Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Apaya, Maria Karmella; Lin, Chih‐Yu; Chiou, Ching-Yi; Yang, Chung-Chih; Ting, Chen-Yun; Shyur, Lie‐Fen

doi:10.2119/molmed.2015.00082

Cited by 18 publications

(24 citation statements)

References 47 publications

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“…17 Recently, we also showed that antiinflammatory dLGG effectively prevented endotoxin-induced sepsis in mice partly through modulating oxylipin dynamics. 18 In this study, we demonstrated the in vivo efficacy of dLGG against melanoma lung metastasis by modulating the tumorassociated microenvironment, lipid mediator (oxylipin) secretion and metabolism, and preventing melanoma cell-promoted pulmonary vascular permeability in mice.…”

Section: Introductionmentioning

confidence: 79%

“…18 Protein samples were resolved by 10% SDS-PAGE and then immunoblotted. 18 Protein samples were resolved by 10% SDS-PAGE and then immunoblotted.…”

Section: Western Blottingmentioning

confidence: 99%

“…18 H&E staining and immunohistochemistry followed the published protocol. 18 H&E staining and immunohistochemistry followed the published protocol.…”

Section: Hematoxylin and Eosin (Hande) Staining And Immunohistochemistrymentioning

confidence: 99%

“…18 The organic layer was collected by centrifugation. 18 The organic layer was collected by centrifugation.…”

Section: Oxylipin Profiling In Mouse Serummentioning

confidence: 99%

“…18 The organic layer was collected by centrifugation. 10,18 Statistical analysis Experimental data are expressed as mean AE SD by using PASW Statistics 18. 20 Quantitative profiling of oxylipin metabolome by liquid chromatography-electrospray-ionization tandem mass spectrometry Samples were separated with ACQUITY UPLC BEH C18 column (particle size 1.7 μm, 2.1 × 100 mm, Waters, Milford, MA) at 400 μL/mL flow rate using 25 min gradient for analysis.…”

Section: Oxylipin Profiling In Mouse Serummentioning

confidence: 99%

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Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF‐α‐mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice

Yang

Chang

et al. 2018

Intl Journal of Cancer

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This study demonstrates the bioefficacy and gives mechanistic insights into a plant galactolipid 1,2-di-O-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) against metastatic melanoma using a syngeneic mouse model implanted with B16 melanoma. dLGG-20 (p.o. dLGG 20 mg/kg) and anti-cancer drug CP-2 (i.p. cisplatin 2 mg/kg) treatment significantly inhibited lung metastasis of melanoma in mice 91 and 57%, respectively, as determined by bioluminescence intensity. Moreover, dLGG-20 and CP-2 treatment prolonged mouse mean survival time. dLGG-20 treatment significantly inhibited the expression levels of several molecular markers, that is, PCNA, MMP2, COX-2, VEGF, vimentin, snail, TGF-β, β-catenin, TNF-α, PD-1 and PD-L1 in mouse lung tissues compared to tumor control mice. Significant inhibition of macrophage and neutrophil infiltration and promotion of CD8 + Tc cell recruitment in the lung microenvironment was observed in dLGG-20-treated mice. A LC/MS-based comparative oxylipin metabolomics study showed that dLGG-20 treatment significantly induced (5.0- to 12.8-fold) the 12/15-LOX catalyzed oxylipin products in mouse serum including 17-HDHA from DHA, 15-HEPE from EPA, 8- and 12-HETEs from AA, and CYP450-derived 20-HETE from AA. CP-2 treatment increased 12/15-LOX derived 8-, 11- and 12-HETEs from AA, and CYP450 derived 11,12-EET from AA ad 9,10-DHOME from LA by 5.3- to 8.1-fold. Of note, dLGG and 17-HDHA were more effective than CP in preventing B16 melanoma cell-induced pulmonary vascular permeability in mice through inhibition of TNF-α production, up-regulation of tight junction proteins claudin1 and ZO-2 and deregulation of Src activation. In conclusion, this study shows the novel therapeutic effect of phytoagent dLGG and suggests its potential as a therapeutic agent for metastatic melanoma.

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Section: Introductionmentioning

confidence: 79%

“…18 Protein samples were resolved by 10% SDS-PAGE and then immunoblotted. 18 Protein samples were resolved by 10% SDS-PAGE and then immunoblotted.…”

Section: Western Blottingmentioning

confidence: 99%

“…18 H&E staining and immunohistochemistry followed the published protocol. 18 H&E staining and immunohistochemistry followed the published protocol.…”

Section: Hematoxylin and Eosin (Hande) Staining And Immunohistochemistrymentioning

confidence: 99%

“…18 The organic layer was collected by centrifugation. 18 The organic layer was collected by centrifugation.…”

Section: Oxylipin Profiling In Mouse Serummentioning

confidence: 99%

Section: Oxylipin Profiling In Mouse Serummentioning

confidence: 99%

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Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF‐α‐mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice

Yang

Chang

et al. 2018

Intl Journal of Cancer

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The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke

Li,

et al. 2024

Mol Neurobiol

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ObjectiveStroke has the characteristics of high morbidity, high mortality, high disability rate, and high recurrence rate, which brings great burden of disease. Ischemic stroke (IS) is the most common subtype of stroke, accounting for 71% of all stroke types. The risk factors and pathogenesis of IS are complex and varied due to different IS subtypes. The development of metabolomics technology provides new ideas for the study of the biomarkers and potential pathophysiological mechanisms of IS. MethodsWe included IS patients who visited Xiangya Hospital of Central South University from October 2017 to September 2018 and divided them into two groups based on the TOAST classi cation: large-artery atherosclerosis (LAA) subtype group (n = 87) and small-vessel occlusion (SVO) subtype group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic pro les in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. ResultsWe identi ed 26 differential metabolites and 3 differential metabolic pathways between LAA and SVO subtype IS. A multiple prediction model based on the differential metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes IS patients were related to the tricarboxylic acid cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. ConclusionThe energy metabolism level of SVO subtype IS patients is more active than that of LAA subtype IS patients.

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A unique inflammation-related mechanism by which high-fat diets induce depression-like behaviors in mice

Qin

et al. 2023

Journal of Affective Disorders

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Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway

Cited by 18 publications

References 47 publications

Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF‐α‐mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice

Plant galactolipid dLGG suppresses lung metastasis of melanoma through deregulating TNF‐α‐mediated pulmonary vascular permeability and circulating oxylipin dynamics in mice

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke

A unique inflammation-related mechanism by which high-fat diets induce depression-like behaviors in mice

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