scholarly journals The Involvement of PPARγ In Anti-Inflammatory Activity of N-Stearoylethanolamide

2021 ◽  
Author(s):  
Halyna Kosiakova ◽  
Andrii Berdyshev ◽  
Victor Dosenko ◽  
Tetyana Drevytska ◽  
Oleksandra Herasymenko ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Methodological Approach ◽  
Mrna Level ◽  
Peritoneal Macrophages ◽  
Insulin Resistant ◽  
Wide Range ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Inflammatory Action

Abstract N-stearoylethanolamide (NSE)– a cannabinoid-like compound with wide range of biological activity. Anti-inflammatory properties of NSE have been indicated on different animal models of pathological conditions. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, the involvement of PPARγ in the NF-kB -dependent anti-inflammatory action of NSE was evaluated using different methodological approach. First method - molecular modeling, evaluated the possibility of NSE to bind with PPAR. Then, in ex vivo experiment, using selective synthetic agonist of PPARα/γ LY-171883 and selective antagonist of PPARγ - GW9662, the role of PPARα /PPARγ in the NSE’s effect on nuclear NF-kB translocation was examined in LPS-activated rat peritoneal macrophages. Finally, the NSE action on the mRNA level of several PPARγ- dependent genes was studied in liver of insulin-resistant rats. The molecular docking results showed that NSE could bind to PPARγ and compete for the binding with antagonist GW9662 and agonist LY171883 in the active site of PPARγ. It also has been found that NSE prevented the LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages during pre-treatment with NSE before LPS application. When NSE was added before GW9662 and LPS treatment, the level of NF-kB translocation and IL-1β content reduced to control cells’ levels. These data confirmed a competitive binding of NSE with GW9662 for the ligand-binding domen of PPARγ. In addition, NSE administration to insulin resistant rats changed the mRNA expression of several PPARγ target gens, including FATP1 and IL1-ra.

scholarly journals Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Hsin-Ling Yang ◽  
Ting-Yu Yang ◽  
Yugandhar Vudhya Gowrisankar ◽  
Chun-Huei Liao ◽  
Jiunn-Wang Liao ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Ex Vivo ◽  
Root Extract ◽  
Piper Methysticum ◽  
Serum Lipase ◽  
Antioxidant Genes ◽  
Anti Inflammatory

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals HIV gp120 Protein Increases the Function of Connexin 43 Hemichannels and Pannexin-1 Channels in Astrocytes: Repercussions on Astroglial Function

2020 ◽  
Vol 21 (7) ◽  
pp. 2503 ◽  
Author(s):  
Rosario Gajardo-Gómez ◽  
Cristian A. Santibañez ◽  
Valeria C. Labra ◽  
Gonzalo I. Gómez ◽  
Eliseo A. Eugenin ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Purinergic Signaling ◽  
Atp Release ◽  
P38 Map Kinase ◽  
Motor Deficits ◽  
Pannexin 1 ◽  
Channel Opening ◽  
Wide Range

At least half of human immunodeficiency virus (HIV)-infected individuals suffer from a wide range of cognitive, behavioral and motor deficits, collectively known as HIV-associated neurocognitive disorders (HAND). The molecular mechanisms that amplify damage within the brain of HIV-infected individuals are unknown. Recently, we described that HIV augments the opening of connexin-43 (Cx43) hemichannels in cultured human astrocytes, which result in the collapse of neuronal processes. Whether HIV soluble viral proteins such as gp120, can regulate hemichannel opening in astrocytes is still ignored. These channels communicate the cytosol with the extracellular space during pathological conditions. We found that gp120 enhances the function of both Cx43 hemichannels and pannexin-1 channels in mouse cortical astrocytes. These effects depended on the activation of IL-1β/TNF-α, p38 MAP kinase, iNOS, cytoplasmic Ca2+ and purinergic signaling. The gp120-induced channel opening resulted in alterations in Ca2+ dynamics, nitric oxide production and ATP release. Although the channel opening evoked by gp120 in astrocytes was reproduced in ex vivo brain preparations, these responses were heterogeneous depending on the CA1 region analyzed. We speculate that soluble gp120-induced activation of astroglial Cx43 hemichannels and pannexin-1 channels could be crucial for the pathogenesis of HAND.

scholarly journals Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Veronica Tisato ◽  
Giorgio Zauli ◽  
Erika Rimondi ◽  
Sergio Gianesini ◽  
Laura Brunelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lipoic Acid ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Disease Patient ◽  
Therapeutic Targets ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Gm Csf ◽  
Anti Inflammatory

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compoundsα-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n=31) in CVD patients’ plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-αstimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted byex vivotreatment withα-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented thatα-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects ofGinkgo bilobaappeared to be predominantly mediated by Akt. Ourdataprovide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

Molecular mechanisms of anti-inflammatory action of glucocorticoids

BioEssays ◽  
1996 ◽  
Vol 18 (5) ◽  
pp. 371-378 ◽  
Author(s):  
Andrew C. B. Cato ◽  
Erik Wade
Keyword(s):  
Molecular Mechanisms ◽  
Anti Inflammatory ◽  
Inflammatory Action

scholarly journals HDAC2 is required by the physiological concentration of glucocorticoid to inhibit inflammation in cardiac fibroblasts

