ABSTRACT
Literature survey reveals that there are several natural and synthetic anti-inflammatory compounds reported till date. As a therapeutic drug target, PLA2 inhibition is preferred over other anti-inflammatory drug targets. The pro-inflammatory effects of group X sPLA2 are acquired from multiple pathways. This study aims to identify the best anti-inflammatory compound among 22 compounds reported in literature using in silico approach. The compound ligands are subjected to docking against the target protein human sPLA2 [PDB ID: 5G3M] at the active site using AutoDock 4.2.6. Based on the ? binding free energy and hydrogen bonding interactions, it was observed that ten compounds fit at the active site. Out of these, compound 1 (14-deoxyandrographolide) was selected as the best compound. Absorption, distribution, metabolism, and excretion (ADME) properties of the ligands are analyzed using pkCSM software available online. Compound 1 exhibited the best conformational fit when compared to the co-crystal inhibitor 4-Benzylbenzamide.
ABSTRACT
Objective To study the characteristics of phospholipase A2 (PLA2) activity and expression of PLA2 subtypes in rat serum and pancreas tissue with an established simple pancreatic trauma model in rats. Methods One hundred and twenty Wistar rats were divided into two groups in a one-to-two ratio: control group and impact group. The two groups were subsequently divided into four subgroups at 6h, 24h, 72h, 7d time point. For the animals in the impact groups, the pancreas was injured by a BIM- III biotical impact machine, and the animals in control group were sham injured. The total catalytic activity of PLA2 in serum and pancreatic tissue, the expressions of mRNA and protein and immunohistochemical localization of secretory PLA2 (sPLA2), cytosolic PLA2 (cPLA2) and calcium independent PLA2 (iPLA2) in pancreatic tissue were determined after the corresponding pretreatments in each group. Results The total catalytic activity of PLA2 in serum and pancreatic tissue of impact groups increased at 6h after injury, and the PLA2 activity reached peak value at 24h in pancreatic tissue and at 72h in serum after trauma, and at 7d in serum and pancreatic tissue were still higher than that in control group at the same time (P<0.05). The results of RT-PCR, Western blotting and immunohistochemistry indicated that the expression of sPLA2 in pancreatic tissue was higher than that of cPLA2 and iPLA2. Conclusions PLA2 activity can be upregulated in serum and pancreas after pancreatic trauma. The expression of sPLA2 is increased most significantly in pancreatic tissue after pancreatic trauma. PLA2 activity may be detected in serum 6h-7d after pancreatic trauma, and is helpful for auxiliary diagnosis of simple pancreatic trauma.
ABSTRACT
Background & objectives: Secretory phospholipase A2 (sPLA2), a member of the phospholipase A2 superfamily of enzymes that hydrolyses phospholipids, is a potentially useful plasma biomarker for atherosclerotic cardiovascular disease. Cardiovascular diseases are the leading cause of mortality in women. The purpose of this study was to investigate the correlation between cardiovascular risk factors and the sPLA2 levels in women with metabolic syndrome as compared to women without metabolic syndrome and men with metabolic syndrome. Methods: Patients (n=100) with various cardiovascular risk factors consecutively evaluated at the Rehabilitation Hospital-Cardiology Department, Cluj-Napoca, Romania were enrolled during 2011, of whom 10 were excluded. The patients were divided in three groups: group 1 (37 women with metabolic syndrome), group 2 (27 men with metabolic syndrome), and group 3 (26 women without metabolic syndrome). Body weight, smoking habits, glycaemia, hypertension, and serum lipids fractions were analysed as cardiovascular factors. Serum sPLA2 activity was measured using the chromogenic method. Results: There were no statistically significant correlations between sPLA2 levels and the investigated risk factors, irrespective of patient groups. However, there were significant positive correlations between sPLA2 and hsCRP in all three groups (P<0.05). In women with no metabolic syndrome an negative correlation was found between sPLA2 levels and HDL-C- r=-0.419, P=0.03. In men with metabolic syndrome there was a direct correlation between sPLA2 levels and HOMA, r=0.43, P<0.05, 95% CI (-0.098; 1.15). Interpretation & conclusions: Women with metabolic syndrome did not display different sPLA2 levels as compared to men with metabolic syndrome and women without metabolic syndrome. However, women with metabolic syndrome demonstrated a low but positive correlation between sPLA2 and hsCRP levels.
ABSTRACT
Allophylus cominia (L) Sw (Sapindaceae), is one of the most popular Cuban medicinal plant. The aimed of this study was to explore, if the antidiabetic organic extract has also anti-inflammatory effect, considering that inflammation is correlationated with diabetes. It was evaluated in vitro inhibitory activity of chloroform extract of leaves on cyclooxygenase-2 (COX-2) and secreted phospholipase A2 (sPLA-2), which are important cellular mediators in the signaling cascade of the inflammatory process. The extract studied shown inhibitory activity on COX-2, while not shown on FLA-2s. This study provides direct evidence of the activity of A. cominia on mechanisms related to anti-inflammatory effects involving the eicosanoid cascade.
Allophylus cominia (L) Sw (Sapindáceas) es una de las plantas medicinales más afamadas de la medicina tradicional en Cuba. El objetivo de este estudio fue explorar si el extracto orgánico con actividad antidiabética tenía también efecto de tipo antiinflamatorio, considerando que la inflamación es un evento relacionado con la diabetes. En tal sentido se evaluó in vitro la actividad inhibitoria del extracto clorofórmico de las hojas de Allophylus cominia (L) Sw sobre cicloxigenasa-2 (COX-2) y fosofolipasa A2 secretada (FLA-2s), las cuales constituyen importantes mediadores celulares en la cascada de señalización del proceso inflamatorio. El extracto estudiado exhibió actividad inhibitoria sobre COX-2, mientras que no la mostró sobre FLA-2s. Este trabajo brinda evidencias directas de la actividad de A. cominia sobre mecanismos vinculados al efecto antinflamatorio que involucran la cascada de eicosanoides.
Subject(s)
Anti-Inflammatory Agents , Plant Extracts/pharmacology , /pharmacology , Sapindaceae/chemistry , Cuba , Plants, MedicinalABSTRACT
Objective: To clone the cDNA of human sPLA2-IIA,construct the engineered Escherischia coli expressing human sPLA2-IIA and identify the expressed human sPLA2-IIA. Methods: Total RNAs were purified from human fetal spleen. The cDNA of human sPLA2-IIA was cloned by RT-PCR and inserted into plasmid pET32a(+) between NcoI and EcoRI sites for expressing the recombinant human sPLA2-IIA in Escherischia coli BL21(DE3). The recombinants were screened by SDS-PAGE. The engineered Escherischia coli expressing trxA-human sPLA2-IIA fusion protein was established. The expressed human sPLA2-IIA exists in the form of inclusion body and accounts for about 25% of the total proteins of Escherischia coli BL21(DE3). Conclusion: the engineered E. coli methods are suitable for preparing plenty of human sPLA2-IIA which has laid base for the large-scale expression,purification and basic studies of human sPLA2-IIA.