Salvianolic acid A suppress lipopolysaccharide-induced NF-κB signaling pathway by targeting IKKβ

Oh, Kwang‐Seok; Oh, Byung Koo; Mun, Jihye; Seo, Ho Won; Lee, Byung Ho

doi:10.1016/j.intimp.2011.07.022

Cited by 60 publications

(39 citation statements)

References 28 publications

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“…2), a finding that further favor the beneficial effect of SalA on vasculature system. The mechanisms elucidating the role of SalA in regulation of biological processes in endothelial cells, vascular smooth muscle cells, and cardiomyocytes have been investigated [25,26,27]. It has been described that SalA might be a cardiovascular protective agent during reperfusion injury, mainly through its anti-apoptosis activity via induction of Bcl-2 and inhibition of Bax [28,29].…”

Section: Discussionmentioning

confidence: 99%

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Xie¹,

Duan

Guo³

et al. 2015

Cell Physiol Biochem

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Background: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. Conclusion: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression.

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Section: Discussionmentioning

confidence: 99%

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Xie¹,

Duan

Guo³

et al. 2015

Cell Physiol Biochem

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“…Studies demonstrated that SalA has various pharmacological effects such as anti-ischemia [12], anti-inflammation [13] and anti-diabetic [14]. Especially, SalA displays a beneficial effect on diabetic complications, including hepatic fibrosis [15], diabetic vascular endothelial dysfunction [16] and diabetic peripheral neuropathy [17].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling

Hou

Qiang

Zhao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Glomerular endothelium dysfunction leads to the progression of renal architectonic and functional abnormalities in early-stage diabetic nephropathy (DN). Advanced glycation end products (AGEs) and receptor for AGEs (RAGE) are proved to play important roles in diabetic nephropathy. This study investigated the role of Salvianolic acid A (SalA) on early-stage DN and its possible underlying mechanism. Methods: In vitro AGEs formation and breaking rate were measured to illustrate the effect of SalA on AGEs. Type 2 diabetic nephropathy rats were induced by high-fat diet and low-dose streptozocin (STZ). After eight-week treatment with SalA 1 mg/kg/day, 24h-urine protein, creatinine clearance was tested and renal structural injury was assessed by PAS and PASM staining. Primary glomerular endothelial cell permeability was evaluated after exposed to AGEs. AGEs-induced RhoA/ROCK and subsequently activated disarrange of cytoskeleton were assessed by western blot and immunofluorescence. Results: Biochemical assay and histological examination demonstrated that SalA markedly reduced endothelium loss and glomerular hyperfiltration, suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced urinary albumin and ameliorated renal function. Further investigation suggested that SalA exerted its renoprotective effects through inhibiting AGE-RAGE signaling. It not only inhibited formation of AGEs and increased its breaking in vitro, but also reduced AGEs accumulation in vivo and downregulated RAGE expression. SalA restored glomerular endothelial permeability through suppressing AGEs-induced rearrangement of actin cytoskeleton via AGE-RAGE-RhoA/ ROCK pathway. Moreover, SalA attenuated oxidative stress induced by AGEs, subsequently alleviated inflammation and restored the disturbed autophagy in glomerular endothelial cell and diabetic rats via AGE-RAGE-Nox4 axis. Conclusion: Our study indicated that SalA restored glomerular endothelial function and alleviated renal structural deterioration through inhibiting AGE-RAGE, thus effectively ameliorated early-stage diabetic nephropathy. SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

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“…The synergistic effect was further confirmed with fixed-ratio experimental design. In fact, previous studies also reported similar anti-inflammatory effect of the pharmacological active constituents of Danshen (salvianolic acid B (SAB) and tanshinone IIA) (Jang et al, 2003;Oh et al, 2011) and Gegen (daidzein) (Jun et al, 2005). However, only hydrophilic constituents can be identified in HPLC analysis of DGE (Lam et al, 2010).…”

Section: Discussionmentioning

confidence: 80%

The roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen) inhibit atherogenic events: A study of the combination effects of the 2-herb formula

Cheung

Koon

et al. 2012

Journal of Ethnopharmacology

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Salvianolic acid A suppress lipopolysaccharide-induced NF-κB signaling pathway by targeting IKKβ

Cited by 60 publications

References 28 publications

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression

Salvianolic Acid A Protects Against Diabetic Nephropathy through Ameliorating Glomerular Endothelial Dysfunction via Inhibiting AGE-RAGE Signaling

The roots of Salvia miltiorrhiza (Danshen) and Pueraria lobata (Gegen) inhibit atherogenic events: A study of the combination effects of the 2-herb formula

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