• Archives of Pharmacal Research
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• v.28 no.8
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• pp.877-884
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• 2005

A number of wogonin derivatives have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of $PGE_2$ production. Wogonin derivatives modified at the B ring of wogonin were obtained from 2,4-Dihydroxy-3,6-dimethoxyacetophenone (1) via several steps. Most wogonin derivatives exhibited much reduced inhibitory activities against COX-2 catalyzed $PGE_2$ production compared to that of wogonin. Alkylation of 5,7-phenol groups and substitution at the B ring of wogonin generally caused reduction of inhibitory activity.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.442-448
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone) is a down-regulator of cyclooxygenase-2 and inducible nitric oxide synthase expression, contributing to anti-inflammatory activity in vivo. For further characterization of modulatory activity on ploinflammatory gene expression in vivo, the effect of wogonin was examined in this experiment using animal models of skin inflammation. By topical application, wogonin inhibited an edematic response as well as ploinflammatory gene expression against contact dermatitis In mice. Wogonin inhibited ear edema ($19.4-22.6\%$) at doses of $50-200\;{\mu}g$/ear and down-regulated interleukin-$1{\beta}$ induction ($23.1\%$) at $200{\mu}g$/ear in phenol-induced simple irritation. Wogonin ($2{\times}50-2{\times}200{\mu}g$/ear) also inhibited edematic response ($51.2-43.9\%$) and down-regulated ploinflammatory gene expression of cyclooxygenase-2, interleukin-$1{\beta}$, interferon-$\gamma$, intercellular adhesion molecule-1 and inducible nitric oxide synthase with some different sensitivity against picryl chloride-induced delayed hypersensitivity reaction. All these results clearly demonstrate that wogonin is a down-regulator of ploinflammatory gene expression in animal models of skin inflammation. Therefore, wogonin may have potential for a new anti-inflammatory agent against skin inflammation.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.216-219
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• 2005

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide ($H_{2}O_2$)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and $H_{2}O_2$-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.39-48
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• 2024

Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.930-936
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.418-421
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• 2009

Structural alterations of wogonin were conducted to observe the role of each functional group at the A-ring of wogonin on the inhibitory activities against COX-2 catalyzed $PGE_2$ production from LPS-induced RAW 264.7 cells. Serial deletion of the functional groups at the A-ring of wogonin exhibited low to comparable bioactivity. The present study validated that all the functional groups at the A-ring of wogonin are important factors to exhibit the optimum inhibitory activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.491-496
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• 2012

The purpose of this study is to investigate the modulatory effect of wogonin on hydrogen peroxide production in human blastoma SH-SY5Y cells induced by the synthetic analog of double-stranded RNA [polyinosinic-polycytidylic acid]. Hydrogen peroxide production was measured by dihydrorhodamine 123 (DHR) assay. Wogonin significantly inhibited the polyinosinic-polycytidylic acid (PIC)-induced production of hydrogen peroxide for 0.5, 2, 12, 18, and 24 hr incubation at the concentrations of 10, 25, and 50 ${\mu}M$ in SH-SY5Y (P < 0.05) in dose dependent manner. These results suggest that wogonin has neuroprotective property related with its inhibition of hydrogen peroxide production in PIC-induced neuronal cells.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.175.4-176
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• 2003

Our long-term research goals involve the SARs study and the synthetic procedure development of wogonin and its analogs. We investigated efficient synthetic pathways of wogonin and its bioisosteres in a large quantity to decipher the structural requirements for anti-inflammatory activities. We plan to serially delete or modify the 5,7-dihydroxyl groups of wogonin to observe the effects of the hydroxyl groups on anti-inflammatory activity. Also we modofied the 8- methoxy group on a ring since it is known to be necessary for biological activity. (omitted)