Chemical modification of ascorbic acid and evaluation of its lipophilic derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity

Abstract

The halo 6-fatty acid esters of L-ascorbic acid 3a, 3b and 6-fatty acid esters of L-ascorbic acid 5a-g were achieved from L-ascorbic acid 1. Compounds 3a, 3b and 5a-g were evaluated for anti-oxidant, anti-lipid peroxidation, and secretory phospholipase A(2) (sPLA(2)) inhibition in vitro, and sPLA(2) induced mouse paw edema. All the derivatives retained their anti-oxidant property compared to ascorbic acid at 6 × 10(-4)M and are good inhibitors of lipid peroxidation at 1 mg ml(-1) as evaluated by 2, 2-Diphenyl-1-picrylhydrazyl radical and thio-barbituric acid methods, respectively. Compounds 5e and 5f significantly inhibited purified group I sPLA(2) from Naja naja and group II sPLA(2) from Vipera russelli, human synovial fluid and human pleural fluid with IC(50) value ranging from 64 ± 1.95 to 82 ± 1.3 and 48 ± 2.27 to 61 ± 2.23 μM, respectively. The compounds 5e and 5f also showed varying degree of potency in neutralizing indirect hemolytic activity of sPLA(2) at 50 μM concentration, and sPLA(2) induced mouse paw edema at the dose 3 mg/kg. Further docking studies also confirmed that compounds 5e and 5f have maximum interaction with increasing negative energy value. Single molecule possessing both anti-oxidant and anti-inflammatory activities is of great therapeutic significance in inflammatory disorders.

Formulation, Characterization and Evaluation of Anti-Inflammatory and Anti-Angiogenic Activities of Memecylaene Nanoemulsion

“…The assay was also carried out in the presence of various concentrations 2, 4,6, 8 and 10 μg of NE. Lysis of erythrocytes by adding 9 ml of distilled water to the control reaction mixture was taken as 100% 9 .…”

“…The leaves are being used as a traditional remedy to cure skin diseases, several stomach disorders, chicken pox, polyuria, menorrhagia and herpes 1 . Memecylaene, 4,9,14,19-Tetramethyl-1,6,11,16-tetraoxacycloeicosa-3,8,13,19-tetraene plays a promising role as an anti-angiogenic, anti-proliferative, pro-apoptotic, anti-oxidant and anti-inflammatory molecule in vivo and ex vivo experiments 2 . The molecule showed a unique structure simulating crown ethers with promising biological potency.…”

Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n−3 fatty acids: molecular mechanisms and potential clinical applications

“…It can diminish ROS production either through stabilization of BH 4 , thereby avoiding eNOS uncoupling, and can down-regulate NADPH oxidase, the latter a property being shared with vitamin E [118]. In addition, anti-inflammatory effects can be induced by vitamin C due to its ability to inhibit sPLA 2 (secretory phospholipase A 2 ) [119]. In turn, vitamin E acts not solely as a ROS scavenger, but also by inhibiting the transcriptional activity of NF-κB [9] or by diminishing ROS production via down-regulating NADPH oxidase.…”

Anti-inflammatory activity studies on the stems and roots of Jasminum lanceolarium Roxb

“…PLA 2 enzyme plays an important role in inflammatory processes by generating arachidonic acid-derived proinflammatory mediators (Mohamed et al, 2010), which can inhibit the production of PGs. The pathway is considered to be a significant source of reactive oxygen species (ROS) .…”