Metabolomic study on the effect of Indonesian propolis in hypertensive rats

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Context: Hypertension is a health problem that is a major factor triggering cardiovascular diseases; however, effective treatment has not been found. Aims: To evaluate the effectiveness of Indonesian propolis in hypertension treatment through metabolomic study. Methods: A total of 36 Sprague Dawley rats were divided into 6 groups, including standard diet group, high-NaCl diet group, high-NaCl diet + captopril group (25 mg/kg), high-NaCl diet + propolis from Riau Archipelago group, high-NaCl diet + propolis from Lampung group, high-NaCl diet + propolis from South Sulawesi group. An 8% NaCl diet was used to induce hypertension for 3 weeks, while 200 mg/ kg propolis was administered for 1 week following the induction. The bioactive compounds of ethanol extract of propolis were identified using UHPLC. Moreover, the metabolomic profile was performed using LC-MS/MS. Data was processed using principal component analysis and was used for metabolic pathway analysis. Results: All propolis samples significantly ameliorated the blood pressure of hypertensive rats. The metabolites that were mainly found in rat serum were amino acids, glycerophospholipids, and acylcarnitine. Rats administered with propolis from South Sulawesi had the closest metabolite profile to the standard group, where L-acetylcarnitine could be the potential marker of hypertension. Several metabolic pathways, including the degradation of tryptophan, β-fatty acid oxidation, degradation of threonine, and 2-oxobutanoic acid, were the most impaired pathways in hypertension. Conclusions: Indonesian propolis, especially from South Sulawesi, could be used for controlling blood pressure.