Plasmodium vivax Tryptophan-Rich Antigen PvTRAg33.5 Contains Alpha Helical Structure and Multidomain Architecture

Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion

AN OVERVIEW ON DRUG-INDUCED HEPATOTOXICITY

Liver is a vital organ, contributing in most of the metabolic and physiological processes of our body. It plays principal role in detoxification of various drugs and xenobiotics. Though liver possess tremendous regenerative capacity, but metabolism of various chemicals severely damage the hepatic system. Drug induced hepatotoxicity (DIHT) is a major concern in this respect. The drugs we consume to treat various diseases, very often, their metabolic intermediates cause liver toxicity. The lion's share of the idiosyncratic drug reactions ultimately results either in liver transplantation or even death. DIHT is a major medical concern at present and several drugs have been withdrawn from the market due to their hepatotoxic phenotype. Therefore, considering the phenomenon of DIHT, we have documented various aspects of DIHT, also discussing about the mode of toxicity of the drugs

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Assessment of haemolytic, cytotoxic and free radical scavenging activities of an underutilized fruit, <i style="mso-bidi-font-style:normal">Baccaurea ramiflora </i>Lour. (Roxb.) Muell. Arg.</span>

115-125<i style="mso-bidi-font-style: normal">Baccaurea ramiflora Lour. (Roxb.) Muell. Arg. is an underutilized juicy fruit bearing plant found in sub-Himalayan area, South China, Indo-Burma region, etc. The fruit is considered to be nutritive, and in this study, we evaluated its antioxidant, haemolytic and cytotoxic properties. The juice was examined for the quenching activity of hydroxyl radical, nitric oxide, singlet oxygen, peroxynitrite, total antioxidant activity (TAA), erythrocyte membrane stabilizing activity (EMSA) along with quantification of phenolic and flavonoid contents and also tested for its potential activity as iron chelator, inhibitor of lipid peroxidation and total reducing power. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also performed to correlate antioxidant capacities with the phenolic and flavonoid content. Haemolytic activity on murine erythrocyte and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxic test was performed on murine splenocytes, thymocytes, hepatocytes and peritoneal exudates macrophage to examine the cytotoxic effect of its juice. The result exhibited its potent free radical scavenging activity. In case of TAA, DPPH (2, 2-diphenyl-1-picrylhydrazyl), EMSA and lipid peroxidation, the fruit juice was found to have significant (P <0.001) antioxidant capacity, which is evident from low IC50 (half maximal inhibitory concentration) value. Results obtained from haemolytic inhibition assay and MTT cytotoxic test confirms that the juice does not contain any cytotoxic effect and the fruit is safe for consumption. Fourier transform infrared (FTIR) spectra analysis exhibited high possibility of presence of flavonoid compounds in the juice

Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders.

In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer's disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug

Oleander Stem and Root Standardized Extracts Mitigate Acute Hyperglycaemia by Limiting Systemic Oxidative Stress Response in Diabetic Mice

The extracts of different parts of Nerium oleander L. are used as antidiabetic remedy in the traditional medicinal systems of different parts of the world. Despite these uses in ethnomedicinal system, the antihyperglycemic potentials of oleander stem (NOSE) and root (NORE) extracts have not been pharmacologically evaluated. Therefore, we aimed at evaluating the antidiabetic ethnomedicinal claims of NOSE and NORE, primarily focusing on glucose homeostasis and associated metabolic implications. Alloxan-treated mice with hyperglycaemia (blood glucose >200 mg/dL) were treated with oleander 70% hydromethanolic extracts (200 mg/kg) for 20 consecutive days, and the results were compared with positive control glibenclamide. Blood glucose level was 52–65% lowered (P0.05) changes in insulin sensitivity throughout the treatments. Improved serum insulin remained associated with lowered glucose level (rP = −0.847 and −0.772; P<0.01). Markers of hyperglycaemia-related hepatic glycogen, glycated haemoglobin (HbA1c), hyperlipidaemia, hepatic injury, and diabetic nephropathy were normalized as well. Improvement of systemic intrinsic antioxidant enzymes (catalase and peroxidase) were correlated (rP = −0.952 to −0.773; P<0.01) with lower lipid peroxidation by-product malondialdehyde (MDA) in the circulation. Principal component analysis coupled with hierarchical cluster analysis represented shift in metabolic homeostasis in diabetic mice, which was further normalized by oleander and glibenclamide treatment. Additionally, molecular docking studies of the phenolic acids measured by HPLC with intracellular cytoprotective transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) revealed strong molecular interactions. The results collectively support the ethnomedicine antidiabetic claims of oleander stem and root and suggest that the oleander mediated elevation of systemic antioxidant status is likely responsible for the improved glycaemic control

Amelioration of CCl₄ induced liver injury in swiss albino mice by antioxidant rich leaf extract of <i>Croton bonplandianus</i> Baill. - Fig 8

<p><b>The effect of <i>Croton bonplandianus</i> on the (A)</b> Peroxidase; <b>(B)</b> Catalase; <b>(C)</b> Reduced glutathione (GSH); <b>(D)</b> Superoxide dismutase (SOD) activities in CCl₄ intoxicated liver samples. Comparisons were made with control for statistical inference (‘t’ test for paired comparison) to interpret significant difference. Data expressed as mean ± S.D (n = 6). ^α p<0.05; ^β p<0.01; ^γ p<0.001; ^NS-Non significant.</p

Changes of body weight (g) and liver weight (g) in different experimental groups.

<p>Data represented as mean ± SD of six observations.</p

Antioxidant activity of <i>Croton bonplandianus</i>.

<p><b>(A)</b>&<b>(B)</b> DPPH scavenging activity; <b>(C)</b> % of hydroxyl radical (OH^●) scavenging Vs standard mannitol; <b>(D)</b> depicts remaining unneutralized OH^●. Data expressed as mean ± S.D (n = 6). ^α p<0.05; ^β p<0.01; ^γ p<0.001; ^NS-Non significant when compared with standard.</p