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.

p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models.

Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.

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.