scholarly journals Based on Proteomics Reveals the Anti-inflammatory Mechanism of Phillygenin by Inhibition NF-κB Pathway

2020 ◽  
Author(s):  
Mengting Zhou ◽  
Yunqiu Tang ◽  
Li Liao ◽  
Meichen Liu ◽  
Ying Deng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Western Blot ◽  
Signaling Pathways ◽  
Inflammatory Factors ◽  
Transcriptional Level ◽  
Inflammatory Genes ◽  
Inflammatory Mechanism ◽  
Pathway Activation ◽  
Anti Inflammatory ◽  
Anti Inflammation

Abstract Background: Inflammation is a common pathological phenomenon when homeostasis is seriously disturbed. Phillygenin (PHI) is a lignin component isolated from Forsythiae Fructus, which showed a good anti-inflammation effect. However, the mechanisms of PHI on anti-inflammation have not yet been systematically elucidated.Methods: In the study, the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to investigate mechanisms of PHI on inflammation. The effect of PHI on LPS-induced IL-1β and PGE2 inflammatory factors was detected by ELISA, and the mRNA expression of IL-1β, IL-6 and TNF-α was detected by RT-qPCR. Proteomics studies the signaling pathways that may be affected by PHI. Molecular docking technology was used to study the possible targets of PHI on NF-kB pathway. Western blot was performed to detect progressive changes in protein expression.Results: The research showed that PHI significantly inhibited the robust increase of IL-1β and PGE2, and lowered the transcriptional level of inflammatory genes including IL-6, IL-1β and PGE2 in LPS-stimulated RAW264.7 cells. Proteomics results indicated that PHI was involved in the regulation of multiple signaling pathways. Molecular docking results indicated that PHI has an affinity for most proteins in NF-kB pathway. Western blot analysis showed that PHI inhibited LPS-induced NF-κB pathway activation. Conclusion: PHI inhibits the activation of NF-κB pathway, thereby inhibiting the expression of related inflammatory genes and the release of cytokines, thus showing remarkable anti-inflammatory effect.

scholarly journals Polyphenols Extracted from Shanxi-Aged Vinegar Inhibit Inflammation in LPS-Induced RAW264.7 Macrophages and ICR Mice via the Suppression of MAPK/NF-κB Pathway Activation

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2745
Author(s):  
Peng Du ◽  
Jia Song ◽  
Huirui Qiu ◽  
Haorui Liu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Comprehensive Evaluation ◽  
Fermented Food ◽  
Gas Chromatography Mass Spectrometry ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Inflammatory Stress ◽  
Icr Mice ◽  
Raw264.7 Macrophages ◽  
Pathway Activation ◽  
Anti Inflammatory

Shanxi-aged vinegar, a traditional Chinese grain-fermented food that is rich in polyphenols, has been shown to have therapeutic effects on a variety of diseases. However, there has been no comprehensive evaluation of the anti-inflammatory activity of polyphenols extracted from Shanxi-aged vinegar (SAVEP) to date. The anti-inflammatory activities of SAVEP, both in RAW 264.7 macrophages and mice, were extensively investigated for the potential application of SAVEP as a novel anti-inflammatory agent. In order to confirm the notion that polyphenols could improve inflammatory symptoms, SAVEP was firstly detected by gas chromatography mass spectrometry (GC-MS). In total, 19 polyphenols were detected, including 12 phenolic acids. The study further investigated the protective effect of SAVEP on lipopolysaccharide-induced inflammation in RAW264.7 macrophages and ICR mice. The results showed that compared with those of the model group, SAVEP could remarkably recover the inflammation of macrophage RAW264.7 and ICR mice. SAVEP can normalise the expression of related proteins via the suppression of MAPK/NF-κB pathway activation, inhibiting the expression of iNOS and COX-2 proteins, and consequently the production of inflammatory factors, thus alleviating inflammatory stress. These results suggest that SAVEP may have a potential function against inflammation.

scholarly journals Astragalus membranaceus Injection Suppresses Production of Interleukin-6 by Activating Autophagy through the AMPK-mTOR Pathway in Lipopolysaccharide-Stimulated Macrophages

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Xiaoyan Zhang ◽  
Taigang Liang ◽  
Wanxia Yang ◽  
Lanfang Zhang ◽  
Shuting Wu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Interleukin 6 ◽  
Mtor Pathway ◽  
The Body ◽  
Astragalus Membranaceus ◽  
Inflammatory Factors ◽  
Repressive Effect ◽  
Sirna Silencing ◽  
Anti Inflammatory

