Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats

2021 ◽  
Vol 18 ◽  
Author(s):  
Mahadev Dhami ◽  
Khadga Raj ◽  
Shamsher Singh
Keyword(s):  
Cognitive Impairment ◽  
Tau Protein ◽  
Cognitive Functions ◽  
Neuroprotective Effect ◽  
High Dose ◽  
Tnf Α ◽  
Protective Strategy ◽  
Significant Impairment ◽  
Anti Inflammatory ◽  
Neuroprotective Actions

Background: Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neuro- transmitter levels, and excessive deposition of Aβ(1–42) plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions. Objective: In the present study, fucoxanthin was employed as a protective strategy in Intracere- broventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment. Methods: STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotrans- mitters (ACh, GABA Glutamate), Aβ(1–42) and Tau protein measurements. Results: STZ-infused rats showed significant impairment in learning and memory, increased oxida- tive stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cy- tokine release, and change in neurotransmitter levels. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and res- tored neurotransmitters concentration. Conclusion: The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuropro- tective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ(1–42) accu- mulation, and tau protein.

scholarly journals Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Fan’ge Kong ◽  
Xue Jiang ◽  
Ruochen Wang ◽  
Siyu Zhai ◽  
Yizhi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Tau Protein ◽  
Calcium Binding ◽  
Neuroprotective Effect ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ht22 Cells ◽  
Anti Inflammatory

Abstract Background Neuroinflammation is a principal element in Alzheimer’s disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. Methods APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. Results In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. Conclusions FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.

Clinical Perspectives of Lithium’s Neuroprotective Effect

2017 ◽  
Vol 51 (05) ◽  
pp. 194-199 ◽  
Author(s):  
Janusz Rybakowski ◽  
Aleksandra Suwalska ◽  
Tomas Hajek
Keyword(s):  
Cognitive Impairment ◽  
Neurodegenerative Disorders ◽  
Cognitive Functions ◽  
Neuroprotective Effect ◽  
Gray Matter Volume ◽  
Brain Structures ◽  
Therapeutic Drug ◽  
Matter Volume ◽  
Favorable Influence ◽  
Neuroprotective Action

AbstractEvidence for a neuroprotective effect of lithium has accumulated over the last 2 decades, and this phenomenon has been regarded as an important mechanism of lithium action in mood disorders. It has been reflected by an increase in cerebral gray matter volume in lithium-treated subjects and by the favorable influence of lithium on cognitive functions. A neuroprotective effect of lithium also makes this ion a possible candidate for use as a therapeutic drug in neurology, especially in neurodegenerative disorders. In this paper, neurochemical mechanisms of neuroprotective action of lithium will be characterized. A possible association between the effect of lithium on brain structures reflected in neuroimaging studies, as well as on cognitive functions, and its neuroprotective action, will be considered. Data from experimental, epidemiological, and clinical studies have also pointed to an antidementia effect of lithium, bringing about some promise of using lithium in the treatment of mild cognitive impairment and Alzheimer’s disease. The results of attempts of employing lithium in other neurodegenerative disorders will also be discussed.

scholarly journals Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

2013 ◽  
Vol 81 (11) ◽  
pp. 4001-4012 ◽  
Author(s):  
Mónica González-Pérez ◽  
Leonardo Mariño-Ramírez ◽  
Carlos Alberto Parra-López ◽  
Martha Isabel Murcia ◽  
Brenda Marquina ◽  
...  
Keyword(s):  
Immune Response ◽  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Mycobacterium Avium ◽  
High Expression ◽  
High Dose ◽  
Content Type ◽  
Subcutaneous Infection ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACTThe genusMycobacteriumcomprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies withMycobacterium tuberculosis. The biological differentiation betweenM. tuberculosisand nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not.Mycobacterium aviumcomplex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after theM. tuberculosiscomplex. Here, we evaluated the virulence and immune response ofM. aviumsubsp.aviumandMycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

Neuroprotective effect of Lithospermum officinale callus extract on inflamed primary microglial cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Maryam Kheyrollah ◽  
Farzaneh Sabouni ◽  
Mohsen Farhadpour ◽  
Kamahldin Haghbeen
Keyword(s):  
Neuroprotective Effect ◽  
Wistar Rat ◽  
Microglial Cells ◽  
Root Extract ◽  
Primary Microglia ◽  
Methanolic Extracts ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Lithospermum Officinale

