Ochnaflavone, Naturally Occurring Biflavonoid, Inhibits Phospholipase A2 Dependent Phosphatidylethanolamine Degradation in a CCl4-Induced Rat Liver Microsome

Abstract

This study investigated the protective effects of a group IIA secretory phospholipase A 2 (sPLA 2 -IIA) inhibitor, ochnaflavone, on the progression of carbon tetrachloride (CCl 4 )-induced acute liver injury in rat liver microsomes in vitro. When rat liver was incubated at 37°C in the presence of CCl 4 , the level of phosphatidylethanolamine (PE) degradation increased markedly compared with the control. The rat 14 kDa platelet PLA 2 antibody, R377, suppressed the degradation of PE. Pretreating the microsome with ochnaflavone (2-16 m mM) reduced the level of PE degradation in a dose dependent manner. In addition, p-bromophenacy bromide (p-BPB), which is a PLA 2 inhibitor, also inhibited PE degradation. However, the inhibitory activity was weaker than that of ochnaflavone. Further investigation showed that ochnaflavone not only inhibited the purified rat platelet sPLA 2 activity in a dose dependent manner with an IC 50 value of 3.45 m mM, when arachidonyl PE was used as a substrate, but also inhibited lipid peroxidation in a dose dependent manner with an IC 50 value of 7.16 m mM. This result suggests that ochnaflavone prevents the progression of CCl 4 -induced PE hydrolysis by inhibiting the endogenous sPLA 2 activity.

Paradoxical Effect of Nonalcoholic Red Wine Polyphenol Extract, Provinols™, in the Regulation of Cyclooxygenases in Vessels from Zucker Fatty Rats (fa/fa)

“…The increase in the PE contribution to total phospholipids suggested that Provinols treatment had a specific effect on phospholipid turnover because neutral lipids and fatty acid molecular species remain unchanged. Indeed, a reduction in PE degradation has been previously observed in platelets and liver microsomes due to inhibition of the secretory phospholipase A2 [42]. This result is suggestive of a reduction in the activity of phospholipase A2 in vessels from Provinols-treated rats especially when taken together with the reduction in the secretion of bioactive prostanoids.…”

Liquid chromatography mass spectrometry-based profiling of phosphatidylcholine and phosphatidylethanolamine in the plasma and liver of acetaminophen-induced liver injured mice

“…There are various phospholipases (PLA1, PLA2, PLC and PLD) that exhibit substrate specificities for different positions in phospholipids. Phospholipase A2 (PLA2) hydrolyzes the sn-2 ester bond in PC/PE, forming arachidonic acid and lyso-PC/lyso-PE [ 17 – 19 ]. These bioactive lipid mediators play important roles in inflammation, phospholipid metabolism, and signal transduction, which participate in the progression of DILI.…”

Synthesis of Ochnaflavone Analogs and Their Inhibitory Activity on PGE2 and NO Production Against LPS‐treated RAW 264.7 Cells

“…Two apigenin units are linked via an etheric linkage bond (Figure ). OC has been reported to possess many effective bioactivities for diverse diseases as described in precedent literatures . Naturally occurring biflavonoids as well as unnatural synthetic biflavonoids exhibited promising anti‐inflammatory activity through multiple mechanisms .…”