wogonin and Disease-Models--Animal

To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)-induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg

Topics: Animals; Caco-2 Cells; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Enterobacteriaceae; Humans; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; PPAR gamma

Ulcerative colitis (UC) is an inflammatory disease on the deepest lining of the colon and rectum. Wogonin is an antitumor flavonoid, which possesses various therapeutic properties. Even if the anti-colitis effect of wogonin was documented earlier, but the wogonin effect on inflammation underlying mechanism is not fully elucidated. In this present study, we hypothesized to study the oxidative damage, anti-inflammatory, and molecular action of wogonin on dextran sulfate sodium (DSS)-induced UC mice model. In methods, mice were categorized into four groups: that is, normal control, DSS alone, DSS + wogonin (30 mg/kg/day), and DSS + sulfasalazine (50 mg/kg/day). We determined the biochemical markers, inflammatory cytokines, histopathology of colon tissue, and western blot analysis. DSS significantly reduced body weight, colon length, and increased inflammation in the colon. Wogonin treatment prevented colonic ulceration, neutrophil infiltration, oxidative stress, pro-inflammatory cytokines, and histological changes. Oxidative damage and inflammatory mediators' elevation were also dramatically diminished by wogonin. Wogonin activates apoptosis via inhibiting Bcl-2 and augmenting Bax, caspase-3, and -9 expressions. Wogonin downregulated the COX-2 and iNOS, thereby repressing NF-κB. Wogonin regulated the Nrf2 signaling pathway and decreased TLR-4/NF-κB triggering. Taken together our study exposed that wogonin has a promising anti-ulcerative agent and recommended for good anti-inflammatory drug in the colon.

Topics: Animals; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Flavanones; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Signal Transduction; Toll-Like Receptor 4

Cardiotoxicity has been well documented as a side effect of cisplatin (CDDP) treatment. The inflammatory response plays a crucial role in the pathological process of CDDP-induced cardiotoxicity. Wogonin is a natural flavonoid compound that possesses cardioprotective and anti-inflammatory qualities. Knowledge of the pharmacological effect and mechanism of wogonin could reveal an efficient way to identify therapeutic strategies. In this study, the potential of wogonin to antagonize CDDP-induced cardiotoxicity was evaluated in C57BL/6 mice in vivo and in H9c2 cells in vitro. The results showed that wogonin protected against CDDP-induced cardiac dysfunction, myocardial injury, and pyroptosis in vivo. Using a Gasdermin D expression plasmid, we revealed that wogonin dramatically reduced CDDP-induced pyroptosis by modulating the Gasdermin D protein in H9c2 cells. In conclusion, wogonin has great potential in attenuating CDDP-induced cardiotoxicity. In addition, greater emphasis should be placed on the antipyroptotic effects of wogonin for the treatment of other diseases.

Topics: Animals; Cardiotoxicity; Cell Line; Cisplatin; Disease Models, Animal; Flavanones; Heart Diseases; Interleukin-18; Interleukin-1beta; Male; Mice, Inbred C57BL; Myocytes, Cardiac; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphate-Binding Proteins; Pore Forming Cytotoxic Proteins; Protective Agents; Pyroptosis; Rats; Signal Transduction

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Topics: Animals; Disease Models, Animal; Flavanones; Lipopolysaccharides; Liver Failure, Acute; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Sepsis; Signal Transduction

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Rheumatoid arthritis (RA) is a chronic and accelerated autoimmune illness with proliferative and damaging synovitis, resulting in joint death and cartilage and bone erosion. This study focused on the potential therapeutic effect of wogonin on complete Freund's adjuvant (CFA) induced RA in rats and the underlying mechanisms. Arthritis was experimentally caused in rats by subcutaneously injecting 0.1 mL of CFA into the subplantar area of the left hind paw under moderate anesthesia on day zero. The regular oral doses of indomethacin/wogonin began on day zero and proceeded after injection to day 35. Wogonin reduced arthritic score considerably, enhanced body weight, and reduced paw thickness. Wogonin also boosted red blood cell considerably along with hemoglobin and reduced white blood cell count and erythrocyte sedimentation rate. Wogonin substantially improved an altered level of oxidative stress markers, antioxidant proteins, and inflammatory cytokines in a dose-dependent way. Wogonin inhibited p38 phosphorylation triggered by CFA and p65 nuclear translocation.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Disease Models, Animal; Flavanones; Freund's Adjuvant; Male; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Signal Transduction

Wogonin (5,7-dihydroxy-8-methoxyflavone) is an ingredient of the extracts from Scutellaria baicalensis, which has documented a wide spectrum of anti-inflammatory and antitumor activities, including inhibiting regulatory T cells, regulating effector T cell functions, and mediating macrophage immunity. However, the potential effect of Wogonin on B cells has not been fully understood. Here, our results showed that Wogonin inhibited IL-10 secretion in B cells. When purified B cells were activated by lipopolysaccharide (LPS) in vitro, the amount of IL-10 production in supernatant was decreased by Wogonin significantly. The protective role of B cells on dextran sulfate sodium- (DSS-) induced colitis was alleviated after exposure to Wogonin. Furthermore, administration of Wogonin on LPS-treated B cells suppressed phosphorylation of STAT3 and ERK, but not AKT. Interestingly, among those IL-10 signaling-associated transcription factors, mRNA and protein levels of Hif-1

Topics: Animals; B-Lymphocytes; Colitis; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Extracellular Signal-Regulated MAP Kinases; Flavanones; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Immunophenotyping; Interleukin-10; Male; Mice; Signal Transduction; STAT3 Transcription Factor; Transcription, Genetic

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is an inflammatory sinonasal disorder characterized by eosinophilic inflammation and T-helper 2 skewing. Eosinophil accumulation in sinonasal mucosa comprises a major feature of CRSwNP. The study aimed to investigate the effect of the flavone wogonin in nasal polyposis by assessing its ability to induce eosinophil apoptosis in vitro and attenuate eosinophilic CRSwNP in mice. Double immunofluorescence, immunohistochemistry, flow cytometry, and immunoblotting were performed to evaluate hypoxia-inducible factor (HIF)-1α, survivin, and apoptotic markers in the human eosinophilic EoL-1 cell line or sinonasal tissues from patients with CRS with or without NPs. In sinonasal specimens from patients with CRS, HIF-1α and survivin were up-regulated in eosinophils from patients with NPs compared with levels in patients without NPs. Under hypoxia, HIF-1α and survivin expression was up-regulated in EoL-1 cells. Wogonin down-regulated both HIF-1α and survivin in EoL-1 cells. In addition, overexpression of survivin protected EoL-1 cells against apoptosis in response to wogonin. Moreover, wogonin attenuated nasal polyp formation in a murine model. Our findings suggest that wogonin could induce caspase-3 activation by suppressing HIF-1α and survivin expression in EoL-1 cells. Further studies regarding novel therapeutic options for CRSwNP targeting eosinophil apoptosis are needed.

Topics: Adult; Aged; Airway Remodeling; Animals; Apoptosis; Biomarkers; Caspase 3; Cell Line; Cytokines; Disease Models, Animal; Eosinophils; Female; Flavanones; Fluorescent Antibody Technique; Gene Expression; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Inflammation; Leukocyte Count; Male; Mice; Mice, Inbred BALB C; Middle Aged; Nasal Polyps; Protein Binding; Survivin

