s-propargylcysteine and Heart-Failure

S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca2+ accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases.

Topics: Animals; Chemistry, Pharmaceutical; Cysteine; Heart Failure; Humans; Hydrogen Sulfide; Myocardial Ischemia; Neovascularization, Physiologic

S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H. Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H. The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H

Topics: Animals; Antioxidants; Cardiotonic Agents; Cystathionine gamma-Lyase; Cysteine; Disease Models, Animal; Fibrosis; Heart Failure; Hydrogen Sulfide; Liposomes; Male; Myocardium; Rats, Sprague-Dawley; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Heart failure (HF) is one of the most serious diseases worldwide. S-propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is proved to be able to protect against acute myocardial ischemia. In order to produce more stable and sustainable hydrogen sulfide, we used controlled release formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on HF rats and investigate involved mechanisms on apoptosis and oxidation.. Left coronary artery was occluded to induce HF model of rat. The survival rats were randomly divided into 7 groups after 24 hours and treated with drugs for 6 weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasmatic level of hydrogen sulfide was detected by modified sulfide electrode. Activity of enzyme and expression of protein were determined by colorimetry and Western blot, respectively.. The cardioprotective effects of CR-SPRC on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects compared to normal SPRC. CR-SPRC modulated antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity of caspases to protect against myocardial apoptosis. The cardioprotective effects of CR-SPRC were mediated by hydrogen sulfide.. All experiment data indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR-SPRC exerted better effects than normal SPRC in all respects, providing a new perspective on hydrogen sulfide-mediated drug therapy.

Topics: Animals; Apoptosis; Cardiotonic Agents; Cysteine; Delayed-Action Preparations; Disease Models, Animal; Fibrosis; Heart Failure; Heart Ventricles; Hydrogen Sulfide; Male; Oxidative Stress; Rats