Wogonin suppresses TNF-α-induced MMP-9 expression by blocking the NF-κB activation via MAPK signaling pathways in human aortic smooth muscle cells

Lee, Syng‐Ook; Jeong, Yun-Jeong; Yu, Mi Hee; Lee, Jiwon; Hwangbo, Mi Hyang; Kim, Cheorl-Ho; Lee, In-Seon

doi:10.1016/j.bbrc.2006.10.006

Cited by 78 publications

(55 citation statements)

References 37 publications

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“…Effects of wogonin on palmitate-induced apoptosis Wogonin modulates endothelial cell and VSMC functions to promote its anti-atherosclerotic effects [15][16][17] . Considering the pivotal roles of VSMC apoptosis [7][8][9][10][11][12] and the elevated plasma FFA levels [4,5] in atherosclerotic plaque ruptures, we investigated the potential effects of wogonin on palmitate-induced VSMC apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…Wogonin (5,7-dihydroxy-8-methoxyflavone) is a major bioactive component of the flavonoids from S baicalensis. Pharmacological findings have highlighted the therapeutic potential regarding the use of plant-derived wogonin to modulate endothelial cell and VSMC function for the prevention and treatment of atherosclerosis [15][16][17] . However, the underlying mechanism is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

et al. 2011

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Aim: To investigate the effects of wogonin (5,7-dihydroxy-8-methoxyflavone) extracted from Scutellaria baicalensis Georgi (S baicalensis) on lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) and the underlying mechanisms. Methods: Cultured VSMCs were used. Apoptosis of VSMCs was induced by palmitate (0.75 mmol/L), and detected using TUNEL assay. The expression levels of protein and phosphorylated protein were measured using Western blot analysis. Results: Treatment of VSMCs with wogonin (10, 25 and 50 µmol/L) significantly attenuated the apoptosis and endoplasmic reticulum (ER) stress induced by palmitate in concentration-and time-dependent manners. Wogonin (50 µmol/L) decreased palmitate-induced reactive oxygen species (ROS) generation. The ER stress inhibitor 4-phenyl butyric acid (5 mmol/L) significantly decreased palmitateinduced apoptotic cells, and occluded the anti-apoptotic effect of wogonin (25 µmol/L). Wogonin (10, 25 and 50 µmol/L) significantly reduced the intracellular diacylglycerol (DAG) accumulation and expression levels of phosphorylated PKCs in palmitate-treated VSMCs. Conclusion: Our results suggest that wogonin inhibits lipotoxicity-induced apoptosis of VSMCs via suppressing the intracellular DAG accumulation and subsequent inhibition of PKC phosphorylation. Wogonin has therapeutic potential for the prevention and treatment of atherosclerosis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

et al. 2011

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“…The flavonoids wogonin was shown to suppress TNF␣-induced MMP-9 expression by blocking NF-B activation via MAP kinase signaling pathways in human aortic smooth muscle cells (49,50). NF-B p65-specific small interfering RNA was shown to inhibit the expression of genes, including MMP-9, in IL-1␤-induced and TNF␣-induced chondrocytes in rats (48).…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C: Relevance to inflammation in rheumatoid arthritis

Xue

March

Sambrook

2007

Arthritis & Rheumatism

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Objective. To investigate the in vitro effect of activated protein C (APC), a natural anticoagulant and novel antiinflammatory agent, on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and MMP-9.Methods. Synovial fibroblasts and peripheral blood monocytes isolated from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and Mono Mac6 cells were used in this study. After treatment, cells and culture supernatants were collected for zymography, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analysis.Results. Fibroblasts and monocytes from RA patients produced substantially more MMP-9 than did those from OA patients; however, there was no difference in MMP-2 production. The addition of recombinant APC markedly reduced MMP-9 at the gene and protein levels. In contrast, APC up-regulated and activated MMP-2. Using a blocking antibody to the endothelial protein C receptor (EPCR), we showed that the inhibition of MMP-9 by APC was EPCR-dependent. Furthermore, APC directly suppressed the production of tumor necrosis factor (TNF) and the activation of NF-B and MAP kinase p38, and inhibitors of NF-B or p38 reduced the production of MMP-9, suggesting that APC inhibits MMP-9 by blocking TNF, NF-B, and p38. Thus, APC acts on MMP-9 by binding to EPCRs on the cell surface and, subsequently, inhibiting the intracellular activation of the proinflammatory signaling molecules NF-B and p38.Conclusion. APC appears to be the first physiologic agent to inhibit the production of proinflammatory MMP-9, yet increase antiinflammatory MMP-2 activity.

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“…Accumulating evidence suggests the therapeutic potential of wogonin for cancer treatment [10,11] . Current studies also [12,13] . We have recently found that wogonin is a potent antioxidant capable of inhibiting lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) via suppression of intracellular DAG generation [14] .…”

Section: Introductionmentioning

confidence: 99%

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Zhang

Tang

et al. 2015

Acta Pharmacol Sin

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Aim: Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes. Methods: Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively. Results: Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZinduced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression. Conclusion: Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.

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Wogonin suppresses TNF-α-induced MMP-9 expression by blocking the NF-κB activation via MAPK signaling pathways in human aortic smooth muscle cells

Cited by 78 publications

References 37 publications

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway

Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C: Relevance to inflammation in rheumatoid arthritis

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

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