Abstract
BackgroundDanggui (Radix Angelicae Sinensis) is an herb often used in Traditional Chinese medicine. It is used to promote blood flow and has been used in the treatment of myocardial ischemia-reperfusion injury in animal models. Angiotensin II (Ang II) has been shown to play important roles in mediating cardiovascular diseases, and may cause cardiac hypertrophy and apoptosis. This study aimed to investigate whether Danggui has protective effects on Ang II-induced apoptosis in H9c2 cardiomyoblast cells and study the mechanisms involved.MethodsWe evaluated the effect of Danggui on Ang II-induced apoptosis in an in vitro model. H9c2 cardiomyoblast cells were cultured in serum-free medium for 4 hr, then treated with Danggui (50, 100 μg/ml) 1 hr pre- or post-Ang II treatment. After a further 23 hr of culture, cells were harvested for analyses with assays for apoptosis markers and cell signaling pathways.ResultsOur results showed that Ang II induced upregulation of pro-apoptotic Bad, instability of the mitochondria membrane potential, cytochrome c release, caspase-9 and caspase-3 activation and cardiomyocyte apoptosis. Pre- or post-treatment with Danggui reversed all of the above Ang II-induced apoptotic effects in H9c2 cells. Furthermore, the JNK (SP600125) inhibitor completely blocked Danggui inhibition of caspase-3 activation in Ang II-treated H9c2 cells.ConclusionsOur results showed that Danggui either pre-treatment or post-treatment highly attenuated the Ang II-induced apoptosis in cardiomyoblast cells. The findings demonstrated that the anti-apoptosis effect of Danggui is mediated by JNK and PI3k inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-358) contains supplementary material, which is available to authorized users.
Highlights
Danggui (Radix Angelicae Sinensis) is an herb often used in Traditional Chinese medicine
We analyzed the cytotoxicity of Danggui extract on H9c2 cells, and found that Danggui extract has no cytotoxic effect on H9c2 cells at concentrations up to 500 μg/ml, but may cause obvious cell death at concentrations higher than 500 μg/ml after 24 hr of incubation
Inhibition of Angiotensin II (Ang II)-induced H9c2 cardiomyoblast apoptosis and DNA fragmentation The results of DAPI staining showed that Ang II treatment induced apoptosis in H9c2 cells, while pre-treatment or post-treatment with Danggui extract (50 to 500 μg/ml) resulted in a significant decrease of Ang II-induced apoptosis (Figure 2)
Summary
Danggui (Radix Angelicae Sinensis) is an herb often used in Traditional Chinese medicine. Cardiovascular disease is a major public health threat for both men and women in many countries It remains the leading cause of death and disability worldwide. Patients with diabetes often show reduced circulating levels of IGF-I and develop IGF-I resistance [7,8] This situation may induce apoptosis of myocardial cells and increase the risk of a heart attack. Studies in our laboratory have shown that the mechanism of apoptosis is synergistically mediated by angiotensin II- (Ang II) and the IGF-IR resistance-activated IGF-IIR signaling pathway [5,9] This suggests that IGF-IIR and its downstream signaling are important in myocardial apoptosis, and suppression of IGF-IIR signaling pathways can protect myocardial cells from apoptosis
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