scholarly journals Immune-Enhancement and Anti-Inflammatory Activities of Fatty Acids Extracted from Halocynthia aurantium Tunic in RAW264.7 Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 309 ◽  
Author(s):  
Chaiwat Monmai ◽  
Seok Go ◽  
II-Shik Shin ◽  
Sang You ◽  
Hyungjae Lee ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acids ◽  
Biologically Active ◽  
Raw264.7 Cells ◽  
Macrophage Cells ◽  
Tnf Α ◽  
Immune Enhancement ◽  
Cox 2 ◽  
Anti Inflammatory

Halocynthia aurantium, an edible ascidian species, has not been studied scientifically, even though tunicates and ascidians are well-known to contain several unique and biologically active materials. The current study investigated the fatty acid profiles of the H. aurantium tunic and its immune-regulatory effects on RAW264.7 macrophage cells. Results of the fatty acid profile analysis showed a difference in ratios, depending on the fatty acids being analysed, including those of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). In particular, omega-3 fatty acids, such as eicosatrienoic acid n-3 (ETA n-3), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), were much higher than omega-6 fatty acids. Moreover, the H. aurantium tunic fatty acids, significantly and dose-dependently, increased the NO and prostaglandin E2 (PGE2) production in RAW264.7 cells, for immune-enhancement without cytotoxicity. In addition, these fatty acids regulated the transcription of immune-associated genes, including iNOS, IL-1β, IL-6, COX-2, and TNF-α. These actions were activated and deactivated via Mitogen-activated protein kinase (MAPK)and NF-κB signaling, to regulate the immune responses. Conversely, the H. aurantium tunic fatty acids effectively suppressed the inflammatory cytokine expressions, including iNOS, IL-1β, IL-6, COX-2, and TNF-α, in LPS-stimulated RAW264.7 cells. Productions of COX-2 and PGE2, which are key biomarkers for inflammation, were also significantly reduced. These results elucidated the immune-enhancement and anti-inflammatory mechanisms of the H. aurantium tunic fatty acids in macrophage cells. Moreover, the H. aurantium tunic might be a potential fatty acid source for immune-modulation.

scholarly journals Anti-Inflammatory Effects of Lipids Extracted from Arctoscopus japonicus Eggs on LPS-Stimulated RAW264.7 Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 580
Author(s):  
Weerawan Rod-in ◽  
Chaiwat Monmai ◽  
Sang-min Lee ◽  
Seok-Kyu Jung ◽  
SangGuan You ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cold Water ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Monounsaturated Fatty Acids ◽  
No Production ◽  
Dependent Manner ◽  
Tnf Α ◽  
Anti Inflammatory

Arctoscopus japonicus is a cold-water marine fish. The present study investigated the fatty acid composition of A. japonicus egg lipids and their anti-inflammatory effects on LPS-stimulated RAW246.7 macrophages. The results showed that A. japonicus egg lipids contained primarily polyunsaturated fatty acids (52.9% of the total fatty acid content; mostly eicosapentaenoic acid [EPA, 21.2 ± 0.5%] and docosahexaenoic acid [DHA, 25.9 ± 0.1%]), followed by monounsaturated fatty acids and saturated fatty acids (23.7% and 23.4%, respectively). A. japonicus egg lipids significantly decreased nitric oxide (NO) production and suppressed the expression of immune-associated genes such as iNOS, COX-2, IL-1β, IL-6, and TNF-α LPS-stimulated RAW246.7 macrophages in dose-dependent manner. A. japonicus egg lipids also reduced the phosphorylation levels of NF-κB p-65, p38, ERK1/2, and JNK, key components of the NF-κB and MAPK pathways, suggesting that the lipid-induced anti-inflammatory activity is related to these signaling pathways. These results indicate that the lipids extracted from A. japonicus eggs have potential biofunctions and might be useful for regulating inflammation in macrophages.

Anti-Inflammatory Effects of Canavalia gladiata in Macrophage Cells and DSS-Induced Colitis Mouse Model

2019 ◽  
Vol 47 (07) ◽  
pp. 1571-1588
Author(s):  
Hwa-Jeong Lee ◽  
Jung Up Park ◽  
Rui Hong Guo ◽  
Bok Yun Kang ◽  
In-Kyu Park ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Interleukin 1 ◽  
Raw264.7 Cells ◽  
Mice Model ◽  
Macrophage Cells ◽  
Canavalia Gladiata ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Peritoneal Macrophage Cells