Intervertebral disc degeneration (IVDD) is a prevalent disease characterized by the progressive loss of the extracellular matrix in the local nucleus pulposus region. Metalloproteinases and pro-inflammatory cytokines play an important role in this process. Thus, anti-inflammatory strategies are an important component of IVDD treatment. Wogonin, a naturally existing monoflavonoid, has been reported to have potential anti-inflammatory effects in some inflammatory diseases. Hence, in our present study we investigated the protective effects and potential mechanisms of wogonin in rat nucleus pulposus cells that had been treated with interleukin-1beta (IL-1β) to induce severe IVDD. An in vivo rat caudal vertebrae needle-stab model was also designed and its validity was evaluated as an IVDD model. The results demonstrated that wogonin suppressed IL-1β-induced inflammatory mediators (iNOS, IL-6 and COX2) and matrix-degrading proteinases (MMP1, MMP3, MMP13 and ADAMTS4). Wogonin also upregulated some of the key components of the extracellular matrix, such as collagen II. Furthermore, we discovered that wogonin exerted anti-inflammatory effects by activating the Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis. Moreover, the IL-1β-induced stimulation of the MAPK signaling pathway was reversed by wogonin treatment. The in vivo MRI and histological results also revealed that wogonin protected the nucleus pulposus from the progression of IVDD. Therefore, wogonin may be a potential agent for the treatment of IVDD.

Topics: Animals; Anti-Inflammatory Agents; Carboxylic Ester Hydrolases; Collagen Type II; Collagenases; Disease Models, Animal; Flavanones; Humans; Inflammation Mediators; Interleukin-1beta; Intervertebral Disc Degeneration; NF-E2-Related Factor 2; Nucleus Pulposus; Rats; Signal Transduction

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.

Topics: Animals; Anti-Inflammatory Agents; Benzamides; Disease Models, Animal; Ethanol; Flavanones; Humans; Immunomodulation; Inflammation Mediators; Interleukin-6; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Pyridines; RAW 264.7 Cells; RNA, Small Interfering; Scutellaria baicalensis; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Vascular inflammation may induce a number of diseases, including organ damage or failure, heart attack and stroke. The present study aimed to investigate the use of wogonin, a compound extracted from herbs, to mediate inflammatory reactions in vascular inflammation. Wogonin was loaded in a well‑characterized polymeric biomaterial carrier. In mice with streptozotocin‑induced vascular inflammation, wogonin treatment regulated the production of inflammatory cytokines, including interleukin‑6, tumor necrosis factor‑α and granulocyte macrophage colony‑stimulating factor. To understand the impact of wogonin on major immune cells, macrophages were treated with wogonin in vitro. It was determined that wogonin did not affect macrophage viability, and that wogonin regulated the relative ratio of M1 versus M2 macrophages. In addition, in co‑culture, wogonin decreased inflammatory cytokine production and regulated the activation of macrophage surface markers including CD80, CD86 and CD40. Results from the present study may aid in our understanding of the effects of wogonin in regulating inflammation, especially its effects on macrophages.

Topics: Animals; Cell Survival; Cells, Cultured; Cytokines; Disease Models, Animal; Female; Flavanones; Macrophages; Mice; Vasculitis

Individuals with ulcerative colitis (UC) are at a high risk for developing colorectal cancer (CRC). Huangqin Decoction (HQD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat gastrointestinal symptoms. However, experimental evidence for supporting the clinical practice is lacking. This study used modern biomedical approaches to investigate the protective/preventive effects of HQD in dextran sulfate sodium (DSS)-induced acute/chronic UC and azoxymethane (AOM)/DSS-induced CRC in mice. HQDs were prepared in 4 different ways: HQD-1 and HQD-2 were prepared in boiling water, whereas HQD-3 and HQD-4 were prepared in heated ethanol (70%). For HQD-1 and HQD-3, the 4 constituent herbs were processed together, whereas for HQD-2 and HQD4, these herbs were processed individually and then combined. The mice were administered 9.1 g/kg HQD via oral gavage daily. HQD-1 significantly inhibited DSS-induced acute UC, whereas HQD-3 and HQD-4 exhibited mild ameliorative effects; but HQD-2 had no protective effect and resulted in a higher mortality rate. This higher mortality rate may be due to the greater abundance of baicalein and wogonin in HQD-2 than HQD-1. Furthermore, HQD-1 protected against DSS-induced chronic UC and significantly inhibited AOM/DSS-induced CRC in mice. HQD-1 also inhibited the production of inflammatory cytokines and increased antioxidant capacity both in chronic DSS and AOM/DSS treated mice. Overall, HQD-1 inhibits the development of acute/chronic colitis and prevents colitis-associated CRC, possibly by inhibiting inflammation and preventing oxidative stress induced cellular damage.

