Homoplantaginin Inhibits Palmitic Acid-induced Endothelial Cells Inflammation by Suppressing TLR4 and NLRP3 Inflammasome. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: He, Baiqiu; Zhang, Baobao; Wu, Feihua; Wang, Liying; Shi, Xiaoji; Qin, Weiwei; Lin, Yining; Ma, Shiping; Liang, Jingyu
• Is Part Of: Journal of cardiovascular pharmacology. Volume 67:Issue 1(2016)
• Publication Date: 2016-01
• Subjects: homoplantaginin -- palmitic acid -- vascular endothelial cells -- TLR4 -- NLRP3 inflammasome; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000318
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Abstract: Palmitic acid (PA)-induced vascular endothelial inflammation plays a pivotal role in the occurrence and development of vascular diseases. The present study was conducted to examine the effect of homoplantaginin, a main flavonoid from a traditional Chinese medicine Salvia plebeia R. Br., on PA-treated human umbilical vein endothelial cells inflammation and the underlying molecular mechanism. Firstly, we found that homoplantaginin (0.1, 1, 10 μM) dose-dependently reduced expression of toll-like receptor-4 evoked by PA (100 μM). The inhibitory effect of homoplantaginin was further confirmed under lipopolysaccharide challenge. In addition, downstream adapted proteins including myeloid differentiation primary response gene 88, toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-β and tumor necrosis factors receptor associated factor-6 were successfully inhibited by homoplantaginin under PA treatment. Also, we found that homoplantaginin tightly controlled PA-induced reactive oxygen species to prevent nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome activation by suppressing reactive oxygen species-sensitive thioredoxin-interacting protein, NLRP3, and caspase-1. Meanwhile, protein and mRNA levels of inflammatory mediators (interleukin-1β, intercellular cell adhesion molecule-1, and monocyte chemotactic protein-1) were decreased by homoplantaginin. Furthermore, homoplantaginin restored PA-impaired nitric oxide generation. Taken together, these results indicated that homoplantaginin protected endothelial cells from ameliorating PA-induced endothelial inflammation via suppressing toll-like receptor-4 and NLRP3 pathways, and restoring nitric oxide generation, suggesting it may be a potential candidate for further development in the prevention and treatment of vascular diseases.