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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-activated RORα reporter luciferase activity. Transient transfected HEK293 cells containing RORα (3× RORE) reporter luciferase plasmids were stimulated with the indicated doses of bavachalcone for 16 h. The cells were lysed and analyzed for luciferase activity (n = 3). Data are expressed as the mean ± SD. ∗P < 0.05 versus vehicle control; ∗∗P < 0.01 versus vehicle control.
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fig1: Bavachalcone-activated RORα reporter luciferase activity. Transient transfected HEK293 cells containing RORα (3× RORE) reporter luciferase plasmids were stimulated with the indicated doses of bavachalcone for 16 h. The cells were lysed and analyzed for luciferase activity (n = 3). Data are expressed as the mean ± SD. ∗P < 0.05 versus vehicle control; ∗∗P < 0.01 versus vehicle control.

Mentions: Bavachalcone Induces RORα1 Expression and Regulates Bmal1 Circadian Rhythm. In the screening of natural ingredient activity, bavachalcone exhibited characteristics that can activate RORα1 expression (Table 1). Bavachalcone's dose effect relationship showed that it dose-dependently activated RORα1 luciferase reporter gene activity, causing a more than 3-fold increase at a dose of 20 μmol/L (n = 3, P < 0.01, Figure 1). Moreover, bavachalcone dose-dependently induced RORα1 expression in mRNA and protein levels, causing a more than 2-fold increase in mRNA expression (n = 3, P < 0.01, Figure 2(a)) and a 6-fold increase in protein expression (n = 3, P < 0.01, Figure 2(b)) at a dose of 20 μmol/L. Furthermore, bavachalcone dynamically regulated circadian gene Bmal1 mRNA expression, a RORα1 downstream signal. As shown in Figures 3(a) and 3(b), from 24 to 48 h after 50% serum shock, treatment with bavachalcone enhanced the circadian amplitude of Bmal1 mRNA expression on 28, 36, and 40 h, which was far wider than other time points compared with the control, with the differences being significant (n = 3, P < 0.01) at each time point.


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-activated RORα reporter luciferase activity. Transient transfected HEK293 cells containing RORα (3× RORE) reporter luciferase plasmids were stimulated with the indicated doses of bavachalcone for 16 h. The cells were lysed and analyzed for luciferase activity (n = 3). Data are expressed as the mean ± SD. ∗P < 0.05 versus vehicle control; ∗∗P < 0.01 versus vehicle control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493309&req=5

fig1: Bavachalcone-activated RORα reporter luciferase activity. Transient transfected HEK293 cells containing RORα (3× RORE) reporter luciferase plasmids were stimulated with the indicated doses of bavachalcone for 16 h. The cells were lysed and analyzed for luciferase activity (n = 3). Data are expressed as the mean ± SD. ∗P < 0.05 versus vehicle control; ∗∗P < 0.01 versus vehicle control.
Mentions: Bavachalcone Induces RORα1 Expression and Regulates Bmal1 Circadian Rhythm. In the screening of natural ingredient activity, bavachalcone exhibited characteristics that can activate RORα1 expression (Table 1). Bavachalcone's dose effect relationship showed that it dose-dependently activated RORα1 luciferase reporter gene activity, causing a more than 3-fold increase at a dose of 20 μmol/L (n = 3, P < 0.01, Figure 1). Moreover, bavachalcone dose-dependently induced RORα1 expression in mRNA and protein levels, causing a more than 2-fold increase in mRNA expression (n = 3, P < 0.01, Figure 2(a)) and a 6-fold increase in protein expression (n = 3, P < 0.01, Figure 2(b)) at a dose of 20 μmol/L. Furthermore, bavachalcone dynamically regulated circadian gene Bmal1 mRNA expression, a RORα1 downstream signal. As shown in Figures 3(a) and 3(b), from 24 to 48 h after 50% serum shock, treatment with bavachalcone enhanced the circadian amplitude of Bmal1 mRNA expression on 28, 36, and 40 h, which was far wider than other time points compared with the control, with the differences being significant (n = 3, P < 0.01) at each time point.

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