Safety assessment of ethanolic extract of Canarium strictum Roxb. leaves: Acute and subchronic toxicity studies.

Canarium strictum Roxb. (Burseraceae) is a tree distributed in India, China and Thailand. In traditional Ayurvedic medicine, it is used to treat asthma, rheumatism, blood impurities, syphilis, fever, epilepsy and cough. Toxicological information is currently unavailable warrants present research. Ethanol leaf extract obtained by soxhlet extraction was used to investigate its toxicity. The acute toxicity data showed ethanolic leaf extract is safe up to 2000mg/kg dose in female albino mice. There were no behavioral or physiological alterations or gross clinical abnormalities. The ethanolic leaf extract was administered orally to Wistar rats (n=5) of both sexes at a dose of 300, 600 and 1200mg/kg/d for 90 days during the investigation of sub-chronic toxicity. There were no treatment-related deleterious effects on general behavior, body weight, relative organ weight, biochemical and hematological parameters in the sub-chronic trial when evaluated daily/weekly. Organ histopathology revealed no significant abnormalities. Additionally, the ethanolic leaf extract improved rats' cholesterol and metabolic profiles. There is no apparent harm with ethanolic leaf extract treatment for 13 weeks, unless the dosage is quite high. Thus, it implies that the leaves are safer to use as a traditional medicine remedy for a variety of conditions in a wide dose range.

Structural stability of antimicrobial peptides rich in tryptophan, proline and arginine: a computational study.

The host defense peptides or antimicrobial peptides (AMPs) often contain short sequence of amino acids, either positive or negatively charged and express broad-spectrum antibacterial, antiviral and antifungal activity. Many researchers had reported that tryptophan, arginine and proline rich AMPs have a promising source of next-generation antibiotics. Nowadays, AMPs are used as a possible therapeutic source for future antibiotics. In the present study, the amino acid sequences of 2924 AMPs belonging to various sources rich in Tryptophan, Proline and Arginine was chosen for investigation. The AMPs were further categorized according to their source, structure and antimicrobial activities. The AMPs with tryptophan, arginine, proline residues in abundance with maximum sequence length of 20 amino acids alone was obtained. Homology modeling was performed with PEP-FOLD and the modeled structures were evaluated using RAMPAGE to identify the structural information. Further, the stability of peptide in aqueous condition was probed using molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.

Mechanistic investigation of PPARγ-facilitated anti-asthmatic effects of Galangin (Norizalpinin): Insights from in silico and in vivo analyses.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifaceted ligand-activated transcription factor that regulates inflammatory responses in asthma pathophysiology. The present study corroborates PPARγ-mediated anti-asthmatic action of the flavonoid, galangin (norizalpinin). In silico molecular interactions reveal that galangin formed three H-bonds (Glu291, Leu340 and Ser342) and a π-sigma bond (Arg288) with PPARγ, contributing to the binding affinity and stability of the complex. In vivo studies explore the role of galangin as a propitious PPARγ agonist in mitigating airway inflammation, thereby excluding ligand-independent action of PPARγ. Accordingly, oral administration of galangin significantly ameliorated airway hyperresponsiveness, inflammation and goblet cell hyperplasia by the suppression of IL-4, 5, 13, 17, TNF-α, NO, ROS, EPO, IgE and increase of IFN-γ in ovalbumin-induced allergic asthma model. PPARγ expression (mRNA and protein) studies were performed to elucidate a possible mechanism by which galangin modulates. Furthermore, to eliminate PPARγ-independent effects of galangin, a specific PPARγ antagonist (GW9662) was administered, which dramatically reversed the effects of galangin on PPARγ up-regulation, confirming the pleiotropic role of galangin as a PPARγ agonist in asthma therapeutics. Taken together, our findings communicate that PPARγ plays as a master regulator in the anti-asthmatic action of galangin.

Insilico Alpha-Helical Structural Recognition of Temporin Antimicrobial Peptides and Its Interactions with Middle East Respiratory Syndrome-Coronavirus.

Many antimicrobial peptides (AMPs) have multiple antimicrobial immunity effects. One such class of peptides is temporins. Temporins are the smallest (AMPs) found in nature and are highly active against gram-positive bacteria. Nowadays, there was a rapid increase in the availability of the 3D structure of proteins in PDB (protein data bank). The conserved residues and 3D structural conformations of temporins (AMPs) were still unknown. The present study explores the sequence analysis, alpha-helical structural conformations of temporins. The sequence of temporins was deracinated from APD3 database, the three-dimensional structure was constructed by homology modeling studies. The sequence analysis results show that the conserved residues among the peptide sequences, the maximum of the sequences are 70% alike to each other. The secondary structure prediction results revealed that 99% of temporin (AMPs) exhibited in alpha-helical form. The 3D structure speculated using RAMPAGE exposes the alpha-helical conformation in all temporins (AMPs). The phylogenetic analysis reveals the evolutionary relationships of temporins (AMPs), which are branched into seven clusters. As a result, we identified a list of potential temporin AMPs which docked to the antiviral protein (MERS-CoV), it shows good protein-peptide binding. This computational approach may serve as a good model for the rationale design of temporin based antibiotics.

Characterization and in vitro antioxidant activity of Albizia stipulata Boiv. gum exudates.

The objective of the present study is to characterize the physicochemical properties and to determine the in vitro antioxidant activity of Albizia stipulata Boiv. gum exudates collected from Northeast India. The total carbohydrate, uronic acid and protein contents, monosaccharide composition and the molecular weight distribution of the purified gum was determined. The powder flow property and preliminary compressibility test were performed on the dried gum exudates. Fourier transform infrared spectroscopy (FTIR) study was performed to analyze the functional groups present in the structure. Differential scanning calorimetry (DSC) and thermogravimetry (TGA/DTA) analyses were performed to study the thermal stability of the gum. The antioxidant properties of the gum were evaluated by determining 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl scavenging activities and reducing power. The total carbohydrate and protein contents of the gum were found to be 75.17±3.21% and 2.60±1.05% respectively. The viscosity of 2% aqueous solution of the gum exhibited non-Newtonian type of flow showing pH dependent swelling. Arabinose and galactose were found to be the main monosaccharides present in the gum exudates and the molecular weight distribution of the gum was also found to be polydispersed. Results from DPPH, hydroxyl scavenging and reducing power studies showed the gum possesses antioxidant properties.

Physicochemical characteristics and antioxidant activity of Prunus cerasoides D. Don gum exudates.

The physicochemical properties and antioxidant activity of Prunus cerasoides D. Don gum exudates was investigated in this study. The total carbohydrate and protein content were found to be 73.72±2.44% and 2.33±1.25%, respectively. Analysis of monosaccharide composition by HPLC-RI system after acid hydrolysis of the gum showed the presence of arabinose, galactose, glucose, rhamnose and xylose. The molecular weight of the gum was also found to be 5.55×10(5)Da. FTIR and DSC studies showed characteristics typical of a natural polysaccharide. The viscosity of 2% aqueous solution of the gum exhibited non-Newtonian type of flow and the gum was also found to show pH dependent swelling. Determination of the angle of repose, Carr's index and Hausner ratio indicate the gum possess fairly good powder flow property. The antioxidant properties of the gum were evaluated by determining DPPH and hydroxyl scavenging activities, reducing power and total phenolic contents which showed the gum possess antioxidant property.