Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene

Abstract

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer. However, few studies have been carried out regarding the anti-inflammatory effects of this class of compounds. Thereby, the aim of this study was to evaluate the anti-inflammatory activity of 1-nitro-2-phenylethene (NPe) using in vitro and in vivo assays. Firstly, the potential anti-inflammatory activity of NPe was evaluated by measuring TNF-α produced by human macrophages stimulated with lipopolysaccharide (LPS). NPe at non-toxic doses opposed the inflammatory effects induced by LPS stimulation, namely production of the inflammatory cytokine TNF-α and activation of NF-κB and ERK pathways (evaluated by phosphorylation of inhibitor of kappa B-alpha [IκB-α] and extracellular signal-regulated kinase 1/2 [ERK1/2], respectively). In a well-established model of acute pleurisy, pretreatment of LPS-challenged mice with NPe reduced neutrophil accumulation in the pleural cavity. This anti-inflammatory effect was associated with reduced activation of NF-κB and ERK1/2 pathways in NPe treated mice as compared to untreated animals. Notably, NPe was as effective as dexamethasone in both, reducing neutrophil accumulation and inhibiting ERK1/2 and IκB-α phosphorylation. Taken together, the results suggest a potential anti-inflammatory activity for NPe via inhibition of ERK1/2 and NF-κB pathways on leukocytes.

C-X-C-Chemokine-Receptor-Type-4 Inhibitor AMD3100 Attenuates Pulmonary Inflammation and Fibrosis in Silicotic Mice

“…Controlling neutrophil numbers via apoptosis can alleviate tissue injury. 35 Neutrophils secrete MPO to delay their own apoptosis and promote their accumulation through the ERK and Akt pathways. 36 , 37 We showed that MPO expression is upregulated in lung tissue after CS exposure and that this CS-induced upregulation is reversed by AMD3100 treatment.…”

Recent advancement in drug development of nitro(NO2)‐heterocyclic compounds as lead scaffolds for the treatment of Mycobacterium tuberculosis

“…Various nitro(NO 2 )‐based analogues are privileged moieties. These analogues have a wide range of biological activities, including anti‐kinetoplastid (Rodriguez Arce et al, 2017; Brancaglion et al, 2018; Papadopoulou et al, 2012; Elias et al, 2016; Papadopoulou, Bloomer, Rosenzweig, Arena, et al, 2014, Papadopoulou et al, 2015, Papadopoulou et al, 2016; Patterson & Wyllie, 2014; Scarim & Chin, 2019; Silva et al, 2016), anthelmintic (Balaji et al, 2014; Dutta, 2014; Fonseca‐Berzal et al, 2016; Moreno & Docampo, 1985; Satyendra et al, 2015), anti‐malarial (Bekhit et al, 2012; Dohutia et al, 2017; Labaied et al, 2004; Malebo et al, 2020; Maroziene et al, 2019; Roberts et al, 2017), antifungal (Kang et al, 2019; Sadeghpour et al, 2017; Zhu et al, 2017), anti‐proliferative (Ahmad et al, 2007; Chinnapaka et al, 2019; Cho et al, 2020; Cuartas et al, 2019; Dunlap et al, 2008; Sakanyan et al, 2014; Shimamura et al, 2003), antimicrobial (Abd El‐Salam et al, 2015; Alasmary et al, 2015; El Azab & Elkanzi, 2020; El‐Hossary et al, 2018; Kozłowska et al, 2019; Kucerova‐Chlupacova et al, 2016; Mladenović et al, 2010; Serban et al, 2018; Sivasankerreddy et al, 2018; Teran et al, 2019), anti‐Alzheimer (Semenov et al, 2020), anti‐inflammatory (El‐Haggar & Al‐Wabli, 2015; Januario et al, 2018; Liu et al, 2019; Rubbo, 2013; Sugimoto et al, 2017; Theodosis‐Nobelos et al, 2020; Tratrat et al, 2021; Tseng et al, 2018), antioxidant (Alshibl et al, 2020; Gallardo et al, 2016…”

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice

“…The assays were performed according to Sugimoto et al [44] using human monocyte-like cell line THP-1 obtained from ATCC. THP-1 cells were cultured in RPMI 1640 medium supplemented with 10 % v/v heat-inactivated FBS and antibiotics (100 µg/mL streptomycin and 100 U/mL penicillin).…”

“…Western blot analyses THP-1 cells were washed with PBS and the whole-cell extracts were prepared as previously described [44,45]. Protein concentrations were quantified with Bradford reagent.…”