Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent.

Alexander disease (AxD) primarily affects the white matter of the central nervous system (CNS). It is an astrogliopathy in which Astroglial cells involved in maintenance homeostasis and providing defence to the brain are affected. Therefore their dysfunction has been implicated in a number of neurological, neuropsychiatric and neurodegerative disorders. GFAP (Glial fibrillary acidic protein) is the major intermediate filament protein present in astrocytes whose heterozygous missense mutations have been reported to be a cause of AxD. In the absence of any effective therapeutic intervention of AxD, in the present study PTGS (Post transcriptional gene silencing) approach to knock down mutant gfap gene. Various mutations causing AxD were checked for their pathogenicity using various in silico tools and 13 mutations were shortlisted based on their pathogenicity and probability of occurrence. Thereafter siRNA were designed against the mutant genes to silence them and thereby preventing the accumulation of mutant gfap that causes the pathophysiology of AxD.

Generally, it is believed that alpha,beta-dehydroamino acid residues are most stable in the Z- form rather than in the E- form. In this study, it has been shown that poly-DeltaAbu exists in alternate Delta(E)Abu and Delta(Z)Abu form, with phi, psi values of approximately 0 degrees , 80 degrees and 35 degrees , 27 degrees for the E- and Z- forms, respectively, rather than the all Z- form. The conformational results for the peptides Ac-DeltaAbu(2)-NHMe and Ac-L/D-Ile-Delta(Z)Abu/Delta(E)Abu-NHMe suggest the incorporation of DeltaAbu in both the Z- and E- forms, which is consistent with the available observations in natural systems. Because of adoption of phi, psi values corresponding to the collagen type structure ( approximately -30 degrees , 120 degrees ) by Ile residue and with phi, psi values in the left-handed helical region for Delta(Z)Abu residue, the peptide Ac-(L-Ile-Delta(Z)Abu)(3)-NHMe adopts an amphipathic left-handed helical beta-sheet type structure. This structure is stabilized by network of hydrogen bonding, carbonyl-carbonyl, and CH-O interactions and can be exploited for the construction of antimicrobial peptides and nanomaterials.

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Ageing is associated with a number of diseases. Alzheimer’s disease (AD) and diabetes are among such most common diseases. These two diseases are considered to be fundamentally similar disorders because they share some common elements, though they differ in the time of onset, tissues affected as well as the magnitudes of their specific traits. The present study was undertaken to prospect the association between the genes involved in Diabetes and AD; and their common pathophysiology. Using a network system biology approach, the genes common between Diabetes and AD were retrieved from DisGeNET database. The common genes were analysed using in silico tool, Cyctoscape’s various plug-ins, ClusterONE, CytoHubba, ClueGO and CluePedia. Eleven genes which can act as potential marker for both Diabetes and AD namely IL4, ICAM1, ALB, INS, CSF2, IL6, TNF, IL10, GAPDH, TLR4, and AKT have been identified in the present study. This is the first study of its kind in which relationship between Diabetes and AD has been investigated to identify their common genes, which can help in better understanding of pathophysiology of these age-related diseases.