scholarly journals Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 207 ◽  
Author(s):  
Hanaa Zbakh ◽  
Eva Zubía ◽  
Carolina de los Reyes ◽  
José M. Calderón-Montaño ◽  
Miguel López-Lázaro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Therapeutic Potential ◽  
A549 Cells ◽  
Brown Seaweed ◽  
Normal Lung ◽  
Cytotoxic Activities ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1–8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1–8 significantly reduced the production of TNF-α, IL-6, and IL-1β, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1–8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer.

scholarly journals Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells

2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  
Keyword(s):  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Scutellaria Baicalensis Georgi ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Clinical Benefits ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.

scholarly journals The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1212
Author(s):  
Getinet M. Adinew ◽  
Equar Taka ◽  
Patricia Mendonca ◽  
Samia S. Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Option ◽  
Mesenchymal Transition ◽  
Anticancer Effects

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

Anti-inflammatory Effects ofScoparia dulcisL. and Betulinic Acid

2011 ◽  
Vol 39 (05) ◽  
pp. 943-956 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Wen-Huang Peng ◽  
Tai-Hui Chiu ◽  
Shang-Chih Lai ◽  
Chao-Ying Lee
Keyword(s):  
Betulinic Acid ◽  
High Performance ◽  
Ethanol Extract ◽  
Paw Edema ◽  
Scoparia Dulcis ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analytical Result

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

scholarly journals N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart
Keyword(s):  
Human Health ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Primary Role ◽  
Necrosis Factor Alpha ◽  
Biochemical Basis ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

scholarly journals Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 540-552 ◽  
Author(s):  
Hany H. Arab ◽  
Samir A. Salama ◽  
Tamer M. Abdelghany ◽  
Hany A. Omar ◽  
El-Shaimaa A. Arafa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mapk Pathway ◽  
Lipid Peroxide ◽  
Mitogen Activated Protein Kinase ◽  
Camel Milk ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

Design and Synthesis of Novel Ibuprofen Derivatives as Selective COX-2 inhibitors and potential anti-inflammatory agents: Evaluation of PGE2, TNF-α, IL-6 and histopathological study

2021 ◽  
Vol 17 ◽  
Author(s):  
Peter Amir Halim ◽  
Hala Bakr El-Nassan ◽  
Yara Sayed El-Dash
Keyword(s):  
Carboxylic Acid ◽  
Gastric Mucosa ◽  
Docking Simulation ◽  
Histopathological Study ◽  
Acid Moiety ◽  
Rat Serum ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Background: The reported binding mode of ibuprofen in the COX-2 binding site indicated that the carboxylic group binds with Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel and does not extend into the pocket. This accounted for the non-selectivity of ibuprofen. Based on this fact, we assumed that extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups carrying H-bonding functions might increase the selectivity and reduce the side effects of ibuprofen while maintaining its analgesic and anti-inflammatory activities. Objective: In this work, four series of ibuprofen derivatives were designed and prepared. The compounds were designed by increasing the length of the carboxylate group along with the incorporation of large hydrophobic groups. Method: Four series of ibuprofen derivatives were synthesized starting from ibuprofen. Their chemical structure was confirmed by spectral data. All the compounds were tested for their COX inhibitory activity. Results : The best COX-2 activity and selectivity were obtained with compounds 5c and 5d, which were subjected to further in vivo testing (carrageenan-induced paw edema, rat serum PGE2, TNF- α and IL-6, hot plate latency test) to investigate their anti-inflammatory and analgesic activities as well as their effects on the gastric mucosa. The anti-inflammatory activity of both compounds was comparable to that of ibuprofen, diclofenac, and indomethacin. Both compounds suppressed the production of PGE2 as well as the rat serum concentrations of both TNF-α and IL-6. This potent anti-inflammatory and analgesic behavior was not accompanied by any effect on the gastric mucosa. Docking simulation studies of the two compounds explained the higher selectivity for the COX-2 enzyme. Conclusion: Potent and selective ibuprofen derivatives can be successively obtained by extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups with H-bonding functions.

scholarly journals Protective effects of Panax notoginseng saponins in a rat model of severe acute pancreatitis occur through regulation of inflammatory pathway signaling by upregulation of miR-181b

2018 ◽  
Vol 32 ◽  
pp. 205873841881863
Author(s):  
Ming-wei Liu ◽  
Yun-qiao Huang ◽  
Ya-ping Qu ◽  
Dong-mei Wang ◽  
Deng-yun Tang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Therapeutic Potential ◽  
Sodium Taurocholate ◽  
Panax Notoginseng ◽  
Serum Levels ◽  
Panax Notoginseng Saponins ◽  
Tnf Α ◽  
Anti Inflammatory

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

scholarly journals Peran Kurkumin Sebagai Terapi Pada Osteoartritis

2020 ◽  
Vol 2 (1) ◽  
pp. 106-110
Author(s):  
Rilianda Abelira
Keyword(s):  
Peptic Ulcer ◽  
Side Effects ◽  
Old Age ◽  
Cyclooxygenase 2 ◽  
Tnf Α ◽  
The World ◽  
Inflammatory Drugs ◽  
Digestive Disorders ◽  
Cox 2 ◽  
Anti Inflammatory

Osteoartritis (OA) merupakan salah satu penyakit penyakit degeneratif atau geriatri yang disebabkan adanya inflamasi yang melibatkan kartilago, lapisan sendi, ligamen, dan tulang yang akibatnya dapat menyebabkan nyeri dan kekakuan pada sendi. Epidemiologi OA di didunia sekitar 15% dengan usia diatas 65-75 dan diperkirakan pada tahun 2020 penderita osteoarthritis akan meningkat 11,6 juta penderita. Kejadian OA di Indonesia dari tahun 1990 hingga 2010 telah mengalami peningkatan sebanyak 44,2% dan berdasarkan usia di Indonesia cukup tinggi dengan 65% pada usia tua (lansia) atau lebih dari 61 tahun. Pengobatan secara farmakologis untuk OA dengan menggunakan Obat Anti Inflamasi Non-Steroid (OAINS) salah satu contohnya adalah meloksikam. Namun, efek samping penggunaan OAINS dapat menimbulkan beberapa masalah seperti timbulnya ulkus peptikum dan gangguan pencernaan. Hal ini menyebabkan sedang dikembangkannya pengobatan herbal untuk OA yang harapannya dapat menjadi pengobatan utama dalam mengatasi OA dengan menggunakan kurkumin. Kurkumin berperan sebagai antiinflamasi dalam kunyit putih dengan menurunkan aktivitas cyclooxygenase 2(COX-2), lipoxygenase dan menghambat produksi sitokin seperti TNF-α, interleukin (IL). Osteoarthritis (OA) is a degenerative or geriatric disease that is caused by inflammation involving cartilages, joint lining, ligaments, and bones which can cause pain and stiffness in the joints. Epidemiology of OA in the world around 15% with ages above 65-75 and it is estimated in 2020, osteoarthritis will increase by 11.6 million. The incidence of OA in Indonesia from 1990 to 2010 has increased by 44.2% and by age in Indonesia is quite high with 65% in old age (elderly) or more than 61 years. Treatment for OA is using non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam. However, side effects of NSAID use can cause several problems such as the emergence of peptic ulcer and digestive disorders. This has led to the development of herbal treatments for OA which hopes to become the main treatment in overcoming OA by using curcumin. Curcumin acts as an anti-inflammatory in white turmeric by reducing the activity of cyclooxygenase 2 (COX-2), lipoxygenase and inhibiting the production of cytokines such as TNF-α, interleukin (IL).

scholarly journals Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 107-121
Author(s):  
Nghia Trong Vo ◽  
Eiichi Kusagawa ◽  
Kaori Nakano ◽  
Chihiro Moriwaki ◽  
Yasunobu Miyake ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Lung Adenocarcinoma ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Lung Adenocarcinoma A549

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.

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