4-(Hydroxymethyl)catechol Extracted From Fungi in Marine Sponges Attenuates Rheumatoid Arthritis by Inhibiting PI3K/Akt/NF-κB Signaling

Lee, Jong Yeon; Kim, Geum J; Choi, Jin Kyeong; Choi, Young‐Ae; Jeong, Na-Hee; Park, Pil-Hoon; Choi, Hyukjae; Kim, Sang-Hyun

doi:10.3389/fphar.2018.00726

Cited by 15 publications

(6 citation statements)

References 65 publications

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“…Importantly, NF-κB is the key target of p38 MAPK and Akt signaling pathways after LPS binding TLR4/MYD88 to initiate intracellular pathways [11,12]. Both p38 MAPK/MK2 and PI3K-Akt can regulate LPS-induced gene expression by controlling NF-kB p65 hyperphosphorylation and nuclear translocation [47,48,49]. Here, our data showed that DHL pre-incubation suppressed NF-κB (p65) phosphorylation and nuclear translocation in LPS-stimulated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

et al. 2019

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Acute lung injury (ALI) is a severe clinical disease marked by dysregulated inflammation response and has a high rate of morbidity and mortality. Macrophages, which play diverse roles in the inflammatory response, are becoming therapeutic targets in ALI. In this study we investigated the effects of dehydrocostus lactone (DHL), a natural sesquiterpene, on macrophage activation and LPS-induced ALI. The macrophage cell line RAW264.7 and primary lung macrophages were incubated with DHL (0, 3, 5, 10 and 30 μmol/L) for 0.5 h and then challenged with LPS (100 ng/mL) for up to 8 hours. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI) and then treated with a range of DHL doses intraperitoneally (5 to 20 mg/kg). The results showed that DHL inhibited LPS-induced production of proinflammatory mediators such as iNOS, NO, and cytokines including TNF-α, IL-6, IL-1β, and IL-12 p35 by suppressing the activity of NF-κB via p38 MAPK/MK2 and Akt signaling pathway in macrophages. The in vivo results revealed that DHL significantly attenuated LPS-induced pathological injury and reduced cytokines expression in the lung. NF-κB, p38 MAPK/MK2 and Akt signaling molecules were also involved in the anti-inflammatory effect. Collectively, our findings suggested that DHL is a promising agent for alleviating LPS-induced ALI.

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Section: Discussionmentioning

confidence: 99%

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

et al. 2019

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“…In addition, the KEGG pathway analysis also indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. The PI3K-Akt signaling pathway is involved in inflammatory cytokine production [ 67 ], proliferation and migration of RAFLS [ 68 ] and chondrocyte proliferation [ 69 ], and apoptosis and autophagy in RA [ 69 ]. Moreover, a pivotal role for the proinflammatory cytokines, including tumor necrosis factor (TNF) [ 70 ] and interleukin- (IL-) 17 [ 71 ], in RA joint pathology has been identified.…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Tang

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

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“…phenolics and benzoquinones derivatives (4-(Hydroxymethyl)-catechol and benzoquinone) modulate immune pathways such as PI3K/Akt/NF-κB, and STAT1 signaling; respectively [ 33 , 34 ]. Hydroxybenzoic acids such as gallic and vanillic acids promote differentiation of regulatory T-cells and enhance immune responses in murine models [ 35 , 36 ].…”

Section: Overview On Immunizations With Carrier-plant-phenolics Conjumentioning

confidence: 99%

Plant Phenolics as Pathogen-Carrier Immunogenicity Modulator Haptens

Castillo-Maldonado

María-de-la-Luz

Delgadillo‐Guzmán

et al. 2020

CPB

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Background: Pathogens use multiple mechanisms to disrupt cell functioning in their host and allow pathogenesis. These mechanisms involve communication between the pathogen and the host cell through protein-protein interactions. Protein-protein interactions chains referred to as signal transduction pathways are the processes by which a chemical or physical signal transmits through a cell as series of molecular events so the pathogen simply needs to intercept these molecular pathways at few positions to induce pathogenesis such as pathogen viability, infection or hypersensitivity. The pathogen nodes of interception are not necessary the most immunogenic; so that, novel immunogenicity-improvement strategies need to be developed thought a chemical conjugation of the pathogen-carrier nodes to develop an efficient immune response in order to block pathogenesis. On the other hand, if pathogen-carriers are immunogens; toleration ought to be induced by this conjugation avoiding hypersensitivity. Thus, this paper addresses the biological plausibility of plant-phenolics as pathogen-carrier immunogenicity modulator haptens. Conclusion: The plant-phenolic compounds have in their structure functional groups such as hydroxyl, carbonyl, carboxyl, ester, or ether, capable of reacting with the amino or carbonyl groups of the amino acids of a pathogen-carrier to form conjugates. Besides, the varied carbon structures that these phenolic compounds have; it is possible to alter the pathogen-carrier related factors that determine the immunogenicity: 1) Structural complexity, 2) Molecular size, 3) Structural heterogeneity, 4) Accesibility to antigenic determinants or epitopes, 5) Optical configuration, 6) Physical state, or 7) Molecular rigidity.

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4-(Hydroxymethyl)catechol Extracted From Fungi in Marine Sponges Attenuates Rheumatoid Arthritis by Inhibiting PI3K/Akt/NF-κB Signaling

Cited by 15 publications

References 65 publications

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-κB Signaling Pathway Mediated by p38 MAPK and Akt

Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Plant Phenolics as Pathogen-Carrier Immunogenicity Modulator Haptens

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