Canavalia gladiata, known as sword bean, has been used as a Chinese traditional medicine for anti-inflammatory effects. However, the action mechanisms of sword bean have not yet been clearly defined. In the present study, the whole parts of a ripened sword bean (RSB) and the green sword bean (GSB) containing bean pod were extracted with ethanol by reflux extraction. The two crude extracts (RSBE and GSBE) from RSB and GSB were validated by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis of gallic acid as a reference chemical. The anti-inflammatory effects of two sword bean extracts were extensively investigated using LPS-stimulated macrophage cells. First, RSBE and GSBE significantly inhibited the production of pro-inflammatory mediators, such as tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-6 (IL-6), prostaglandinE2 (PGE2), and nitric oxide (NO) in LPS-induced RAW264.7 cells. RSBE and GSBE showed no cytotoxicity to RAW264.7 cells and mouse peritoneal macrophage cells. In addition, the overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induced by LPS in RAW264.7 cells was significantly decreased by RSBE and GSBE. Western blotting and immunostaining analysis showed that RSBE and GSBE inhibited the nuclear translocation of NF-[Formula: see text]B subunits, which correlated with the inhibitory effects on inhibitor kappa B (I[Formula: see text]B) degradation. In dextran sulfated sodium (DSS)-induced colitis mice model, RSBE restored body weight, colon length, and the levels of pro-inflammatory cytokines, such as TNF-[Formula: see text], IL-6, interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interferon-[Formula: see text] (IFN-[Formula: see text]). In addition, RSBE significantly suppressed the expression of COX-2, iNOS, and NF-[Formula: see text]B.

scholarly journals Anti-Inflammatory Effects of Berchemia floribunda in LPS-Stimulated RAW264.7 Cells through Regulation of NF-κB and MAPKs Signaling Pathway

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 586
Author(s):  
Hyun Ji Eo ◽  
Jun Hyuk Jang ◽  
Gwang Hun Park
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Activity ◽  
Nuclear Accumulation ◽  
Raw264.7 Cells ◽  
No Production ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Berchemia floribunda (Wall.) Brongn. (BF), which belongs to Rhamnaceae, is a special plant of Anmyeon Island in Korea. BF has been reported to have antioxidant and whitening effects. However, the anti-inflammatory activity of BR has not been elucidated. In this study, we evaluated the anti-inflammatory effect of leaves (BR-L), branches (BR-B) and fruit (BR-F) extracted with 70% ethanol of BR and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. BR-L showed a strong anti-inflammatory activity through the inhibition of NO production. BR-L significantly suppressed the production of the pro-inflammatory mediators such as iNOS, COX-2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells. BR-L suppressed the degradation and phosphorylation of IκB-α, which contributed to the inhibition of p65 nuclear accumulation and NF-κB activation. BR-L obstructed the phosphorylation of MAPKs (ERK1/2, p38 and JNK) in LPS-stimulated RAW264.7 cells. Consequently, these results suggest that BR-L may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory disorders.

Moringa Fruit Inhibits LPS-Induced NO/iNOS Expression through Suppressing the NF-κB Activation in RAW264.7 Cells

2013 ◽  
Vol 41 (05) ◽  
pp. 1109-1123 ◽  
Author(s):  
Hyo-Jin Lee ◽  
Yun-Jeong Jeong ◽  
Tae-Sung Lee ◽  
Yoon-Yub Park ◽  
Whi-Gun Chae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Biologically Active ◽  
Raw264.7 Cells ◽  
No Production ◽  
Dependent Manner ◽  
Fruit Extract ◽  
Tnf Α ◽  
Anti Inflammatory

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

scholarly journals Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3093 ◽  
Author(s):  
Jingyi Hou ◽  
Yu Gu ◽  
Shuai Zhao ◽  
Mengqi Huo ◽  
Shifeng Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Protein Expression ◽  
Therapeutic Agent ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cassia Obtusifolia ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Aurantio-obtusin, an anthraquinone compound, isolated from dried seeds of Cassia obtusifolia L. (syn. Senna obtusifolia; Fabaceae) and Cassia tora L. (syn. Senna tora). Although the biological activities of Semen Cassiae have been reported, the anti-inflammatory mechanism of aurantio-obtusin, its main compound, on RAW264.7 cells, remained unknown. We investigated the anti-inflammatory effect of aurantio-obtusin on lipopolysaccharide- (LPS)-induced RAW264.7 cells in vitro and elucidated the possible underlying molecular mechanisms. Nitric oxide production (NO) and prostaglandin E2 (PGE2) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA. The mRNA expression of nitric oxide synthase (iNOS), COX-2, and the critical pro-inflammatory cytokines (IL-6 and TNF-α) were detected by quantitative real-time PCR. Aurantio-obtusin significantly decreased the production of NO, PGE2, and inhibited the protein expression of COX-2, TNF-α and IL-6, which were similar to those gene expression of iNOS, COX-2, TNF-α and IL-6 (p < 0.01). Consistent with the pro-inflammatory gene expression, the Aurantio-obtusin efficiently reduced the LPS-induced activation of nuclear factor-κB in RAW264.7 cells. These results suggested that aurantio-obtusin may function as a therapeutic agent and can be considered in the further development of treatments for a variety of inflammatory diseases. Further studies may provide scientific evidence for the use of aurantio-obstusin as a new therapeutic agent for inflammation-related diseases.

