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A probable problem of disconnection between chemical fingerprints and drug effects for TCMs would be contrary to the original intention of fingerprint research, and limits the development and application of fingerprints. In this study, Shenmai injection, as a treatment dosage form of coronary heart disease, shock, and viral myocarditis clinically, was applied as the research object. The fingerprint of Shenmai injection was constructed, and the pharmacodynamic test of antioxidant effect was carried out to obtain quantitative characteristics and pharmacodynamic data. On this basis, a monitoring model based on the HPLC pharmacodynamic fingerprint was established to evaluate the quality of Shenmai injections from different batches and different manufacturers. Results showed that the optimized HPLC method had good repeatability, precision, and stability. A total of 28 characteristic peaks were identified to provide more chemical information. Furthermore, 13 ginsenosides and notoginsenoside have been selected as characteristic components of LC/MS fingerprint method. 8 peaks closely related to antioxidant properties by multiple linear regression method, which were identified as Rg1, Re, Rf, Rb1, and some other ginsenosides using MS analysis. The monitoring model based on HPLC pharmacodynamic fingerprint could successfully identify quality differences for Shenmai injections. Based on the case study of Shenmai injection, the novel and practical fingerprint analytical strategy could be further applied to monitor or predict the quality of TCMs.
A probable problem of disconnection between chemical fingerprints and drug effects for TCMs would be contrary to the original intention of fingerprint research, and limits the development and application of fingerprints. In this study, Shenmai injection, as a treatment dosage form of coronary heart disease, shock, and viral myocarditis clinically, was applied as the research object. The fingerprint of Shenmai injection was constructed, and the pharmacodynamic test of antioxidant effect was carried out to obtain quantitative characteristics and pharmacodynamic data. On this basis, a monitoring model based on the HPLC pharmacodynamic fingerprint was established to evaluate the quality of Shenmai injections from different batches and different manufacturers. Results showed that the optimized HPLC method had good repeatability, precision, and stability. A total of 28 characteristic peaks were identified to provide more chemical information. Furthermore, 13 ginsenosides and notoginsenoside have been selected as characteristic components of LC/MS fingerprint method. 8 peaks closely related to antioxidant properties by multiple linear regression method, which were identified as Rg1, Re, Rf, Rb1, and some other ginsenosides using MS analysis. The monitoring model based on HPLC pharmacodynamic fingerprint could successfully identify quality differences for Shenmai injections. Based on the case study of Shenmai injection, the novel and practical fingerprint analytical strategy could be further applied to monitor or predict the quality of TCMs.
Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.
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