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Abstract
Danshen has been used in traditional Chinese medicine for hundreds of years to treat cardiovascular diseases. However, its precise cardioprotective components and the underlying mechanism are still unclear. In the present study, we demonstrated that in a rat model of acute myocardial infarction, the treatment with magnesium lithospermate B (MLB), the representative component of phenolic acids in Danshen, significantly reduced the infarct size and the blood lactate dehydrogenase level. In contrast, tanshinone IIA, the representative component of lipophilic tanshinones in Danshen, had no such protective effects. Moreover, in the simulated ischemia cell model, MLB treatment considerably increased the cell viability and reduced the sub-G1 population and the apoptotic nuclei, indicating its anti-apoptotic effect. Further mechanism study revealed that the ischemia-induced p38 phosphorylation was abolished by MLB treatment. Interestingly, MLB specifically inhibited the TGFβ-activated protein kinase 1-binding protein 1 (TAB1) mediated p38 phosphorylation through disrupting the interaction between TAB1 and p38, but it did not affect the mitogen-activated protein kinase 3/6 mediated p38 phosphorylation. In conclusion, the present study identifies MLB as an active component of Danshen in protecting cardiomyocytes from ischemic injury through specific inhibition of TAB1–p38 apoptosis signaling. These results indicate TAB1–p38 interaction as a putative drug target in treating ischemic heart diseases.
Highlights
Danshen, the rhizome of Salvia miltiorrhiza, is one of the famous ancient Chinese herbal medicines and is traditionally believed to “invigorate” the blood and reduce blood clotting
We investigated the protective effects of two representative components of Danshen, magnesium lithospermate B (MLB) and tanshinone IIA, in experimental models of ischemia
MLB treatment attenuates ischemic heart injury in rat In order to test the protective effect of Danshen in myocardial ischemic injury, rat ischemia model was established by 1 h left anterior descending artery (LAD) ligation.“Danshen Injection,”a total extraction from Danshen (Wu et al, 2007), MLB and tanshinone IIA, two representative components of Danshen, were applied just before the surgery at a dosage normalized to their natural composition in the plant (Figure 1)
Summary
The rhizome of Salvia miltiorrhiza, is one of the famous ancient Chinese herbal medicines and is traditionally believed to “invigorate” the blood and reduce blood clotting. Remedies containing Danshen have been used customarily to treat coronary heart diseases, angina pectoris and myocardial infarction (MI) (Ji et al, 2000). Danshen is officially listed in the Chinese Pharmacopoeia and is used widely and successfully in clinics in China, the exact mechanism for its therapeutic basis is poorly understood. Over the last 50 years, the chemical constituents and biological activities of Danshen have been widely studied. More than 60 ingredients have been identified in Danshen, which are mainly divided into water-soluble phenolic acids and lipophilic tanshinones (Wang et al, 2007). Phenolic acids possess antioxidant and anticoagulant activities, whereas tanshinones show antibacterial, antioxidant, and antineoplastic activities. The main active component with cardioprotective effects on ischemic heart diseases and the underlying mechanism remain unresolved
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