Topics: Animals; Antioxidants; Azoxymethane; Chromatography, High Pressure Liquid; Colitis, Ulcerative; Colorectal Neoplasms; Cytokines; Dextran Sulfate; Disease Models, Animal; Drugs, Chinese Herbal; Flavanones; Inflammation; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Oxidative Stress; Plant Extracts; Scutellaria baicalensis

Chronic neuro-inflammation is involved in the death of retinal ganglion cells (RGCs) in glaucoma. The aim of this study is to determine whether wogonin can suppress inflammatory responses and rescue RGCs death after optic nerve crush (ONC), an ideal animal model of glaucoma. Wogonin was administered intraperitoneally 10 min after establishment of ONC model. In this study, wogonin treatment reduced RGCs loss and inhibited RGCs apoptosis demonstrated by the increased Brn3a labeling RGCs at day 14 and the decreased cleaved caspase-3 expression at day 7 after ONC, respectively. In ONC model, number of GFAP-positive glial cells and iba1-positive microglial cells were increased, combined of the elevated level of pro-inflammatory cytokines released in retina at day 7. However, most of these responses were inhibited after wogonin treatment. The level of TLR4 expression, NF-κB-P65 nucleus location and NF-κB-P65 phosphorylation were increased in retina at day 1 after ONC, which was significantly reduced after wogonin treatment. These results demonstrated that wogonin protected RGCs survival and suppressed neuro-inflammation in retina after ONC by inhibiting TLR4-NF-κB pathways. We conclude that wogonin could be a possible strategy for the treatment of glaucoma.

Topics: Animals; Cell Survival; Disease Models, Animal; Down-Regulation; Drugs, Chinese Herbal; Flavanones; Glaucoma; Male; Nerve Crush; Neurogenic Inflammation; NF-kappa B; Optic Nerve; Random Allocation; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells; Toll-Like Receptor 4

Wogonin exerts effective antitumor activities through direct cytotoxicity against cancer cells and indirect immune modulation. However, the molecular mechanisms of these activities remain poorly understood and need further study. We found that wogonin could efficiently downregulate the expression of B7H1, retinoic acid early induced transcript-1ε (RAE-1ε), and vascular endothelial growth factor in gastric cancer cells. Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies from dying tumor cells treated with wogonin were susceptible for uptake by neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were inversely correlated with expression levels of vascular endothelial growth factor, B7H1, and RAE-1ε of tumor tissues. Wogonin directly inhibited the activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane. Our study confirmed the immune-enhancing function of wogonin, and indicated that wogonin could be used in collaboration with DC vaccine or activated lymphocytes for tumor therapy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; B7-H1 Antigen; Cell Line, Tumor; Dendritic Cells; Disease Models, Animal; Down-Regulation; Flavanones; Histocompatibility Antigens Class I; Humans; Immunomodulation; Lymphocytes, Tumor-Infiltrating; Mice; Neoplasms; Phagocytosis; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; T-Lymphocyte Subsets; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by wogonin. In addition, wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cell Line; Cytokines; Disease Models, Animal; Female; Flavanones; Gene Expression Regulation; Inflammation Mediators; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Inbred C57BL; NF-kappa B; Pneumonia; PPAR gamma; RNA Interference; Signal Transduction; Time Factors; Transfection

