Research progress on regulation effect of Panax notoginseng saponins on mitochondria / 中国中药杂志

Mitochondria is the key energy source of cells and plays an important role in energy synthesis and release, and maintenance of cellular functions. As the most important active ingredients in Chinese medicine pseudo-ginseng, Panax notoginseng saponins(PNS) have pharmacological effects on protecting against thrombosis, dilating blood vessels, lowering the blood pressure, anti-inflammation, and antioxidant, etc. Domestic and foreign studies have shown that PNS participates in regulating mitochondrial energy metabolism, oxidative stress, biosynthesis, apoptosis, mitophagy and the status of membrane channels. Therefore, the mitochondria is one of the important targets of PNS. In this paper, the regulation effects of P. notoginseng saponins on mitochondria were reviewed.

Opening of ATP-sensitive K+channels protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting TLR4/NF-κB pathway / 中国病理生理杂志

AIM:To investigate whether the opening of ATP-sensitive K+(KATP) channels protects H9c2 car-diac cells against high glucose ( HG)-induced injury and inflammation by inhibiting the Toll-like receptor 4 ( TLR4 )/nu-clear factor-κB ( NF-κB) pathway.METHODS:The protein levels of TLR4 and NF-κB p65 were determined by Western blot.The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.The cell viabil-ity was measured by CCK-8 assay.Mitochondrial membrane potential (MMP) was examined by rhodamine 123 (Rh 123) staining followed by photofluorography.The intracellular levels of reactive oxygen species ( ROS) were detected by 2′, 7′- dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The number of apoptotic cells was ob-served by Hoechst 33258 nuclear staining followed by photofluorography.RESULTS: After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the protein levels of TLR4 and phosphorylated NF-κB p65 ( p-NF-κB p65) were significantly increased.Pretreatment of the cells with 100 μmol/L diazoxide ( DZ, a KATP channel opener) for 30 min before exposure to HG considerably blocked the up-regulation of the TLR4 and p-NF-κB protein levels induced by HG.Moreover, co-treatment of the cells with 30 μmol/L TAK-242 (an inhibitor of TLR4) obviously inhibited the HG-in-duced up-regulation of the p-NF-κB p65 protein level.On the other hand, pretreatment of the cells with 100 μmol/L DZ had a clear myocardial protection effect, which attenuated the HG-induced cytotoxicity, inflammatory response, mitochon-drial damage, oxidative stress and apoptosis, evidenced by an increase in the cell viability, and decreases in the levels of IL-1βand TNF-α, MMP loss, ROS generation and the number of apoptotic cells.Similarly, co-treatment of H9c2 cardiac cells with 30μmol/L TAK-242 or 100μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries and inflammation induced by HG.CONCLUSION: The opening of KATP channels protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the TLR4/NF-κB pathway.

Increased Expression of ATP-sensitive K+ Channels Improves the Right Ventricular Tolerance to Hypoxia in Rabbit Hearts

ATP-sensitive K+ channels (KATP) are major component of preventing ischemia-reperfusion injury. However, there is little information regarding to the expressional difference of K(ATP) and its function between left and right ventricles. In this study, we measured the lactate dehydrogenase release of rabbit heart slices in vitro and determined the difference of the K(ATP) expression at the both ventricles by measuring the level of K(ATP)-forming Kir6.2 (OcKir6.2) mRNA using in situ hybridization. The hearts were preconditioned with 15 min hypoxia and reoxygenated for 15 min before a hypoxic period of 60 min, followed by reoxygenation for 180 min. With hypoxic preconditioning (100% N2) with 15 min, left ventricles (LV) showed higher release of LDH comparing with right ventricles (RV). Adding KATP blocker glibenclamide (10 microM) prior to a hypoxic period of 60 min, hypoxic preconditioning effect of RV was more abolished than LV. With in situ hybridization, the optical density of OcKir6.2 was higher in RV. Therefore, we suggest that different K(ATP) expression between LV and RV is responsible for the different response to hypoxia and hypoxic preconditioning of rabbit hearts.

Influence of sulfonylureas on cardiovascular system: Progress in basic research and clinical research / 第二军医大学学报

Previous studies have showed that sulfonylureas possess a bidirectional effect on cardiovascular system: they can raise the coronary artery tone, aggravate ischemic injury to the cardiovascular tissues, and accelerate cardiac hypertrophy through closing cardiovascular ATP-sensitive K+ channels; meanwhile, they can also regulate glucolipid metabolism, modulate inflammatory reaction and inhibit atherosclerosis through activating peroxisome proliferator-activated receptors. Clinical-epidemiological study showed different opinions on whether sulfonylureas can increase the mortality of patients with cardiovascular diseases.

Inhibition of Pacemaker Activity of Interstitial Cells of Cajal by Hydrogen Peroxide via Activating ATP-sensitive K(+) Channels

To investigate whether hydrogen peroxide (H2O2) affects intestinal motility, pacemaker currents and membrane potential were recorded in cultured interstitial cells of Cajal (ICC) from murine small intestine by using a whole-cell patch clamp. In whole cell patch technique at 30 degress C, ICC generated spontaneous pacemaker potential under current clamp mode (I=0) and inward currents (pacemaker currents) under voltage clamp mode at a holding potential of -70 mV. When ICC were treated with H2O2 in ICC, H2O2 hyperpolarized the membrane potential under currents clamp mode and decreased both the frequency and amplitude of pacemaker currents and increased the resting currents in outward direction under voltage clamp mode. Also, H2O2 inhibited the pacemaker currents in a dose-dependent manner. Because the properties of H2O2 action on pacemaker currents were same as the effects of pinacidil (ATP-sensitive K+ channels opener), we tested the effects of glibenclamide (ATP-sensitive K+ channels blocker) on H2O2 action in ICC, and found that the effects of H2O2 on pacemaker currents were blocked by co- or pre-treatment of glibenclamide. These results suggest that H2O2 inhibits pacemaker currents of ICC by activating ATP-sensitive K(+) channels.

Influence of sulfonylureas on cardiovascular system:progress in basic research and clinical research / 第二军医大学学报

Previous studies have showed that sulfonylureas possess a bidirectional effect on cardiovascular system:they can raise the coronary artery tone,aggravate ischemic injury to the cardiovascular tissues,and accelerate cardiac hypertrophy through closing cardiovascular ATP-sensitive K+ channels;meanwhile,they can also regulate glucolipid metabolism,modulate inflammatory reaction and inhibit atherosclerosis through activating peroxisome proliferator-activated receptors.Clinical-epidemiological study showed different opinions on whether sulfonylureas can increase the mortality of patients with cardiovascular diseases.