Activating endogenous resolution pathways by soluble epoxide hydrolase inhibitors for the management of COVID‐19

Kang

et al. 2022

Foods

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines and is an important fishery resource of Jeju Island. In this study, we performed a preliminary study on anti-inflammatory effect of 70% ethanol extract obtained from T. cornutus viscera (TVE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and zebrafish embryos in vivo. TVE reduced the production of LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) without any toxic effects. TVE also decreased the protein expression of LPS-induced inducible NO synthase and cyclooxygenase-2 and suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Furthermore, mechanistic studies indicated that TVE suppressed c-Jun N-terminal kinase phosphorylation and nuclear factor-kB activation. In zebrafish embryos, TVE did not show developmental toxicity based on the survival rate and cell death findings. In LPS-stimulated zebrafish embryos, TVE suppressed NO production and cell death. In conclusion, the result from this preliminary study showed TVE has a potential anti-inflammatory property that can be exploited as a functional food ingredient.

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effect of Turbo cornutus Viscera Ethanolic Extract against Lipopolysaccharide-Stimulated Inflammatory Response via the Regulation of the JNK/NF-kB Signaling Pathway in Murine Macrophage RAW 264.7 Cells and a Zebrafish Model: A Preliminary Study

Kang

et al. 2022

Foods

“…Among the individual markers, 15(S)-HETE is considered a major metabolite from arachidonic acid from the 15-lipoxygenase pathway [36], and 13-oxoODE that is putatively linked to the maturation of reticulocytes to erythrocytes through the activity of 15-LOX [37][38][39][40][41]. From these eicosanoid inflammatory biomarkers, some have already been associated with dysregulation due to SARS-CoV2, and a subset of them are known to be formed in macrophages during the response to infection [42].…”

Section: Covid Effect On Specific Oxylipinsmentioning

confidence: 99%

Oxylipin concentration shift in exhaled breath condensate (EBC) of SARS-CoV-2 infected patients

Borras,

McCartney,

Rojas

et al. 2023

J. Breath Res.

Infection of airway epithelial cells with severe acute respiratory coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and lung injury with hypoxia. It is challenging to sample the lower airways non-invasively and the capability to identify a highly representative specimen that can be collected in a non-invasive way would provide opportunities to investigate metabolomic consequences of COVID-19 disease. In the present study, we performed a targeted metabolomic approach using liquid chromatography coupled with high resolution chromatography (LC-MS) on exhaled breath condensate (EBC) collected from hospitalized COVID-19 patients (COVID+) and negative controls, both non-hospitalized and hospitalized for other reasons (COVID-). We were able to noninvasively identify and quantify inflammatory oxylipin shifts and dysregulation that may ultimately be used to monitor COVID-19 disease progression or severity and response to therapy. The results indicate ten targeted oxylipins with significant differences between SAR-CoV-2 infected EBC samples and negative control samples. These compounds were prostaglandins A2 and D2, LXA4, 5-HETE, 12-HETE, 15-HETE, 5-HEPE, 9-HODE, 13-oxoODE and 19(20)-EpDPA, which are associated with specific pathways (i.e. P450, COX, 15-LOX) related to inflammatory and oxidative stress processes. Moreover, all these compounds were up-regulated in the COVID+ group, meaning their concentrations were higher in subjects with SAR-CoV-2 infection. Given that many COVID symptoms are inflammatory in nature, this is interesting insight into the pathophysiology of the disease. Breath monitoring of these and other EBC metabolites presents an interesting opportunity to monitor key indicators of disease progression and severity.

“…It is hypothesized that AA-derived EETS could attenuate SARS-CoV2-induced hyperinflammation. It has been proposed that sEH inhibitors could be utilized in SARS-CoV2 (e.g., GSK-2256294) and other respiratory infections [198,199]. Eicosanoid signaling is tied to immune function, and therefore further research is critical to understand the basis of various drug classes effects on healthy and pathological lipidome profiles.…”

Section: Therapeutic Applicationsmentioning

confidence: 99%

Lipidomics in Understanding Pathophysiology and Pharmacologic Effects in Inflammatory Diseases: Considerations for Drug Development

et al. 2022

The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade. This has unlocked the power of metabolomics/lipidomics allowing the dynamic characterization of metabolic systems. Lipidomics is a subset of metabolomics for multianalyte identification and quantification of endogenous lipids and their metabolites. Lipidomics-based technology has the potential to drive novel biomarker discovery and therapeutic development programs; however, appropriate standards have not been established for the field. Standardization would improve lipidomic analyses and accelerate the development of innovative therapies. This review aims to summarize considerations for lipidomic study designs including instrumentation, sample stabilization, data validation, and data analysis. In addition, this review highlights how lipidomics can be applied to biomarker discovery and drug mechanism dissection in various inflammatory diseases including cardiovascular disease, neurodegeneration, lung disease, and autoimmune disease.