scholarly journals Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

2020 ◽  
Vol 11 ◽  
Author(s):  
Natalie Vivien Gunter ◽  
Soek Sin Teh ◽  
Yang Mooi Lim ◽  
Siau Hui Mah
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Mapk Signaling ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Wide Range ◽  
Anti Inflammatory

The pathogenesis of skin inflammatory diseases such as atopic dermatitis, acne, psoriasis, and skin cancers generally involve the generation of oxidative stress and chronic inflammation. Exposure of the skin to external aggressors such as ultraviolet (UV) radiation and xenobiotics induces the generation of reactive oxygen species (ROS) which subsequently activates immune responses and causes immunological aberrations. Hence, antioxidant and anti-inflammatory agents were considered to be potential compounds to treat skin inflammatory diseases. A prime example of such compounds is xanthone (xanthene-9-one), a class of natural compounds that possess a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and chemotherapeutic effects. Many studies reported various mechanisms of action by xanthones for the treatment of skin inflammatory diseases. These mechanisms of action commonly involve the modulation of various pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α), as well as anti-inflammatory cytokines such as IL-10. Other mechanisms of action include the regulation of NF-κB and MAPK signaling pathways, besides immune cell recruitment via modulation of chemokines, activation, and infiltration. Moreover, disease-specific activity contributed by xanthones, such as antibacterial action against Propionibacterium acnes and Staphylococcus epidermidis for acne treatment, and numerous cytotoxic mechanisms involving pro-apoptotic and anti-metastatic effects for skin cancer treatment have been extensively elucidated. Furthermore, xanthones have been reported to modulate pathways responsible for mediating oxidative stress and inflammation such as PPAR, nuclear factor erythroid 2-related factor and prostaglandin cascades. These pathways were also implicated in skin inflammatory diseases. Xanthones including the prenylated α-mangostin (2) and γ-mangostin (3), glucosylated mangiferin (4) and the caged xanthone gambogic acid (8) are potential lead compounds to be further developed into pharmaceutical agents for the treatment of skin inflammatory diseases. Future studies on the structure-activity relationships, molecular mechanisms, and applications of xanthones for the treatment of skin inflammatory diseases are thus highly recommended.

scholarly journals Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 549 ◽  
Author(s):  
Chao Zhang ◽  
Alan Hsu ◽  
He Pan ◽  
Yinuo Gu ◽  
Xu Zuo ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Bioactive Constituents ◽  
Cellular Apoptosis ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Although the anti-inflammatory activity of CBN has been reported, the underpinning mechanism of this remains unclear. In this study, we investigated the anti-inflammatory effect of CBN on lipopolysaccharide (LPS)-stimulated THP-1 cells and explored the possible underlying molecular mechanisms. The results showed that CBN suppressed LPS-mediated inflammatory response mainly through the inactivation of the NOD1 and NF- κ B p65 signaling pathways. Knockdown of NOD1 reduced the degree to which inflammatory cytokines decreased following CBN treatment, whereas forced expression of NOD1 and CBN treatment reduced NF- κ B p65 activation and the secretion of inflammatory cytokines. Furthermore, CBN significantly reduced cellular apoptosis by inhibiting the NOD1 pathway. Collectively, our results indicate that CBN suppressed the LPS-mediated inflammatory response by inhibiting NOD1/NF- κ B activation. Further investigations are required to determine the mechanisms of action of CBN in the inhibition of NOD signaling: However, CBN may be employed as a therapeutic agent for multiple inflammatory diseases.

scholarly journals Tackling Chronic Inflammation with Withanolide Phytochemicals—A Withaferin A Perspective

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1107
Author(s):  
Emilie Logie ◽  
Wim Vanden Berghe
Keyword(s):  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Withaferin A ◽  
Related Factor ◽  
Nuclear Factor ◽  
Pharmaceutical Drugs ◽  
In Vivo Models ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory

Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis.

scholarly journals Protective Effects of Aqueous Extract of Mentha suaveolens against Oxidative Stress-Induced Damages in Human Keratinocyte HaCaT Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
HansongI Lee ◽  
Miji Yeom ◽  
Seoungwoo Shin ◽  
Kyungeun Jeon ◽  
Deokhoon Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Phase Ii ◽  
Aqueous Extract ◽  
Biological Activities ◽  
Ros Generation ◽  
Related Factor ◽  
Hacat Cells ◽  
Human Keratinocyte ◽  
Wide Range ◽  
Phase Ii Enzyme

Mentha suaveolens is an aromatic herb that has a wide range of biological activities, including antimicrobial, antifungal, anti-inflammatory, and hepatoprotective properties. Although there are a few reports on the antioxidant property of M. suaveolens, its cytoprotective activity against oxidative stress has not been reported yet. The objective of this study was to determine the protective activity of M. suaveolens aqueous extract (MSAE) against hydrogen peroxide- (H2O2-) induced oxidative stress and apoptosis in human keratinocyte HaCaT cells. MSAE pretreatment decreased H2O2-induced cytotoxicity and suppressed H2O2-induced intracellular ROS generation. Furthermore, MSAE suppressed expression levels of H2O2-induced apoptotic genes such as cleaved caspase-3, caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP). Pretreatment with MSAE induced expression of phase II enzyme such as HO-1 through translocation of NF-E2-related factor (Nrf2) upon H2O2 exposure. These results revealed that the cytoprotective effect of MSAE against oxidative stress-induced cell death was associated with activation of Nrf2-mediated phase II enzyme expression.

Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

2019 ◽  
Vol 86 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Chenxu Zhao ◽  
Yazhou Wang ◽  
Xue Yuan ◽  
Guoquan Sun ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Rumen Epithelial Cells

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

scholarly journals Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110209
Author(s):  
Yun Sil Kang ◽  
You Chul Chung ◽  
Jung No Lee ◽  
Bong Seok Kim ◽  
Chang-Gu Hyun
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Coumarin derivatives, such as esculetin, have various physiological functions, including antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-cancer. 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4MC) is a derivative of esculetin, and its anti-inflammatory effect and mechanism in macrophages have not been studied. In this study, the anti-inflammatory activity of 6,7-DH-4MC was evaluated by measuring the expression of inflammatory factors (NO and PGE2) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 macrophages. The results revealed that 6,7-DH-4MC significantly reduced NO levels and PGE2 expression without inducing cytotoxicity; it was confirmed that the inhibition of NO and PGE2 expression was related to iNOS and COX-2 downregulation in response to 6,7-DH-4MC treatment. Moreover, 6,7-DH-4MC decreased the levels of pro-inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. Mechanistic studies revealed reduced phosphorylation of ERK and p38-MAPK upon 6,7-DH-4MC treatment. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in cells treated with LPS were interrupted by 6,7-DH-4MC treatment. These results suggest that 6,7-DH-4MC is a potential therapeutic agent for inflammatory diseases. To the best of our knowledge, this is the first report demonstrating the anti-inflammatory effects of 6,7-DH-4MC in RAW 264.7 cells via MAPK and NF-κB signaling pathways.

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 Effects of Launaea sarmentosa Extract on Lipopolysaccharide-Induced Inflammation via Suppression of NF-κB/MAPK Signaling and Nrf2 Activation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2586 ◽  
Author(s):  
Thanh Q. C. Nguyen ◽  
Tran Duy Binh ◽  
Ryo Kusunoki ◽  
Tuan L. A. Pham ◽  
Yen D. H. Nguyen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Akt Phosphorylation

Launaea sarmentosa has been extensively used as a nutrient herb in traditional Vietnamese remedies for the treatment of various diseases, especially inflammatory diseases. However, no detailed research has been conducted examining the molecular mechanisms involved in the suppression of inflammatory response. Here, we studied the effects of L. sarmentosa methanol extract on lipopolysaccharide (LPS)-induced inflammation using RAW 264.7 macrophages. The extract demonstrated potent antioxidant activity owing to the presence of polyphenolic and flavonoid components. Pretreatment with the extract inhibited LPS-mediated secretion of nitric oxide, reactive oxygen species, and tumor necrosis factor-α as well as the expression of inflammatory cytokines. Furthermore, the activation of the nuclear factor-kappa B pathway and phosphoinositide-3-kinase/protein kinase B pathways was blocked by the extract by inhibiting Akt phosphorylation. Additionally, the mitogen-activated protein kinase pathway was suppressed, and endoplasmic reticulum stress was attenuated. Furthermore, the extract promoted the activity of nuclear factor erythroid-2-related factor 2 resulting in the up-regulation of heme oxygenase-1 pathway, leading to the suppression of oxidative stress and inflammatory response. Taken together, the results indicate that L. sarmentosa exhibits anti-inflammatory effects, and hence, can be further developed as a novel drug for the treatment of diseases associated with excessive inflammation.

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 Turkish Endemic Achillea Species Protect Human Neuroblastoma SH-SY5Y Cells Against Hydrogen Peroxide-Induced Cytotoxicity

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 43
Author(s):  
Kübra Uzun ◽  
Ayşe Kübra Karaboğa Arslan
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Phenolic Compounds ◽  
Neurodegenerative Diseases ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Antioxidant Systems ◽  
Human Neuroblastoma ◽  
Wide Range ◽  
Anti Inflammatory

The genus Achillea L. belongs to Asteraceae (Compositae), the largest family of vascular plants. There are 50 species, which of 24 is endemic in this genus in Turkey. Achillae species are used as a tonic, anti-inflammatory, anti-spasmodic, diaphoretic, diuretic and emmenagogic agents and have been used for treatment of hemorrhage, pneumonia, rheumatic pain and wounds healing traditionally. The imbalanced antioxidant systems leads to various pathophysiological conditions such as inflammation, neurodegenerative diseases and cancer. Achillea species have several components; essential oils, sesquiterpenes and phenolic compounds such as flavonoids and phenolic acids. Phenolic compounds and flavonoids are the most important medicinal metabolites of Achillea species. Flavonoids have been reported to exert a wide range of biological activities including anti-inflammatory, antioxidant and anti-tumor effects. This study aimed to assess the in vitro antioxidant properties of the methanol extracts from the aerial parts of A. cucullata (ACME) and A. sieheana (ASME) against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study showed that the ACME and ASME provided neuroprotection against H2O2-induced oxidative stress. In conclusion, ACME and ASME might help in reducing oxidative stress for preventive therapy associated with neurodegenerative diseases and cancer.

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