Brazilin Ameliorates High Glucose-Induced Vascular Inflammation via Inhibiting ROS and CAMs Production in Human Umbilical Vein Endothelial Cells

Jayakumar, Thanasekaran; Chang, Chao; Lin, Shoei Loong; Huang, Yung Kai; Hu, Chien Ming; Elizebeth, Antoinet Ramola; Lin, Shih Chang; Choy, Cheuk-Sing

doi:10.1155/2014/403703

Cited by 37 publications

(38 citation statements)

References 48 publications

(46 reference statements)

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“…These major cytokines also mediate the trans-migration of leukocytes to the endothelium leading to endothelial dysfunction and tissue damage. Activation of microvascular endothelial cell by TNF-α and IL-1β lead to increase COX-2 expression and PGE2 production (Turini and DuBois, 2002) while NFκB activation is associated with transcriptional regulation of ICAM-1 and VCAM-1 genes (Jayakumar et al, 2014). In order to determine specific mechanisms that underlie the possible anti-inflammatory effect of BRE, we used our organ specific human primary endothelial cells for modeling the endothelial-leukocyte interaction.…”

Section: Discussionmentioning

confidence: 99%

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

Medda

Lyros

Schmidt

et al. 2015

Microvascular Research

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Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat’s digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-α/IL-1β with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-α/IL-1β-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1β activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.

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Section: Discussionmentioning

confidence: 99%

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

Medda

Lyros

Schmidt

et al. 2015

Microvascular Research

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“…The levels of superoxide are elevated and the activities of antioxidant defense substances are reduced in the vessels of diabetic patients and rats, and in endothelial cells exposed to high glucose (HG) (7)(8)(9)(10). Elevated oxidative stress may cause injuries in vascular endothelial cells during the process of diabetic vascular complications (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…Elevated oxidative stress may cause injuries in vascular endothelial cells during the process of diabetic vascular complications (11)(12)(13). Excessive reactive oxygen species (ROS) and lipid peroxide initiate and promote endotheliocyte damage (1,7). The antioxidant status of diabetic patients is crucial in preventing oxidative stress and the process of vascular complications.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidant and anti-inflammatory effects of DHK-medicated serum on high glucose-induced injury in endothelial cells

Zhang

Chen

Wang

et al. 2017

Molecular Medicine Reports

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It has been shown that oxidative damage and inflammation caused by hyperglycemia in endothelial cells are key factors triggering diabetic vascular complications. The aim of the present study was to investigate the antioxidant and anti‑inflammatory effects of Danhong Huayu Koufuye (DHK)‑medicated serum on high glucose (HG)‑induced injury in endothelial cells, and examine its underlying mechanisms. EA. hy926 cells were treated with normal glucose, HG, or HG with DHK‑medicated serum. Cell viability was assessed using the MTT method. Apoptosis was detected using flow cytometry. Intracellular reactive oxygen species (ROS) levels were measured using the 2',7'‑dichlorodihydrofluorescein method. Cell culture supernatant was collected for detecting the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA). The protein expression levels of intercellular adhesion molecule‑1 (ICAM‑1), nuclear factor‑κB (NF‑κB), hypoxia‑inducible factor‑1α (HIF‑1α) and vascular endothelial growth factor (VEGF) were determined using western blot analysis. The results revealed that DHK‑medicated serum accelerated the proliferation and inhibited the apoptosis of cells treated with HG (P<0.01) in a dose‑dependent manner. Compared with the HG group, the high levels of ROS and MDA were significantly reduced by DHK‑medicated serum (P<0.01). A 10% concentration of DHK‑medicated serum increased the activities of SOD and GPx by 59.4 and 95.5%, respectively. The high protein expression levels of ICAM‑1, NF‑κB, VEGF and HIF‑1α were significantly ameliorated by DHK‑medicated serum (P<0.01, vs. HG group). These findings indicated that DHK‑medicated serum protected EA. hy926 cells from HG‑induced injury and apoptosis through antioxidation and anti‑inflammatory effects.

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“…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)-BB [17] and ameliorates high glucose-induced vascular inflammation in human umbilical vein endothelial cells [18] . In addition, the effects and some related mechanisms of brazilin in the vascular system have been described.…”

Section: Introductionmentioning

confidence: 99%

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

Yan¹,

Chen²,

Lin³

et al. 2015

Acta Pharmacol Sin

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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 EC 50 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 endotheliumdenuded 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 receptoroperated Ca 2+ channels.

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Brazilin Ameliorates High Glucose-Induced Vascular Inflammation via Inhibiting ROS and CAMs Production in Human Umbilical Vein Endothelial Cells

Cited by 37 publications

References 48 publications

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

Antioxidant and anti-inflammatory effects of DHK-medicated serum on high glucose-induced injury in endothelial cells

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

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