Varagu in Sangam Literature

The Sangam literature is the foundation for the early life of the Tamils. Food, shelter and clothing play a very important role in the building up of the culture of a race. Accordingly, paddy, samai, varagu and millet were the four most important food grains in the life of Tamils during the Sangam Age as can be seen from Sangam literature like Narrinai, Akananuru, Purananooru, Ainkurunuru, Perumpanaruppadai, Mullaipattu and Madurai Kanchi. At the same time, they discuss in detail the cultivation of varagu, the time of cultivation, the soil, the origin and nature of the plant, the method of roasting it and the manner in which it is presented to the guests. Accordingly, this article compiles and analyses the information about Varagu in the above Sangam literature

FORMULATION AND EVALUATION OF ISORHAMNETIN LOADED POLY LACTIC-CO-GLYCOLIC ACID NANOPARTICLES

  Objective: The aim of the present study was formulation and evaluation of isorhamnetin loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (NPs).Methods: The present study was designed to incorporate the isorhamnetin in PLGA formulation by double emulsion solvent evaporation method, which offers a dynamic and flexible technology for enhancing drug solubility due to their biphasic characteristic, variety in design, composition and assembly. Synthesized isorhamnetin-PLGA NPs were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and particle size analyzer. We tested the efficacy of isorhamnetin-PLGA NPs in HepG2 cell lines.Results: From the FTIR result, we concluded that -C-N-, -C=C-, N-H, C-N, N-O, O-H, and C-H are the functional groups present in isorhamnetin-PLGA NPs, SEM image shows spherical shape of particles. The particle size analysis result shows 255-342 nm range of particles. Isorhamnetin-PLGA NPs significantly enhanced (p<0.05) the antiproliferative effect when compared to the plain drug.Conclusion: This study concluded that the newly formulated NP drug delivery systems of isorhamnetin provided an insight into the therapeutic effectiveness of the designed formulation for the treatment of chemotherapy

COMPUTATIONAL STUDIES ON DIFFERENT TYPES OF APOPTOTIC PROTEINS DOCKED WITH A DIETARY FLAVONOID ERIODICTYOL IN COLON CANCER

Objective: In this study, to evaluate the computational studies of eriodictyol docked with apoptotic proteins.Methods: AutoDock Vina and Molecular Graphics Laboratory tools were used to determine the interaction between proteins and eriodictyol. Discovery studio visualizer and PyMOL were used to determine the interaction of amino acid residues between apoptotic proteins and eriodictyol.Results: The obtained results revealed more binding affinities of p53, caspase 8, B-cell lymphoma (Bcl)-2, Bcl-2 - associated X protein (BAX), and adenomatous polyposis coli (APC) of −10.6, −10.9, −9.0, −9.5, and 7.2 kcal/mol, respectively. Interaction of hydrophobic polar contacts of amino acid residues of p53 (CYS-277 and ALA-276), caspase 8 [THR-467, THR-337 (2), and GLU-396 (2)], Bcl-2 [ARG-103 (3), ALA-104 (2), and PHE-105, TYR-101], BAX [GLY-108, TRY-107, ASN-106, and GLN-155 (2)], and APC [GLU-40 (2) and LEU-37 (2)] were notified between macromolecules and small molecules. The calculation of root-mean-square deviation of proteins and eriodictyol showed the lower binding energies to be 11.6, 12.5, 15.9, 19.6, and 15.8 and the upper binding energies to be 12.4, 15.3, 16.9, 20.7, and 18, respectively. The homology of binding energies was determined below 2Å which is computationally less expensive and easily determined the hydrophobic polar contacts.Conclusions: The  homology  of  binding  energies  was  determined  below  2Å which  is  computationally  less  expensive  and  easily  determined the hydrophobic polar contacts. The results were proved that the eriodictyol highly interacted with apoptotic proteins. It might be a strong anti-inflammatory activity of colon cancer. In future, computational molecular docking studies should aid further in vitro and in vivo studies.Keywords: AutoDock Vina, p53, Eriodictyol, Caspase 8, B-cell lymphoma-2, Bcl-2 - associated X protein, Adenomatous polyposis coli

Repurposing cancer drugs, batimastat and marimastat, to inhibit the activity of a group I metalloprotease from the venom of the Western Diamondback rattlesnake, Crotalus atrox

