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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 reversed PA-induced collapse of mitochondrial membrane potential (Δψm) in HUVECs.Cells were pretreated with tectorigenin (0.1, 1, 10 μM) or GSH for 30 min, and then stimulated without or with PA (100 μM) for an additional 30 min. The blank was treated with an equal amount of the vehicle (medium containing 0.1% DMSO and 10% BSA). Fluorescence images were shown by using a fluorescence microscope, and the intensity of red fluorescence is used to assess Δψm.
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pone-0066417-g002: Tectorigenin reversed PA-induced collapse of mitochondrial membrane potential (Δψm) in HUVECs.Cells were pretreated with tectorigenin (0.1, 1, 10 μM) or GSH for 30 min, and then stimulated without or with PA (100 μM) for an additional 30 min. The blank was treated with an equal amount of the vehicle (medium containing 0.1% DMSO and 10% BSA). Fluorescence images were shown by using a fluorescence microscope, and the intensity of red fluorescence is used to assess Δψm.

Mentions: The effect of tectorigenin on mitochondrial membrane potential of cells was determined by a JC-1 mitochondrial membrane potential assay kit. JC-1 is a fluorescent dye that is concentrated by respiring mitochondria. JC-1 exists as a monomer that fluoresces green and forms J-aggregates with red fluorescence at low and high Δψm, respectively. In this study, Δψm was measured in terms of the relative intensity of JC-1 after HUVECs were stimulated with PA and tectorigenin. Figure 2 showed that PA stimulation decreased the mitochondrial membrane potential of HUVECs, implying the mitochondria damage. On the contrary, treatment of HUVECs with tectorigenin treament reversed this change evidenced by the restored Δψm. As a potent antioxidant, GSH was used as a positive control for the depolarized mitochondrial membrane potential and also showed a similar protective effect as tectorigenin.


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 reversed PA-induced collapse of mitochondrial membrane potential (Δψm) in HUVECs.Cells were pretreated with tectorigenin (0.1, 1, 10 μM) or GSH for 30 min, and then stimulated without or with PA (100 μM) for an additional 30 min. The blank was treated with an equal amount of the vehicle (medium containing 0.1% DMSO and 10% BSA). Fluorescence images were shown by using a fluorescence microscope, and the intensity of red fluorescence is used to assess Δψm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3686685&req=5

pone-0066417-g002: Tectorigenin reversed PA-induced collapse of mitochondrial membrane potential (Δψm) in HUVECs.Cells were pretreated with tectorigenin (0.1, 1, 10 μM) or GSH for 30 min, and then stimulated without or with PA (100 μM) for an additional 30 min. The blank was treated with an equal amount of the vehicle (medium containing 0.1% DMSO and 10% BSA). Fluorescence images were shown by using a fluorescence microscope, and the intensity of red fluorescence is used to assess Δψm.
Mentions: The effect of tectorigenin on mitochondrial membrane potential of cells was determined by a JC-1 mitochondrial membrane potential assay kit. JC-1 is a fluorescent dye that is concentrated by respiring mitochondria. JC-1 exists as a monomer that fluoresces green and forms J-aggregates with red fluorescence at low and high Δψm, respectively. In this study, Δψm was measured in terms of the relative intensity of JC-1 after HUVECs were stimulated with PA and tectorigenin. Figure 2 showed that PA stimulation decreased the mitochondrial membrane potential of HUVECs, implying the mitochondria damage. On the contrary, treatment of HUVECs with tectorigenin treament reversed this change evidenced by the restored Δψm. As a potent antioxidant, GSH was used as a positive control for the depolarized mitochondrial membrane potential and also showed a similar protective effect as tectorigenin.

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