Urokinase (UK) [EC 3.4.99.26] is a serine protease that activates plasminogen to plasmin, which in turn degrades fibrin clots. Hence, UK finds its value as an important anti-thromboembolic drug. Plasmin has diverse physiological roles apart from its fibrinolytic role in the regulation of blood clotting. It has been implicated in complement activation, cell migration, wound healing, and generation of localized extracellular proteolysis during tissue remodelling, pro-hormone conversion, carcinogenesis and neoplasia. Among the plasminogen activators, UK provides a superior alternative for the simple reasons of its being more potent as compared to tissue-plasminogen activator and non-antigenic by virtue of its human origin unlike streptokinase. Based on these observations, UK is a very popular cardiovascular agent. Hence, UK, as one of the most potent plasminogen activators is attracting a great deal of attention. We will summarize recent patents related to the occurrence, mechanism of action, structure and function, physico-chemical properties, in vitro production, cloning and expression, purification and applications of UK.

Embryonic development in humans is controlled by the Hedgehog pathway, which becomes inactive in mature tissues. Except for tissue maintenance and healing, activation of this pathway results in tumorigenesis with only a few exceptions. The drugs currently in use have shown no effectiveness in blocking the key proteins responsible for tumorigenesis. Therefore, it is crucial to find new inhibitors that can stop the abnormal activation of the pathway. A preliminary Insilco screening of naturally occurring compounds was carried out to identify potential inhibitors of the pathway. Docking of seventeen naturally occurring antitumorigenic compounds against the four key proteins of the regulatory proteins of the Hedgehog pathway using AutoDock v4.2.6 software was carried out. Liriodenine exhibited the strongest binding affinity towards three out of the four regulatory proteins (-7.61 kcal/mol with Smoothened, -8.14 kcal/mol with Patched-I, and -6.15 kcal/mol with Gli-II) of the Hedgehog pathway, whereas 2’,4-dihydroxy-3-methoxychalcone displayed the highest binding affinity of -7.04 kcal/mol with the Sonic Hedgehog protein. Additional molecular dynamic simulation was conducted using Gromacs with Liriodenine and 2’,4-dihydroxy-3-methoxy chalcone. Every protein-ligand complex underwent simulation using v5.1.4 software for a duration of 100 nanoseconds. The findings from the simulation indicate that Liriodenine and 2’,4-dihydroxy-3-methoxy chalcone form a strong bond with their corresponding protein. Our findings show that the two aforementioned molecules have potential as new inhibitors of the pathway and should be further investigated in both invitro and in vivo experiments.

Exacum bicolor Roxb., is popularly documented in folklore medicine for treatment of diabetes mellitus besides other ailments such as fever, inflammation, diseases related to skin and eyes. In this present investigation, diet induced obese mice were treated with aqueous extracts of in vitro propagated Exacum bicolor plantlets at three different concentrations of 1, 10, and 100 mg/ kg body-weight of mice/day respectively. Diet induced obese mice treated with Glibenclamide 2 mg/kg body-weight of mice/ day were used as a standard. The results displayed reduced blood glucose, triglycerides, cholesterol and free fatty acids in a dose dependent manner in the diet induced obese mice treated with aqueous extracts of in vitro propagated Exacum bicolor. The results were supported by the histopathological studies of the extracts showing their ability to restore the acini architecture and beta cell number in pancreatic tissues. Further, the study was extended comparing the pharmacological properties such as alpha amylase binding assay between the in vitro and native plant extracts of the Exacum bicolor. The in vivo and in vitro studies of the current research validated and confirmed enhanced antidiabetic properties of the aqueous extracts of in vitro propagated plantlets over the methanolic extracts from native Exacum bicolor plants, corroborating the in vitro propagation and their applications in drug development. Key words: Alpha amylase, anti-diabetic, diet induced obese mice, Exacum bicolor, in vitro propagation