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Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings.

Yan Y, Chen YC, Lin YH, Guo J, Niu ZR, Li L, Wang SB, Fang LH, Du GH - Acta Pharmacol. Sin. (2015)

Bottom Line: The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin.Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC.Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.

ABSTRACT

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms.

Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay.

Results: Application of brazilin (10-100 μmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings.

Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

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Chemical structure of brazilin.
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fig1: Chemical structure of brazilin.

Mentions: Brazilin [7,11b-dihydrobenz(b)indeno[1,2-d]pyran-3,6a,9,10(6H)-tetrol] (Figure 1), one of the major components isolated from the heartwood of Caesalpinia sappan L, is a natural red pigment largely used for histological staining. In previous studies, several biological activities of brazilin have been reported, including anti-diabetic8,9, anti-inflammatory10,11, anti-asthma12, anti-platelet aggregation13, anti-tumor14, anti-oxidation15 and anti-acne16 effects. As a natural product, brazilin has aroused much attention, especially concerning its effect on cardiovascular diseases. Studies focused on the cardiovascular system showed that brazilin inhibits vascular smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB17 and ameliorates high glucose-induced vascular inflammation in human umbilical vein endothelial cells18. In addition, the effects and some related mechanisms of brazilin in the vascular system have been described. Brazilin relaxed phenylephrine-induced vasoconstriction, and this response could be inhibited by Nω-nitro-L-arginine methyl ester (L-NAME), Nω-monomethyl-L-arginine acetate (L-NMMA), methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and hemoglobin, suggesting that the mechanism by which brazilin caused vasodilation might be endothelium-dependent19,20. However, vasoconstriction is a complicated process, involving not only endothelium but also other factors such as K+ channels and Ca2+ channels. Therefore, it is not enough to explain mechanisms of brazilin-induced vasodilation from the endothelium and related factors because complete and clear mechanisms for interpretation still need to be clarified.


Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings.

Yan Y, Chen YC, Lin YH, Guo J, Niu ZR, Li L, Wang SB, Fang LH, Du GH - Acta Pharmacol. Sin. (2015)

Chemical structure of brazilin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644902&req=5

fig1: Chemical structure of brazilin.
Mentions: Brazilin [7,11b-dihydrobenz(b)indeno[1,2-d]pyran-3,6a,9,10(6H)-tetrol] (Figure 1), one of the major components isolated from the heartwood of Caesalpinia sappan L, is a natural red pigment largely used for histological staining. In previous studies, several biological activities of brazilin have been reported, including anti-diabetic8,9, anti-inflammatory10,11, anti-asthma12, anti-platelet aggregation13, anti-tumor14, anti-oxidation15 and anti-acne16 effects. As a natural product, brazilin has aroused much attention, especially concerning its effect on cardiovascular diseases. Studies focused on the cardiovascular system showed that brazilin inhibits vascular smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB17 and ameliorates high glucose-induced vascular inflammation in human umbilical vein endothelial cells18. In addition, the effects and some related mechanisms of brazilin in the vascular system have been described. Brazilin relaxed phenylephrine-induced vasoconstriction, and this response could be inhibited by Nω-nitro-L-arginine methyl ester (L-NAME), Nω-monomethyl-L-arginine acetate (L-NMMA), methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and hemoglobin, suggesting that the mechanism by which brazilin caused vasodilation might be endothelium-dependent19,20. However, vasoconstriction is a complicated process, involving not only endothelium but also other factors such as K+ channels and Ca2+ channels. Therefore, it is not enough to explain mechanisms of brazilin-induced vasodilation from the endothelium and related factors because complete and clear mechanisms for interpretation still need to be clarified.

Bottom Line: The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin.Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC.Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.

ABSTRACT

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms.

Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay.

Results: Application of brazilin (10-100 μmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings.

Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

Show MeSH
Related in: MedlinePlus