Berberine combined with atorvastatin downregulates LOX‑1 expression through the ET‑1 receptor in monocyte/macrophages.
Studies have shown that the oxidative modification of low‑density lipoprotein (oxLDL) plays a major role in atherogenesis. Lectin‑like oxidized low‑density lipoprotein receptor‑1 (LOX‑1) mediated the transport of oxLDL into macrophages, which promoted foam cell formation. Targeting LOX‑1 may therefore be a promising approach to inhibit atherosclerosis. In the present study, we aimed to investigate the effect of berberine combined with atorvastatin on LOX‑1 and explore the underlying molecular mechanism involved. Expression of LOX‑1 in monocyte‑derived macrophages (MDMs) exposed to berberine (0, 0.1, 1, 10 and 100 nM) and atorvastatin (100 nM) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. Results showed that the expression of LOX‑1 was decreased in a dose‑dependent manner. Additionally, knockdown of the endothelin‑1 (ET‑1) receptor significantly blocked the inhibitory effect of berberine on LOX‑1 expression. Body weight (BW), liver weight (LW) and kidney weight (KW) in the model rats were markedly increased at concentrations of berberine ≥1 µmol/kg, while heart weight (HW) and spleen weight (SW) remained constant among all groups. Berberine combined with atorvastatin also decreased serum total cholesterol (TC), triglyceride (TG) and low‑density lipoprotein‑cholesterol (LDL‑C) levels in the rat model as well as inflammation and oxidative stress. Furthermore, plasma ET‑1 levels and LOX‑1 expression were decreased by berberine combined with atorvastatin treatment, and the inhibitory effect on LOX‑1 was impeded by an ET‑1 receptor antagonist. The results demonstrated that berberine combined with atorvastatin downregulates LOX‑1 expression through ET‑1 receptors in monocyte/macrophages in vitro and in vivo.
Department of Neurology, The 451st Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Liyi
L
Chi
Department of Cardiovascular Medicine, The 451st Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Lijing
L
Peng
Department of Cardiovascular Medicine, Ninth Hospital of Xi'an, Xi'an, Shaanxi 710054, P.R. China.
Xiaojing
X
Hu
Department of Neurology, The 451st Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Na
N
Pan
Department of Cadres Ward, The 451st Hospital of People's Liberation Army, Xi'an, Shaanxi 710054, P.R. China.
Yanhai
Y
Zhang
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000069059:Atorvastatin; D001599:Berberine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics* / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D004041:Dietary Fats; D006538:Heptanoic Acids; C495136:OLR1 protein, rat; D011758:Pyrroles; D034741:RNA, Small Interfering; D044022:Receptor, Endothelin A; D051127:Scavenger Receptors, Class E; D014280:Triglycerides; D001599:Berberine; D002784:Cholesterol; D000069059:Atorvastatin