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BACKGROUND The aim of this study was to evaluate the cardioprotective effects of aqueous fraction of Marrubium vulgare hydroalcoholic extract on cardiac parameters in ischaemic-reperfused isolated rat hearts. MATERIALS AND METHODS The aerial parts of the plant were extracted with methanol 70% by maceration. The water-soluble portion of the total hydroalcoholic extract was prepared with liquid-liquid extraction (LLE). Afterwards, the antioxidant activity, total phenolic and flavonoids content of the aqueous fraction were determined. In order to evaluate the effects of the aqueous fraction on cardiac parameters and ischaemia-reperfusion (I/R) injury, the Langendroff method was used on male Wistar rats. Harvested hearts were cannulated immediately to the Langendroff apparatus and subjected into 30 min regional ischaemia and 2 h reperfusion, either by a modified Krebs-Henseleit buffer (KHB) solution or enriched KHB solution with plant extract (10, 20, 40 μg/mL). RESULTS The aqueous fraction was found to be a scavenger of DPPH radical with RC50 value of 47 μg/mL. The total phenolic and flavonoids content of the fraction was 6.05 g gallic acid equivalent and 36.13 mg quercetin equivalent per 100 g of dry plant material. In addition, 40 μg/mL of Marrubium vulgare aqueous fraction significantly decreased infarct size in comparison to control group. All doses considerably reduced the total ventricular ectopic beats during 30 min of ischaemia. The extract at dose of 40 μg/mL noticeably decreased the arrhythmias during the first 30 min of reperfusion. CONCLUSIONS The results of the study indicated aqueous fraction of Marrubium vulgare possesses a protective effect against I/R injuries in isolated rat hearts.