Characterization, Large-Scale HSCCC Separation and Neuroprotective Effects of Polyphenols from Moringa oleifera Leaves.

Moringa oleifera leaves have been widely used for the treatment of inflammation, diabetes, high blood pressure, and other diseases, due to being rich in polyphenols. The main objective of this work was to largely separate the main polyphenols from Moringa oleifera leaves using the technique of high-speed counter-current chromatography (HSCCC). The phenolic composition in Moringa oleifera leaves was first analyzed qualitatively and quantitatively by UPLC-Q-Exactive Orbitrap/MS and UPLC-QqQ/MS, respectively, indicating that quercetin and kaempferol derivatives, phenolic acid and apigenin are the main polyphenols in Moringa oleifera leaves, with quercetin and kaempferol derivatives predominating. Furthermore, the conditions of HSCCC for large-scale separation of polyphenols from Moringa oleifera leaves were optimized, which included the selection of the solvent system, flow rate and the sample load. Only by one-step HSCCC separation (within 120 min) under the optimized conditions, six quercetin and kaempferol derivatives, a phenolic acid and an apigenin could be individually isolated at a large scale (yield from 10% to 98%), each of which possessed high purity. Finally, the isolated polyphenols and phenolic extract from Moringa oleifera leaves (MLPE) were verified to have strong neuroprotective activities against H2O2-induced oxidative stress in PC-12 cells, suggesting that these compounds would contribute to the main beneficial effects of Moringa oleifera leaves.

Panaxadiol as a major metabolite of AD-1 can significantly inhibit the proliferation and migration of breast cancer cells: In vitro and in vivo study.

Previous studies have shown that 20 (R)-25-methoxyl-dammarane-3ß, 12ß, 20 triol (AD-1) can inhibit various cancer cell lines. This study aimed to explore the effect and mechanism of AD-1 metabolite M2 (Panaxadiol; PD) on breast cancer cells of nude mice. Five AD-1 metabolites were isolated and identified using various chromatographic techniques. PD was the main component. In vitro results showed that PD could inhibit the proliferation and migration of MDA-MB-231 cells by inducing G1-phase arrest. In addition, PD down-regulated the expression of Cyclin D1, cdk2, cdk4, cdk6, P-p38, and MMP9, and up-regulated p21 and p27. In vivo results showed that PD could effectively reduce the volume, weight, and migration of breast cancer Transcriptomics analyzed 491 differentially expressed genes by GO and KEGG enrichment. RT-PCR verification confirmed that the significant down-regulation of MMP9 was consistent with transcriptomics results. In further research showed that PD regulated the protein expression of P-p38 and MMP9 in MAPK pathway. In summary, in vivo and in vitro studies showed that PD significantly inhibit the occurrence and development of breast cancer, possibly through the MAPK pathway.

Qualitative and quantitative analysis of phenolic compounds in blueberries and protective effects on hydrogen peroxide-induced cell injury.

This work was conducted to optimize an accelerated solvent extraction for ultra high performance liquid chromatography-mass spectrometry/mass spectrometry analysis of blueberry phenolic compounds. The conditions for accelerated solvent extraction were verified using response surface methodology to obtain the following optimized conditions: ethanol concentration (pH = 3), 48%; temperature, 50℃, and static cycle times, 3. Further, ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry and ultra high performance liquid chromatography with triple-quadrupole tandem mass methods for determination of the detailed phenolic composition were developed and validated. Total of 81 phenolic compounds were identified by ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry including 23 anthocyanins, 32 flavonols, 11 proanthocyanidins, 2 other flavonoids, and 13 phenolic acids. Fifty-one of these compounds have been simultaneously quantified by ultra high performance liquid chromatography with triple-quadrupole tandem mass including 31 anthocyanins, 8 flavonols, 6 proanthocyanidins, 2 other flavonoids, and 8 phenolic acids. Malvidin-dinhexoside has, for the first time, been detected in wild. Moreover, by verifying the protection on PC12 cells against oxidative damage, it was showed that the phenolic extracts (500 µg/mL) can improve significantly the viability (9.26-24.78%) of hydrogen peroxide-induced PC12 cells, activities of superoxide dismutase (34.59-37.90 U/mg) and glutathione peroxidase (6.87-14.42 mU/mg) and decrease the content of malonic dialdehyde (13.27-24.62 nmol/mg). Correlation analysis suggested that anthocyanins might contribute most to these activities.

Roles of glial ion transporters in brain diseases.

Glial ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions of the central nervous system (CNS). In response to acute or chronic brain injuries, these ion transporters can be activated and differentially regulate glial functions, which has subsequent impact on brain injury or tissue repair and functional recovery. In this review, we summarized the current knowledge about major glial ion transporters, including Na+ /H+ exchangers (NHE), Na+ /Ca2+ exchangers (NCX), Na+ -K+ -Cl- cotransporters (NKCC), and Na+ -HCO3- cotransporters (NBC). In acute neurological diseases, such as ischemic stroke and traumatic brain injury (TBI), these ion transporters are rapidly activated and play significant roles in regulation of the intra- and extracellular pH, Na+ , K+ , and Ca2+ homeostasis, synaptic plasticity, and myelin formation. However, overstimulation of these ion transporters can contribute to glial apoptosis, demyelination, inflammation, and excitotoxicity. In chronic brain diseases, such as glioma, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), glial ion transporters are involved in the glioma Warburg effect, glial activation, neuroinflammation, and neuronal damages. These findings suggest that glial ion transporters are involved in tissue structural and functional restoration, or brain injury and neurological disease development and progression. A better understanding of these ion transporters in acute and chronic neurological diseases will provide insights for their potential as therapeutic targets.

Grape and wine polymeric polyphenols: Their importance in enology.

Phenolic compounds are important constituents of red wine, contributing to its sensory properties and antioxidant activity. Owing to the diversity and structural complexity, study of these compounds was mainly limited, during the last three decades, on their low-molecular-mass compounds or simple phenolic compounds. Only in recent years, much attention has been paid to highly polymerized polyphenols in grape and red wines. The reason for this is largely due to the development of analytical techniques, especially those of HPLC-ESI-MS, permitting the structural characterization of highly polymerized polyphenols. Furthermore, the knowledge on the biological properties of polymeric polyphenols of red wine is very limited. Grape polyphenols mainly consist of proanthocyanidins (oligomers and polymers) and anthocyanins, and low amount of other phenolics. Red wine polyphenols include both grape polyphenols and new phenolic products formed from them during winemaking process. This leads to a great diversity of new polyphenols and makes wine polyphenol composition more complex. The present paper summarizes the advances in the research of polymeric polyphenols in grape and red wine and their important role in Enology. Scientific results indicate that polymeric polyphenols, as the major polyphenols in grape and red wine, play a major role in red wine sensory properties, color stability and antioxidant activities.

Novel approach for extraction of grape skin antioxidants by accelerated solvent extraction: Box-Behnken design optimization.

Grape skin can be considered as an excellent and inexpensive source of polyphenol antioxidant compounds. A high-efficiency accelerated solvent extraction (ASE) method was developed for antioxidant polyphenols from grape skin. A three-factors three-level Box-Behnken design by response surface methodology was employed for optimization of extraction parameters in terms of total phenolic content, total anthocyanins content and antioxidant activity. The optimized condition was ethanol concentration of 48.80%, temperature of 50.79 °C and extraction time of 14.82 min. Under these conditions, the highest yields of polyphenol, the total phenolic content (15.24 mg GAE/g), total anthocyanins content (346.68 mg CGE/100 g) in grape skin, were obtained with significant antioxidant properties by DPPH, ABTS and FRAP assays. Moreover, the extracts from various grape skins by ASE, possessed ten main antioxidant polyphenols with the highest concentration of p-hydroxybenzoic acid and malvidin-3-O-glucoside. Compared with conventional solvent extraction, ASE extracted more amounts of polyphenols, exhibited more extraction level with shorter time and higher reproducibility.

Preparation and Antioxidant Activity of Ethyl-Linked Anthocyanin-Flavanol Pigments from Model Wine Solutions.

Anthocyanin-flavanol pigments, formed during red wine fermentation and storage by condensation reactions between anthocyanins and flavanols (monomers, oligomers, and polymers), are one of the major groups of polyphenols in aged red wine. However, knowledge of their biological activities is lacking. This is probably due to the structural diversity and complexity of these molecules, which makes the large-scale separation and isolation of the individual compounds very difficult, thus restricting their further study. In this study, anthocyanins (i.e., malvidin-3-glucoside, cyanidin-3-glucoside, and peonidin-3-glucoside) and (⁻)-epicatechin were first isolated at a preparative scale by high-speed counter-current chromatography. The condensation reaction between each of the isolated anthocyanins and (⁻)-epicatechin, mediated by acetaldehyde, was conducted in model wine solutions to obtain ethyl-linked anthocyanin-flavanol pigments. The effects of pH, molar ratio, and temperature on the reaction rate were investigated, and the reaction conditions of pH 1.7, molar ratio 1:6:10 (anthocyanin/(⁻)-epicatechin/acetaldehyde), and reaction temperature of 35 °C were identified as optimal for conversion of anthocyanins to ethyl-linked anthocyanin-flavanol pigments. Six ethyl-linked anthocyanin-flavanol pigments were isolated in larger quantities and collected under optimal reaction conditions, and their chemical structures were identified by HPLC-QTOF-MS and ECD analyses. Furthermore, DPPH, ABTS, and FRAP assays indicate that ethyl-linked anthocyanin-flavanol pigments show stronger antioxidant activities than their precursor anthocyanins.

Evaluation of lower blepharoplasty treated with the SmartLipo 1064-nm system and its clinical implications: A retrospective review.

INTRODUCTION: This study used the SmartLipo 1064-nm system to remove herniated orbital fat tissue to improve lower eyelid appearance. A retrospective review of 128 patients was performed to evaluate the size of prominent fat pads and complications. MATERIALS AND METHODS: Altogether, 128 patients underwent a procedure using the SmartLipo 1064-nm system via postseptal access, which helped locate fat tissue more precisely. Digital photographs were taken preoperatively and at one week and six months postoperatively. Eyebag sizes were determined preoperatively and six months postoperatively using the Non-Contact 3D Digitizer. RESULTS: Altogether, 118 primary and 10 revision patients (average age 31 years) were placed in one of two groups: mildly protruding fat pads (group 1, 86 patients) and moderately protruding fat pads (group 2, 42 patients). After injection of about 1 ml of anesthetic and 1 ml of 0.9% iced saline on each side, the patients received an average 450 joules of energy delivered at 20 Hz and 3 W. Postoperatively, the eyebag's height, depth, and area were significantly reduced in both groups (р = 0.000). The main symptoms (swelling, chemosis, engorgement, and pain) subsided within 5-7 days. CONCLUSION: The SmartLipo 1064-nm system with postseptal access, a minimally invasive procedure, can be used to correct mildly and moderately prominent fat pads.

A Study of the Morbidity Involved in Whole Rib Harvesting and In Situ Splitting Rib Harvesting Surgery.

BACKGROUND: Although there have been several reports that detail the in situ rib splitting harvesting surgical procedure, there are limited published studies evaluating this procedure and the traditional whole rib harvesting approach. In this study, the authors conducted a retrospective controlled study on the complications related to the 2 rib harvesting approaches. METHODS: From March 2012 to May 2014, 24 patients were treated with rib grating, of whom 9 patients received conventional rib harvesting surgery and 15 patients received in situ splitting harvesting surgery. In all patients, a 3-dimensional computed tomography study of the chest was performed 7 days postoperatively. Postoperative complications were assessed and postoperative pain was assessed using a visual analog scale after the first 24, 48, and 72 hours after the surgery. RESULTS: The complication rate for in situ splitting rib harvesting was 6.67% versus 44.44% for patients treated with whole rib grafting surgery. After 48 and 72 hours, the visual analog scale scores in patients treated with in situ splitting rib grafts were significantly lower than the patients treated with traditional surgery. CONCLUSION: The in situ splitting approach for obtaining a rib results in a clinically significant reduction in complications compared with the traditional approach.

UHPLC-MS/MS analysis and protective effects on neurodegenerative diseases of phenolic compounds in different parts of Diospyros kaki L. cv. Mopan.

Persimmon (Diospyros kaki L. cv. Mopan.), an important commercial crop belonging to the genus of Diospyros in the Ebenaceae family, is rich in bioactive phenolic compounds. In this study, the phenolic compounds from fruits, leaves, and calyces of persimmon were qualitatively and quantitatively determined by UPLC-Q-Exactive-Orbitrap/MS and UPLC-QqQ-MS/MS, respectively. Furthermore, the role of phenolic extract from different parts of persimmon on neuroprotective activity in vitro, through against oxidative stress and anti-neuroinflammation effect was firstly evaluated. The results showed that 75 phenolic compounds, and 3 other kinds of compounds were identified, among which 44 of phenolic compounds were quantified from different parts of persimmon. It is the first time that epicatechin-epigallocatechin, catechin-epigallocatechin, catechin-epigallocatechin (A-type), and glycoside derivatives of laricitrin were identified in persimmon extract. The dominated phenolic compounds in three parts of persimmon were significantly different. All phenolic extracts from each part of persimmon showed strong neuroprotective activities against H2O2-induced oxidative stress in PC-12 cells and LPS-induced BV2 cells. The fruit extract presented the strongest activity, followed by calyx and leaf extract. The systematic knowledge on the phytochemical composition along with activity evaluation of different parts of persimmon could contribute to their targeted selection and development.

Novel l-Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3'-O-Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'-O-gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.

Effects of Different Brewing Technologies on Polyphenols and Aroma Components of Black Chokeberry Wine.

The black chokeberry is a shrub of the Rosaceae family, which is characterized by strong acidity and astringency and is widely processed into wine and alcoholic beverages. However, due to the characteristics of black chokeberries, the wine brewed by traditional methods often has a strong sour taste, weak aroma, and poor sensory quality. In order to improve the sensory quality and explore the effects of different brewing technologies on polyphenols of black chokeberry wine, five brewing technologies (traditional fermentation, frozen fruit fermentation, co-fermentation, carbonic maceration, and co-carbonic maceration) were used in this study. The results showed that compared with the traditional method, the four alternative brewing technologies could reduce acidity, increase the contents of several major polyphenols, and enrich floral scents and fruity aroma, thus significantly improving the sensory qualities of black chokeberry wine. The proposed brewing technologies would be applied to the production of quality black chokeberry or other fruit wines.

Wrinkling and Strengthening Behaviors in the Two-Layer-Sheet Hot-Forming-Quenching Integrated Process for an Al-Cu-Mg-Alloy Thin-Walled Curved-Surface Shell.

The thin-walled curved-surface component is an important structural element in aerospace. Wrinkling, springback and thermal distortion occur easily when forming these components. To form thin-walled components with high precision and strength, a two-layer-sheet hot-forming-quenching integrated process was proposed, in which wrinkling is prevented by thickening the upper sheet and springback is reduced by solution and die quenching. Selecting an appropriate upper sheet is crucial to suppress wrinkling and accomplish effective die quenching. The effect of the upper sheet on the wrinkling and strengthening behaviors of an Al-Cu-Mg-alloy melon-petal shell was thus studied in detail. The anti-wrinkle mechanism was analyzed through numerical simulation. The forming quality, including forming precision, deformation uniformity and strength, were further evaluated. The wrinkle gradually decreased with the increasing thickness of the upper sheet, resulting from the depressed compressive stress at the edge of the target sheet. A defect-free specimen with a smooth surface was finally formed when the thickness of the upper sheet reached three times that of the target sheet. The profile deviation was ±0.5 mm. Excellent thickness uniformity in a specimen can be obtained with a maximum thinning rate of 6%. The full strength, ranging from 455 to 466 MPa, can be obtained in all regions of the specimen, indicating that effective strengthening can be accomplished with the two-layer-sheet die quenching. The results indicated that high forming quality and full strength can be obtained in a two-layer-sheet hot-forming-quenching integrated process. This research has great potential for engineering applications using aluminum-alloy curved-surface thin-walled components.

A Novel Deep Learning Model for Medical Image Segmentation with Convolutional Neural Network and Transformer.

Accurate segmentation of medical images is essential for clinical decision-making, and deep learning techniques have shown remarkable results in this area. However, existing segmentation models that combine transformer and convolutional neural networks often use skip connections in U-shaped networks, which may limit their ability to capture contextual information in medical images. To address this limitation, we propose a coordinated mobile and residual transformer UNet (MRC-TransUNet) that combines the strengths of transformer and UNet architectures. Our approach uses a lightweight MR-ViT to address the semantic gap and a reciprocal attention module to compensate for the potential loss of details. To better explore long-range contextual information, we use skip connections only in the first layer and add MR-ViT and RPA modules in the subsequent downsampling layers. In our study, we evaluated the effectiveness of our proposed method on three different medical image segmentation datasets, namely, breast, brain, and lung. Our proposed method outperformed state-of-the-art methods in terms of various evaluation metrics, including the Dice coefficient and Hausdorff distance. These results demonstrate that our proposed method can significantly improve the accuracy of medical image segmentation and has the potential for clinical applications. Illustration of the proposed MRC-TransUNet. For the input medical images, we first subject them to an intrinsic downsampling operation and then replace the original jump connection structure using MR-ViT. The output feature representations at different scales are fused by the RPA module. Finally, an upsampling operation is performed to fuse the features to restore them to the same resolution as the input image.

High-speed countercurrent chromatography as an efficient technique for large separation of plant polyphenols: A review.

Polyphenols, which are commonly found in fruits, vegetables, cereals, and legumes, are the most abundant dietary antioxidants. To date, numerous studies have demonstrated the ability of polyphenols to prevent the development of several diseases and established the corresponding structure-activity relationships. However, polyphenol standards are either not commercially available or very expensive, mainly because the structural complexity and diversity of polyphenols complicate their fractionation and isolation from plant extracts by conventional separation techniques. High-speed countercurrent chromatography (HSCCC) is based on continuous liquid-liquid partitioning, which enables one to eliminate irreversible adsorption on solid supports. This technique has been extensively used for natural product isolation and is well suited to the effective large-scale separation of polyphenols and their derivatives, achieving high purities and yields of up to several hundred milligrams per run within several hours. The present review briefly introduces briefly HSCCC technology and summarizes its applications in the separation and purification of plant polyphenols, including the recent achievements in the large-scale preparation of proanthocyanidins and anthocyanins by our laboratory.

Impact of Different Oak Chips' Aging on the Volatile Compounds and Sensory Characteristics of Vitis amurensis Wines.

In this work, different oak chips were used to age Vitis amurensis wine, and the effects on sensory properties were observed. Twenty-one different oak chips were added to a one-year-old wine made by a traditional technique. The wine was aged for 6 months before analysis by CIELab for color parameters, GC-MS for volatile compounds, and electronic tongue and a tasting panel for sensory properties. The results showed that the addition of any tested oak chip could significantly strengthen the wine's red color. Among 61 volatile compounds, alcohols presented the highest concentrations (873 to 1401 mg/L), followed by esters (568 to 1039 mg/L) and organic acids (157 to 435 mg/L), while aldehydes and volatile phenols occurred at low concentrations. Different oak species with different toasting levels could affect, to varying degrees, the concentrations of esters, alcohols, and volatile phenols, but to a lesser extent those of aldehydes. Sensory analysis by a tasting panel indicated that non- and moderately roasted oak chips gave the wines higher scores than those with heavy toasting levels. The major mouthfeel descriptors determined by electronic tongue were in good agreement with those from the tasting panel.

Leaf Removal at Véraison and Foliar K+ Application to Beibinghong Vines Improved Berry Quality under Cold-Climate Conditions.

(1) Background: Beibinghong is a grapevine variety that is well distributed in Northeastern China due to its adaptation to extreme cold conditions and vine diseases. Nonetheless, Beibinghong wines are extremely acidic and rich in phenolic compounds. The aim of this research was to study the effects of leaf removal at véraison and foliar K+ applications on Beibinghong vines to reduce the acidity and increase their polyphenol content. (2) Methods: Beibinghong berries were harvested when they reached close to 20 °Brix, and the physicochemical parameters were determined. (3) Results: Leaf removal at véraison plus K+ foliar applications to Beibinghong vines decreased the titratable acidity and increased the total phenolic and phenolic acid contents compared with the control. Moreover, the titratable acidity in the Beibinghong berries was negatively related to their total contents of phenols, proanthocyanidins, and anthocyanins. (4) Conclusions: Leaf removal at véraison performed with foliar K+ applications to vines could be an interesting alternative for Beibinghong production under cold-climate viticulture because it allows for a decrease in the acidity and an increase in the phenolic content of the berries, without incurring the risk of sunburn.

Corrigendum to "Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice" [Bioactive materials 6 (2021) 529-542].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.08.017.].

The effects of linalool acupoint application therapy on sleep regulation.

The Shenque acupoint is located in the umbilicus of the human body. In the human body meridians, the Shenque acupoint can regulate body functions. The Shenque acupoint was one of the important acupuncture acupoints for the treatment of insomnia. However, the effect of linalool applied at the Shenque acupoint to improve sleep was unknown. This study explored the hypnotic and sedative effects of the main component of lavender, linalool, on the Shenque acupoint of mice and rats. The effects on the sleep latency and sleep duration were studied with the supra-threshold dose of pentobarbital sodium, and the effects on the sleep rate were studied with the sub-threshold dose of pentobarbital sodium. In order to further study the feasibility and superiority of linalool administered at the Shenque acupoint, a pharmacokinetic study was carried out. The pharmacodynamic results showed that the mice and rats treated with linalool at Shenque had the highest sleep rate, the shortest sleep latency, and the longest sleep duration compared with other groups. The T max and t 1/2 of the LS were longer than those of the LO, and had the characteristics of sustained release. The relative bioavailability of LS was 323.0 ± 31.66%. This showed that the combination of linalool and the Shenque acupoint had greater medicinal effects. This development will provide a new direction for improving sleep.

Ion channels and transporters in microglial function in physiology and brain diseases.

Microglial cells interact with all components of the central nervous system (CNS) and are increasingly recognized to play essential roles during brain development, homeostasis and disease pathologies. Functions of microglia include maintaining tissue integrity, clearing cellular debris and dead neurons through the process of phagocytosis, and providing tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. Changes of microglial ionic homeostasis (Na+, Ca2+, K+, H+, Cl-) are important for microglial activation, including proliferation, migration, cytokine release and reactive oxygen species production, etc. These are mediated by ion channels and ion transporters in microglial cells. Here, we review the current knowledge about the role of major microglial ion channels and transporters, including several types of Ca2+ channels (store-operated Ca2+ entry (SOCE) channels, transient receptor potential (TRP) channels and voltage-gated Ca2+ channels (VGCCs)) and Na+ channels (voltage-gated Na+ channels (Nav) and acid-sensing ion channels (ASICs)), K+ channels (inward rectifier K+ channels (Kir), voltage-gated K+ channels (KV) and calcium-activated K+ channels (KCa)), proton channels (voltage-gated proton channel (Hv1)), and Cl- channels (volume (or swelling)-regulated Cl- channels (VRCCs) and chloride intracellular channels (CLICs)). In addition, ion transporter proteins such as Na+/Ca2+ exchanger (NCX), Na+-K+-Cl- cotransporter (NKCC1), and Na+/H+ exchanger (NHE1) are also involved in microglial function in physiology and brain diseases. We discussed microglial activation and neuroinflammation in relation to the ion channel/transporter stimulation under brain disease conditions and therapeutic aspects of targeting microglial ion channels/transporters for neurodegenerative disease, ischemic stroke, traumatic brain injury and neuropathic pain.