Silver nanoparticles (AgNPs) made by green synthesis offer a variety of biochemical properties and are an excellent alternative to traditional medications due to their low cost. In the current study, we synthesised AgNPs from the leaf extract of the medicinal plant Uvaria narum, commonly called narumpanal. The nanoparticles were characterised by ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM analysis showed AgNPs are highly crystalline and spherical with an average diameter of 7.13 nm. The outstanding catalytic activity of AgNPs was demonstrated by employing the reduction of 4-nitrophenol to 4-aminophenol. The AgNPs showed antiangiogenic activity in the chick chorioallantoic membrane (CAM) assay. AgNPs demonstrated anticancer activity against Dalton’s lymphoma ascites cells (DLA cells) in trypan blue assay and cytotoxicity against three fish cell lines: Oreochromis niloticus liver (onlL; National Repository of Fish Cell Lines, India (NRFC) Accession number—NRFC052) cells, Cyprinus carpio koi fin (CCKF; NRFC Accession number—NRFC007) cells and Cyprinus carpio gill (CyCKG; NRFC Accession number—NRFC064). Furthermore, the AgNPs demonstrated their ability to inhibit pathogenic microorganisms, Staphylococcus aureus, and Escherichia coli. The results from the study displayed green synthesised AgNPs exhibit antiangiogenic activity, cytotoxicity, antimicrobial and catalytic properties, which are crucial characteristics of a molecule with excellent clinical applications.

Background and purpose:  Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.Experimental approach:  Cell‐based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).Key results:  Thalidomide inhibited pro‐angiogenic functions in endothelial cell cultures, whereas 8‐bromo‐cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8‐bromo‐cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration‐dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO‐dependent angiogenesis.Conclusion and implications:  Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti‐angiogenic effects. These results could lead to the formulation of thalidomide‐based drugs to curb angiogenesis by targeting sGC.

Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities.