The effect of chronic administration of lemon balm extract (Melissa officinalis, Lamiaceae) on the development and progression of autoimmune myocarditis in rats

[N. D. Lazarević]

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Cilj ove studije bio je da se ispita uticaj primene ekstrakta Melissa officinalis (MOE) na razvoj i progresiju eksperimentalnog auotimunskog miokarditisa (EAM) kod pacova. Kako bi se identifikovao ekstrakt MOE sa potencijalno najboljim kardioprotektivnim efektom, prvo su hemijski okarakterisani vodeni i etanolni MOE, a potom ispitan i njihov antinflamacijski i antioksidacioni potencijal. Na osnovu toga odabran je etanolni ekstrakt pod refluksom za dalje istraživanje. Drugi deo istraživanja sproveden je na 80 Dark Agouti pacova podeljenih u 10 grupa u zavisnosti od toga da li su životinje zdrave ili im je indukovan EAM, od primenjene doze MOE (50, 100 i 200 mg/kg) i dužine tretmana (3/6 nedelja). EAM je indukovan imunizacijom pacova miozinom 0. dana protokola. Hemodinamski parametri praćeni su 0., 21. i 42. dana. Nakon završenog protokola životinje su žrtvovane, prikupljeni su uzorci krvi za određivanje različitih biohemijskih parametara i izolovana su srca u cilju patohistoloških analiza, i analize relativne ekspresije gena uključenih u oksidacioni stres, apoptozu i inflamaciju. Tretman MOE poboljšao je funkciju i morfologiju miokarda, u akutnoj i hroničnoj fazi EAM (smanjenje inflamatornog infiltrata, kolagenih vlakana i apoptotskih ćelija u tkivu miokarda uz poboljšanje hemodinamskih parametara). Mehanizmi postignutih efekata najverovatnije podrazumevaju sinergiju antioksidacionih, antiinflamacijskih i antiapoptotskih svojstava MOE. Ova studija sugeriše da MOE, posebno u dozi od 200mg/kg, poboljšava funkciju i arhitekturu miokarda u EAM, čime se sprečava remodelovanje srca i razvoj dilatativne kardiomiopatije. Stoga se MOE mogu smatrati potencijalno korisnom adjuvantnom terapijom kod pacijenata sa autoimunskim miokarditisom.

The aim of this study was to investigate the effect of Melissa officinalis extract (MOE) administration on the development and progression of experimental autoimmune myocarditis (EAM) in rats. In order to identify MOE extract with potentially the best cardioprotective effect, aqueous and ethanolic MOE were chemically characterized, and their anti-inflammatory and antioxidant potential was examined. Based on this, ethanolic extract under reflux was selected for further research. The second part included 80 Dark Agouti rats divided into 10 groups depending on the animals` health, applied dose of MOE (50, 100 and 200 mg/kg) and the length of treatment (3/6 weeks). EAM was induced by rat immunization with myosin on day 0. Hemodynamic parameters were monitored on days 0, 21 and 42. After finishing the protocol, animals were sacrificed, and blood samples collected in order to measure different biochemical parameters hearts were isolated for pathohistological analysis, and the relative expression of genes involved in oxidative stress, apoptosis, and inflammation. MOE treatment improved myocardial function and morphology, both in acute and chronic phase of EAM (reduction of inflammatory infiltrate, collagen, and apoptotic cells in myocardial tissue with improvement of hemodynamic parameters). The mechanisms of the achieved effects most likely involve the synergy of antioxidant, antiinflammatory and antiapoptotic properties of MOE. This study suggests that MOE, especially at 200mg/kg, improves myocardial function and architecture in EAM, thus preventing cardiac remodeling and development of dilated cardiomyopathy. Therefore, MOE can be considered a potentially useful adjuvant therapy in patients with autoimmune myocarditis.

Melissa officinalis; ekstrakt; eksperimentalni autoimunski miokarditis; oksidacioni stres; inflamacija.

lemon balm; Melissa officinalis; extract; experimental autoimmune myocarditis; oxidative stress; inflammation.

612(043.3) 615.451.1:616.12(043.3)

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