Baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating ATP-sensitive potassium channels.

Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.

Baicalein Attenuates Brain Iron Accumulation through Protecting Aconitase 1 from Oxidative Stress in Rotenone-Induced Parkinson's Disease in Rats.

Aconitase 1 (ACO1) links oxidative stress and iron accumulation in Parkinson's disease (PD). ACO1 loses its aconitase activity and turns into iron regulatory protein 1 (IRP1) upon oxidative stress. IRP1 plays an important role in the accumulation of intracellular iron. Baicalein is a flavonoid isolated from the roots of Scutellaria baicalensis. The present results show that baicalein could bind to ACO1 and protect its isoform from the oxidative stress induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Furthermore, baicalein promoted aconitase activity and inhibited IRP1 activation in rotenone-induced PD models. Additionally, baicalein decreased the hydroxyl radicals generated by iron. In conclusion, baicalein attenuated iron accumulation and iron-induced oxidative stress in the brain of PD rats by protecting ACO1.

Impact Behavior of Hydrophilic Micron Particles on a Planar Gas-Liquid Interface.

The behavior of hydrophilic micron particles impacting on the gas-liquid interface has been further experimentally studied using a high-speed camera at different surface tensions and dynamic viscosities of liquids. The results show that the impact behavior exhibits suspension and submergence modes, whose boundary cannot be clearly identified because the overlap between the impact velocity ranges occurs because of the unstable pinning of the three-phase contact line on the surface of hydrophilic particles. The liquid properties have little effect on the wettability of hydrophilic particles but greatly influence the hydrodynamic and capillary force exerted on the particles, leading to the expansion of the suspension mode range. In addition, the penetration probability changes little with the decrease in surface tension, while it significantly reduces with the increase in dynamic viscosity. A penetration probability model is predicted as an exponential function of the inertial and supporting forces, and the experimental values agree well with the predicted values. The outcomes of this research will be helpful for understanding the mechanism of particle-interface interaction and providing guidance for enhancing the separation of hydrophilic fine ash via a bubble scrubbing system.

Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging.

Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI-TOF-MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to verify the results obtained from MALDI-TOF-MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate-glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI-TOF-MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC-MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO.