scholarly journals Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection

2021 ◽  
Vol 22 (6) ◽  
pp. 3037
Author(s):  
Chun-Yuan Cheng ◽  
Lassina Barro ◽  
Shang-Ting Tsai ◽  
Tai-Wei Feng ◽  
Xiao-Yu Wu ◽  
...  
Keyword(s):  
Green Tea ◽  
Neuroprotective Effect ◽  
Motor Impairment ◽  
Cell Uptake ◽  
Microglial Cells ◽  
Neuroprotective Activity ◽  
Sprague Dawley ◽  
Disease Modifying Therapy

Microglia-mediated neuroinflammation is recognized to mainly contribute to the progression of neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG), known as a natural antioxidant in green tea, can inhibit microglia-mediated inflammation and protect neurons but has disadvantages such as high instability and low bioavailability. We developed an EGCG liposomal formulation to improve its bioavailability and evaluated the neuroprotective activity in in vitro and in vivo neuroinflammation models. EGCG-loaded liposomes have been prepared from phosphatidylcholine (PC) or phosphatidylserine (PS) coated with or without vitamin E (VE) by hydration and membrane extrusion method. The anti-inflammatory effect has been evaluated against lipopolysaccharide (LPS)-induced BV-2 microglial cells activation and the inflammation in the substantia nigra of Sprague Dawley rats. In the cellular inflammation model, murine BV-2 microglial cells changed their morphology from normal spheroid to activated spindle shape after 24 h of induction of LPS. In the in vitro free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, EGCG scavenged 80% of DPPH within 3 min. EGCG-loaded liposomes could be phagocytized by BV-2 cells after 1 h of cell culture from cell uptake experiments. EGCG-loaded liposomes improved the production of BV-2 microglia-derived nitric oxide and TNF-α following LPS. In the in vivo Parkinsonian syndrome rat model, simultaneous intra-nigral injection of EGCG-loaded liposomes attenuated LPS-induced pro-inflammatory cytokines and restored motor impairment. We demonstrated that EGCG-loaded liposomes exert a neuroprotective effect by modulating microglia activation. EGCG extracted from green tea and loaded liposomes could be a valuable candidate for disease-modifying therapy for Parkinson’s disease (PD).

scholarly journals Red Ginseng Extract Attenuates Kainate-Induced Excitotoxicity by Antioxidative Effects

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Yi Han ◽  
Sun-Young Ahn ◽  
Eun-Hye Oh ◽  
Sang-Yoon Nam ◽  
Jin Tae Hong ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Mossy Fiber ◽  
Neuroprotective Effect ◽  
Order Rate Constant ◽  
Neuroprotective Activity ◽  
Dependent Manner ◽  
Red Ginseng ◽  
Ginseng Extract

This study investigated the neuroprotective activity of red ginseng extract (RGE,Panax ginseng, C. A. Meyer) against kainic acid- (KA-) induced excitotoxicityin vitroandin vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS) and [Ca2+]iin cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca2+]ielevation. Oral administration of RGE (30 and 200 mg/kg) in mice decreased the malondialdehyde (MDA) level induced by KA injection (30 mg/kg, i.p.). In addition, similar results were obtained after pretreatment with the radical scavengers Trolox andN,N′-dimethylthiourea (DMTU). Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF) protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the IC50was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical (•OH), was similar to trolox. The second-order rate constant of RGE for•OH was 3.5–4.5×109 M−1·S−1. Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.

scholarly journals Effect of Different Processing Methods on Phytochemical Contents and Neuroprotective Activity of Camellia euphlebia Leaves Extract

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Dongye He ◽  
Shu Jia ◽  
Yongping Xu
Keyword(s):  
Particle Size ◽  
Neuroprotective Effect ◽  
Antidepressant Activity ◽  
Neuroprotective Activity ◽  
Powder Particle Size ◽  
Shell Powder ◽  
Phytochemical Contents ◽  
Camellia Euphlebia

Camellia euphlebia is a new food source and traditional folk medicine in China. Previous studies have demonstrated the antidepressant activity of Camellia euphlebia extract by both in vivo and in vitro experiments. The effects of different pretreatments on phytochemical contents and neuroprotective activity of Camellia euphlebia extract were further investigated in order to develop an optimal processing method that makes the extraction more efficient. Six different powders of Camellia euphlebia leaves were prepared by different pretreatments. The particle size and morphology were examined by using a Malvern particle size analyzer and scanning electron microscopy, respectively. The results showed that the percentage of powder particle size within a range of 0.2∼40 μm was up to 79.18% after press-shear assisted interaction technology pretreatment by 2% addition of shellfish shell powder, and the cells were broken completely. Additionally, the contents of flavonoids, polysaccharides, polyphenols, saponins, and catechin in the extract were 11.78 ± 0.62%, 34.60 ± 3.37%, 6.15 ± 0.29%, 9.43 ± 1.19%, and 1.99 ± 0.11%, respectively, which were higher than those of the other five extracts. Moreover, the extract had the strongest neuroprotective activity by comparing the neuroprotective effect of different extracts on corticosterone-induced neurotoxicity in differentiated PC12 cells. It is concluded that press-shear assisted interaction technology with 2% addition of shellfish shell powder pretreatment, to a great extent, improved the dissolution of bioactive ingredients in Camellia euphlebia.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Neuroprotective Potential of a Small Molecule RET Agonist in Cultured Dopamine Neurons and Hemiparkinsonian Rats

2021 ◽  
pp. 1-24
Author(s):  
Juho-Matti Renko ◽  
Arun Kumar Mahato ◽  
Tanel Visnapuu ◽  
Konsta Valkonen ◽  
Mati Karelson ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Wild Type ◽  
Disease Modifying Therapy ◽  
Immortalized Cells ◽  
Midbrain Dopamine ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurological disorder where loss of dopamine neurons in the substantia nigra and dopamine depletion in the striatum cause characteristic motor symptoms. Currently, no treatment is able to halt the progression of PD. Glial cell line-derived neurotrophic factor (GDNF) rescues degenerating dopamine neurons both in vitro and in animal models of PD. When tested in PD patients, however, the outcomes from intracranial GDNF infusion paradigms have been inconclusive, mainly due to poor pharmacokinetic properties. Objective: We have developed drug-like small molecules, named BT compounds that activate signaling through GDNF’s receptor, the transmembrane receptor tyrosine kinase RET, both in vitro and in vivo and are able to penetrate through the blood-brain barrier. Here we evaluated the properties of BT44, a second generation RET agonist, in immortalized cells, dopamine neurons and rat 6-hydroxydopamine model of PD. Methods: We used biochemical, immunohistochemical and behavioral methods to evaluate the effects of BT44 on dopamine system in vitro and in vivo. Results: BT44 selectively activated RET and intracellular pro-survival AKT and MAPK signaling pathways in immortalized cells. In primary midbrain dopamine neurons cultured in serum-deprived conditions, BT44 promoted the survival of the neurons derived from wild-type, but not from RET knockout mice. BT44 also protected cultured wild-type dopamine neurons from MPP +-induced toxicity. In a rat 6-hydroxydopamine model of PD, BT44 reduced motor imbalance and could have protected dopaminergic fibers in the striatum. Conclusion: BT44 holds potential for further development into a novel, possibly disease-modifying therapy for PD.

scholarly journals Experimental and theoretical explorations of nanocarriers’ multistep delivery performance for rational design and anticancer prediction

2021 ◽  
Vol 7 (6) ◽  
pp. eaba2458
Author(s):  
Weier Bao ◽  
Falin Tian ◽  
Chengliang Lyu ◽  
Bin Liu ◽  
Bin Li ◽  
...  
Keyword(s):  
Physical Properties ◽  
Rational Design ◽  
Theoretical Models ◽  
Cell Uptake ◽  
Anticancer Efficacy ◽  
Delivery Performance ◽  
Simulation Based ◽  
Multistep Process

The poor understanding of the complex multistep process taken by nanocarriers during the delivery process limits the delivery efficiencies and further hinders the translation of these systems into medicine. Here, we describe a series of six self-assembled nanocarrier types with systematically altered physical properties including size, shape, and rigidity, as well as both in vitro and in vivo analyses of their performance in blood circulation, tumor penetration, cancer cell uptake, and anticancer efficacy. We also developed both data and simulation-based models for understanding the influence of physical properties, both individually and considered together, on each delivery step and overall delivery process. Thus, beyond finding that nanocarriers that are simultaneously endowed with tubular shape, short length, and low rigidity outperformed the other types, we now have a suit of theoretical models that can predict how nanocarrier properties will individually and collectively perform in the multistep delivery of anticancer therapies.

scholarly journals Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sheng-Yu Cui ◽  
Wei Zhang ◽  
Zhi-Ming Cui ◽  
Hong Yi ◽  
Da-Wei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Viability ◽  
Microglial Cells ◽  
Protective Effects ◽  
Loss Of Function ◽  
Sprague Dawley ◽  
Cord Injury ◽  
Apoptosis And Inflammation

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

scholarly journals Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2223
Author(s):  
Manon Dominique ◽  
Nicolas Lucas ◽  
Romain Legrand ◽  
Illona-Marie Bouleté ◽  
Christine Bôle-Feysot ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Molecular Mimicry ◽  
Potential Effect ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
E Coli ◽  
In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

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