scholarly journals Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6757
Author(s):  
Payungsak Tantipaiboonwong ◽  
Wittaya Chaiwangyen ◽  
Maitree Suttajit ◽  
Napapan Kangwan ◽  
Sirichat Kaowinn ◽  
...  

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.

Author(s):  
Chakkrit Khanaree ◽  
◽  
Wanisa Punfa ◽  
Payungsak Tantipaiboonwong ◽  
Maitree Suttajit ◽  
...  

Abstract Thai perilla (Perilla frutescens) extracts, which contain a substantial quantity of bioactive substances including phenolics and flavonoids, have shown marked anti-inflammatory activities in several investigated models. In the present study, the effect of perilla seed extract (PSE) and seed meal extract (PSME) on TNF-α-induced inflammatory response in human lung adenocarcinoma A549 cells was investigated. The total phenolic and flavonoid contents in PSME was lower than PSE. Markedly, rosmarinic acid was identified as the main constituent in both extracts. However, the DPPH and ABTS assays indicated that the antioxidant capacity of PSME was equal to PSE. Moreover, the iron-binding activity of PSE and PSME were exhibited by complex formation with Fe3+-NTA, indicating that the extracts may inhibit hydroxyl radical production via Fenton reaction. In vitro cytotoxicity analysis showed that both PSE or PSME co-treated with TNF-α, at 24 h exposure, were not toxic to the A549 cells. Interestingly, PSE and PSME dramatically exhibited an anti-inflammatory activity by inhibiting the mRNA expression of pro-inflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α, but did not influence iNOS and COX-2 mRNA expressions. Moreover, both extracts significantly reduced reactive oxygen species (ROS) production in TNF-α-induced A549 cells. The findings presented in this paper suggest that PSE and PSME could mitigate TNF-α-mediated inflammatory responses via limiting pro-inflammatory cytokine expressions and decreasing ROS production. Thus, perilla seed and seed meal, the by-product of a perilla seed oil cold-pressed extraction process, could be developed as food supplements or functional foods for the prevention of inflammation-induced lung carcinogenesis development. Keywords: Human lung adenocarcinoma cell line, Inflammation, Perilla seed, Perilla seed meal, Tumor necrosis factor-alpha (TNF-α)


Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4100 ◽  
Author(s):  
Chanatip Ooppachai ◽  
Pornngarm Limtrakul (Dejkriengkraikul) ◽  
Supachai Yodkeeree

Numerous studies have indicated that tumor necrosis factor-alpha (TNF-α) could induce cancer cell survival and metastasis via activation of transcriptional activity of NF-κB and AP-1. Therefore, the inhibition of TNF-α-induced NF-κB and AP-1 activity has been considered in the search for drugs that could effectively treat cancer. Dicentrine, an aporphinic alkaloid, exerts anti-inflammatory and anticancer activities. Therefore, we investigated the effects of dicentrine on TNF-α-induced tumor progression in A549 lung adenocarcinoma cells. Our results demonstrated that dicentrine effectively sensitizes TNF-α-induced apoptosis in A549 cells when compared with dicentrine alone. In addition, dicentrine increases caspase-8, -9, -3, and poly (ADP-ribose) polymerase (PARP) activities by upregulating the death-inducing signaling complex and by inhibiting the expression of antiapoptotic proteins including cIAP2, cFLIP, and Bcl-XL. Furthermore, dicentrine inhibits the TNF-α-induced A549 cells invasion and migration. This inhibition is correlated with the suppression of invasive proteins in the presence of dicentrine. Moreover, dicentrine significantly blockes TNF-α-activated TAK1, p38, JNK, and Akt, leading to reduced levels of the transcriptional activity of NF-κB and AP-1. Taken together, our results suggest that dicentrine could enhance TNF-α-induced A549 cell death by inducing apoptosis and reducing cell invasion due to, at least in part, the suppression of TAK-1, MAPK, Akt, AP-1, and NF-κB signaling pathways.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1090
Author(s):  
Komsak Pintha ◽  
Wittaya Chaiwangyen ◽  
Supachai Yodkeeree ◽  
Maitree Suttajit ◽  
Payungsak Tantipaiboonwong

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.


BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 107-121
Author(s):  
Nghia Trong Vo ◽  
Eiichi Kusagawa ◽  
Kaori Nakano ◽  
Chihiro Moriwaki ◽  
Yasunobu Miyake ◽  
...  

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.


2018 ◽  
Vol 45 (3) ◽  
pp. 917-934 ◽  
Author(s):  
Fangqiong Li ◽  
Dongxiao Zhao ◽  
Suwen Yang ◽  
Juan Wang ◽  
Qin Liu ◽  
...  

Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatography-mass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.


2003 ◽  
Vol 68 (3) ◽  
pp. 207-212 ◽  
Author(s):  
E.M Kurowska ◽  
G.K Dresser ◽  
L Deutsch ◽  
D Vachon ◽  
W Khalil

2014 ◽  
Vol 1033-1034 ◽  
pp. 777-780
Author(s):  
Xu Dong Wang ◽  
Xi Liu ◽  
Xing Yu Zhao ◽  
Wei Jie Zhu ◽  
Jun Wang

Unsaturated free fatty acids (UFFAs), which are rich inα-linolenic and omega-3 fatty acids, were obtained by alkali hydrolysis and urea complexation methods from perilla seed oil and used as the acyl donor to produce structured triacylglycerols (STAGs) catalyzed by Lipozyme RM IM. The results indicated that the content ofα-linolenic acid was increased to 73.16 % after urea complexation methods. The highest incorporation rate ofα-linolenic acid was 58.78 %, which were achieved under the optimum conditions: a molar mass ratio of tripalmitin to UFFAs of 1:12, a reaction time of 48 h and a temperature of 60 °C.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 307
Author(s):  
Kanokkarn Phromnoi ◽  
Maitree Suttajit ◽  
Chalermpong Saenjum ◽  
Pornngarm Limtrakul (Dejkriengkraikul)

The aim of this study is to determine antioxidant and anti-inflammatory activities relating to the antiosteoporosis effects of various perilla seed meal (PSM) fractions. The remaining waste of perilla seed obtained from cold oil compression was extracted with 70% ethanol and sequentially fractionated according to solvent polarity with hexane, dichloromethane, ethyl acetate, and water. The results indicated that the seed-meal ethyl acetate fraction (SMEF) exhibited the highest antioxidant and anti-inflammatory activities, and rosmarinic acid (RA) content. The signaling pathways induced by the receptor activator of the nuclear factor kappa B (NF-κB) ligand (RANKL) that trigger reactive oxygen species (ROS) and several transcription factors, leading to the induction of osteoclastogenesis, were also investigated. The SMEF clearly showed attenuated RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and TRAP activity. A Western blot analysis showed that the SMEF significantly downregulated RANKL-induced NF-κB, AP-1 activation, and the nuclear factor of activated T-cell 1 (NFATc1) expression. SMEF also suppressed RANKL-induced osteoclast-specific marker gene-like MMP-9 using zymography. Furthermore, the SMEF showed inhibition of RANKL-induced ROS production in RAW 264.7 cells. The results suggest that the SMEF, which contained high quantities of RA, could be developed as a natural active pharmaceutical ingredient for osteoclastogenic protection and health promotion.


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