Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats

Abstract

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.

Pre‑treatment with a combination of Shenmai and Danshen injection protects cardiomyocytes against hypoxia/reoxygenation‑ and H2O2‑induced injury by inhibiting mitochondrial permeability transition pore opening

“…The mechanisms underlying reperfusion injury are complex and multifactorial, with ROS generation, Ca 2+ overload, opening of the mPTP, endothelial dysfunction and pronounced inflammatory responses all implicated in causing the damage (31). Radix Ginseng Rubra, Radix Ophiopogonis and S. miltiorrhiza Bunge, which are included in YYH, have been investigated to determine their potential combined pharmaceutical properties, including anti-inflammatory, anti-oxidant, microcirculation promotion and cardioprotective abilities (32,33). In the clinic, it has been reported that YYH improved myocardial reperfusion injury following PCI in patients with acute myocardial infarction (18).…”

Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway

“…SMI is widely used for the treatment of atherosclerotic coronary heart disease and chronic pulmonary heart disease in China (Li et al 2011). SMI has high antioxidant activity and anticancer effects, balances blood pressure, and eliminates surplus free radicals (Yu et al 2014;Shi et al 2015;Zhou et al 2017). Nevertheless, there were few reports that ginsenosides could reverse MDR except 20(S)-Rh 2 (Zhang et al 2012a(Zhang et al , 2012b.…”

Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

“…Shenmai injection (SMI) is an injection-based on traditional Chinese medicine; it contains traditional Chinese remedy extracts Ophiopogonjaponicas (lilia-ceae), and Ginseng Rubra (araliaceae) [11] and is widely used to clinically treat heart diseases, sepsis, osteoarthritis and asthma [12][13][14][15]. The toxicity of SMI has been evaluated and is generally considered to be safe to use [16,17].…”