Melissa officinalis L. Supplementation Provides Cardioprotection in a Rat Model of Experimental Autoimmune Myocarditis

Abstract

Due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts (MOEs), this study was aimed at investigating the potential of ethanolic MOE to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating MOE effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; EAM, nontreated rats with EAM; MOE50, MOE100, and MOE200, rats with EAM treated with either 50, 100, or 200 mg/kg of MOE for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The EAM group characteristically showed greater LV wall thickness and lower ejection fraction ( 50.33 ± 7.94 % vs. 84.81 ± 7.74 %) and fractional shortening compared to CTRL ( p < 0.05 ). MOE significantly improved echocardiographic parameters (EF in MOE200 81.44 ± 5.51 %) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001 ) and collagen content (by 76.39%; p < 0.001 ) in the heart tissues, especially in the MOE200 group compared to the EAM group. In addition, MOEs induced a significant decrease of prooxidants production (O2-, H2O2, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to EAM, with medium and high dose being more effective than low dose ( p < 0.05 ). The present study suggests that ethanolic MOEs, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with EAM. MOEs might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.

Short-Term Administration of Lemon Balm Extract Ameliorates Myocardial Ischemia/Reperfusion Injury: Focus on Oxidative Stress

“…However, insufficient evidence is available regarding the ME effects on cardiac morphology, except for the decrement in the infarct size after a 5-day reperfusion period, found in a study by Sedighi et al [26]. Additionally, we found that 7-day preconditioning with ME200 achieved to prevent myocardial fibrosis induced by I/R injury, which is in line with our previous research in a different model of heart disease, autoimmune myocarditis [28]. This can partly be explained by the fact that rosmarinic acid exerts antifibrotic action in the heart via AMPKα/Smad3 signaling pathway, proved both in vivo and in vitro [34].…”

“…On the contrary, other research provided evidence that HR decrement can be induced by a low dose of lemon balm extract (ME50) after the reperfusion period [ 26 ]. This can be explained by the fact that lemon balm may act negatively chronotropic in different ways: by blockage of K + channels or by cardiac muscarinic receptors activation [ 27 , 28 ].…”

“…Additionally, we observed a significant drop in other ROS, such as O 2 − and H 2 O 2, after preconditioning with ME. There is evidence that lemon balm extract may lower O 2 − levels in different models of cardiac pathologies such as autoimmune myocarditis [ 28 ], and also in vitro can act cytoprotective against H 2 O 2 -induced oxidative stress in HUVECs by decreasing hydroperoxides concentration [ 29 ]. Interestingly, we found that ME induced an increase in the level of nitrites as an indirect indicator of nitric oxide (NO), correlating with elevated CF in treated animals, indicating the vasodilatory potential of ME.…”

Modulation of NRF-2 Pathway Contributes to the Therapeutic Effects of Boswellia serrata Gum Resin Extract in a Model of Experimental Autoimmune Myocarditis

“…This EAM model is histologically similar to acute human myocarditis, with macrophage, lymphocyte, and neutrophil recruitment accompanying cardiac fibrosis [ 4 ]. Given that the present therapy choices for myocarditis are confined to symptoms as arrhythmias and heart failure, and that no other strategy has yet been discovered [ 5 ], innovative effectual therapeutic alternative is indispensable. Natural products are becoming more popular in the treatment of cardiovascular disease due to their security, less side effects, and reduced prices.…”

“…Natural products are becoming more popular in the treatment of cardiovascular disease due to their security, less side effects, and reduced prices. In current years, preclinical and clinical research has concentrated on discovery novel phyto-medicines, such as plant extracts with significant anti-inflammatory and antioxidant action, and, in particular, active constituents for cardioprotection [ 5 ]. Some plants, such as the Indian plant Boswellia serrata (B. serrata ), have antioxidant qualities that are useful in the treatment and prevention of various ailments.…”