Ethnopharmacological relevance: The plant Anchusa italica Retz. (Anchusa azurea Mill.) has been traditionally used in Uygur medicine for the treatment of cardiovascular and cerebrovascular diseases in China. Our previous study showed that total flavonoids from Anchusa italica Retz. (TFAI) exhibited potent cardioprotection in acute ischemia/reperfusion injured rats.
Aim of the study: This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction (MI) in mice and the underlying mechanism.
Materials and methods: Total flavonoids were extracted from the whole herb of Anchusa italica Retz. and were characterized using HPLC-MS analysis. The left anterior descending branch of the coronary artery was ligated to simulate MI injury in mice. After surgery, mice were orally fed with TFAI at the doses of 10, 30 and 50 mg/kg body weight/day for a total of four weeks. Cardiac function and infarct size were measured, and inflammatory mediators were detected. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed on heart sections. The apoptotic factors, such as Bax, Bcl-2 and cleaved caspase 3, as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blot.
Results: The content of total flavonoids in TFAI was 56.2%. Four weeks following the MI surgery, TFAI enhanced the survival rate in post-MI mice. TFAI treatment at the doses of 30 and 50 mg/kg remarkably reduced infarct size and improved cardiac function as indicated by elevated EF and FS. Assay of the inflammatory factors showed that sera levels of TNF-α, IL-1β and IL-6 were markedly decreased by TFAI treatment compared to the MI group. H&E staining and Masson's trichrome staining demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis as indicated by the decreased cross-section area and collagen volume. Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were significantly downregulated following TFAI treatment. Furthermore, TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway.
Conclusions: Our data suggest that TFAI exerts a potent protective effect against chronic MI injury, and its beneficial effects on cardiac function and cardiac remodeling might be attributable, at least in part, to anti-inflammation and inhibition of the PI3K/Akt/mTOR signaling pathway.
Keywords: Adverse remodeling; Anchusa italica Retz.; Cardiac function; Myocardial infarction; Total flavonoids.
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