Novel Stable Protease Inhibitor from Flowers with Antimicrobial and Antitumoral Activities.

A novel protease inhibitor isolated from date palm flowers (PIDF) was purified and characterized. A heat and acidic treatment step followed by ethanol precipitation and reverse-phase high-performance chromatography was applied to purify this natural protease inhibitor to homogeneity with a single band of about 19 kDa. The stability study depicted that PIDF was fully stable at 40 °C and retained 65% of its initial activity after heating at 50 °C for 24 h.

Evaluation of the in vitro anti-inflammatory and cytotoxic potential of ethanolic and aqueous extracts of Origanum syriacum and Salvia lanigera leaves.

In this study, the chemical compositions of the ethanolic and aqueous extracts of the leaves of Origanum syriacum and Salvia lanigera were identified based on GC-MS spectrometric analyses. The in vitro anti-inflammatory potential of the different extracts was evaluated by determining the membrane stabilization of human red blood cells and the percent inhibition of the COX1/2, 5LOX, and sPLA-V enzymes. Both ethanolic extracts showed maximum membrane stabilization (≤ 91%, at 100 μg/mL) compared to the aqueous extracts (≤ 45%) and the reference drug diclofenac sodium (90.

The role of the calmodulin-binding and calmodulin-like domains of the epidermal growth factor receptor in tyrosine kinase activation.

The epidermal growth factor receptor (EGFR) harbors a calmodulin (CaM)-binding domain (CaM-BD) and a CaM-like domain (CaM-LD) upstream and downstream, respectively, of the tyrosine kinase (TK) domain. We demonstrate in this paper that deletion of the positively charged CaM-BD (EGFR/CaM-BD∆) inactivated the TK activity of the receptor. Moreover, deletion of the negatively charged CaM-LD (EGFR/CaM-LD∆), leaving a single negative residue (glutamate), reduced the activity of the receptor.

Inhibitory effects of various solvent extracts from Rhamnus frangula leaves on some inflammatory and metabolic enzymes.

Many enzymes are involved in numerous pathologies which are related to metabolic reactions and inflammatory diseases such as pancreatic lipase, α-amylase, α-glucosidase and xanthine oxidase and secreted phospholipases A2 (Group IIA, V and X), respectively. Therefore, inhibiting these enzymes offer the potential to block production of more inflammatory substances and decrease the risk factors for cardiovascular diseases. The purpose of this study was to investigate some potent, bioavailable and selective inhibitors of some catalytic proteins implicated to metabolic syndrome and their antioxidant effects from various solvent extracts of R.

Purification and characterization of a newly serine protease inhibitor from Rhamnus frangula with potential for use as therapeutic drug.

Protease inhibitors from plants are well known to be potent inhibitors of the growth of bacteria, fungi, and even certain viruses which make them excellent candidates for use as the lead compounds for the development of novel antimicrobial agents for applications in medicine. In this study, Rhamnus frangula was selected as a protease inhibitor source. The maximum recovery of the protease inhibitor against trypsin was recorded in the crude extract made in 0.

In vitro anti-Plasmodium falciparum properties of the full set of human secreted phospholipases A2.

We have previously shown that secreted phospholipases A2 (sPLA2s) from animal venoms inhibit the in vitro development of Plasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense against P.

Effects of the propeptide of group X secreted phospholipase A(2) on substrate specificity and interfacial activity on phospholipid monolayers.

Group X secreted phospholipase A(2) (GX sPLA(2)) plays important physiological roles in the gastrointestinal tract, in immune and sperm cells and is involved in several types of inflammatory diseases. It is secreted either as a mature enzyme or as a mixture of proenzyme (with a basic 11 amino acid propeptide) and mature enzyme. The role of the propeptide in the repression of sPLA(2) activity has been studied extensively using liposomes and micelles as model interfaces.

Monoclonal antibodies as cancer therapeutics.

Three main targets were subjected for the most approved monoclonal antibodies (mAbs) in cancer therapy: EGFR in solid cancer, the clusters of differentiation in blood cancer and VEGF in angiogenesis. Meanwhile side effects, the elevated costs and resistance problems are limiting the efficiency of mAbs as targeted therapy. The combinatory therapy with chemo or radiotherapy has improved the efficiency of mAbs.

The offer of chemistry to targeted therapy in cancer.

Cancer therapy is facing the big challenge of destroying selectively tumour cells without harming the normal tissues. Chemotherapy was trying from the beginning to kill malignant cells because of their proliferative activity since normal cells are in general quiescent. Meanwhile side effects were produced due to the destruction of some normal cells that need regular proliferation.

Group X secreted phospholipase A2 proenzyme is matured by a furin-like proprotein convertase and releases arachidonic acid inside of human HEK293 cells.

Among mammalian secreted phospholipases A(2) (sPLA(2)s), group X sPLA(2) has the most potent hydrolyzing activity toward phosphatidylcholine and is involved in arachidonic acid (AA) release. Group X sPLA(2) is produced as a proenzyme and contains a short propeptide of 11 amino acids ending with a dibasic motif, suggesting cleavage by proprotein convertases. Although the removal of this propeptide is clearly required for enzymatic activity, the cellular location and the protease(s) involved in proenzyme conversion are unknown.

Group X phospholipase A2 stimulates the proliferation of colon cancer cells by producing various lipid mediators.

Among mammalian secreted phospholipases A2 (sPLA(2)s), the group X enzyme has the most potent hydrolyzing capacity toward phosphatidylcholine, the major phospholipid of cell membrane and lipoproteins. This enzyme has recently been implicated in chronic inflammatory diseases such as atherosclerosis and asthma and may also play a role in colon tumorigenesis. We show here that group X sPLA(2) [mouse (m)GX] is one of the most highly expressed PLA(2) in the mouse colon and that recombinant mouse and human enzymes stimulate proliferation and mitogen-activated protein kinase activation of various colon cell lines, including Colon-26 cancer cells.

Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease.

Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2.

Kinetic properties of dromedary pancreatic lipase: a comparative study on emulsified and monomolecular substrate.

Using the classical emulsified system and the monomolecular film technique, we compared several interfacial properties of dromedary pancreatic lipase (DrPL) with those of a mammal (human) and an avian (turkey) model. Like turkey pancreatic lipase (TPL) and unlike human pancreatic lipase (HPL), in the absence of colipase and bile salts, using tributyrin emulsion or monomolecular films of dicaprin at low surface pressure, DrPL hydrolyses pure tributyrin emulsion, as well as dicaprin films maintained at low surface pressures. DrPL was also able to hydrolyse triolein emulsion in the absence of any additive and despite the accumulation of long-chain free fatty acids at the interface.