2017 ◽  
Vol 95 (9) ◽  
pp. 1030-1038 ◽  
Author(s):  
Haining Zhang ◽  
Yanhua He ◽  
Guiping Zhang ◽  
Xiaobin Li ◽  
Suikai Yan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Myocardial Inflammation ◽  
Physiological Concentration ◽  
Physiological Level ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1β in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.

scholarly journals Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xichun Wang ◽  
Shibin Feng ◽  
Nana Ding ◽  
Yanting He ◽  
Cheng Li ◽  
...  
Keyword(s):  
Murine Model ◽  
Molecular Mechanisms ◽  
Neutrophil Infiltration ◽  
Mammary Glands ◽  
Histopathological Changes ◽  
Berberine Hydrochloride ◽  
Treatment Groups ◽  
Qrt Pcr ◽  
Anti Inflammatory ◽  
Inflammatory Action

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

scholarly journals Biodata Mining-based Elucidation of Mechanisms of Hesperetin as a Candidate for Atherosclerosis

2020 ◽  
Author(s):  
Lianzhou Huang ◽  
Zexiu Huang ◽  
Yuanqiu Chen ◽  
Xin Jin ◽  
Ji Xiao ◽  
...  
Keyword(s):  
Active Ingredient ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Biological Activities ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Citrus Aurantium ◽  
Wide Range ◽  
Anti Inflammatory

Abstract BackgroundHesperetin, an active ingredient derived from Citrus × aurantium L., possesses a wide range of biological activities, including anti-inflammatory, anti-oxidation, and anti-cancer activity. Notably, hesperetin has been proposed as a candidate for atherosclerosis owing to the lipid-regulating and anti-inflammatory effect, while the underlying mechanisms remains obscure.ResultsIn our present study, the pharmacological and molecular properties of hesperetin were first evaluated to determine the druggability of hesperetin. Subsequently, 53 hesperetin-atherosclerosis crossover targets were collected to establish the protein-protein interaction network. The result of Gene Ontology enrichment analysis indicated that the crossover targets were involved in the regulation of lipid metabolism and inflammatory response. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the crossover targets were highly correlated with the pathogenesis of atherosclerosis, such as fluid shear stress and atherosclerosis pathway and the TNF signaling pathway. Finally, an entire hesperetin-target-pathway network was constructed to provide a systematic overview of the pharmacological mechanisms of action of hesperetin against atherosclerosis.ConclusionsThe pharmacological mechanisms of actions of hesperetin against atherosclerosis was unveiled based on biodata mining from the public database and the bioinformatics data analysis-based strategy in this study, contributing to a deeper understanding of the molecular mechanisms of hesperetin in the treatment of atherosclerosis. Based on the results of network pharmacology analysis, we can conclude that hesperetin is surely an excellent candidate for atherosclerosis. We believe our work would be beneficial for further research and development of hesperetin as a natural active ingredient derived from Citrus × aurantium L. for the treatment of atherosclerosis.

scholarly journals Medicinal Plants in the Records of Latvian Folk Medicine and Analysis of Their Practical Applications. Doctoral Thesis

2021 ◽  
Author(s):  
◽  
Inga Sīle ◽  
Keyword(s):  
Medicinal Plants ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Folk Medicine ◽  
European Medicines Agency ◽  
Evidence Based ◽  
Traditional Use ◽  
Practical Applications ◽  
Anti Inflammatory

Medicinal plant knowledge in Europe is rooted in a long history of health traditions. Numerous ethnobotanical studies across Europe have addressed the increasing importance of the traditional use of medicinal plants. Latvia is a country with old folk medicine traditions and an extensive folk knowledge archive. The aim of this thesis was to collect and analyse knowledge about the use of the medicinal plants found in the records of Latvian folk medicine and to search for new ideas regarding the practical applications of these plants. This thesis reveals, for the first time to the international scientific community, the important ethnobotanical information contained in the records of Latvian folk medicine that had not yet been translated into English and are therefore less visible to researchers from all over the world. This thesis provides a list of the used plant species and plant parts, the dosage forms of herbal medicines, the routes of administration, and the disorders treated with medicinal plants mentioned in the records of Latvian folk medicine and used by indigenous people of Latvia in the end of 19th and the beginning of 20th centuries. In total, the thesis includes information on 211 plant taxa, most of which were utilized for the treatment of digestive and respiratory system disorders. To understand whether the information mentioned in the folklore material is relevant today, it was compared with evidence-based information regarding the uses of the listed plant, including official herbal monographs. During this study, it was concluded that only 59 plant taxa mentioned in the studied records of Latvian folk medicine are included in the official monographs of the European Medicines Agency, and most of the plant indications mentioned in the records have not been described in evidence-based monographs. After the systematic analysis of folklore materials, additional information on the molecular mechanisms of the anti-inflammatory activities of Pelargonium sidoides DC. and Prunus padus L. were investigated to confirm their traditional use for the treatment of inflammatory conditions. The obtained results provide evidence that both plant extracts exhibit pronounced in vitro and ex vivo anti-inflammatory activities, supporting their use in Latvian ethnomedicine as effective anti-inflammatory agents. The obtained results are important as they provide ideas for further research related to possibilities regarding the use of plants growing in the territory of Latvia and allow new perspectives to be gained for both national and international ethnobotanical research.

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