Anticancer potential of rhamnocitrin 4′-β-d-galactopyranoside against N-diethylnitrosamine-induced hepatocellular carcinoma in rats

The hepatoprotective activity of flavonoid rhamnocitrin 4′-β-d-galactopyranoside (RGP) obtained from leaves of Astragalus hamosus L. against N-diethylnitrosamine (DENA)-induced hepatic cancer in Wistar albino rats was evaluated. Hepatic cancer in rats was induced by single-dose intraperitoneal administration of DENA (200 mg/kg). Induction of hepatic cancer was confirmed after 7 days of DENA administration by measurement of elevated level of serum α-feto protein (AFP). Administration of DENA in a single dose lofted the levels of serum biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein and AFP. Antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and lipid per oxidation (LPO) were annealed significantly by administration of RGP in a dose-dependant manner. The histopathological examination of rat liver section was found to reinforce the biochemical observations significantly. It was observed that a substantial and dose-dependent reversal of DENA-diminished activity of antioxidant enzymes like SOD, CAT, GPx, GST and the reduced DENA-elevated level of LPO with a marked change. Any elevation in the levels of serum markers along with suppression of free radical formation by scavenging the hydroxyl radicals is significantly prevented by RGP. It also modulates the levels of LPO and perceptibly increases the endogenous antioxidant enzymes level in DENA-induced hepatocellular carcinogenesis. The findings suggest that RGP prevents hepatocellular carcinoma by suppressing the marked increase in the levels of serum marker enzymes, and suppresses the free radical by scavenging hydroxyl radicals.     

Chemical composition and antifeedant activity of some aromatic plants against pine weevil (Hylobius abietis)

The pine weevil Hylobius abietis is an important pest causing severe damage to conifer seedlings in reforestation areas in Europe and Asia. Plants that have no evolutionary history with the pine weevil are of special interest in the search for compounds with a strong antifeedant activity. Thus, the essential oils of nine aromatic plants, viz Amomum subulatum, Cinnamomum tamala, Curcuma longa, Laurus nobilis, Ocimum basilicum, Origanum majorana, Origanum vulgare, Syzygium aromaticum and Trachyspermum ammi were extracted by hydrodistillation. The essential oil constituents were identified by gas chromatography–mass spectrometry, and antifeedant properties towards the pine weevil were assessed using choice feeding bioassay. The essential oils of C. longa, O. majorana, S. aromaticum and T. ammi showed an excellent antifeedant activity towards the pine weevil for 24 hr, whereas the essential oil of other plants showed the activity for 6 hr. There was a positive correlation between the amount of benzenoid compounds and the antifeedant activity of the essential oils. This study suggests that pine weevil non-host plant compounds have potential to be used for the protection of seedlings against pine weevil feeding. However, further study will be needed to explore the antifeedant activity of individual components and oils in the laboratory as well as in the field.     

Juliflorine: A potent natural peripheral anionic-site-binding inhibitor of acetylcholinesterase with calcium-channel blocking potential, a leading candidate for Alzheimer’s disease therapy

The alkaloid juliflorine (1) from Prosopis juliflora inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC₅₀ values 0.42 and 0.12 μM, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that the nature of inhibition was purely of non-competitive type with K_i values 0.4 and 0.1 μM, against AChE and BChE, respectively. By molecular docking studies compound 1 was found to be ideally spaced inside the aromatic gorge of AChE with rings A/B remaining at the top and rings C/D penetrating deep into the gorge, that might be due to the greater hydrophobicity of rings C/D as compared to rings A/B, allowing their simultaneous interaction with the peripheral anionic and quaternary ammonium-binding sites. The 1-AChE complex was found to be stabilized by hydrophobic contacts, hydrogen bonding, and π-π stacking between the compound 1 and amino acid residues of the aromatic gorge of AChE. Amino acid residues Tyr70, Asp72, Tyr121, Trp279, and Tyr334 of the peripheral anionic site (PAS) of AChE were found to be exclusively involved in the hydrophobic contacts with compound 1 that might be responsible for the competitive mode of inhibition. Compound 1 also showed dose-dependent (30-500 μg/mL) spasmolytic and Ca²⁺-channel blocking activities in isolated rabbit jejunum preparations. The cholinesterase inhibitory potential along with calcium-channel blocking activity of compound 1 and safe profile in human neutrophils viable assay could make it a possible drug candidate for Alzheimer’s disease.     

Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease

Hyperphosphorylated tau, which is the major protein of the neurofibrillary tangles in Alzheimer's disease brain, is most probably the result of an imbalance of tau kinase and phosphatase activities in the affected neurons. By using metabolically competent rat brain slices as a model, we found that selective inhibition of protein phosphatase 2A by okadaic acid induced an Alzheimer-like hyperphosphorylation and accumulation of tau. The hyperphosphorylated tau had a reduced ability to bind to microtubules and to promote microtubule assembly in vitro. Immunocytochemical staining revealed hyperphosphorylated tau accumulation in pyramidal neurons in cornu ammonis and in neocortical neurons. The topography of these changes recalls the distribution of neurofibrillary tangles in Alzheimer's disease brain. Selective inhibition of protein phosphatase 2B with cyclosporin A did not have any significant effect on tau phosphorylation, accumulation, or function. These studies suggest that protein phosphatase 2A participates in regulation of tau phosphorylation, processing, and function in vivo. A down-regulation of protein phosphatase 2A activity can lead to Alzheimer-like abnormal hyperphosphorylation of tau.     

