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Bavachalcone Enhances RORα Expression, Controls Bmal1 Circadian Transcription, and Depresses Cellular Senescence in Human Endothelial Cells.

Dang Y, Ling S, Ma J, Ni R, Xu JW - Evid Based Complement Alternat Med (2015)

Bottom Line: Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker of replicative senescence) and IL-1α (a proinflammatory cytokine of the senescence-associated secretory phenotype).These inhibitory effects were partially reversed by the RORα inhibitor VPR-66.Our results demonstrate that bavachalcone, as a natural medicine ingredient, has a pharmacological function in regulating RORα1.

View Article: PubMed Central - PubMed

Affiliation: Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
The circadian clock regulates many aspects of (patho)physiology in the central nervous system and in the peripheral tissues. RAR-related orphan receptor α (RORα), an orphan nuclear receptor, is involved in circadian rhythm regulation, including regulation of cardiovascular function. Bavachalcone, a prenylchalcone, is a major bioactive chalcone isolated from Psoralea corylifolia. This natural ingredient activated RORα1 luciferase reporter activity on drug screening. In addition, bavachalcone induced RORα1 expression in mRNA and protein levels in a dose-dependent manner and enhanced the circadian amplitude of Bmal1 mRNA expression after serum shock. Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker of replicative senescence) and IL-1α (a proinflammatory cytokine of the senescence-associated secretory phenotype). These inhibitory effects were partially reversed by the RORα inhibitor VPR-66. Our results demonstrate that bavachalcone, as a natural medicine ingredient, has a pharmacological function in regulating RORα1.

No MeSH data available.


Related in: MedlinePlus

Bavachalcone-delayed senescence of HUVEC. (a and b) HUVECs were passaged from the 10th to the 40th generation and cultured with or without bavachalcone. Subsequently, the cells were dyed using a β-galactosidase senescence assay kit. The percentage of senescent cells was obtained by counting more than 500 cells in each sample (n = 5 each). Data are expressed as the mean ± SD. ∗∗P < 0.01 versus p10 passage vehicle control. ##P < 0.01 versus p40 passage vehicle control.
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fig4: Bavachalcone-delayed senescence of HUVEC. (a and b) HUVECs were passaged from the 10th to the 40th generation and cultured with or without bavachalcone. Subsequently, the cells were dyed using a β-galactosidase senescence assay kit. The percentage of senescent cells was obtained by counting more than 500 cells in each sample (n = 5 each). Data are expressed as the mean ± SD. ∗∗P < 0.01 versus p10 passage vehicle control. ##P < 0.01 versus p40 passage vehicle control.

Mentions: Bavachalcone Suppressed Replicative Senescence of Endothelial Cells Partially through RORα1-Bmal1 Pathway. Bavachalcone saliently delayed the replicative senescence of endothelial cells; bavachalcone treatment reduced the senescent cell ratio from 26.4% ± 3.0% to 11.3% ± 1.2% at the p40 passage (n = 5, P < 0.01, Figures 4(a) and 4(b)). Subsequently, to determine the relationship between cellular senescence and RORα, endothelial cells were incubated with the RORα inhibitor VPR-66 for 24 h. The results revealed that VPR-66 partially antagonized the antiaging effect of bavachalcone (n = 5, P < 0.05, Figures 5(a) and 5(b)). To clearly define the status of cellular senescence, the mRNA expression of p16ink4a and IL-1α was determined. Vascular endothelial cells undergoing replicative senescence exhibited increased expression of p16ink4a and IL-1α mRNA, but their expression was significantly suppressed by bavachalcone (n = 3 each, P < 0.01, Figures 5(c) and 5(d)). However, coincubation with the RORα inhibitor VPR-66 for 24 h partially reversed the inhibitory effect of bavachalcone on the mRNA expressions of p16ink4a and IL-1α (n = 3, P < 0.05, Figures 5(c) and 5(d)).


