Abstract
BackgroundRadix Salvia miltiorrhiza (Danshen) has been used as a principal herb in treating cardiovascular diseases in Chinese medicine. Salvianolic acid B (SA-B), a water-soluble active component of Danshen, was found to have anti-myocardial ischemia (anti-MI) effect. This study aims to investigate mechanisms of SA-B on MI.MethodsFive conventional Western medicines (isosorbide dinitrate, verapamil, propranolol, captopril and trimethazine) with different mechanisms for treating cardiovascular diseases were selected as positive references to compare with SA-B in changing of the metabolomic profiles in MI rats under treatment. Potential mechanisms of SA-B were further investigated in H9C2 cell line.ResultsThe metabolomic profiles between SA-B- and propranolol-treated MI rats were similar, since there was a big overlap between the two groups in the PLS-DA score plot. Finally, it was demonstrated that SA-B exhibited a protective effect on MI mainly by decreasing the concentration of cyclic adenosine monophosphate (cAMP) and Ca2+ and inhibiting protein kinase A (PKA).ConclusionSA-B and propanolol exhibited similar metabolomic profiles, indicating that the two drugs might have a similar mechanism.
Highlights
Radix Salvia miltiorrhiza (Danshen) has been used as a principal herb in treating cardiovascular diseases in Chinese medicine
This study aims to investigate mechanisms of Salvianolic acid B (SA-B) on Myocardial ischemia (MI)
Ions were significantly changed in MI rats as compared with sham rats; 22 out of 160 ions were identified as biomarkers of MI, including 15(S)-HETE, 2’,3’-Cyclic AMP, dihydrosphingosine, 5-phosphoribosylamine, phytosphingosine, L-isoleucyl-L-proline, 2’,3’-Cyclic GMP, 1-phenylethylamine, thromboxane B2, xanthine, hypoxanthine, inosine, L-homoserine, carnosine, allantoin, Lvaline, L-phenylalanine, dihydrobiopterin, 2-oxoisocaproic acid, L-isoleucine, L-tryptophan and glyceraldehydes
Summary
Radix Salvia miltiorrhiza (Danshen) has been used as a principal herb in treating cardiovascular diseases in Chinese medicine. Myocardial ischemia (MI) is characterized by ischemia in the heart muscle. It is the most common cause of death, and a major reason for hospital admissions [1]. CAMP in turn activates the cAMP-dependent protein kinase A (PKA). This kinase phosphorylates several proteins related to excitation-contraction coupling, such as L-type Ca2+ channel and phospholamban. The phosphorylation of phospholamban accelerates Ca2+ uptake into the sarcoplasmic b-adrenergic blockers such as propranolol [4] could inhibit the activation of b-adrenoceptor and decrease the concentration levels of cAMP, PKA and Ca2+, leading to slow heart rate, decreased myocardial contractility, reduced cardiac output, and decreased myocardial oxygen consumption. Western medicines with other mechanisms of action, such as isosorbide dinitrate (a vasodilator), verapamil (a calcium antagonist), captopril (an angiotensin converting enzyme inhibitor) and trimethazine (a fatty acid oxidation inhibitor), are commonly used in the prevention and treatment of MI
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