A high concentration of fatty acids induces TNF-α as well as NO release mediated by the P2X4 receptor, and the protective effects of puerarin in RAW264.7 cells

2017 ◽  
Vol 8 (12) ◽  
pp. 4336-4346 ◽  
Author(s):  
Yun-ming Tu ◽  
Cheng-xin Gong ◽  
Lu Ding ◽  
Xing-zi Liu ◽  
Tao Li ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Raw264.7 Cells ◽  
Protective Effects ◽  
High Concentration ◽  
P2x4 Receptor ◽  
Tnf Α ◽  
No Release

Puerarin exerts its protective effects on high concentration fatty acid-induced TNF-α and NO release in RAW264.7 cells.

scholarly journals Correlation between Fatty Acid Profile and Anti-Inflammatory Activity in Common Australian Seafood by-Products

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155 ◽  
Author(s):  
Tarek Ahmad ◽  
David Rudd ◽  
Michael Kotiw ◽  
Lei Liu ◽  
Kirsten Benkendorff
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Complex Mixture ◽  
Acid Methyl Ester ◽  
Biologically Active ◽  
Inflammatory Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Waste Products ◽  
Anti Inflammatory

Marine organisms are a rich source of biologically active lipids with anti-inflammatory activities. These lipids may be enriched in visceral organs that are waste products from common seafood. Gas chromatography-mass spectrometry and fatty acid methyl ester (FAME) analyses were performed to compare the fatty acid compositions of lipid extracts from some common seafood organisms, including octopus (Octopus tetricus), squid (Sepioteuthis australis), Australian sardine (Sardinops sagax), salmon (Salmo salar) and school prawns (Penaeus plebejus). The lipid extracts were tested for anti-inflammatory activity by assessing their inhibition of nitric oxide (NO) and tumor necrosis factor alpha (TNFα) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse cells. The lipid extract from both the flesh and waste tissue all contained high amounts of polyunsaturated fatty acids (PUFAs) and significantly inhibited NO and TNFα production. Lipid extracts from the cephalopod mollusks S. australis and O. tetricus demonstrated the highest total PUFA content, the highest level of omega 3 (ω-3) PUFAs, and the highest anti-inflammatory activity. However, multivariate analysis indicates the complex mixture of saturated, monounsaturated, and polyunsaturated fatty acids may all influence the anti-inflammatory activity of marine lipid extracts. This study confirms that discarded parts of commonly consumed seafood species provide promising sources for the development of new potential anti-inflammatory nutraceuticals.

scholarly journals Coccomyxa Gloeobotrydiformis Polysaccharide Inhibits Lipopolysaccharide-Induced Inflammation in RAW 264.7 Macrophages

2018 ◽  
Vol 51 (6) ◽  
pp. 2523-2535 ◽  
Author(s):  
Bo Dai ◽  
Dan Wei ◽  
Ning-ning Zheng ◽  
Zhi-hong Chi ◽  
Na Xin ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Raw264.7 Cells ◽  
No Production ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Inflammation plays a vital role in the etiology and pathogenesis of chronic noncommunicable diseases (NCDs), which are the leading health issues throughout the world. Our previous studies verified the satisfactory therapeutic effects of Coccomyxa gloeobotrydiformis (CGD) polysaccharide on several NCDs. In this study, we aimed to investigate the anti-inflammatory effects of CGD polysaccharide, and the corresponding molecular mechanisms, on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Methods: A viability assay and a lactate dehydrogenase (LDH) assay were used to measure the cytotoxic effects of CGD polysaccharide on LPS-stimulated RAW264.7 cells. To investigate the potential anti-inflammatory mechanisms of CGD polysaccharide in LPS-stimulated RAW264.7 cells, nitric oxide (NO) production was determined using a NO assay and the expression of inflammatory mediators (PGE2, iNOS and COX-2), inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and inflammation-related signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1pathways) were observed by western blotting. The translocation of NF-κB p65 was also observed using an immunofluorescent assay. Results: CGD polysaccharide significantly inhibited LPS-induced NO production and PGE2 expression by reducing the expression of iNOS and COX-2. It also suppressed the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, and up-regulated the expression of the anti-inflammatory cytokine IL-10. Further experiments demonstrated that CGD polysaccharide could inhibit inflammatory signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK and JAK/STAT pathways). At the same time, it enhanced the anti-inflammatory pathway Nrf2/HO-1. In addition, CGD polysaccharide did not display any cytotoxic effects, even at a high concentration. Conclusion: Taken together, the results suggest that CGD polysaccharide significantly inhibits LPS-induced inflammation in RAW264.7 cells. This effect lies in its regulatory effects on the signaling pathways MAPK/ NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1.Our findings reveal that CGD polysaccharide has the potential to be used as a relatively safe and effective drug as part of the treatment of NCDs.

