title: Anti-inflammatory effects of a Chinese herbal medicine in atherosclerosis via estrogen receptor β mediating nitric oxide production and NF-κB suppression in endothelial cells.
abstract: Bu-Shen-Ning-Xin Decoction (BSNXD) administration has alleviated the early pathologic damage of atherosclerosis by inhibiting the adhesion molecule expression and upregulating the estrogen receptor (ER) β expression in endothelial cells, and increasing the serum nitric oxide (NO) level without any effect on serum lipid status, endometrium and fat deposition in liver in ovariectomized rabbits. The BSNXD-derived serum increases ER β expression in the human umbilical vein endothelial cells (HUVECs), and decreases malondialdehyde (MDA) production, and upregulates eNOS expression then increases NO synthesis through ERβ-dependent pathway. NO not only suppresses the LPS-induced NF-κB transcription in HUVECs, but also decreases apoptosis of endothelial cells. The BSNXD-derived serum decreases monocyte chemoattractant protein-1 production, and suppresses cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin) expression in HUVECs injured by oxidized low-density lipoproteins (ox-LDL), and these effects can be abolished by ERβ antagonist (R,RTHC) and NO synthase inhibitor (L-NAME). The BSNXD-derived serum-treated HUVECs supernatant reduces CCR2, LFA-1 and VLA-4 expression in monocytes cell line U937 cells, which in turn inhibits adherence of U937 to injured endothelial cells. NO synthesis increases, and MDA production decreases through ERβ-mediated pathway that suppresses apoptosis and NF-κB activity in endothelial cells that downregulates adhesion molecules expression on endothelial cells via ERβ/NO/NF-κB pathway, and in turn leukocyte adhesion, which suggests BSNXD potential value in prophylaxis atherosclerosis.
authors.affiliation: Department of Obstetrics and Gynecology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: X-M
authors.initials: XM
authors.lastname: Qiu
authors.forename: Q
authors.initials: Q
authors.lastname: Hao
authors.forename: D-J
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C111835:CCL2 protein, human; C496871:CUL5 protein, human; D018932:Chemokine CCL2; D044842:Cullin Proteins; D004365:Drugs, Chinese Herbal; D019040:E-Selectin; D047629:Estrogen Receptor beta; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III