Antioxidant and cytotoxic activities of Artemisia monosperma L. and Tamarix aphylla L. essential oils

Essential (volatile) oil from leaves of Artemisia monosperma L. belonging to family Asteraceae, and aerial parts of Tamarix aphylla L. (Athel) belonging to family Tamaricaceae were collected from the desert of Ha'il region, northern region of Saudi Arabia, hydro distilled by Clevenger apparatus and analysed by means of GC-MS techniques. Antioxidant activities of essential oils of A. monosperma and T. aphylla compared with ascorbic acid and butylated hydroxytoluene (BHT) as reference antioxidant compound were determined by method of DPPH radical scavenging assay and ABTS assay. In vitro screening of potential cytotoxicity of essential oils was also evaluated against human promyelocytic leukaemia cell lines (HL60 and NB4). The GC/MS analysis of A. monosperma essential oil resulted in identification of 61 components predominated mainly by β-Pinene as principal component (29.87%) and T. aphylla resulted in identification of 37 components of essential oil predominated mainly by 6,10,14- trimethyl-2-pentadecanone (21.43%) as principal component. Antioxidant activity as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and 2,2 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) increased with increasing essential oil concentrations of A. monosperma and T. aphylla (25, 50, 75, 100 and 200 μg mL-1). The most pronounced increases detected in the high concentrations of the two essential oils. Biologically, essential oil extracts exhibited cytotoxicity effects in dose dependent manner against human promyelocytic leukaemia cell lines (HL60 and NB4). In conclusion, A. monosperma and T. aphylla essential oils could be valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles

Deacetylases and NF-kappaB in redox regulation of cigarette smoke-induced lung inflammation: epigenetics in pathogenesis of COPD

Oxidative stress has been implicated in the pathogenesis of several inflammatory lung disorders including chronic obstructive pulmonary disease (COPD) due to its effect on pro-inflammatory gene transcription. Cigarette smoke-mediated oxidative stress activates NF-κB-dependent transcription of pro-inflammatory mediators either through activation of inhibitor κB-α kinase (IKK) and/or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-κB-co-activator complex formation results in targeted increase in chromatin modifications, such as histone acetylation leading to inflammatory gene transcription. NF-κB-dependent gene expression, at least in part, is regulated by changes in deacetylases such as histone deacetylases (HDACs) and sirtuins. Cigarette smoke and oxidants also alter the levels/activity of HDAC by post-translational modifications and in doing so further induces gene expression of pro-inflammatory mediators. In addition, cigarette smoke/oxidants can reduce glucocorticoid sensitivity by attenuating HDAC2 activity and expression, which may account for the glucocorticoid insensitivity in patients with COPD. Understanding the mechanisms of NF-κB regulation, and the balance between histone acetylation and deacetylation may lead to the development of novel therapies based on the pharmacological manipulation of IKK and deacetylases in lung inflammation and injury

Phytochemical Screening and Antimicrobial Activity of Various Extracts of Aerial Parts of Rhanterium epapposum

Rhanterium epapposum, native to the Arabian Peninsula, is traditionally used to cure skin infections. The objective is to screen the phytochemical content and antimicrobial activity of aqueous, methanol and 80% methanol extracts of aerial parts of R. epapposum. The phytochemical screening of aqueous, methanolic, and 80% methanol extracts of R. epapposum was conducted using gas chromatographymass spectrometry. The antimicrobial activities of the extracts were assessed by well diffusion and microdilution methods. Qualitative phytochemical analysis revealed the presence of 2-methoxy-4-vinylphenol in all three extracts, whereas ethanol, 2-methoxy-, acetate; n-hexadecanoic acid; and 2,3-butanediol are present in higher amount exclusively in the methanol, 80% methanol and aqueous extracts of the aerial parts of R. epapposum, respectively. The highest antibacterial activity was shown by the aqueous extract S. aureus, P. aeruginosa, E. cloacae, and K. pneumoniae, methanolic extract against S. aureus, methicillin-resistant S. aureus, and E. coli, and 80% methanol extract against S. epidermidis, and S. paucimobilis. Interestingly, 80% methanol extracts showed the highest antifungal activity against C. albicans, C. guillermondii, C. vaginalis, C. utilis, and C. tropicalis. The aerial parts of R. epapposum showed broad-spread antimicrobial activity against bacteria and fungi. Especially, the 80% methanol extract showed potent antifungal activity against all the tested fungal strains

SIRT1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease

Rationale: Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Human sirtuin (SIRT1), an antiaging and antiinflammatory protein, is a metabolic NAD+-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins

Targeted disruption of NF-κB1 (p50) augments cigarette smoke-induced lung inflammation and emphysema in mice: a critical role of p50 in chromatin remodeling

NF-κB-mediated proinflammatory response to cigarette smoke (CS) plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The heterodimer of RelA/p65-p50 (subunits of NF-κB) is involved in transactivation of NF-κB-dependent genes, but interestingly p50 has no transactivation domain. The endogenous role of p50 subunit, particularly in regulation of CS-mediated inflammation in vivo, is not known. We therefore hypothesized that p50 subunit plays a regulatory role on RelA/p65, and genetic ablation of p50 (p50−/−) leads to increased lung inflammation and lung destruction in response to CS exposure in mouse. To test this hypothesis, p50-knockout and wild-type (WT) mice were exposed to CS for 3 days to 6 mo, and inflammatory responses as well as air space enlargement were assessed. Lungs of p50-deficient mice showed augmented proinflammatory response to acute and chronic CS exposures as evidenced by increased inflammatory cell influx and proinflammatory mediators release such as monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) compared with WT mice. IKK2 inhibitor (IMD-0354), which reduces the nuclear translocation of RelA/p65, attenuated CS-mediated neutrophil influx in bronchoalveolar lavage fluid and cytokine (MCP-1 and IP-10) levels in lungs of WT but not in p50-deficient mice. Importantly, p50 deficiency resulted in increased phosphorylation (Ser276 and Ser536), acetylation (Lys310), and DNA binding activity of RelA/p65 in mouse lung, associated with increased chromatin remodeling evidenced by specific phosphoacetylation of histone H3 (Ser10/Lys9) and acetylation of H4 (Lys12) in response to CS exposure. Surprisingly, p50-null mice showed spontaneous air space enlargement, which was further increased after CS exposure compared with WT mice. Thus our data showed that p50 endogenously regulates the activity of RelA/p65 by decreasing its phosphoacetylation and DNA binding activity and specific histone modifications and that genetic ablation of p50 leads to air space enlargement in mouse