Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin

Abu-Elsaad, Nashwa; El-Karef, Amr

doi:10.1016/j.pharep.2019.03.009

Cited by 33 publications

(23 citation statements)

References 39 publications

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“…Quercetin can be used as a therapeutic approach for high fat diet (HFD) induced NAFLD due to its anti-inflammatory, antioxidant and prebiotic integrative response in C57BL/6J mice [42]. Previous reports indicate that luteolin decreases the adiposity and dyslipidemia by decreasing lipogenesis and increasing fatty acid oxidation [43,44] and anti-inflammatory [45], which contributes to protection against NAFLD. Puerarin could be a promising and practical therapeutic strategy for NAFLD by modulating PARP-1/PI3K/AKT signalling pathway [46], and by activation of AMPK and its downstream effectors involved in lipid metabolism [47,48] and JAK2/ STAT3 signalling pathways in hepatocytes [48,49].…”

Section: Discussionmentioning

confidence: 99%

Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network pharmacology and validation in ageing rats

et al. 2020

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Background: Based on therapy with syndrome differentiation and clinical studies on Xiaochaihu decoction (XCHD), we hypothesize that Modified Xiaochaihu Decoction (MXD) has an ability to ameliorate non-alcoholic fatty liver disease (NAFLD). This study aims to elucidate the pharmacological efficacy of MXD and its mechanism in the treatment of NAFLD by network pharmacology and experimental validation. Methods: The active ingredients in MXD and their potential targets were identified using network analysis followed by experimental validation. First, we used data on the ingredients and targets obtained from professional database and related literature to do PPI network analysis, GO functional analysis, and KEGG pathway enrichment analysis. Core targets identified by network pharmacology were then tested in natural ageing female rats model. Indexes of lipid and glucose homeostasis were determined enzymatically and/or histologically. Gene expression was analyzed by realtime PCR and/or Western blot (WB). Results: In total, 4009 NAFLD-related targets and 1953 chemical ingredients of MXD were obtained. In-depth network analysis of 140 common targets indicated that MXD played a critical role in anti-NAFLD via multiple targets and pathways. Based on the data of PPI analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and literatures on the mechanism of NAFLD, we chose the core targets related to lipid metabolism (SREBP-1c, ChREBP, FASN, PPARα, and ACACA) and inflammation (IL-6 and NF-κB) to do further study. Significantly, in further animal verification experiment we using naturally ageing rats with NAFLD as a model, we found that MXD administration ameliorated age-related NAFLD and mechanistically down-regulated the mRNA/protein expression of core targets in lipid metabolism and inflammation related pathways such as FASN, ACACA, IL-6, and NF-κB. In addition, 12 of 24 potential ingredients acting on verified targets came from BC, and 11 of 24 potential ingredients acting on verified targets were derived from SM, implying that both BC and SM served as the key role in MXD against NAFLD.

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Section: Discussionmentioning

confidence: 99%

Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network pharmacology and validation in ageing rats

et al. 2020

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“…Quercetin exhibits extremely antiproliferative, proapoptotic, and antimetastatic activities on NSCLC by enhancing cytotoxic efficacy [37], regulating the pathways related to the inhibition of snaildependent Akt activation and Snail-independent ADAM9 expression [38], mediating BCL2/BAX gene [39], and regulating-down IL-6/STAT-3 signals [40]. Similarity, Luteolin possesses a wide spectra of pharmacological actions, including anti-inflammation [41][42] [43], neuroprotective effect [43], protection against nonalcoholic steatohepatitis [44], anti-tumor [45] [46], anti-ischemia/reperfusion injury [47], and anti-diabetic cardiomyopathy [48]. A recent pharmacological study presented that luteolin modulates the expression of genes relevant to steroidogenesis, apoptosis, and stress response, such as Fas, Tp53, and PARP.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Identification of Pharmacological Mechanisms of Inula japonica Thunb. on Non-small Cell Lung Cancer

