Cardioprotective effects and mechanism of Radix Salviae miltiorrhizae and Lignum Dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury

Abstract

Radix Salviae miltiorrhizae (SM) and Lignum Dalbergiae odoriferae (DO) are traditional Chinese medicinal herbs used to treat ischemic heart disease and other cardiovascular diseases; however, to the best of our knowledge, there are currently few studies regarding their effects. The present study aimed to investigate the cardioprotective effects of SM and DO during myocardial ischemia/reperfusion (MI/R) injury in rats, and explore the molecular mechanisms that underlie their actions. In the present study, Sprague-Dawley rats were pretreated with SM, the aqueous extract of DO (DOA) and the volatile oil of DO (DOO), either as a monotherapy or in combination for 7 days. Subsequently, the rats were subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry were used to identify the therapeutic effects of these traditional Chinese medicines. The results revealed that SM, DOA and DOO monotherapies ameliorated cardiac function, and this effect was strengthened further when used in combined therapies. Among the combined treatments, SM + DOO exhibited the greatest potential (P<0.05) to improve electrocardiogram results and heart rate, reduce the heart weight index and myocardial infarct size, and decrease the levels of creatine kinase-MB and lactate dehydrogenase. In addition, metabonomics-based findings, including the principal component analysis and partial least squares discriminant analysis score plot of the metabolic state in rat serum, provided confirmation for the aforementioned results, verifying that SM + DOO exerted synergistic therapeutic efficacies to exhibit a greater effect on rats with MI/R injury when compared with the other pretreatment groups. Furthermore, the most effective duration of SM + DOO treatment was 30 min and the least effective duration was 180 min. Treatment with SM + DOO also significantly (P<0.01) reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells, tumor necrosis factor-α andinterleukin-6 expression, and malondialdehyde content, and increased the serum and tissue activity of superoxide dismutase. These results indicated that the combined effects of SM + DOO may be more effective compared with the single pretreatments against MI/R injury in rats. This effect may be achieved partly through anti-apoptotic, antioxidant and anti-inflammatory activities. Therefore, SM + DOO may be considered an effective and promising novel strategy for the prophylaxis and treatment of ischemic heart disease.

Effect of methanol extract of Salviae miltiorrhizae Radix in high-fat diet-induced hyperlipidemic mice

“…Salviae miltiorrhizae Radix, the dried root of S. miltiorrhiza , is one of the most well-known medicinal resources in Asian traditional medicine [ 10 – 14 , 17 ]. Many studies have been conducted on SR, which have provided information on its traditional uses [ 22 ], chemical constituents [ 23 , 24 ], and pharmacological effects [ 15 , 25 , 26 ]; however, the identification of molecular targets and specific effects is still required.…”

“…Salviae miltiorrhizae Radix has been reported to affect coronary heart disease [ 14 ], ischemia/reperfusion-induced myocardial injury [ 15 ], cancer [ 16 ], metabolic syndrome [ 10 ], Alzheimer’s disease [ 17 ], and osteoporosis [ 12 ]. Several research articles have reported the effects of SR on diet-induced hyperlipidemia in rats; in one study, rats were administered SR extract for 4 weeks, which resulted in a significant decrease in serum lipid levels [ 18 – 20 ].…”

“…As SR exerts various pharmacological activities, it has great potential as a pharmacological agent [ 12 , 15 , 18 ]. In this study, we aimed to confirm the anti-hyperlipidemic effects in mice and to determine the molecular targets of SR.…”

Cardioprotective effects and underlying mechanism of Radix Salvia�miltiorrhiza and Lignum Dalbergia�odorifera in a pig chronic myocardial ischemia model

“…After one week of acclimation, the pigs were randomized into 3 groups as follows: i) Sham group (n=6), oral administration of regular diet and sham-operated without ameroid constrictor implantation; ii) Model group (n=6), oral administration of regular diet; iii) SM-DOO group (n=6), oral administration of regular diet with 1 g/kg/day SM and 0.1 ml/kg/day DOO. The dosages of SM and DOO were determined based on our previous studies, and adjusted for pigs according to a previously published method ( 15 , 17 ). Pigs were provided free access to water and were fed twice a day.…”

“…In our previous experiment, the cardioprotective effects of SM and DO were evaluated in a rat myocardial ischemia-reperfusion model. The results indicated that combined treatment with SM and DO had significant cardioprotective effects, and that the combination of SM with DO volatile oil (DOO) (SM 5 g/kg/day, DOO 0.5 ml/kg/day) was significantly more effective than SM, DO or DOO alone ( 15 ). However, the effects of SM-DOO in chronic myocardial ischemia have yet to be reported.…”