| Description: |
Wogonin is an inhibitor of CDK9, which has anti-inflammatory and anti-tumor activities, it could be developed into an efficient natural sensitizer for resistant human myelogenous leukemia. It has a wide spectrum of targets including PGE2, NO, Nrf2, Src, MEK1/2, ERK1/2, NFκB,MLCK, MLC.
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| Targets: |
Caspase | Nrf2 | PGE | NO | Src | MEK | ERK | NF-kB | COX | VEGFR | TLR | DNA-PK | PI3K | Akt | IFN-γ | p65 | p38MAPK | JNK | MLCK | MLC | CDK9 |
| In vitro: |
| Am J Respir Crit Care Med. 2015 Mar 15;191(6):626-36. | | Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation.[Pubmed: 25629436] | Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites.
To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice.
METHODS AND RESULTS:
Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured.
Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo.
CONCLUSIONS:
Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. | | Environ Toxicol. 2014 Oct;29(10):1162-70. | | Wogonin attenuates endotoxin-induced prostaglandin E2 and nitric oxide production via Src-ERK1/2-NFκB pathway in BV-2 microglial cells.[Pubmed: 23362215] | Microglia are the major component of intrinsic brain immune system in neuroinflammation. Although wogonin expresses anti-inflammatory function in microglia, little is known about the molecular mechanisms of the protective effect of wogonin against microglia activation. The aim of this study was to evaluate how wogonin exerts its anti-inflammatory function in BV2 microglial cells after LPS/INFγ administration.
METHODS AND RESULTS:
Wogonin not only inhibited LPS/ INFγ-induced PGE2 and NO production without affecting cell viability but also exhibited parallel inhibition on LPS/INFγ-induced expression of iNOS and COX-2 in the same concentration range. While LPS/INFγ-induced expression of P-p65 and P-IκB was inhibited by wogonin-only weak inhibition on P-p38 and P-JNK were observed, whereas it significantly attenuated the P-ERK1/2 and its upstream activators P-MEK1/2 and P-Src in a parallel concentration-dependent manner.
CONCLUSIONS:
These results indicated that the blockade of PGE2 and NO production by wogonin in LPS/INFγ-stimulated BV2 cells is attributed mainly to interference in the Src-MEK1/2-ERK1/2-NFκB-signaling pathway. |
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| In vivo: |
| 2017 Sep;50:95-106. | | Wogonin attenuates inflammation by activating PPAR-γ in alcoholic liver disease[Pubmed: 28646664] | | Alcoholic liver disease (ALD) is one of the predominant causes of liver-related morbidity and mortality worldwide. However, effective therapy for ALD is still lacking. Wogonin, a major flavonoid compound, is found in Scutellaria baicalensis Georgi. Accumulating studies have revealed that wogonin possesses anti-inflammatory and anti-tumour activities in various models. However, the hepatoprotective activity of wogonin in ALD is still obscure. In this study, we found that wogonin significantly attenuated inflammatory response in EtOH-fed mice, and reduced the expression of inflammatory cytokines such as TNF-α and IL-6 in EtOH-induced RAW264.7 cells. Furthermore, our findings showed that wogonin remarkably induced the expression of PPAR-γ in vivo and in vitro. Compared with the wogonin-treated group, blockade of PPAR-γ with inhibitor (T0070907) or PPAR-γ small interfering (si)-RNA were applied in RAW264.7 cells to evaluate the involvement of wogonin in alleviating EtOH-induced inflammation. Moreover, forced expression of PPAR-γ further suppressed the expression of TNF-α and IL-6 when treated with wogonin on EtOH-induced RAW264.7 cells. In addition, it was demonstrated that wogonin remarkably suppressed PPAR-γ-meditated phosphorylation and activation of NF-κB-P65. In conclusion, our results indicated that wogonin may serve as an effective modulator of PPAR-γ by down-regulating NF-κB pathway, thereby attenuated inflammatory response in ALD.
Keywords: Alcoholic liver disease (ALD); Inflammation; NF-κB; PPAR-γ; Wogonin. |
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