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.

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…Levels of DHEA peak during the third decade of life and then decline with age (66). A previous study by the current authors found that BSNXD up-regulated ER rather than E2 in OVX rabbits (6). BSNXD pharmacological serum and DHEA affect osteoblasts via the MAPK pathway (11,67).…”

“…A previous study showed that BSNXD up-regulated serum levels of the estrogen receptor (ER) without affecting E2 in OVX rabbits (6). Hence, a question was whether BSNXD prevented osteoporosis by affecting the production/metabolism of ER ligands, such as DHEA, DHEAS, and E2, in mice.…”

“…Bu-Shen-Ning-Xin decoction (BSNXD), a traditional Chinese medicine, contains dried Rehmannia Root, common Anemarrhena rhizome, bark of the Chinese Corktree, Barbary Wolfberry fruit, Chinese Dodder seed, Shorthorned Epimedium, Spina Date seed, and Oriental Waterplantain rhizome (Table 1). BSNXD has been used for hundreds of years to treat and prevent menopauserelated disorders and age-related diseases (6), including osteoporosis.…”

Irradiated U937 Cells Trigger Inflammatory Bystander Responses in Human Umbilical Vein Endothelial Cells through the p38 Pathway

“…NO can react with reactive oxygen species (ROS) to form peroxynitrite that may lead to nitrosylation or nitration on tyrosine residues of proteins (52,53) and thus alter the activities of these proteins. The small quantity of NO generated through eNOS has a protective effect in atherosclerotic lesions (54). Conversely, the inflammatory environment in human atherosclerotic lesion results in The relative expression level of MMP-9 activity.…”

Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines

“…The availability of well curated databases of ingredients of traditional Chinese medicines has opened up new avenues for molecular screening as well as in-silico studies, including target-based docking (Chen et al, 2006; Fang et al, 2008; Chen, 2011; Zhou, Xie & Yan, 2011). In depth screens of Chinese medicine derived compounds have been performed for a variety of pathophysiologies, including cancer (Hu et al, 2013), inflammatory diseases (Han & Guo, 2012; Su & Hsieh, 2011), cardiovascular diseases (Wang et al, 2013) and infections (Jiang, Deng & Wu, 2013), just to name a few. These databases are being extensively used for therapeutic development (Cheng et al, 2010).…”