Qian¹,

Wang²,

Zhang³

et al. 2020

Preprint

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Background Inula japonica Thunb. (IJT) is an extensively applied herbal medicine for treating non-small cell lung cancer (NSCLC) due to its anti-asthma, antitussive, and expectorant properties. However, the mechanism of IJT against NSCLC remains to be elucidated. Methods Network pharmacology analysis was applied to determine the function mechanism of IJT against NSCLC. Databases were used to collect compounds and their related and known therapeutic targets. The compound–target (C–T) and target–target networks were then constructed to screen the kernel compounds and NSCLC-related targets of IJT. Moreover, the NSCLC-related targets of IJT were input in the DAVID Bioinformatics Resources (version 6.8) for Gene Ontology Biological Processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding affinity of major compounds with the NSCLC-relevant targets of IJT was further verified by molecular docking. Results Two active compounds (quercetin and luteolin) and six putative targets (RAC-alpha serine/threonine-protein kinase, G1/S-specific cyclin-D1, cyclin-dependent kinase inhibitor 2A, epidermal growth factor receptor, receptor tyrosine-protein kinase erbB-2, and cellular tumor antigen p53) were screened as the effective compounds and NSCLC-related targets of IJT. GOBP and KEGG enrichment analysis indicated that NSCLC was the major pathway of IJT in the treatment of NSCLC and the mediation of apoptosis, cell cycle, tumor progression, and proliferation of biological processes, including the Ras, ERBB, MAPK, PI3K–Akt, calcium, and p53 signaling pathways. The results of molecular docking validated that 10 of the 12 pairs of compound-target had effective binding. Conclusions The mechanisms of IJT against NSCLC through multi-compounds, multi-targets, and multi-pathways were elucidated.

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“…NLRP3, a significant member of the PRRs, combines with ASC and Caspase-1 to form a multiprotein called the NLRP3 inflammasome, which can then promote the maturation of Caspase-1 [7,18]. Mature Caspase-1 can finally promote the maturation and production of the proinflammatory factors IL-1β and IL-18, which leads to inflammatory injury in different organs [9,10,19]. NLRP3 has been verified to be widely expressed in the gastrointestinal tract and can be found in epithelial cells at mucosal sites, which is important in maintaining intestinal homeostasis [11].…”

Section: Discussionmentioning

confidence: 99%

“…Experiments have indicated that it often causes severe detrimental neurotoxic effects by increasing the levels of dopamine, norepinephrine, and serotonin in plasma, while blocking their degradation [3]. Through a literature review, we found that in addition to its neurotoxic effects, METH, orally taken, also has caused severe bleeding and perforation, such as in inflammatory injury of the intestine, in several clinical cases [4–8]. However, there has been no literature on systematic experiments focused on inflammatory intestinal injury due to METH.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Induces Intestinal Inflammatory Injury via Nod-Like Receptor 3 Protein (NLRP3) Inflammasome Overexpression In Vitro and In Vivo

et al. 2019

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BackgroundMethamphetamine (METH), a confirmed neurotoxic drug, has also reportedly caused several intestinal inflammatory injury cases. The NLRP3 (Nod-like receptor 3 protein) inflammasome can induce several inflammatory injuries by activating IL-1β and IL-18 when overexpressed. We designed experiments to determine whether METH can cause intestinal inflammatory injury via NLRP3 inflammasome overexpression.Material/MethodsIEC-6 cells were classified as control, METH (0.5 mM), and METH (0.5 mM)+MCC950 (100 μM) groups. C57BL/6 mice were separated into control, NS, METH (5 mg/kg), and METH (5 mg/kg)+MCC950 (10 mg/kg) groups (n=10). We detected apoptosis, transepithelial electrical resistance (TEER), and proinflammatory factors (IL-6, INF-γ, TNF-α, and NF-κB) in the METH cell model. We also assessed proinflammatory factors (IL-6, INF-γ, TNF-α, and NF-κB) and observed intestinal tissues stained with hematoxylin and eosin (HE) in the METH animal model to explore intestinal inflammatory injury due to METH. After adding MCC950 (an NLRP3 inflammasome inhibitor), we additionally detected NLRP3 inflammasome components (NLRP3, Caspase-1, and ASC), IL-1β, and IL-18 to estimate the relationship of the NLRP3 inflammasome with intestinal inflammatory injury due to METH.ResultsMETH can lead apoptosis, increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-α, and NF-κB), and decrease TEER in the METH cell model. In the METH animal model, METH can cause obvious injury and increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-α, and NF-κB). All the intestinal inflammatory changes due to METH depended on overexpression of the NLRP3 inflammasome and could be ameliorated by MCC950, except for ASC and NF-κB.ConclusionsMETH, in addition to being a confirmed neurotoxic drug, can also cause severe intestinal inflammatory injury via NLRP3 inflammasome overexpression. NF-κB may be an activator of the NLRP3 inflammasome in METH intestinal inflammatory injury.

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Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin

Cited by 33 publications

References 39 publications

Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network pharmacology and validation in ageing rats

Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network pharmacology and validation in ageing rats

Network Pharmacology-Based Identification of Pharmacological Mechanisms of Inula japonica Thunb. on Non-small Cell Lung Cancer

Methamphetamine Induces Intestinal Inflammatory Injury via Nod-Like Receptor 3 Protein (NLRP3) Inflammasome Overexpression In Vitro and In Vivo

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