Mannose-Induced Modulations in Antioxidants,Protease Activity,Lipid Peroxidation,and Total Phenolics in Etiolated Wheat Leaves

Modulation of different antioxidants, total phenolics, lipid peroxidation, and protease activity as a result of mannose treatment (1%) was studied in leaves of etiolated wheat seedlings. Changes in these biochemicals were monitored up to 96 h after treatment at 24-h intervals. Mannose treatment induced a significant increase in protease activity throughout the scanning period, coupled with a gradual decrease in leaf protein content. Membrane lipid peroxidation (MDA content) was higher at 24 and 72 h after treatment. MDA content remained higher for a longer period due to mannose treatment. During the initial 24 h of mannose treatment, only catalase and total phenolic contents were increased. Catalase activity was down regulated with increasing duration of treatment. On the other hand, peroxidase (POD, APX) activities were initially unaffected but increased with increasing treatment duration. The decreased level of lipid peroxidation at 96 h may be due to detoxification of H₂O₂ by peroxidases. Superoxide dismutase activity was not affected by mannose treatment. In conclusion, evidence is provided that mannose can modulate the expression of the enzymatic antioxidant defense system in wheat leaves.     

Lysinibacillus composti sp. nov., isolated from compost

A Gram-negative, motile, rod-shaped, endospore-forming bacterial strain, designated as NCCP-36^T, was isolated from the compost of fruit and vegetable wastes. The strain NCCP-36^T grew within a temperature range of 10–45?^○C (optimum 28?^○C) and a pH range of 6.5–8.5 (optimum 7.0), and its cells tolerated <50 mM boron (optimum growth without boron) and 0–5 % NaCl (w/v) in tryptic soya broth medium. Based on comparative analysis of 16S rRNA gene sequence, strain NCCP-36^T showed the highest similarity to Lysinibacillus sinduriensis BLB-1^T (97.52 %) and L. xylanilyticus XDB9^T (96.96 %), and <97 % similarity with other closely related taxa. However, DNA–DNA relatedness between strain NCCP-36^T and the closely related type strains of genus Lysinibacillus was ≤37 %. Phylogenetic and chemotaxonomic analyses [major polar lipids: diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and phospholipids; predominant menaquinone: MK-7; major cellular fatty acids: iso-C_15:0, antieso-C_15:0, and iso-C_16:0; DNA G+C contents: 37 mol %; Lys-Asp (type A4α) in cell-wall peptidoglycans as diagnostic amino acids] also support the affiliation of strain NCCP-36^T to genus Lysinibacillus. Based upon DNA–DNA relatedness as well as distinctive chemotaxonomic, phylogenetic, and genotypic data, we conclude that strain NCCP-36^T belongs to a novel species of genus Lysinibacillus, for which the name Lysinibacillus composti sp. nov. is proposed. The type strain is NCCP-36^T (JCM 18777^T?=?KCTC 13796^T?=?DSMZ 24785^T).     

Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA

Production of alpha/beta interferon in response to viral double-stranded RNA (dsRNA) produced during viral replication is a first line of defense against viral infections. Here we demonstrate that the Erns glycoprotein of the pestivirus bovine viral diarrhea virus can act as an inhibitor of dsRNA-induced responses of cells. This effect is seen whether Erns is constitutively expressed in cells or exogenously added to the culture medium. The Erns effect is specific to dsRNA since activation of NF-kappaB in cells infected with Semliki Forest virus or treated with tumor necrosis factor alpha was not affected. We also show that Erns contains a dsRNA-binding activity, and its RNase is active against dsRNA at a low pH. Both the dsRNA binding and RNase activities are required for the inhibition of dsRNA signaling, and we discuss here a model to account for these observations.     

Guar Gum,Xanthan Gum,and HPMC Can Define Release Mechanisms and Sustain Release of Propranolol Hydrochloride

The objectives were to characterize propranolol hydrochloride-loaded matrix tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as rate-retarding polymers. Tablets were prepared by wet granulation using these polymers alone and in combination, and physical properties of the granules and tablets were studied. Drug release was evaluated in simulated gastric and intestinal media. Rugged tablets with appropriate physical properties were obtained. Empirical and semi-empirical models were fit to release data to elucidate release mechanisms. Guar gum alone was unable to control drug release until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile. Matrix tablets incorporating HPMC provided near zero-order release over 12 h and erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan gum resulted in a Higuchi release profile, revealing the dominance of the high viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum retarded release over 24 h and the Higuchi model best fit the data. When mixed with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as if xanthan gum was the sole rate-retarding gum and drug was released by Fickian diffusion. Release profiles from certain tablets match 12-h literature profiles and the 24-h profile of Inderal^® LA. The results confirm that guar gum, xanthan gum, and HPMC can be used for the successful preparation of sustained release oral propranolol hydrochoride tablets.     

3D-QSAR studies on natural acetylcholinesterase inhibitors of Sarcococca saligna by comparative molecular field analysis (CoMFA)

We have derived a comprehensive structure–activity relationship (SAR) picture for a new series of natural acetylcholinesterase inhibitors isolated from Sarcococca saligna. A set of 32 previously isolated and tested pregnane-type steroidal alkaloids inhibitors were investigated with respect to their IC₅₀ values (pIC₅₀) against the AChE enzyme in order to derive CoMFA models using atom-based alignment. A highly significant CoMFA model was obtained with r² value of 0.974. The q² (cross validation r²) value also confirms the statistical significance of our model.     

Plasma Adiponectin Increases Postprandially in Obese,but not in Lean,Subjects

Objective: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. Research Methods and Procedures: We studied 13 lean and 11 obese subjects after a 10‐hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. Results: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) μg/mL vs. 8.6 (6.5 to 11.3) μg/mL], but rose 4‐fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) μg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) μg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. Discussion: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.