Snakebite envenomation causes over 140,000 deaths every year predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with an incredibly complex pathophysiology due to the vast number of unique toxins/proteins found in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a group I metalloprotease (CAMP-2) from the venom of the western diamondback rattlesnake, Crotalus atrox. Its sensitivity to matrix metalloprotease inhibitors (batimastat and marimastat) was established using specific in vitro experiments and in silico molecular docking analysis. CAMP-2 shows high sequence homology to atroxase from the venom of Crotalus atrox and exhibits collagenolytic, fibrinogenolytic and mild haemolytic activities. It exerts a mild inhibitory effect on agonist-induced platelet aggregation in the absence of plasma proteins. Its collagenolytic activity was completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 M, while it is partially potentiated by calcium chloride. Molecular docking studies demonstrate that batimastat and marimastat are able to bind strongly to the active site residues of CAMP-2. This study demonstrates the impact of matrix metalloprotease inhibitors in the modulation of a purified, group I metalloprotease activities in comparison to the whole venom. By improving our understanding of snake venom metalloproteases and their sensitivity to small molecule inhibitors, we can begin to develop novel and improved treatment strategies for snakebites

Challenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: the views of clinicians

Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future

IN SILICO DOCKING STUDIES ON KAEMPFERITRIN WITH DIVERSE INFLAMMATORY AND APOPTOTIC PROTEINS FUNCTIONAL APPROACH TOWARDS THE COLON CANCER

Objective: The objective of this research was to formulate the binding energies and interaction of amino acid residues in kaempferitrin with different types of apoptotic and inflammatory proteins of colon cancer.Methods: AutoDock Vina and MGL tool were used for docking calculations. Both programs require the pdbqt input files and allow for flexibility of all the torsional bonds of small molecules. Discovery Studio Visualizer v3.5 was used for removal of water molecules and ligands and the pymol program was used to do analysis of the docking with various apoptotic proteins BAX, Bcl-2, COX-2, Protein kinase B.Results: In our study was developed binding energy scoring function of kaempferitrin docked with different types of inflammatory proteins and apoptotic proteins. Binding score values for-6.9 (BAX),-7.2 (Bcl-2),-7.3 (caspase-3),-8.8 (Cox-2),-7.4 (Cytochrome P450),-6.7 (Proteinase kinase B),-8.0 (TNF-α) and-7.2 (VEGF) kcal/mol, respectively. Amino acid interaction of kaempferitrin with proteins for ARG-25, LEU-52, ASN-54, PHE-55, GLU-17, LYS-14, TRP-22, THR-21 GLY-16 (Protein Kinase B), ASP-102, ASN-48, GLN-52, ASP-104 (BAX), GLU-176, TRP-173, GLU-132, PHE-135 (Bcl-2), SER-249, ASP-2, ASN-208, GLN-217, LEU-242 (Caspase 3), TYR-55, HIS-39, SER-49, GLU-322, GLY-326 (COX-2), SER-95, LEU-94, ARG-82, VAL-123, ALA-96 (TNF-α), ASP-414, LYS-322, GLU-326, GLU-416, GLU-438, ALA-439, GLU-437 (Cytochrome P450) and LEU-47, GLN-46, CYS-61, CYS-60, ASP-63, GLU-67, GLY-65, LEU-66 (VEGF) respectively.Conclusion: The results obtained in this research work clearly indicated the docking scores of apoptotic and Inflammatory proteins imply that kaempferitrin is an effective inhibitory compound for colon cancer

Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a coordinated manner to prevent loss of blood and control wound repair. Recent reports indicate that the stability and functions of a thrombus are maintained through sustained, contact dependent signalling between platelets. Given the role of gap junctions in the coordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed

Connexin40 regulates platelet function

The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor 37,43Gap27 on Cx40-/- mouse platelets and of the Cx40 inhibitor 40Gap27 on Cx37-/- mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis

Sequence and phylogenetic analysis of viper venom serine proteases

Snakebites are a major neglected tropical disease responsible for as many as 95000 deaths every year worldwide. Viper venom serine proteases disrupt haemostasis of prey and victims by affecting various stages of the blood coagulation system. A better understanding of their sequence, structure, function and phylogenetic relationships will improve the knowledge on the pathological conditions and aid in the development of novel therapeutics for treating snakebites. A large dataset for all available viper venom serine proteases was developed and analysed to study various features of these enzymes. Despite the large number of venom serine protease sequences available, only a small proportion of these have been functionally characterised. Although, they share some of the common features such as a C-terminal extension, GWG motif and disulphide linkages, they vary widely between each other in features such as isoelectric points, potential N-glycosylation sites and functional characteristics. Some of the serine proteases contain substitutions for one or more of the critical residues in catalytic triad or primary specificity pockets. Phylogenetic analysis clustered all the sequences in three major groups. The sequences with substitutions in catalytic triad or specificity pocket clustered together in separate groups. Our study provides the most complete information on viper venom serine proteases to date and improves the current knowledge on the sequence, structure, function and phylogenetic relationships of these enzymes. This collective analysis of venom serine proteases will help in understanding the complexity of envenomation and potential therapeutic avenues