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Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway.

Wang Q, Cheng XL, Zhang DY, Gao XJ, Zhou L, Qin XY, Xie GY, Liu K, Qin Y, Liu BL, Qin MJ - PLoS ONE (2013)

Bottom Line: Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential.Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation.Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Resource Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

ABSTRACT
Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance.

No MeSH data available.


Related in: MedlinePlus

Tectorigenin reduced ET-1 and VCAM-1 expression in PA-stimulated endothelial cells.HUVECs were pretreated with tectorigenin, PD98059 or wortmannin (Wort) for 0.5 h and incubated with PA (100 μM) for another 2 h. Then cells were stimulated with or without insulin (0.1 μM) for 20 min. ET-1 (A) and VCAM-1 (B) mRNA expression was detected by RT-PCR. Salicylate was taken as a positive control. The results were expressed as the mean±SD of three independent experiments. #p<0.05 vs. blank 2 (Bla2); * p<.05 vs. control 2 (Cont2).
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pone-0066417-g007: Tectorigenin reduced ET-1 and VCAM-1 expression in PA-stimulated endothelial cells.HUVECs were pretreated with tectorigenin, PD98059 or wortmannin (Wort) for 0.5 h and incubated with PA (100 μM) for another 2 h. Then cells were stimulated with or without insulin (0.1 μM) for 20 min. ET-1 (A) and VCAM-1 (B) mRNA expression was detected by RT-PCR. Salicylate was taken as a positive control. The results were expressed as the mean±SD of three independent experiments. #p<0.05 vs. blank 2 (Bla2); * p<.05 vs. control 2 (Cont2).

Mentions: In addition to promoting NO production, insulin also stimulates ET-1 and adhesion molecule expression (VCAM-1) in endothelial cells through MAPK (ERK) pathways. The balance between PI3K-dependent and MAPK-dependent functions of insulin plays a key role in the maintenance of the endothelial homeostasis. In this study, insulin increased the basal expression of ET-1 and VCAM-1, and this action was enhanced by wortmannin treatment. When endothelial cells were exposed to PA, ET-1 and VCAM-1 expression in response to insulin was further increased. But tectorigenin effectively inhibited ET-1 and VCAM-1 overexpression in a concentration-dependent manner. PD98059, a specific inhibitor of ERK, also downregulated ET-1 and VCAM-1 expression as tectorigenin did, indicating the involvement of ERK activation. The results were shown in Figure 7A and B.


Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway.

Wang Q, Cheng XL, Zhang DY, Gao XJ, Zhou L, Qin XY, Xie GY, Liu K, Qin Y, Liu BL, Qin MJ - PLoS ONE (2013)

Tectorigenin reduced ET-1 and VCAM-1 expression in PA-stimulated endothelial cells.HUVECs were pretreated with tectorigenin, PD98059 or wortmannin (Wort) for 0.5 h and incubated with PA (100 μM) for another 2 h. Then cells were stimulated with or without insulin (0.1 μM) for 20 min. ET-1 (A) and VCAM-1 (B) mRNA expression was detected by RT-PCR. Salicylate was taken as a positive control. The results were expressed as the mean±SD of three independent experiments. #p<0.05 vs. blank 2 (Bla2); * p<.05 vs. control 2 (Cont2).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3686685&req=5

pone-0066417-g007: Tectorigenin reduced ET-1 and VCAM-1 expression in PA-stimulated endothelial cells.HUVECs were pretreated with tectorigenin, PD98059 or wortmannin (Wort) for 0.5 h and incubated with PA (100 μM) for another 2 h. Then cells were stimulated with or without insulin (0.1 μM) for 20 min. ET-1 (A) and VCAM-1 (B) mRNA expression was detected by RT-PCR. Salicylate was taken as a positive control. The results were expressed as the mean±SD of three independent experiments. #p<0.05 vs. blank 2 (Bla2); * p<.05 vs. control 2 (Cont2).
Mentions: In addition to promoting NO production, insulin also stimulates ET-1 and adhesion molecule expression (VCAM-1) in endothelial cells through MAPK (ERK) pathways. The balance between PI3K-dependent and MAPK-dependent functions of insulin plays a key role in the maintenance of the endothelial homeostasis. In this study, insulin increased the basal expression of ET-1 and VCAM-1, and this action was enhanced by wortmannin treatment. When endothelial cells were exposed to PA, ET-1 and VCAM-1 expression in response to insulin was further increased. But tectorigenin effectively inhibited ET-1 and VCAM-1 overexpression in a concentration-dependent manner. PD98059, a specific inhibitor of ERK, also downregulated ET-1 and VCAM-1 expression as tectorigenin did, indicating the involvement of ERK activation. The results were shown in Figure 7A and B.

Bottom Line: Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential.Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation.Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Resource Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

ABSTRACT
Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance.

No MeSH data available.


Related in: MedlinePlus