Astragalus membranaceus (AM), used in traditional Chinese medicine, has been shown to enhance immune functions, and recently, its anti-inflammatory effects were identified. However, the mechanisms of action remain unclear. Most studies have shown that autophagy might be involved in the immune response of the body, including inflammation. Here, we developed an inflammatory model by stimulating macrophages with lipopolysaccharides (LPS) to explore the anti-inflammatory effect and mechanisms of AM injection from the perspective of the regulation of autophagy. Immunoblot, immunofluorescence, and ELISA were used to determine the effects of AM injection on the production of interleukin-6 (IL-6) and alterations of autophagy markers. It was found that AM injection reduced the expression of IL-6 in LPS-stimulated macrophages and reversed the LPS-induced inhibition of cellular autophagy. After treatment with inhibitors of signaling pathways, it was shown that LPS downregulated autophagy and upregulated the production of IL-6 in macrophages via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. AM injection reversed the effects of LPS by activating the AMP-activated protein kinase (AMPK) instead of inhibiting Akt. These results were further confirmed by testing activators and siRNA silencing of AMPK. Hence, these 2 distinct signaling molecules appear to exert opposite effects on mTOR, which integrates information from multiple upstream signaling pathways, negatively regulating autophagy. In addition, we demonstrated that autophagy might play a key role in regulating the production of IL-6 by testing activators and inhibitors of autophagy and siRNA silencing of ATG5. These findings showed that AM injection might enhance autophagy by activating AMPK and might further play a repressive effect on the LPS-stimulated expression of IL-6. This study explored the relationship between autophagy, signaling pathways, and the production of inflammatory factors in a model of endotoxin infection and treatment with AM injection.

Proinflammatory and Anti-inflammatory Genes in Stroke Pathogenesis

2020 ◽  
Vol 26 (34) ◽  
pp. 4220-4233
Author(s):  
Mengmeng Jiang ◽  
Penglin Yin ◽  
Xiaodan Bai ◽  
Liji Yang ◽  
Junping Zhang ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Ischemic Brain ◽  
Inflammatory Genes ◽  
Proinflammatory Mediators ◽  
Inflammatory Mechanism ◽  
Ischemic Brain Tissue ◽  
Anti Inflammatory ◽  
The Brain

The brain's response to ischemic injury is an acute and long-term inflammatory process. This process involves activation of resident cells (mainly microglia, hematogenous macrophages), production of proinflammatory mediators and infiltration of various proinflammatory cells (mainly neutrophils and lymphocytes). These cells play an essential role in ischemic brain tissue by releasing either proinflammatory or anti-inflammatory mediators at different time points. However, the exact pathogenesis of proinflammatory or anti-inflammatory genes in this process has not yet been elucidated. This review aims to investigate the inflammatory process of stroke, especially the role of proinflammatory and anti-inflammatory genes in the pathogenesis of stroke. We also summarize the current clinical trials of drugs that target the inflammatory mechanism for intervention.

Inspired by magnolol: design of NSAID-based compounds with excellent anti-inflammatory effects

MedChemComm ◽  
2015 ◽  
Vol 6 (12) ◽  
pp. 2129-2139 ◽  
Author(s):  
Wenfeng Liu ◽  
Yuan Yue ◽  
Yonglian Li ◽  
Xi Zheng ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Transcriptional Level ◽  
Inflammatory Agent ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory

A10was selected to elucidate the anti-inflammatory mechanism at the transcriptional level, suggesting its potential to serve as a novel anti-inflammatory agent.

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 Anti-inflammatory Properties of Fangji Huangqi Tang: Discovery Based on Network Pharmacology, Molecular Docking and Arrowsmith Tools

2021 ◽  
Author(s):  
Qingtao Jiang ◽  
Lei Han ◽  
Xin Liu ◽  
Feng Zhang
Keyword(s):  
Gene Ontology ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
Tight Binding ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Classical Formula ◽  
Anti Inflammatory ◽  
Principal Elements ◽  
Compound Target

Abstract Fangji Huangqi Tang (FHT) is a classical formula widely used in Chinese clinical practice. In this study, a creative application of FHT for inflammation has been identified by network pharmacology-based framework. Specifically, a total of 17 bioactive compounds including 42 potential targets of FHT, and 205 related targets involved in inflammation were retrieved from mainstream databases and subjected to network analysis. 13 intersection targets indicated the principal elements linked to inflammation therapy. Top terms of Gene Ontology (GO) analysis were identified, while 7 related signaling pathways were revealed by Kyoto Encyclopedia of Genes and Genomes (KEGG) results. Subsequently, Calycosin-PTGS2 with tight binding affinity (BA) was manifested by molecular docking as the critical compound-target couple. Meaningful links between Calycosin and inflammation were implied through Arrowsmith, which overlapped with the findings in enrichment analysis, such as MAPK, NF-κB that could be regulators of PTGS2. In summary, the present study explored the potential targets and signaling pathways of FHT against inflammation, which may help to illustrate the mechanisms responsible for the action of FHT and provide a better understanding of its anti-inflammatory effects.

scholarly journals Assessing the Anti-inflammatory Mechanism of Reduning Injection by Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fuda Xie ◽  
Mingxiang Xie ◽  
Yibing Yang ◽  
Miaomiao Zhang ◽  
Xiaojie Xu ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Inflammatory Diseases ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Inflammatory Mechanism ◽  
Reduning Injection ◽  
Anti Inflammatory

Reduning Injection (RDNI) is a traditional Chinese medicine formula indicated for the treatment of inflammatory diseases. However, the molecular mechanism of RDNI is unclear. The information of RDNI ingredients was collected from previous studies. Targets of them were obtained by data mining and molecular docking. The information of targets and related pathways was collected in UniProt and KEGG. Networks were constructed and analyzed by Cytoscape to identify key compounds, targets, and pathways. Data mining and molecular docking identified 11 compounds, 84 targets, and 201 pathways that are related to the anti-inflammatory activity of RDNI. Network analysis identified two key compounds (caffeic acid and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) which would play critical roles in the treatment of inflammatory diseases by RDNI. The cross-talks among pathways provided a deeper understanding of anti-inflammatory effect of RDNI. RDNI is capable of regulating multiple biological processes and treating inflammation at a systems level. Network pharmacology is a practical approach to explore the therapeutic mechanism of TCM for complex disease.

scholarly journals Sweroside Alleviated LPS-Induced Inflammation via SIRT1 Mediating NF-κB and FOXO1 Signaling Pathways in RAW264.7 Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 872 ◽  
Author(s):  
Rui Wang ◽  
Zhaoyue Dong ◽  
Xiaozhong Lan ◽  
Zhihua Liao ◽  
Min Chen
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Raw264.7 Cells ◽  
Content Increase ◽  
Forkhead Transcription Factor ◽  
Mechanism Research ◽  
Anti Inflammatory ◽  
Anti Inflammation ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Pterocephalus hookeri was used as a traditional Chinese medicine for the treatment of rheumatoid arthritis. Sweroside was a main iridoid isolated from P. hookeri. The present study aimed to investigate the anti-inflammatory effect mechanism of sweroside. In RAW264.7 cells induced by lipopolysaccharide (LPS), the abnormal proliferation, the NO content increase, and the downregulated Sirtuin1 (SIRT1) expression were observed. Sweroside could alleviate the inflammation by inhibiting cell proliferation through arresting the cell cycle at the G0/G1 phase, by suppressing pro-inflammatory cytokines and by promoting anti-inflammatory cytokines in LPS-induced RAW264.7 cells. Further mechanism research indicated that sweroside could activate the SIRT1, then suppress the nuclear factor-kappa B (NF-κB) and promote the Forkhead transcription factor O1 (FOXO1) signaling pathways. The present study indicated that sweroside may be the main anti-inflammatory constituent of P. hookeri and a promising candidate for anti-inflammation therapy.

scholarly journals Network pharmacology integrated with experimental validation revealed the anti-inflammatory effects of Andrographis paniculata

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naiqiang Zhu ◽  
Jingyi Hou ◽  
Ning Yang
Keyword(s):  
Molecular Docking ◽  
Western Blot ◽  
Cancer Immunology ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Rt Pcr ◽  
Hub Genes ◽  
Bioactive Ingredients ◽  
Anti Inflammatory ◽  
Key Pathways

AbstractInflammation is a key factor in the development and complications of various diseases because it has a complex pathogenesis. Andrographis paniculate (Burm. f.) Nees (Chuan Xinlian) is a well-known form of Traditional Chinese Medicine (TCM) applied in clearing heat and detoxification. Also, it is rich in bioactive lactones, with various anti-inflammatory activities. Here, network pharmacology combined with molecular biology experimental approach was used to predict and verify the potential molecular mechanism of Chuan Xinlian in treating inflammation. The bioactive ingredients of Chuan Xinlian were obtained from the TCMSP database and literature. Besides, the targets of Chuan Xinlian and inflammation were collected based on the multi-source databases and used to generate the PPI network. Network topology analysis and functional enrichment analysis were used to screen hub genes and their mechanisms. Molecular docking simulation was performed to evaluate the binding activity between the predicted hub genes and the bioactive ingredients. Additionally, LPS-induced NO production in RAW264.7 cell inflammatory response, RT-PCR and Western blot were used to validate the efficacy of the Chuan Xinlian in the treatment of inflammation. Network analysis outcomes indicated that five targets (IL-6, VEGFA, PTGST2, TNF-α, and MMP-9) were identified as the key targets of Chuan Xinlian in the treatment of inflammation. Further, molecular docking findings revealed that the majority of the bioactive ingredients exhibited a strong binding efficacy towards the predicted hub genes. Functional analysis results showed that the potential mechanisms were primarily concentrated in key pathways including cancer, immunology, and inflammation process. Moreover, RT-PCR and Western blot analysis indicated that Chuan Xinlian extract suppressed the production of inflammatory mediators with anti-inflammatory effects. Our study shows that Chuan Xinlian potentially exerts an anti-inflammatory effect via key pathways including cancer, immunology, and inflammation process. This suggests that Chuan Xinlian has a potential anti-inflammatory action, thereby providing a scientific reference for clinical studies.

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