Dung-shen (Codonopsis pilosula) attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells

Previous studies from our lab showed that increase in AngII in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-β3 via Gαq, insertion into mitochondrial membranes of Bad, and apoptosis via caspases 9 and 3. Codonopsis pilosula is traditionally used to lower blood pressure. The purpose of our study is to investigate if C. pilosula attenuates AngII plus Leu27-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts. C. pilosula significantly attenuated AngII induced IGFIIR promoter activity. Leu27-IGFII was applied to enhance the AngII effect. C. pilosula also reversed Ca2+ influx, MOMP and apoptosis increased by AngII plus Leu27-IGFII. Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-Gαq association were downregulated by C. pilosula. However, p-BadSer136 and Bcl-2 were increased. Therefore, C. pilosula suppresses AngII plus Leu27-IGFII-induced IGFII/IGFIIR pathway in myocardial cells.