Ochnaflavone, naturally occurring biflavonoid, inhibits phospholipase A2 dependent phosphatidylethanolamine degradation in a CCl4-induced rat liver microsome.
This study investigated the protective effects of a group IIA secretory phospholipase A2 (sPLA2-IIA) inhibitor, ochnaflavone, on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rat liver microsomes in vitro. When rat liver was incubated at 37 degrees C in the presence of CCl4, the level of phosphatidylethanolamine (PE) degradation increased markedly compared with the control. The rat 14 kDa platelet PLA2 antibody, R377, suppressed the degradation of PE. Pretreating the microsome with ochnaflavone (2-16 microM) reduced the level of PE degradation in a dose dependent manner. In addition, p-bromophenacy bromide (p-BPB), which is a PLA2 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 sPLA2 activity in a dose dependent manner with an IC50 value of 3.45 microM, when arachidonyl PE was used as a substrate, but also inhibited lipid peroxidation in a dose dependent manner with an IC50 value of 7.16 microM. This result suggests that ochnaflavone prevents the progression of CCl4-induced PE hydrolysis by inhibiting the endogenous sPLA2 activity.
Moon
Tae Chul
TC
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Hwang
Hwa Shin
HS
Quan
Zhejiu
Z
Son
Kun Ho
KH
Kim
Cheorl-Ho
CH
Kim
Hyun Pyo
HP
Kang
Sam Sik
SS
Son
Jong Keun
JK
Chang
Hyeun Wook
HW
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006868:Hydrolysis; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; C090940:ochnaflavone; D002251:Carbon Tetrachloride; D010741:Phospholipases A; D054467:Phospholipases A2