Fucosterol attenuates lipopolysaccharide-induced acute lung injury in mice

Li, Yuexia; Li, Xiaohui; Liu, Gang; Sun, Rong; Wang, Lirui; Wang, Jing; Wang, Hongmin

doi:10.1016/j.jss.2014.12.054

Cited by 27 publications

(19 citation statements)

References 28 publications

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“…Lipopolysaccharide (LPS)‐induced ALI mice are the most commonly used pharmacological research animal models, as LPS augments the production of inflammatory mediators through infiltration of inflammatory cells (Rossol et al, ; Dung et al, ; Li et al, ). Toll‐like receptor 4 (TLR4) has been identified as the pattern recognition receptor for LPS (Rhee, ).…”

Section: Introductionmentioning

confidence: 99%

Mogroside IIIE Attenuates LPS‐Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF‐κB Axis via AMPK Activation

Tao

Cao

et al. 2017

Phytotherapy Research

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Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1β, IL-6, TNF-α and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor κB (NF-κB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-κB signalling pathways. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Mogroside IIIE Attenuates LPS‐Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF‐κB Axis via AMPK Activation

Tao

Cao

et al. 2017

Phytotherapy Research

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“…of 23 attenuated lung histopathologic changes and the wet-to-dry ratio of lungs in LPS-induced ALI in mice. Furthermore, fucosterol significantly inhibited TNF-a, IL-1ß, and IL-6 levels in both the broncho-alveolar lavage fluid (BALF) and the LPS-stimulated alveolar macrophages, reducing their expression by about 50%, when compared to the untreated group [149]. The fact that 23 is able to inhibit the production of pro-inflammatory molecules suggests that it could be used for the treatment of other inflammatory diseases.…”

Section: Fucosterolmentioning

confidence: 99%

“…Fucosterol 23 also exhibits a protective effect on LPS-induced acute lung injury (ALI), by modulating the expression of pro-inflammatory factors [149]. A dosage of 30 mg/kg (b.w.)…”

Section: Fucosterolmentioning

confidence: 99%

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

et al. 2019

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Macroalgae are increasingly viewed as a source of secondary metabolites with great potential for the development of new drugs. In this development, in vitro studies are only the first step in a long process, while in vivo studies and clinical trials are the most revealing stages of the true potential and limitations that a given metabolite may have as a new drug. This literature review aims to give a critical overview of the secondary metabolites that reveal the most interesting results in these two steps. Phlorotannins show great pharmaceutical potential in in vivo models and, among the several examples, the anti-dyslipidemia activity of dieckol must be highlighted because it was more effective than lovastatin in an in vivo model. The IRLIIVLMPILMA tridecapeptide that exhibits an in vivo level of activity similar to the hypotensive clinical drug captopril should still be stressed, as well as griffithsin which showed such stunning results over a variety of animal models and which will probably move onto clinical trials soon. Regarding clinical trials, studies with pure algal metabolites are scarce, limited to those carried out with kahalalide F and fucoxanthin. The majority of clinical trials currently aim to ascertain the effect of algae consumption, as extracts or fractions, on obesity and diabetes.Studies focusing on the preparation of macroalgae extracts and their chemical characterization revealed a large range of seaweed compounds with very interesting biological activities including antitumor, anti-inflammatory, antimicrobial, antidiabetic, antivirus, antihypertensive, fat-lowering, and neuroprotective activities [12][13][14][15].The large volume of studies proving the seaweed compound activities in in vitro systems [16][17][18][19] hints the need for further advancements in the knowledge about macroalgae compound efficiency in living systems (in vivo) and their use in the development of pharmaceuticals. In vitro studies are very relevant and yield very important information, but they only represent the first step of a long process, and the results obtained rarely reveal anything about the effects of a compound in vivo, because the responses observed in vitro can be magnified, diminished, or totally different in a more complex and integrated system. In fact, in vivo studies and clinical trials are those which contribute most to truly understanding the real potential of compounds as future pharmaceuticals.In this regard, the present work intends to present insight into the results obtained in the last few years regarding secondary metabolites, such as phlorotannins, halogenated compounds, fucoxanthin, and fucosterol isolated from macroalgae, involved in in vivo studies and clinical trials, identifying the research opportunities and knowledge gaps, to valorize these compounds and their natural resources. The intention is not to present an exhaustive survey of all published works, but rather a selection of authors based on the following criteria: in-depth studies involving pure compounds most characteristic f...

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“…Brown algae is a kind of macroalgae in the ocean. Fucosterol is a sort of algal phytosterol in ethanol extract of brown algae, which has been proved to have multiple biological activities, including antioxidant [14][15][16], anti-inflammatory [17][18][19], anticancer [20], antimicrobial [21], anti-depression [22], etc. Previous research have reported fucosterol on anti-cervical cancer [20], anti-leukemia [23], anti-colorectal cancer [24], etc., but there are few studies on the mechanisms of fucosterol in treating non-small cell lung cancer, and its potential therapeutic targets and related pathways have not been reported in detail.…”

Section: Introductionmentioning

confidence: 99%

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

Lin

et al. 2020

Preprint

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Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

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Fucosterol attenuates lipopolysaccharide-induced acute lung injury in mice

Cited by 27 publications

References 28 publications

Mogroside IIIE Attenuates LPS‐Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF‐κB Axis via AMPK Activation

Mogroside IIIE Attenuates LPS‐Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF‐κB Axis via AMPK Activation

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

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