Inhibition of sPLA enzyme activity by cell-permeable antioxidant EUK-8 and downregulation of p38, Akt, and p65 signals induced by sPLA in inflammatory mouse paw edema model.

The arachidonic acid (AA) metabolic pathway, plays a vital role in the production of eicosanoids by the action of pro-inflammatory secretory phospholipase A (PLA ). Release of eicosanoids is known to be involved in many inflammatory diseases. Identification of the inhibitory molecules of this AA pathway enzyme along with the regulation of intracellular signaling cascades may be a finer choice to develop as a powerful anti-inflammatory drug.

Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA, COX-2, IκBα, p38 and MPO signaling in sPLA induced mice paw oedema.

Eleusine coracana (L.) Gaertn (E. coracana) is one of the highest consuming food crops in Asia and Africa.

Neutralization of local toxicity induced by vipera russelli phospholipase A2 by lipophilic derivative of ascorbic acid.

L-ascorbic acid upon condensation with palmitic acid in the presence of sulphuric acid results in L-ascorbic acid-6-palmitate (AP). The effect of L-ascorbic acid derivative, AP on the pharmacological activities of purified basic multi-toxic PLA2 enzyme, VRV-PL-VIIIa from Vipera russelli snake venom along with in vitro activities is described. AP inhibited VRV-PL-VIIIa enzyme activity in a concentration dependent manner with IC50 value of 48.

Constitutive release of powerful antioxidant-scavenging activity by hepatic stellate cells: protection of hepatocytes from ischemia/reperfusion injury.

Within the liver, reactive oxygen species produced by infiltrating blood cells and Kupffer cells (resident macrophages) can injure hepatocytes. We hypothesized that hepatocyte survival is influenced by the relatively small juxtaposed population of hepatic stellate cells (HSCs). We used cultures of primary rat hepatocytes as targets for superoxide-induced damage, which was determined by crystal violet assay and lactate dehydrogenase release.

p38-MAPK- and caspase-3-mediated superoxide-induced apoptosis of rat hepatic stellate cells: reversal by retinoic acid.

Reactive oxygen species (ROS) activate retinoid-containing quiescent hepatic stellate cells (qHSCs) to retinoid-deficient fibrogenic myofibroblast-like cells (aHSCs). However, ROS also cause apoptosis of aHSCs, and apoptotic aHSCs are observed in inflammatory fibrotic liver. Here, we investigated mechanisms of the effects of oxidative stress on the survival of qHSCs and aHSCs.

Alpha-lipoic acid: an inhibitor of secretory phospholipase A2 with anti-inflammatory activity.

Alpha-lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants both in hydrophilic and lipophylic environments with diverse pharmacological properties including anti-inflammatory activity. The mechanism of anti-inflammatory activity of ALA and DHALA is not known. The present study describes the interaction of ALA and DHALA with pro-inflammatory secretory PLA(2) enzymes from inflammatory fluids and snake venoms.

Inhibition of secretory phospholipase A(2) enzyme by bilirubin: a new role as endogenous anti-inflammatory molecule.

Bilirubin is a powerful antioxidant that suppresses the inflammatory process. However its interaction with proinflammatory PLA(2) enzyme is not known. Inhibition of several secretory phospholipase A(2) (sPLA(2)) enzyme activities by bilirubin was studied using (14)C-oleate labeled Escherichia coli as substrate.