ABSTRACT
Paeoniflorin (PF) is the main active component in Paeonia lactiflora Pall, and it has multiple effects. However, the precise mechanism of PF in hypercholesterolemia is unclear. In this study, rats were either fed a high-cholesterol diet (HCD) for 4 weeks to establish the hypercholesterolemic model or administered normal saline or PF (20 mg/kg/day). PF significantly reduced liver weight and the liver index. PF reduced hepatic lipid deposition and inflammation, improved serum lipid metabolism, and significantly inhibited serum and hepatic oxidative stress and the inflammatory response. PF treatment caused a marked decrease in the phosphorylated myosin phosphatase target subunit (p-MYPT)-1, nuclear sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS) levels, and an increase in the low-density lipoprotein receptor (LDLR) and phosphorylated-AMP-activated protein kinase (p-AMPK). Thus, PF could alleviate liver injury in hypercholesterolemic rats, and the specific mechanism may be related to the antioxidant, anti-inflammatory properties, and ROCK/AMPK/SREBP-1c signaling pathway.
ABSTRACT
18ß-Glycyrrhetinic acid (18ß-GA) is a component extracted from licorice. This study aimed to evaluate the effects of 18ß-GA on isoproterenol (ISO)-induced acute myocardial infarction in rats and mice. Two consecutive days of subcutaneous injection of ISO (85 mg/kg/day) resulted in acute myocardial infarction. We examined the pathological changes, oxidative stress, inflammatory response, and expression of apoptosis in mouse hearts. The expressions of phosphoinositol-3-kinase (PI3K), protein kinase B (Akt), and the phosphorylation levels of PI3K (p-PI3K) and Akt (p-Akt) were determined by western blotting. The whole-cell patch-clamp technique was applied to observe the L-type Ca2+ currents, and the Ion Optix detection system was used for cell contraction and Ca2+ transient in isolated rat cardiac ventricular myocytes. In ISO-induced myocardial infarction, the J-point, heart rate, creatine kinase, lactate dehydrogenase, superoxide dismutase, catalase, malondialdehyde, glutathion, and reactive oxygen species decreased in mice after 18ß-GA treatment. 18ß-GA improved ISO-induced morphologic pathology, inhibited the inflammatory pathway response and cardiomyocyte apoptosis, and inhibited PI3K/Akt signaling. 18ß-GA could significantly inhibit ICa-L, myocardial contraction, and Ca2+ transient. This study demonstrates that 18ß-GA has cardioprotective effects on acute myocardial infarction, which may be related to inhibiting oxidative stress, inflammation, apoptosis via the PI3K/Akt pathway, and reducing cell contractility and Ca2+ concentration via L-type Ca2+ channels.
ABSTRACT
Crocetin is a major bioactive ingredient in saffron (Crocus sativus L.) and has favorable cardiovascular effects. Here, the effects of crocetin on L-type Ca2+ current (ICa-L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. A 600 µg/mL dose of crocetin decreased ICa-L 31.50 ± 2.53% in normal myocytes and 35.56 ± 2.42% in ischemic myocytes, respectively. The current voltage nexus of the calcium current, the reversal of the calcium current, and the activation/deactivation of the calcium current was not changed. At 600 µg/mL, crocetin abated cell shortening by 28.6 ± 2.31%, with a decrease in the time to 50% of the peak and a decrease in the time to 50% of the baseline. At 600 µg/mL, crocetin abated the crest value of the ephemeral Ca2+ by 31.87 ± 2.57%. The time to half maximal of Ca2+ peak and the time constant of decay of Ca2+ transient were both reduced. Our results suggest that crocetin inhibits L-type Ca2+ channels, causing decreased intracellular Ca2+ concentration and contractility in adult rat ventricular myocytes. These findings reveal crocetin's potential use as a calcium channel antagonist for the treatment of cardiovascular disease.
