Inhibitory effect of Salvia miltiorrhia BGE on matrix metalloproteinase-9 activity and migration of TNF-alpha-induced human aortic smooth muscle cells.

The migration and matrix metalloproteinases (MMPs) production of vascular smooth muscle cells (VSMC) may play a key role in the development of atherosclerosis. The Radix of Salvia miltiorrhiza Bunge (Labiatae) (SM), an eminent herb, is often included as an ingredient in various herbal remedies recommended for vascular therapies and has been used to treat vascular diseases for many centuries. In this study, we investigated the inhibitory effect of SM on TNF-alpha induced human aortic smooth muscle cells (HASMC) migration and MMP-9 activity. Various extracts prepared from stems of SM were tested for cytotoxic activity on HASMC using the XTT assay method. The ethanol extract (IC50 > 100 microg/ml), water extract (IC50 > 100 microg/ml) and chloroform (IC50 = 90 microg/ml) fraction exhibited weak cytotoxic activity. However, buthanol (IC50 = 80 microg/ml) and ethyl acetate (EtOAc; IC50 = 70 microg/ml) fraction exhibited strongly cytotoxic activity. Also, the extracts and fractions were investigated the inhibitory effects on MMP-9 activity using gelatin zymography. Gelatin zymography showed that the TNF-alpha-treated HASMC secreted MMP, probably including MMP-9, which may be involved in HASMC migration. The EtOAc fraction showed stronger inhibitory effect of proteolytic activity than other fractions. The EtOAc fraction was able to decrease the proteolytic activity of MMP-9 in a concentration-dependent manner on zymography. The Matrigel migration assay showed that SM effectively inhibited the TNF-alpha induced migration of HASMC as compared with the control group in a dose-dependent manner (IC50 = 65 microg/ml) and that the EtOAc fraction effectively inhibited the migration of HASMC, as compared with the control group in a dose-dependent manner. These results suggest that SM could be used as potential anti-atherosclerotic agent for anti-migration in TNF-alpha treated HASMC.

Effect of Continuous Infusion of Low Concentrations of Ketamine on the Bispectral Index and Recovery from Propofol-N2O-O2 Anesthesia / 대한마취과학회지

BACKGROUND: Ketamine as an analgesic adjunct in propofol-based anesthesia has the benefit of potent analgesic action and more stable vital signs due to sympathetic stimulation. However, its impact on the bispectral index and speed of recovery is still controvertial. The aim of this study was to evaluate the effects of continuous infusion of low concentrations of ketamine (0.1 microgram/ml) on the bispectral index and speed of recovery from propofol-N2O-O2 anesthesia. METHODS: Forty ASA I or II adult patients scheduled for elective orthopedic surgery were randomly allocated to one of two groups according to intraoperative ketamine use. In group P, anesthesia was induced and maintained with propofol (Ct: 3 - 6 microgram/ml), 67% nitrous oxide and 33% oxygen and the target concentration of propofol was kept at 4 microgram/ml at least 20 min before the end of propofol infusion. In group P + K, the method of anesthesia was same as in group P, but the low concentration (0.1 microgram/ml) of ketamine was continuously infused until discontinuation of propofol using computer-assisted continuous infusion. Bispectral index, recovery time from anesthesia, current/effect concentration of drugs, vital signs before and at induction, end of drug infusion, eye opening time on verbal command, and orientation time were checked. RESULTS: Changes in vital signs showed no differences between the groups. For bispectral index, there was no difference between groups initially, but it was higher (4 - 8) after the end of drug infusion in group P K than in group P. Also, recovery from anesthesia was delayed significantly in group P + K (P < 0.05). CONCLUSIONS: From these observations, we concluded that the use of low concentrations of ketamine during propofol-N2O-O2 anesthesia increased BIS, delayed eye opening and recovery from anesthesia without any benefit to vital sign stability.