Molecular docking studies of withanolides against Cox-2 enzyme

Withaniasomnifera [Ashwaganda] belonging to the family solanaceae is the subject of our present study. Withanoloides which are the major chemical constituents have been proved of interest because of their structural variations in the hybrids of different races. Docking is the process which brings the two structures together. In the present study we focus the extensive use of tool and graphical software for the identification of the binding energy of selected Withanolides like Withaferin -A, Withanolide-D from Withaniasomnifera and to screen the phytoconstituents that will dock/bind to the active sites of COX-2 enzyme. The relief from the symptoms of inflammation and pain can be by the Pharmacological inhibition of COX which involves the prediction of potential ligand for the treatment of inflammation. The energy value of docking between the target and the phytoconstituents under investigation and comparison with Diclofenac sodium was taken into consideration for coming into conclusion regarding the best pose and the binding ability

Solubility and dissolution improvement of rofecoxib using solid dispesion technique

Rofecoxib [RXB] is a potent and selective cyclo-oxygenase-2 [COX-2] inhibitor, highly effective in the treatment of various pains, inflammatory condition, post-operative pain, rheumatoid arthritis, other musculoskeletal and joint disorders. Although they are completely absorbed upon oral administration, the peak plasma concentration is reached 2-3 hours after oral ingestion. The reason for delay being slow rate of absorption due to poor aqueous solubility. An attempt has been made to enhance solubility and dissolution of rofecoxib by solid dispersion[SD] technique using various hydrophilic excipients like PEG 4000, PEG 6000, PVP at different ratios by melting method and solvent evaporation method. The prepared SD of RXB were characterized to various physico-chemical properties and in vitro drug dissolution studies in 0.1N HCl with 0.25% SLS [pH 1.1] media for a period of 90 min using USP XXIII electro lab 8 basket tab dissolution test apparatus using paddle. The result of study indicated that there was no drug-polymer interaction found. The drug dissolution was found to enhance percent in PEG 4000, PEG 6000 and PVP, after 90mins of dissolution study 79.02%, 88.02%, 98.57% respectively. On comparison of various polymers used at varied concentrations PVP at 75:25 ratio by fusion method was found to be best suitable for the enhancement of dissolution and solubility of RXB

Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor / 대한간학회지

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC.