Dietary Evodiamine Inhibits Atherosclerosis-Associated Changes in Vascular Smooth Muscle Cells.

Evodia rutaecarpa (Juss.) Benth is a traditional Chinese medicine. The active ingredient, evodiamine, is a quinolone alkaloid and is found in Evodiae fructus. We investigated the effect of evodiamine on atherosclerosis using LDLR-/- mice fed on a high-fat diet and ox-LDL-induced MOVAS cell lines to construct mouse models and cell-line models. We report a significant reduction in atherosclerotic plaque formation in mice exposed to evodiamine. Our mechanistic studies have revealled that evodiamine can regulate the proliferation, migration, and inflammatory response of and oxidative stress in vascular smooth muscle cells by inhibiting the activation of the PI3K/Akt axis, thus inhibiting the occurrence and development of atherosclerosis. In conclusion, our findings reveal a role for evodiamine in the regulation of vascular smooth muscle cells in atherosclerosis, highlighting a potential future role for the compound as an anti-atherosclerotic agent.

Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells.

Voltage-dependent K+ (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC50 value of 8.91 ± 1.75 µM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

Combination of Epidural Blockade and Parecoxib in Enhanced Recovery After Gastrointestinal Surgery.

OBJECTIVE: To investigation effects of the combination use of epidural blockade and parecoxib in postoperative recovery of colorectal cancer (CRC) patients. METHODS: The present prospective single-blinded study included 186 CRC patients who received radical resection during April 2016 to December 2017. All patients were randomized into 3 different groups, the epidural blockade group, the combined-group with both epidural blockade and pre-intravenous injection of parecoxib, and the control group. The mean operative time, bleeding volume, the first out of bed activity time and hospital stay time were recorded. The mini-mental state examination (MMSE) score and Ramsay score were measured for cognitive function and the Visual Analog Score (VAS) was determined for the pain condition. RESULTS: The surgery time for the control group was significantly shorter than the other 2 groups (P < 0.05). The VAS scores were significantly lower in both the combined group and the epidural blockade group when compared with the control group and were dramatically lower in the combined group than the others 2 groups (all P < 0.05). The first out of bed activity time and hospital stay time were the shortest in the combined group, and the control group had the longest time (all P < 0.05). Both the Ramsay and MMSE scores were the highest in the combination group than other groups (all P < 0.05) and no significant difference was observed between the epidural blockade group and the control. CONCLUSION: The combination of epidural blockade and parecoxib could enhance the recovery process, as well as reduce the pain for the CRC patients.