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Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from Padina boryana as a Potent Protector, Activated via NF-?B/MAPK Pathways and Nrf2/HO-1 Involvement.

ABSTRACT: Fucosterol is a phytosterol that is abundant in marine brown algae and is a renowned secondary metabolite. However, its ability to protect macrophages against particulate matter (PM) has not been clarified with regard to inflammation; thus, this study aimed to illustrate the above. Padina boryana, a brown algae that is widespread in Indo-Pacific waters, was applied in the isolation of fucosterol. Isolation was conducted using silica open columns, while identification was assisted with gas chromatography-mass spectroscopy (GC-MS) and NMR. Elevated levels of PM led the research objectives toward the implementation of it as a stimulant. Both inflammation and oxidative stress were caused due the fact of its effect. RAW 264.7 macrophages were used as a model system to evaluate the process. It was apparent that the increased NO production levels, due to the PM, were mediated through the inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines (i.e., interleukin-6 (IL-6), interleukin-1 (IL-1?) and tumor necrosis factor-? (TNF-?), including prostaglandin E2 (PGE₂)). Further, investigations provided solid evidence regarding the involvement of NF-?B and mitogen-activated protein kinases (MAPKs) in the process. Oxidative stress/inflammation which are inseparable components of the cellular homeostasis were intersected through the Nrf2/HO-1 pathway. Conclusively, fucosterol is a potent protector against PM-induced inflammation in macrophages and hence be utilized as natural product secondary metabolite in a sustainable manner.

SUBMITTER: Jayawardena TU

PROVIDER: S-EPMC7763233 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from <i>Padina boryana</i> as a Potent Protector, Activated via NF-κB/MAPK Pathways and Nrf2/HO-1 Involvement.

Jayawardena Thilina U TU Sanjeewa K K Asanka KKA Lee Hyo-Geun HG Nagahawatta D P DP Yang Hye-Won HW Kang Min-Cheol MC Jeon You-Jin YJ

Marine drugs 20201209 12

Fucosterol is a phytosterol that is abundant in marine brown algae and is a renowned secondary metabolite. However, its ability to protect macrophages against particulate matter (PM) has not been clarified with regard to inflammation; thus, this study aimed to illustrate the above. <i>Padina boryana,</i> a brown algae that is widespread in Indo-Pacific waters, was applied in the isolation of fucosterol. Isolation was conducted using silica open columns, while identification was assisted with gas ...[more]

PMID: 33317054

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Project description:As part of our continuous effort to find potential anti-inflammatory agents from endophytic fungi, a Fusariumsolani strain, isolated from the plant Aponogetonundulatus Roxb., was investigated. Cerevisterol (CRVS) was identified from endophytic fungi, a Fusariumsolani strain, and moreover exhibited anti-inflammatory activity. However, the underlying mode of action remains poorly understood. The aim of this study is to reveal the potential mechanisms of CRVS against inflammation on a molecular level in LPS-activated RAW 264.7 peritoneal macrophage cells. CRVS was isolated from F.solani and characterized based on spectral data analysis. The MTT assay was performed to measure cell viability in CRVS-treated macrophages. Anti-inflammatory activity was assessed by measurement of nitric oxide (NO) and prostaglandin E2 (PGE2) levels, as well as the production of various cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and -6 (IL-6) in LPS-stimulated macrophages. RT-PCR and immunoblotting analyses were done to examine the expression of various inflammatory response genes. A reporter gene assay was conducted to measure the level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1 (AP-1) transactivation. CRVS suppresses the LPS-induced production of NO and PGE2, which is a plausible mechanism for this effect is by reducing the expression of iNOS and COX-2. CRVS also decreases the expression of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β. CRVS halted the nuclear translocation of NF-κB by blocking the phosphorylation of inhibitory protein κBα (IκBα) and suppressing NF-κB transactivation. The mitogen-activated protein kinases (MAPK) signaling pathways are also suppressed. CRVS treatment also inhibited the transactivation of AP-1 and the phosphorylation of c-Fos. Furthermore, CRVS could induce the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by down-regulating Kelch-like ECH-associated protein 1 (Keap-1) and up-regulating hemeoxygenases-1 (HO-1) expression. The results suggest that CRVS acts as a natural agent for treating inflammatory diseases by targeting an MAPK, NF-κB, AP-1, and Nrf2-mediated HO-1 signaling cascade.

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Dataset Information

Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from Padina boryana as a Potent Protector, Activated via NF-?B/MAPK Pathways and Nrf2/HO-1 Involvement.

Publications

Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from <i>Padina boryana</i> as a Potent Protector, Activated via NF-κB/MAPK Pathways and Nrf2/HO-1 Involvement.

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