Wogonin is a flavonoid isolated from Scutellaria baicalensis Georgi, a traditional Chinese medicine, and it possesses antioxidant and anti-inflammatory effects. The aim of this study is to investigate the in vivo effect of wogonin on myocardial ischemia/reperfusion injury in an open-chest anesthetized rat model, which was induced by 45-minute left coronary artery occlusion and 2-hour reperfusion. Rats were treated with wogonin (5, 10, and 20 mg/kg, intraperitoneal) 40 minutes before ischemia or treatment with 10 mg/kg of wogonin 15 minutes after occlusion. Pretreatment with 10 mg/kg of wogonin significantly delayed the occurrence of ventricular premature contractions and tachycardia, and it suppressed the incidence of ventricular tachycardia and ventricular fibrillation, and mortality elicited by ischemia when compared with that in the control group, accompanied by reducing the arrhythmia scores. After 2-hour reperfusion, pretreatment and posttreatment with wogonin significantly reduced the infarct size and plasma levels of creatine kinase muscle-brain fraction and lactate dehydrogenase. Wogonin also significantly reduced the elevation of plasma tissue necrosis factor-α and superoxide anion production in the myocardium with ischemia/reperfusion. The expression of monocyte chemoattractant protein-1, phosphorylated p38 mitogen-activated protein kinase, p65 and IκBα, and active caspase-3 in ischemic myocardium pronouncedly increased in the control group; these were significantly attenuated by treatment with wogonin. In conclusion, wogonin demonstrated in vivo cardioprotective effects by the attenuation of the severity of ischemia-induced arrhythmias and irreversible ischemia/reperfusion injury, which is associated with its antioxidant capacity and anti-inflammatory effects. The suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation and the inhibition of monocyte chemoattractant protein-1 expression contribute to the beneficial effects of wogonin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Arrhythmias, Cardiac; Blotting, Western; Chemokine CCL2; Disease Models, Animal; Dose-Response Relationship, Drug; Flavanones; Hemodynamics; Male; Myocardial Reperfusion Injury; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley; Superoxides

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 proinflammatory 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 proinflammatory gene expression against contact dermatitis in mice. Wogonin inhibited ear edema (19.4-22.6%) at doses of 50-200 microg/ear and down-regulated interleukin-1beta induction (23.1%) at 200 microg/ear in phenol-induced simple irritation. Wogonin (2x50-2x200 microg/ear) also inhibited edematic response (51.2-43.9%) and down-regulated proinflammatory gene expression of cyclooxygenase-2, interleukin-1beta, 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 proinflammatory gene expression in animal models of skin inflammation. Therefore, wogonin may have potential for a new anti-inflammatory agent against skin inflammation.

Topics: Administration, Topical; Animals; Dermatitis, Contact; Disease Models, Animal; Flavanones; Flavonoids; Gene Expression Profiling; Gene Expression Regulation; Inflammation Mediators; Male; Mice; Mice, Inbred ICR

The present study evaluated the effect of wogonin, a flavonoid originated from the root of Scutellaria baicalensis GEORGI, on focal ischemic brain injury in rats. Focal brain ischemia was induced by the permanent occlusion of middle cerebral artery (pMCAO) for 24 h with a silicone rubber cylinder inserted through the right internal carotid artery. We found that wogonin, intraperitoneally administered at a dosage of 20 mg/kg at 30 min before and 4 h after the surgery, reduced the pMCAO-induced infarct areas in the cerebral cortex as well as in the striatum. The total volume of infarction was significantly reduced by the treatment with wogonin. In addition, wogonin was found to significantly improve the pMCAO-induced behavioral deficits at 24 h after the surgery. Taken together, these results demonstrate that wogonin inhibits ischemic brain injury and improves behavioral dysfunction caused by pMCAO. These findings, along with previous reports demonstrating the neuroprotective effects of wogonin, provide strong pharmacological basis for the use of wogonin or Scutellaria baicalensis in the treatment of stroke.

Topics: Animals; Arterial Occlusive Diseases; Behavior, Animal; Brain Infarction; Brain Ischemia; Cerebral Cortex; Corpus Striatum; Disease Models, Animal; Flavanones; Male; Middle Cerebral Artery; Neuroprotective Agents; Phytotherapy; Plant Roots; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis

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