title: Homoplantaginin Inhibits Palmitic Acid-induced Endothelial Cells Inflammation by Suppressing TLR4 and NLRP3 Inflammasome.
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.
authors.affiliation: Departments of *Pharmacology of Chinese Materia Medica; †Traditional Chinese Pharmacy; and ‡Natural Medicinal Chemistry, China Pharmaceutical University, Jiangsu, China.
authors.forename: Baiqiu
authors.initials: B
authors.lastname: He
authors.forename: Baobao
authors.initials: B
authors.lastname: Zhang
authors.forename: Feihua
authors.initials: F
authors.lastname: Wu
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Shi
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.forename: Yining
authors.initials: Y
authors.lastname: Lin
authors.forename: Shiping
authors.initials: S
authors.lastname: Ma
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liang
mesh_terms: D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019308:Palmitic Acid / Q000633:toxicity*; D027561:Salvia miltiorrhiza; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C403862:6-methoxy-4',5-dihydroxyflavone-7-O-glucoside; D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D005960:Glucosides; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019308:Palmitic Acid