Biochemical pathways in the antiatherosclerotic effect of berberine.
BACKGROUND
This study investigated the inhibitory effect of berberine (BBR) on lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the mitogen activated protein kinase (MAPK) signalling cascade pathways in human peripheral blood monocytes (PBMC).


METHODS
PBMC from whole blood were isolated and cultured for up to 24 hours after division into 5 groups treated with LPS, LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and untreated. Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated kinases 1/2 (ERK1/2) signalling pathways.


RESULTS
COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05). With the increasing concentration of BBR treatment, the COX-2 expression decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at three doses, ERK1/2 protein expression was significantly inhibited. For the JNK pathway, only with the treatment of BBR at the concentration of 100 micromol/L was JNK protein expression inhibited compared with the LPS stimulation group (P < 0.01). Irrespective of the BBR concentration, no difference was shown between the BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2 mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited when incubated with PD98059, SP600125 and SB203580 (P < 0.05).


CONCLUSIONS
Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and, possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.
Guo
Yi
Y
Department of Neurology, Second Affiliated Hospital of Jinan University, Shenzhen, Guangdong, China. yi_g4326@yahoo.com.cn
Wang
Qi-zhang
QZ
Li
Fang-ming
FM
Jiang
Xin
X
Zuo
Yan-fang
YF
Wang
Ling
L
D050197:Atherosclerosis / Q000188:drug therapy*; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D001599:Berberine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases