury of the isolated rat heart and vessels. Phytother Res 2013; 27: 1018-1022.
18. Osakabe N, Yasuda A, Natsume M, Sanbongi C, Kato Y, Osawa T, et al.  Rosmarinic acid, a major polyphenolic component of Perilla frutescens, reduces lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-GalN)-sensitized mice. Free Radic Biol Med 2002; 33: 798-806.
19. Karthik D, Viswanathan P, Anuradha CV. Administration of rosmarinic acid reduces cardiopathology and blood pressure through inhibition of p22phox NADPH oxidase in fructose-fed hypertensive rats. J Cardiovasc Pharmacol 2011; 58: 514-521.
20. Takeda H, Tsuji M, Inazu M, Egashira T, Matsumiya T. Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice. Eur J Pharmacol 2002; 449: 261-267.
21. Moon DO, Kim MO, Lee JD, Choi YH, Kim GY. Rosmarinic acid sensitizes cell death through suppression of TNF-α-induced NF-κB activation and ROS generation in human leukemia U937 cells. Cancer Lett 2010; 288: 183-191.
22. Senanayake SN. Green tea extract: Chemistry, antioxidant properties, and food applications: A review. J Funct Foods 2013; 5: 1529-1541.
23. Carocho M, Ferreira IC. A review on antioxidants, prooxidants, and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol 2013; 51: 15-25.
24. Lee MY, Tsai KB, Hsu JH, Shin SJ, Wu JR, Yeh JL. Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways. Sci Rep 2016; 6: 31788.
25. Jiang WL, Xu Y, Zhang SP, Hou J, Zhu HB. Effect of rosmarinic acid on experimental diabetic nephropathy. Basic Clin Pharmacol Toxicol 2012; 110: 390-395.
26. Hasanein P, Mahtaj AK. Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats. Neurosci Lett 2015; 585: 23-27.
27. Dianat M, Radan M, Badavi M, Mard SA, Bayati V, Ahmadizadeh M. Crocin attenuates cigarette smoke-induced lung injury and cardiac dysfunction by anti-oxidative effects: the role of Nrf2 antioxidant system in preventing oxidative stress. Respir Res 2018; 19: 1-20.
28. Dianat M, Esmaeilizadeh M, Badavi M, Samarbaf-Zadeh AR, Naghizadeh B. Protective effects of crocin on ischemia-reperfusion induced oxidative stress in comparison with vitamin E in isolated rat hearts. Jundishapur J Nat Pharm Prod 2014; 9:e17187.
29. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Effects of gallic Acid and cyclosporine on antioxidant capacity and cardiac markers of rat isolated heart after ischemia/reperfusion. Iran Red Crescent Med J 2014; 16:e16424.
30. Ma Z, Mao L, Rajagopal S. Hemodynamic characterization of rodent models of pulmonary arterial hypertension. J Vis Exp 2016; 110: e53335.
31. Wei XL, Fang RT, Yang YH, Bi XY, Ren GX, Luo AL, et al. Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med 2015; 15: 1-9.
32. Mard SA, Veisi A, Ahangarpour A, Gharib-Naseri MK. Mucosal acidification increases hydrogen sulfide release through up-regulating gene and protein expressions of cystathionine gamma-lyase in the rat gastric mucosa. Iran J Basic Med Sci 2016; 19: 172-177.
33. Chen QM, Tu VC, Purdom S, Wood J, Dilley T. Molecular mechanisms of cardiac hypertrophy induced by toxicants. Cardiovasc Toxicol 2001; 1: 267-283.
34. Molinari F, Malara N, Mollace V, Rosano G, Ferraro E. Animal models of cardiac cachexia. Int J Cardiol 2016; 219: 105-110.
35. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006; 114: 1883-1891.
36. Cho YK, Eom GH, Kee HJ, Kim HS, Choi WY, Nam KI, et al. Sodium valproate, a histone deacetylase inhibitor, but not captopril, prevents right ventricular hypertrophy in rats. Circ J 2010; 74: 760-770.
37. Bueno-Beti C, Sassi Y, Hajjar RJ, Hadri L. Pulmonary artery hypertension model in rats by monocrotaline administration.  Experimental models of cardiovascular diseases: Methods Protoc 2018: 233-241.
38. Carlino C, Schneider RI, Dellsperger KC, Tobias JD, Heller RL, Demarco VG, et al. Pulmonary hemodynamic response to acute combination and monotherapy with sildenafil and brain natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension. Am J Med Sci 2010; 339: 55-59.
39. Hadzi‐Petrushev N, Angelovski M, Rebok K, Mitrokhin V, Kamkin A, Mladenov M. Antioxidant and anti‐inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline‐induced right ventricular hypertrophy. J Biochem Mol Toxicol 2019; 33: e22353.
40. Osada M, Netticadan T, Tamura K, Dhalla NS. Modification of ischemia-reperfusion-induced changes in cardiac sarcoplasmic reticulum by preconditioning. Am J Physiol Heart Circ Physiol 1998; 274: H2025-H2034.
41. Goldspink DF, Burniston JG, Ellison GM, Clark WA, Tan LB. Catecholamine‐induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo: the same or separate death pathways? Exp Physiol 2004; 89: 407-416.
42. Abdullaev FI, Espinosa-Aguirre JJ. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 2004; 28: 426-342.
43. Ndrepepa G, Cassese S, Emmer M, Mayer K, Kufner S, Xhepa E, et al. Relation of ratio of left ventricular ejection fraction to left ventricular end-diastolic pressure to long-term prognosis after ST-segment elevation acute myocardial infarction. Am J Cardiol 2019; 123: 199-205.
44. Feng W, Hu Y, An N, Feng Z, Liu J, Mou J, et al. Alginate oligosaccharide alleviates monocrotaline-induced pulmonary hypertension via anti-oxidant and anti-inflammation pathways in rats. Int Heart J 2020; 61: 160-168.
45. Coballase-Urrutia E, Navarro L, Ortiz JL, Verdugo-Díaz L, Gallardo JM, Hernández ME, Estrada-Rojo F. Static magnetic fields modulate the response of different oxidative stress markers in a restraint stress model animal. Biomed Res Int 2018; 2018: 3960408.
46. Lin GM, Lu HH. A 12-lead ECG-based system with physiological parameters and machine learning to identify right ventricular hypertrophy in young adults. IEEE J Transl Eng Health Med 2020; 8: 1-10.
47. Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene 2004; 341: 19-39.