Healing Properties of Some Indian Medicinal Plants against Indomethacin-Induced Gastric Ulceration of Rats

The healing activity of the ethanol extracts of Piper betel, Emblica officinalis, Terminalia bellerica, and Terminalia chebula against the indomethacin-induced stomach ulceration has been studied and compared with that of misoprostol. Compared to autohealing, all the drugs accelerated the healing process, albeit to different extents. The relative healing activities of the extracts was P. betel>E. officinalis>T. bellerica~T. chebula, that correlated well with their in vivo antioxidant and mucin augmenting activities. The excellent healing activity of the extracts of P. betel and E. officinalis indicated a major role of mucin protection and regeneration in the healing of nonsteroidal anti-inflammatory drugs mediated stomach ulceration

Genetic loci associated with plasma phospholipid N-3 fatty acids: A Meta-Analysis of Genome-Wide association studies from the charge consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10-64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10-58) and docosapentaenoic acid (DPA, p = 4×10-154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10-12) and DPA (p = 1×10-43) and lower docosahexaenoic acid (DHA, p = 1×10-15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10-8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries

Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells

HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol

Bioinspired Olefin <i>cis</i>-Dihydroxylation and Aliphatic C–H Bond Hydroxylation with Dioxygen Catalyzed by a Nonheme Iron Complex

A mononuclear iron­(II)-α-hydroxy acid complex [(Tp^Ph,Me)­Fe^II(benzilate)] (Tp^Ph,Me = hydrotris­(3-phenyl-5-methylpyrazol-1-yl)­borate) of a facial tridentate ligand has been isolated and characterized to explore its catalytic efficiency for aerial oxidation of organic substrates. In the reaction between the iron­(II)-benzilate complex and O₂, the metal-coordinated benzilate is stoichiometrically converted to benzophenone with concomitant reduction of dioxygen on the iron center. Based on the results from interception experiments and labeling studies, different iron-oxygen oxidants are proposed to generate in situ in the reaction pathway depending upon the absence or presence of an external additive (such as protic acid or Lewis acid). The five-coordinate iron­(II) complex catalytically <i>cis</i>-dihydroxylates olefins and oxygenates the C–H bonds of aliphatic substrates using O₂ as the terminal oxidant. The iron­(II) complex exhibits better catalytic activity in the presence of a Lewis acid

Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway

The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE2 synthesis and augmenting e-NOS/i-NOS ratio

Syntheses, structures and efficient catalysis for C–C coupling of some benzaldehyde thiosemicarbazone complexes of palladium

Reaction of the 4-R-benzaldehyde thiosemicarbazones (denoted in general as L-R; R = OCH(3), CH(3), H, Cl and NO(2)) with trans-[Pd(PPh(3))(2)Cl(2)] afforded a group of mixed-ligand complexes (denoted in general as 1-R) incorporating a N,S-coordinated thiosemicarbazone. a triphenylphosphine and a chloride. Similar reaction with Na(2)[PdCl(4)] afforded a family of bis-thiosemicarbazone complexes (denoted in general as 2-R), where each ligand is N,S-coordinated. Crystal structures of 1-CH(3), 1-NO(2), 2-OCH(3), 2-NO(2) and L-NO(2) have been determined. In all the complexes the thiosemicarbazones are coordinated to the metal center, via dissociation of the acidic proton, as bidentate N,S-donors forming five-membered chelate rings. With reference to the structure of the uncoordinated thiosemicarbazone, this coordination mode is associated with a conformational change around the C=N bond. All the 1-R and 2-R complexes display intense absorptions in the visible region. Catalytic activity of the 1-R and 2-R complexes towards some C-C coupling reactions (e.g. Suzuki, Heck and Sonogashira) has been examined and while both are found to be efficient catalysts, 1-R is much better catalyst than 2-R