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.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Beta Amyloid ◽  
Microglial Cells ◽  
Root Extracts ◽  
Tnf Α ◽  
P38α Mapk ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

scholarly journals Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

2021 ◽  
pp. 026988112110264
Author(s):  
Emma Kopra ◽  
Valeria Mondelli ◽  
Carmine Pariante ◽  
Naghmeh Nikkheslat
Keyword(s):  
Systematic Review ◽  
Animal Studies ◽  
Bipolar Depression ◽  
Strong Support ◽  
Kynurenine Pathway ◽  
Future Research ◽  
Downstream Effects ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

scholarly journals Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3697
Author(s):  
Tae-Kyeong Lee ◽  
Bora Kim ◽  
Dae Won Kim ◽  
Ji Hyeon Ahn ◽  
Hyejin Sim ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hair Growth ◽  
Hair Follicles ◽  
Control Group ◽  
Root Extract ◽  
Dorsal Skin ◽  
Angelica Gigas ◽  
Angelica Gigas Nakai ◽  
Tnf Α ◽  
Anti Inflammatory

This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1β as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1β in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.

scholarly journals Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4796
Author(s):  
Jiali Chen ◽  
Cailin Tang ◽  
Yang Zhou ◽  
Rongfei Zhang ◽  
Shaoxia Ye ◽  
...  
Keyword(s):  
Essential Oil ◽  
Mrna Expression ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Microglial Cells ◽  
Cinnamomum Camphora ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Bv2 Microglial Cells

Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora leaves; however, its anti-inflammatory activity and the underlying mechanism have not been clearly demonstrated. Thus, the present study investigated its anti-inflammatory property. Our data revealed that EO significantly decreased the release of nitric oxide (NO) and the mRNA expression of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the metabolic profiles of LPS-induced BV2 microglial cells treated with or without EO were explored. Thirty-nine metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones. Five pathways were enriched by shared differential metabolites. Compared with the control cells, the glucose level was decreased, while the lactate level was increased, in the culture supernatant from LPS-stimulated cells, which were reversed by EO treatment. Moreover, compared to the LPS-treated group, the activities of phosphofructokinase (PFK) and pyruvate kinase (PK) in EO group were decreased. In summary, the current study demonstrated that EO from C. camphora leaves acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.

scholarly journals MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8425
Author(s):  
Giovanni Pallio ◽  
Angela D’Ascola ◽  
Luigi Cardia ◽  
Federica Mannino ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Monoamine Oxidase A ◽  
Microglial Cells ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tnf Α ◽  
Mao A ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1β (IL-1β). Control cells and IL-1β-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1β stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1β also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.

scholarly journals The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2163 ◽  
Author(s):  
Nilson Carlos Ferreira Junior ◽  
Maurício dos Santos Pereira ◽  
Nour Francis ◽  
Paola Ramirez ◽  
Paula Martorell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Inflammatory Responses ◽  
Parent Compound ◽  
Antioxidant Properties ◽  
Microglial Cells ◽  
Activated Microglia ◽  
Tnf Α ◽  
Immunosuppressive Action ◽  
Anti Inflammatory

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.

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 Treatment with Peanut Sprout Root Extract Alleviates Inflammation in a Lipopolysaccharide-Stimulated Mouse Macrophage Cell Line by Inhibiting the MAPK Signaling Pathway

2019 ◽  
Vol 20 (23) ◽  
pp. 5907 ◽  
Author(s):  
Yun Mi Lee ◽  
Eunjung Son ◽  
Dong-Seon Kim
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Significant Inhibition ◽  
Inflammatory Activity ◽  
No Production ◽  
Root Extract ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Dose Dependent

Inflammation is a key response of the immune system to infection but aberrant inflammatory activity can lead to tissue damage and inflammatory diseases. Increasing evidence suggests that peanut sprout root extract (PSRE) has anti-inflammatory activity, and the aim of this study is therefore to investigate the effects of PSRE on the inflammatory response and the molecular mechanisms underpinning this effect in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Using a combination of cell viability, ELISA, and nitric oxide (NO) assays, together with Western blotting, we showed that PSRE effectively inhibited NO production in LPS-stimulated cells and significantly reduced the expression of pro-inflammatory cytokines, including IL-6, IL-1β, and PGE2, at a dose of 200 µg/mL of PSRE, whereas TNF-α expression tended to decrease under PSRE treatment. We also confirmed a dose-dependent and significant inhibition of iNOS and COX-2 protein expression. In addition, PSRE treatment induced anti-inflammatory effects by inhibiting the phosphorylation of MAPKs (ERK, JNK, and p38) and NF-κB activation. Our results indicate that the anti-inflammatory properties of PSRE may result from inhibition of the MAPK pathways, which are known promoters of cytokine secretion.

scholarly journals Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways

2019 ◽  
Vol 20 (23) ◽  
pp. 6039 ◽  
Author(s):  
Luigi Chiricosta ◽  
Serena Silvestro ◽  
Jacopo Pizzicannella ◽  
Francesca Diomede ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Mesenchymal Stem Cells ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Stat Pathway

Inflammation is a common feature of many neurodegenerative diseases. The treatment of stem cells as a therapeutic approach to repair damage in the central nervous system represents a valid alternative. In this study, using Next-Generation Sequencing (NGS) technology, we analyzed the transcriptomic profile of human Gingival Mesenchymal Stem Cells (hGMSCs) treated with Moringin [4-(α-l-ramanosyloxy)-benzyl isothiocyanate] (hGMSCs-MOR) or with Cannabidiol (hGMSCs-CBD) at dose of 0.5 or 5 µM, respectively. Moreover, we compared their transcriptomic profiles in order to evaluate analogies and differences in pro- and anti-inflammatory pathways. The hGMSCs-MOR selectively downregulate TNF-α signaling from the beginning, reducing the expression of TNF-α receptor while hGMSCs-CBD limit its activity after the process started. The treatment with CBD downregulates the pro-inflammatory pathway mediated by the IL-1 family, including its receptor while MOR is less efficient. Furthermore, both the treatments are efficient in the IL-6 signaling. In particular, CBD reduces the effect of the pro-inflammatory JAK/STAT pathway while MOR enhances the pro-survival PI3K/AKT/mTOR. In addition, both hGMSCs-MOR and hGMSCs-CBD improve the anti-inflammatory activity enhancing the TGF-β pathway.

Anti-inflammatory effects of kinins via microglia in the central nervous system

2006 ◽  
Vol 387 (2) ◽  
pp. 167-171 ◽  
Author(s):  
Mami Noda ◽  
Helmut Kettenmann ◽  
Keiji Wada
Keyword(s):  
Biologically Active ◽  
Prostaglandin E ◽  
Active Peptides ◽  
Tnf Α ◽  
Biologically Active Peptides ◽  
Murine Microglia ◽  
Intracellular Ca ◽  
The Central Nervous System ◽  
Microglial Migration ◽  
Anti Inflammatory

Abstract Kinins are important biologically active peptides that are up-regulated after lesions in both the peripheral and central (CNS) nervous systems. Microglia are immune cells in the CNS and play an important role in the defense of the neuronal parenchyma. In cultured murine microglia, bradykinin (BK) induces mobilization of intracellular Ca2+, microglial migration, and increases the release of nitric oxide and prostaglandin E2. On the other hand, BK attenuates lipopolysaccharide-activated TNF-α and IL-1β release. These results suggest that BK functions as a signal in brain trauma and may have an anti-inflammatory role in the CNS.

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