Background and Objective: Lithospermum officinale is a famous medicinal herb in the traditional medicine of India. However, the medicinal use of its root extract is limited due to the presence of pyrrolizidine alkaloids (PzAl). It was recently shown that PzAl are not accumulated in the cell culture of L. officinale while the biosynthetic pathway of phenolic acids remains active so that rosmarinic acid (RsA) is the main product in the proliferated callus. Considering the existing literature on the anti-inflammatory effects of caffeic acid (CfA) and its derivatives, this research was devoted to the evaluation of the anti-inflammatory capacity of methanolic extracts of L. officinale callus (LoE) on the rat microglial cells as the immune cells of the Central Nervous System, which play an essential role in the responses to neuroinflammation. Methods: primary microglia were obtained from Wistar rat, then they were subjected to various amounts of CfA and methanolic extracts of 17 and 31-day L. officinale callus prior to stimulation by LPS. In addition to HPLC analysis of the extracts, viability, nitric oxide production, evaluation of the pro-inflammatory genes and cytokines in the inflamed microglia were investigated. Results: Methanolic extract of the 17-day old callus of L. officinale exhibited anti-inflammatory effects on the LPS- stimulated microglial cells much higher than that was observed for CfA. The data was further supported by the decreased expression of NOS2, TNF-α, and Cox-2 mRNA and the suppression of TNF-α and IL-1β release in the activated microglial cells pretreated with the effective dose of LoE (0.8 mg mL-1). Conclusion: It was assumed that better anti-neuroinflammatory performance of LoE than CfA in LPS-activated primary microglia could be a result of synergism of the components of the extract and the lipophilic nature of RsA as the main phenolic acid of LoE. Considering the fact that LoE shows high antioxidant capacity and lacks PzAl, it is anticipated that LoE is considered as a reliable substitute to the extract of the natural root of L. officinale and plays a key role in the preparation of neuroprotective pharmaceutical formula.

scholarly journals The Effects of New Zealand Grown Ginseng Fractions on Cytokine Production from Human Monocytic THP-1 Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1158
Author(s):  
Wei Chen ◽  
Prabhu Balan ◽  
David G. Popovich
Keyword(s):  
New Zealand ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Inflammatory Cytokine ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.

scholarly journals The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

2019 ◽  
Author(s):  
Jie Guo ◽  
Xiaolu Cao ◽  
Xianmin Hu ◽  
Shulan Li ◽  
Jun Wang
Keyword(s):  
Oxidative Stress ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Tunel Staining ◽  
High Dose ◽  
Sprague Dawley ◽  
Curcumin Treatment ◽  
Concurrent Administration ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background: As a chemical extensively used in industrial areas as well as formed during heating of carbohydrate-rich food and tobacco, acrylamide (ACR) has been known as well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cerebral homogenates were detected using ELISA assay. Results: Concurrent administration of curcumin at the oral doses of 50 and 100 mg/kg with ACR significantly protected the rats from ACR-induced weigh loss and motor function deficits, and improved the pathological alterations in the ACR-intoxicated brains. Curcumin treatment especially at a high dose enhanced the TERT mRNA expression level and increased the number of TERT-positive nerve cells in cortex tissues of ACR intoxicated rats. The levels of MDA, TNF-α and IL-1β in the cerebral homogenates were reduced, the contents of GSH as well as the activities of SOD and GSH-Px were increased by curcumin treatment, compared to ACR control group. Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. And maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

scholarly journals Anti-inflammatory effects of high-dose IgG on TNF-α-activated human coronary artery endothelial cells

2012 ◽  
Vol 42 (8) ◽  
pp. 2121-2131 ◽  
Author(s):  
Akio Matsuda ◽  
Hideaki Morita ◽  
Hirotoshi Unno ◽  
Hirohisa Saito ◽  
Kenji Matsumoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
High Dose ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Anti Inflammatory

scholarly journals Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Katharina Mörs ◽  
Ramona Sturm ◽  
Jason-Alexander Hörauf ◽  
Shinwan Kany ◽  
Paola Cavalli ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Acute Inflammation ◽  
In Vitro Model ◽  
Prolonged Exposure ◽  
Acute Exposure ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Vitro Model

Background. In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods. HepG2 cells were stimulated with IL-1β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results. In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1β-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1β-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion. EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.

scholarly journals High Dose of Intravenous Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells (CLV-100) Infusion Displays Better Immunomodulatory Effect among Healthy Volunteers: A Phase 1 Clinical Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Sze-Piaw Chin ◽  
Mohd-Yusoff Mohd-Shahrizal ◽  
Mohd-Zuhar Liyana ◽  
Kong Yong Then ◽  
Soon Keng Cheong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Healthy Volunteers ◽  
Umbilical Cord ◽  
Phase 1 ◽  
Interleukin 1 ◽  
Immunomodulatory Effect ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory

Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD, n = 5 ; HD, n = 6 ; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA ( 705 ± 160 vs. 306 ± 36   pg / mL ; p = 0.02 ) and IL-10 ( 321 ± 27 vs. 251 ± 28   pg / m L; p = 0.02 ); and lower levels of proinflammatory marker TNF-α ( 74 ± 23 vs. 115 ± 15   pg / mL ; p = 0.04 ) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

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