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Dragon's Blood (DB), a Chinese traditional herb, was validated to have definite protective effects on activating circulation to remove blood stasis. More evidence demonstrated that DB has a dramatic efficacy on treating acute myocardial infarction (AMI). However, governing mechanism of its therapeutic effects remains unclear. This study is to reveal the underlying mechanism of the anti-myocardial ischemia effect of DB extract (DBE).
C57 mice were randomly divided into 5 groups: sham group, model group, DBE groups (with 600mg/kg dose and 300mg/kg dose respectively), and aspirin group. After pre- therapeutic administration for 7 days, the mice were subjected to left anterior descending (LAD) artery ligation. While in sham group, needle was only passed around the artery without ligation. 24 hours after surgery, heart function was evaluated by 2D echocardiography. CK-MB and LDH in serum, TXB2 and 6-keto-PGF1α in plasma were detected. Protein expressions of COX-1, COX-2, p-JAK2, p-STAT3, VEGF, P-S6, TGF-β and PPARγ were measured by western-blot.
Echocardiography results showed that EF and FS significantly decreased in model group compared to sham group. An increase in values of LVEDd and LVESd was also observed in the model group, suggesting that myocardial ischemia was successfully induced. In DBE treated group, EF and FS were significantly up-regulated compared with those in the model group. In addition, DBE could decrease CK-MB and LDH obviously compared with model group. Moreover, the DBE can also up-regulate 6-keto-PGF1α and down-regulate TXB2 so as to keep balance between 6-keto-PGF1α and TXB2 compared with the model group and be closer to the sham group when compared to aspirin group. Different doses of DBE can reduce apoptosis mediated by different subtypes of cyclooxygenases, especially through COX2. DBE also can up-regulate the expression of proteins in JAK-STAT pathway, including p-JAK2, and p-STAT3, which has been found as the key pathway of inflammatory and oxidative stress. mTOR pathway also was activated by DBE through up-regulating the P-S6 protein, thereby activating the expression of VEGF, HIF-1α and PPARγ proteins in mTOR pathway. Besides, the Western Blot results also showed that DB can inhibit fibrosis mediated by TGF-β.
DBE has definite cardiac protective efficacy in improving cardiac function mainly mediated by down-regulating the COX2, JAK-STAT pathway, TGF-β-smad pathway and up-regulating the mTOR pathway. These findings provide strong evidence for cardiac protective efficacy of DBE and validate the beneficial effects of DBE in the clinical application for myocardial ischemia.