ReferenceID 4859

Cardamonin inhibits osteogenic differentiation of human valve interstitial cells and ameliorates aortic valve calcification via interfering in the NF-κB/NLRP3 inflammasome pathway

Food Funct

Cardamonin (CDM) is a natural chalcone with strong anti-inflammatory properties. Inflammation-induced osteogenic changes in valve interstitial cells (VICs) play crucial roles in the development of calcific aortic valve d

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Reference Id: 4859
Evidence Id: 21449
Core Evidence Id: 21449
Source Reference Id: 2963
Herb2 Reference Id: HBREF003760
Subject Paper Key: HBIN019722_34766179
Pubmed Id: 34766179
Doi: 10.1039/d1fo00813g
Paper Title: Cardamonin inhibits osteogenic differentiation of human valve interstitial cells and ameliorates aortic valve calcification via interfering in the NF-κB/NLRP3 inflammasome pathway
Paper Abstract: Cardamonin (CDM) is a natural chalcone with strong anti-inflammatory properties. Inflammation-induced osteogenic changes in valve interstitial cells (VICs) play crucial roles in the development of calcific aortic valve disease (CAVD), a degenerative disease characterized by degeneration, thickening, fibrosis, and calcification of the heart valve tissues. To investigate the anti-osteogenic differentiation role of CDM in human valve interstitial cells (hVICs), which consequently reverses the calcification of the aortic valve, human VICs were exposed to osteogenic induction medium (OM) with CDM for further cell viability, osteogenic gene and protein expression analyses, and anti-calcification testing. mRNA sequencing was utilized to analyze the differentially expressed genes (DEGs) and related signaling pathways as potential molecular targets involved in CDM's anti-calcification activity. Human aortic valve leaflet ex vivo calcific cultures were used to investigate the CDM inhibition of osteogenic differentiation of hVICs at the tissue level. ApoE-/- mice fed with a high-fat (HF) diet were used to evaluate the effect of CDM on aortic valve calcification. No significant CDM cytotoxicity was seen in the hVICs at 10 muM. The addition of CDM to OM prevented calcified nodule accumulation, and a decrease in the gene/protein expression levels of BMP2, RUNX2, SPP1, TNF-alpha, and COL1A2 was observed. Venn diagram analysis of the DEGs identified 666 common DEGs and highlighted the NOD-like receptor signaling pathway (ko04621) as an anti-calcification target of CDM. CDM also repressed the activation of p-AKT, p-ERK1/2, and p-IkappaBalpha, and prevented the OM-induced nuclear transcription of NF-kappaB p65. In the in vitro and ex vivo calcific conditional culture experiments, CDM exhibited anti-inflammatory and anti-calcification effects by suppressing the activation of the NLRP3 inflammasome and downregulating IL-1beta expression. In vivo, CDM ameliorated aortic valve calcification by interfering with NLRP3 expression. Our study demonstrated that CDM inhibited the phenotypical calcific transformation of hVICs by mediating the inactivation of the NF-kappaB/NLRP3 inflammasome. Therefore, it is considered to be a promising natural compound for use in preventing the progression of heart valve calcification disease.
Journal: Food Funct
Publish Year: 2021
Experiment Subject: mouse; human
Experiment Type: Cell Experiment
Phenotype Related: Aortic Valve Calcification; Heart Valve Calcification Disease; Degeneration, Thickening; Fibrosis; Calcific Aortic Valve Disease; Calcification Of The Heart Valve; Degenerative Disease
Paper Title Cn
Paper Title En: Cardamonin inhibits osteogenic differentiation of human valve interstitial cells and ameliorates aortic valve calcification via interfering in the NF-κB/NLRP3 inflammasome pathway
Bilingual Status: semi_complete