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Coumarins, identified as plant secondary metabolites possess diverse biological activities including anti-angiogenic properties. Daphnetin (DAP), a plant derived dihydroxylated derivative of coumarin has shown significant pharmacological properties such as anticancer, anti-arthritic and anti-inflammatory. The present study was performed to investigate the anti-angiogenic potential of DAP, focusing on the mechanism of action. The in vivo anti-angiogenic potential of DAP was evaluated by vascular endothelial growth factor (VEGF)-induced rat aortic ring (RAR) assay and chick chorioallantoic membrane (CAM) assay. For in vitro evaluation, wounding migration, transwell invasion, tube formation and apoptosis assays were performed on VEGF (8 ng/mL)-induced human umbilical vein endothelial cells (HUVECs). The cellular mechanism of DAP was examined on TNFα (10 ng/mL) and VEGF-induced HUVECs by extracting the mRNA and protein levels using RT-qPCR and western blotting. Our data demonstrated that DAP inhibited the in vivo angiogenesis in the RAR and CAM assay. DAP also inhibited the different steps of angiogenesis, such as migration, invasion, and tube formation in HUVECs. DAP inhibited nuclear factor-κB signalling together including TNF-α induced IκBα degradation; phosphorylation of IκB kinase (IKKα/β) and translocation of the NF-κB-p65 protein. Furthermore, western blotting revealed that DAP significantly down-regulated the VEGF-induced signalling such as c-Src, FAK, ERK1/2 and the related phosphorylation of protein kinase B (Akt) and VEGFR2 expressions. DAP reduced the elevated mRNA expression of iNOS, MMP2 and also, induced apoptosis in VEGF-stimulated HUVECs by the caspase-3 dependent pathway. Taken together, this study reveals that DAP may have novel prospective as a new multi-targeted medication for the anti-angiogenesis and cancer therapy.

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High performance polymer, Polyether Ether Ketone (PEEK) (service temperature À250C to þ300 C, tensile strength: 120 MPa) is gaining significant interest in aerospace and automotive industries. In this investigation, attention is given to understand adhesion properties of PEEK, when surface of the PEEK is modified by two different plasma processes (i) atmospheric pressure plasma and (ii) low pressure plasma under DC Glow Discharge. The PEEK sheets are fabricated by ultra high temperature resistant epoxy adhesive (DURALCO 4703, service temperature À260 C to þ350 C). The surface of the PEEK is modified through atmospheric pressure plasma with 30 and 60 s of exposure and low pressure plasma with 30, 60, 120, 240, and 480 s of exposure. It is observed that polar component of surface energy leading to total surface energy of the polymer increases significantly when exposed to atmospheric pressure plasma. In the case of low pressure plasma, polar component of surface energy leading to total surface energy of the polymer increases with time of exposure up to 120 s and thereafter, it deteriorates with increasing time of exposure. The fractured surface of the adhesively bonded PEEK is examined under SEM. It is observed that unmodified PEEK fails essentially from the adhesive to PEEK interface resulting in low adhesive bond strength. In the case of surface modified PEEK under atmospheric pressure plasma, the failure is entirely from the PEEK and essentially tensile failure at the end of the overlap resulting in significant increase in adhesive bond strength.