wogonin and Edema

Glucocorticoid, such as dexamethasone, has anti-inflammatory and immunosuppressive action as major pharmacological effects. The latter action caused by lymphocyte apoptosis is not only a therapeutic effect but also an adverse reaction. Wogonin, a plant flavone found in Scutellaria baicalensis Georgi, inhibited dexamethasone-induced apoptotic changes, such as DNA fragmentation, nuclear condensation, phosphatidylserine translocation, and caspase activation in rat thymocytes. Since wogonin inhibited dexamethasone-induced DNA fragmentation in a noncompetitive manner, a target of this flavone is unlikely to be an antagonist of glucocorticoid receptor. Wogonin did not only act as an inhibitor of caspases, but also protected apoptosis induced by other glucocorticoids. Since wogonin reduced one of the major pharmacological effects of dexamethasone, we examined whether this flavone diminishes the anti-inflammatory action, another pharmacological effect. The anti-inflammatory action of dexamethasone was evaluated by carrageenan-induced paw edema model. Although dexamethasone significantly suppressed paw edema induced by carrageenan, wogonin had no effect on the anti-inflammatory action of dexamethasone. These results suggest that wogonin may be a useful compound to reduce the immunosuppressive side effect of glucocorticoid.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cells, Cultured; Dexamethasone; Drugs, Chinese Herbal; Edema; Flavanones; Hydrocortisone; Immunosuppressive Agents; Lymphocytes; Male; Rats; Rats, Sprague-Dawley; Thymus Gland

The effect of wogonin, a flavone highly purified from the roots of Scutellaria baicalensis, on apoptotic cell death was re-evaluated in rat thymocytes. This flavone inhibited glucocorticoid-induced apoptotic changes such as DNA fragmentation, phosphatidylserine translocation, and nuclear condensation in rat thymocytes. Similar inhibition was also observed in apoptosis induced by other inducers such as etoposide. No significant changes of these apoptotic features were observed in rat thymocytes treated with wogonin alone, suggesting that this flavone protects against glucocorticoid-mediated immunosuppression caused by thymocyte apoptosis. Wogonin was reported to possess anti-inflammatory action in some previous studies, but this flavone had no effect on carrageenan-induced paw edema in this study. The simultaneous treatment of wogonin and glucocorticoid neither enhanced nor reduced the anti-inflammatory effect of glucocorticoid. These results indicate that wogonin is likely to prevent the immunosuppression of glucocorticoid without diminishing its drug efficacy as an anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Biological Transport; Dexamethasone; DNA Fragmentation; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Edema; Etoposide; Flavanones; Glucocorticoids; Immunosuppression Therapy; In Vitro Techniques; Inflammation; Male; Phosphatidylserines; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis; Thymus Gland

The active ingredients of 'golden root' of Scutellaria baicalensis GEORGI (Huang-Qin), a valuable traditional Chinese medicine, are polyhydroxyflavonoids, namely baicalein, oroxylin A and wogonin. With the objective of overcoming their poor solubility and to investigate their structure and activity relationships, baicaleinyl 7-O-sulfate was prepared, and extensive comparative antioxidative and anti-inflammatory tests were conducted. All the polyhydroxyflavonoids exhibited significant antioxidative and free-radical scavenging activities. In respect of their nitric oxide (NO) inhibition, wogonin was superior to all the other flavonoids, while oroxylin A was most potent in the inhibition of lipid peroxidation. Wogonin proved to be the most potent (82.9% inhibition, p<0.05) in its anti-inflammatory activity against carrageenan-induced rat hind paw edema. There was a correlation between the in-vivo anti-inflammatory activity and the in-vitro antioxidative activities.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Drugs, Chinese Herbal; Edema; Flavanones; Flavonoids; Free Radical Scavengers; Lipid Peroxidation; Nitric Oxide; Phytotherapy; Rats; Scutellaria baicalensis; Solubility; Structure-Activity Relationship

Wogonin (5,7-dihydroxy-8-methoxyflavone), isolated from Scutellaria radix, was previously reported to inhibit the expression and activity of the enzyme cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated cells of a mouse macrophage cell line, RAW 264.7. Here, in order to find in vivo effects, inhibition by wogonin of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 expression and anti-inflammatory activity in vivo were investigated. When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.

Topics: Animals; Antioxidants; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Edema; Flavanones; Flavones; Flavonoids; Gene Expression; Isoenzymes; Magnoliopsida; Male; Mice; Mice, Inbred ICR; Plant Extracts; Prostaglandin-Endoperoxide Synthases; Skin Diseases; Tetradecanoylphorbol Acetate