Methyl Dehydro-Jasmonate Has Anti-Inflammatory Effect Cells and Its Molecular Targets Mir-155 and NF-Kb Pathway against LPS Stimulation On RAW264.7.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1357-1357
Author(s):  
Hye-Ja Lee ◽  
Hung-The Dang ◽  
Gyeoung-Jin Kang ◽  
Jee H Jung ◽  
Hee-Kyoung Kang ◽  
...  
Keyword(s):  
Methyl Jasmonate ◽  
Mapk Pathway ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2 ◽  
Microbial Products ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Effect

Abstract Abstract 1357 Poster Board I-380 Jasmonic acid and methyl jasmonate are fatty acid-derived cyclopentanones, found in the plants, and play major roles in a defense against insects and disease. Methyl jasmonate suppresses cellular proliferation and induces apoptosis in human and mouse cancer cell lines. Methyl jasmonate increased the life span of EL-4 lymphoma-bearing mice with selective cytotoxicity against lymphoma cells while sparing normal blood lymphocytes. Inflammation is one of the defence mechanisms against pathogens, caused by diverse microbial products. Microbial products are detected by the Toll-like receptors (TLRs) that are expressed at high levels on macrophages and dendritic cells. The complex of the TLRs and their ligand initiates a wide spectrum of responses from phagocytosis to production of a variety of cytokines, which enhance the inflammatory and adaptive immune responses. Of these TLRs, TLR4 recognizes the product of gram-negative bacteria, LPS. LPS stimulated-cells produce inflammatory cytokines (TNF-α and IL-6), and inducible enzymes of iNOS and COX-2. Recent evidence reveal that some microRNAs (miRNAs) play important roles in inflammation; miRNA-146a plays central roles in the negative feedback regulation of IL-1b-induced inflammation and miR-155 enhances the release of inflammatory mediators during the innate immune responses. Our structural analysis shows that methyl jasmonate contains enone group which is a common functional moiety in anti-inflammatory drugs. Our previous works found that methyl jasmonate has anti-inflammatory effects and the related compound methyl dehydro-jasmonate (J2) had the highest anti-inflammatory effect in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells of all synthesized methyl jasmonate analogues. In this study, we wanted to elucidate molecular targets of J2 action in its anti-inflammatory properties. We observed that a LPS stimulation of RAW264.7 cell line also induced known inflammatory markers; TNF-α, IL-6, iNOS and COX-2. Our analysis of miRNAs changes revealed an increase of miR-155 (>8 fold) and miR-146a (>3 fold), but not miR-125b. In a J2 toxicity test on the LPS stimulated RAW264.7 cells, the J2 treatment protected LPS treated RAW264.7 cells starting at 6.25 μM. We then tested J2 effects on various mediators of inflammation. We found that J2 suppressed inductions of TNF-α, IL-6, iNOS and COX-2 at a transcript level in a dose-dependent manner (IC50 = 18∼25 μM) and confirmed it also at a protein level for iNOS and COX-2. We then found that miR-155 induction was inhibited by J2 dose-dependent manner, J2 suppressed miR-146a only at 50 μM. The NF-kB pathway and MAPK pathway are thought to be important mediators of LPS induced inflammation and we show that J2 had significant effects on NF-kB, p65, and IkB while no or minimal effect on JNK, p38, and ERK. In conclusion, the present study demonstrates that J2 supressed LPS stimulation in RAW264.7 cells and it targets miR-155, and NF-kB pathway. In addition, our results also suggest that MAPK pathway may not contribute to the induction of inflammatory markers (i.e. TNF-α, IL-6, iNOS, and COX-2). Disclosures No relevant conflicts of interest to declare.

scholarly journals The Mechanisms of the Anti-Inflammatory and Anti-Apoptotic Effects of Omega-3 Polyunsaturated Fatty Acids during Methotrexate-Induced Intestinal Damage in Cell Line and in a Rat Model

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 888
Author(s):  
Tal Koppelmann ◽  
Yulia Pollak ◽  
Yoav Ben-Shahar ◽  
Gregory Gorelik ◽  
Igor Sukhotnik
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cell Viability ◽  
Rat Model ◽  
Intestinal Damage ◽  
Omega 3 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.

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