Bavachalcone Enhances RORα Expression, Controls Bmal1 Circadian Transcription, and Depresses Cellular Senescence in Human Endothelial Cells.

Dang Y, Ling S, Ma J, Ni R, Xu JW - Evid Based Complement Alternat Med (2015)

Bavachalcone-delayed senescence of HUVEC. (a and b) HUVECs were passaged from the 10th to the 40th generation and cultured with or without bavachalcone. Subsequently, the cells were dyed using a β-galactosidase senescence assay kit. The percentage of senescent cells was obtained by counting more than 500 cells in each sample (n = 5 each). Data are expressed as the mean ± SD. ∗∗P < 0.01 versus p10 passage vehicle control. ##P < 0.01 versus p40 passage vehicle control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: Bavachalcone-delayed senescence of HUVEC. (a and b) HUVECs were passaged from the 10th to the 40th generation and cultured with or without bavachalcone. Subsequently, the cells were dyed using a β-galactosidase senescence assay kit. The percentage of senescent cells was obtained by counting more than 500 cells in each sample (n = 5 each). Data are expressed as the mean ± SD. ∗∗P < 0.01 versus p10 passage vehicle control. ##P < 0.01 versus p40 passage vehicle control.
Mentions: Bavachalcone Suppressed Replicative Senescence of Endothelial Cells Partially through RORα1-Bmal1 Pathway. Bavachalcone saliently delayed the replicative senescence of endothelial cells; bavachalcone treatment reduced the senescent cell ratio from 26.4% ± 3.0% to 11.3% ± 1.2% at the p40 passage (n = 5, P < 0.01, Figures 4(a) and 4(b)). Subsequently, to determine the relationship between cellular senescence and RORα, endothelial cells were incubated with the RORα inhibitor VPR-66 for 24 h. The results revealed that VPR-66 partially antagonized the antiaging effect of bavachalcone (n = 5, P < 0.05, Figures 5(a) and 5(b)). To clearly define the status of cellular senescence, the mRNA expression of p16ink4a and IL-1α was determined. Vascular endothelial cells undergoing replicative senescence exhibited increased expression of p16ink4a and IL-1α mRNA, but their expression was significantly suppressed by bavachalcone (n = 3 each, P < 0.01, Figures 5(c) and 5(d)). However, coincubation with the RORα inhibitor VPR-66 for 24 h partially reversed the inhibitory effect of bavachalcone on the mRNA expressions of p16ink4a and IL-1α (n = 3, P < 0.05, Figures 5(c) and 5(d)).

Bottom Line: Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker of replicative senescence) and IL-1α (a proinflammatory cytokine of the senescence-associated secretory phenotype).These inhibitory effects were partially reversed by the RORα inhibitor VPR-66.Our results demonstrate that bavachalcone, as a natural medicine ingredient, has a pharmacological function in regulating RORα1.

View Article: PubMed Central - PubMed

Affiliation: Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
The circadian clock regulates many aspects of (patho)physiology in the central nervous system and in the peripheral tissues. RAR-related orphan receptor α (RORα), an orphan nuclear receptor, is involved in circadian rhythm regulation, including regulation of cardiovascular function. Bavachalcone, a prenylchalcone, is a major bioactive chalcone isolated from Psoralea corylifolia. This natural ingredient activated RORα1 luciferase reporter activity on drug screening. In addition, bavachalcone induced RORα1 expression in mRNA and protein levels in a dose-dependent manner and enhanced the circadian amplitude of Bmal1 mRNA expression after serum shock. Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker of replicative senescence) and IL-1α (a proinflammatory cytokine of the senescence-associated secretory phenotype). These inhibitory effects were partially reversed by the RORα inhibitor VPR-66. Our results demonstrate that bavachalcone, as a natural medicine ingredient, has a pharmacological function in regulating RORα1.

No MeSH data available.


Related in: MedlinePlus