Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway.
Macrophages are the main source of cytokines in atherosclerotic plaques. Modified low-density lipoproteins may stimulate macrophages to produce large quantities of proinflammatory cytokines that promote atherosclerosis. Berberine is the main component of the traditional Chinese medicine umbellatine, which has a widespread effect and was used to treat many diseases clinically. Our previous study found that berberine could increase adipophilin expression in macrophages, which is a target gene of PPARgamma. PPARgamma agonist could decrease proinflammatory cytokines in macrophage. In this study, we investigated the effects and the mechanism of action of berberine on the expression and secretion of TNFalpha, MCP-1, and IL-6 in vitro to identify new pharmacological actions of berberine. The results of RT-PCR and ELISA shows that berberine may inhibit the expression and secretion of the tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6) in macrophages stimulated by acetylated low-density lipoprotein (AcLDL), whereas the peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor GW9662 could attenuate this effect of berberine. This study demonstrates that berberine may inhibit the expression and production of TNF-alpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages. This effect might be partially mediated through PPARgamma activity.
Chen
F L
FL
Department of Endocrinology, Huashan Hospital, Fudan University, 12# Middle Urumqi Road, Shanghai 200040, China.
Yang
Z H
ZH
Liu
Y
Y
Li
L X
LX
Liang
W C
WC
Wang
X C
XC
Zhou
W B
WB
Yang
Y H
YH
Hu
Ren-Ming
RM
D000813:Anilides / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000633:toxicity; D015850:Interleukin-6 / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C032629:acetyl-LDL; D000077154:Rosiglitazone; D001599:Berberine