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Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. Wogonin, a flavone isolated from S. baicalensis , significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure. [Display omitted] [ABSTRACT FROM AUTHOR]

The clinical effect of Yupingfeng (YPF) has been confirmed in asthma patients, however, it lacks a study to verify its pharmacological mechanism. To reveal the molecular basis and potential pharmacological mechanism of YPF in the treatment of asthma. First, a systems pharmacology-based method integrating pharmacokinetic screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of YPF in asthma. Second, differentially expressed genes (DEGs) between asthma patients and healthy controls were identified by GEO2R online tool. Third, based on systems pharmacology and DEGs results, molecular docking was performed utilizing the Discovery Studio 2020 Client version to detect the binding capacity between compounds and targets. Finally, ovalbumin (OVA)-challenged C57BL/6 mice were treated with YPF or its effective compound to assess the predictions. A total of 35 active compounds were filtered out, with 87 potential targets being identified for further analysis after target fishing and matching. Quercetin, kaempferol, and wogonin were identified as the main ingredients in YPF. The signaling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), tumor necrosis factor (TNF) and IL-17 were identified as the top signaling pathways in KEGG enrichment analysis. GEO2R tools of NCBI discovered five DEGs that overlapped with the therapeutic targets of YPF. Wogonin was proven to be the top active compound in YPF through the results of molecular docking. In vivo experiments indicated that YPF and wogonin significantly attenuated airway resistance and lung inflammation by decreasing the levels of inflammatory cytokines and key factors in PI3K/AKT, IL-17, and TNF signaling pathways. YPF and its main active compound wogonin may exert some therapeutic effects on asthma inflammation through multiple molecular targets and signaling pathways including PI3K/AKT, IL-17 and TNF-α. [Display omitted] [ABSTRACT FROM AUTHOR]

Background/purpose: Wogonin (5,7-dihydroxy-8-methoxyflavone) is a bioactive compound from Scutellariae radix that has been shown to have anticancer effects. However, the effects of wogonin on oral cancer cells still remain speculative. Materials and methods: Cytotoxicity and invasion assays were used to investigate the effects of the human oral cancer cell line OC2 cells exposed to wogonin. To examine the precise involvement of wogonin in cancer metastasis, gelatin and casein zymography were performed to evaluate the impacts of wogonin on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (u-PA) secretion in OC2 cells. Results: Wogonin exhibited a dose-dependent inhibitory effect on the invasion of OC2 cells in the absence of cytotoxicity (P

Wogonin is a natural anticancer candidate. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, excretion and plasma protein binding of wogonin in Sprague—Dawley rats. A rapid, sensitive, and specific LC-MS/MS method has been developed for the determination of wogonin in different rat biological samples. After i.v. dosing of wogonin at different levels (10, 20 and 40 mg/kg) the elimination half-life was approximately 14 min, the AUC0-∞ increased in a dose disproportional manner from 112.13 mg/L·min for 10 mg/kg to 758.19 mg/L·min for 40 mg/kg, indicating a non linear pharmacokinetic profile. After i.g. dosing at 100 mg/kg, plasma levels of wogonin peaked at 28 min with a Cmax value of 300 ng/mL and a very low oral bioavailability (1.10%). Following i.v. single dose (20 mg/kg), wogonin was detected in all examined tissues (including testis) with the highest levels in kidney and liver. Approximately 21% of the administered dose was excreted as unchanged drug (mainly via non-biliairy fecal route (16.33%). Equilibrium dialysis was used to evaluate plasma protein binding of wogonin at three concentrations (0.1, 0.5 and 2 µg/mL). Results indicated a very high protein binding degree (over 90%), reducing substantially the free fraction of the compound.

Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex vivo and in vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for analyses of cytokine production and cell viability. Mice sensitized with OVA were orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig) and cytokine levels were measured by enzyme-linked immunosorbent assays. Treatment with skullcap significantly inhibited interleukin (IL)-4 production without reduction of cell viability. Moreover, wogonin, but not baicalin and baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5 prediction. Wogonin as an active component of skullcap may be applied as a therapeutic agent for IgE- and IL-5-mediated allergic disorders.

B-ring unsubstituted flavones (of which the most widely known are chrysin, baicalein, wogonin, and oroxylin A) are 2-phenylchromen-4-one molecules of which the B-ring is devoid of any hydroxy, methoxy, or other substituent. They may be found naturally in a number of herbal products used for therapeutic purposes, and several have been designed by researchers and obtained in the laboratory. They have generated interest in the scientific community for their potential use in a variety of pathologies, and understanding their pharmacokinetics is important for a grasp of their optimal use. Based on a comprehensive survey of the relevant literature, this paper examines their absorption (with deglycosylation as a preliminary step) and their fate in the body, from metabolism to excretion. Differences among species (inter-individual) and within the same species (intra-individual) variability have been examined based on the available data, and finally, knowledge gaps and directions of future research are discussed.

Phenotypic screening of high quality compound library is one of the most effective strategy to obtain novel bioactive compounds. Recently, our group have constructed a Wogonin-scaffold library with substituents diversity and successfully obtained a series of potent compounds. Herein, we reported the synthesis of these compounds and evaluated the in vitro antitumor activity against a panel of human tumor cell lines. Most of them showed good activity with a broad spectrum and preliminary structure-activity relationship for the substitutions were obtained. Further biological assays showed that the most potent compounds 18n and 20b could significantly enhance the intracellular ROS level and induce the cell apoptosis at low micromole level. Through similarity searching, CDK9 was identified as the potential target for 20b , which could be a start point for next structure-based drug design. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of wogonin on the mechanism of melanin synthesis in the A375 melanoma cell line. A375 cells, cultured in vitro, were treated with wogonin and the activity of tyrosinase (TYR) and melanin synthesis were examined via MTT assay, L-dopa oxidation assay and an NaOH lysis assay. Protein expression levels of TYR and c-Jun N-terminal kinase (JNK) were examined via western blotting. mRNA expression levels of TYR, tyrosinase related protein (TRP)-1, TRP-2, extracellular signal-regulated kinase (ERK)-1, ERK-2 and JNK-2 were analyzed by reverse transcription-quantitative polymerase chain reaction. Furthermore, the effect of wogonin on estrogen receptor inhibitor (ICI182780) and ERK pathway inhibitor (U0126) was investigated. Safe doses of wogonin (10, 1, 10-1, 10-2 or 10-3 µmol/l) significantly inhibited melanin synthesis and TYR activity (P<0.05). Wogonin (10 µmol/l) inhibited the protein expression levels of TYR, JNK and mRNA expression levels of TYR, TRP-1, TRP-2, ERK-1, ERK-2, JNK-2 in A375 cells (P<0.01). The estrogen receptor inhibitor, ICI182780, and MEK inhibitor, U0126, significantly reversed the effects of wogonin on protein and mRNA expression levels of TYR, TRP-1, TRP-2, ERK-1, ERK-2 and JNK-2 (all P<0.01). To conclude, the present study identified that wogonin is able to inhibit the synthesis of melanin in A375 cells, through inhibiting protein and mRNA expression levels of TYR, TRP-1, and TRP-2, and ERK1, ERK2 and JNK2, respectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A highly sensitive and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for simultaneous quantification of the four main bioactive compounds, i.e. baicalin, baicalein, wogonoside and wogonin, in rat plasma after oral administration of Radix Scutellariae extract. Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100 × 2.1 mm, 1.7 μm) at a flow rate of 0.4 mL/min, using 0.1% formic acid-acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 447.5 → 270.1 for baicalin, 270.1 → 168.1 for baicalein, 461.2 → 284.0 for wogonoside, 284.2 → 168.1 for wogonin and 748.5 → 158.1 for IS. Method validation was performed according to US Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 1.13 ng/mL for baicalin, 1.23 ng/mL for baicalein, 0.82 ng/mL for wogonoside and 0.36 ng/mL for wogonin. The calibration curves obtained were linear ( r > 0.99) over the concentration range ~ 1-1000 ng/mL. The intra- and inter-day precision was <15% and the accuracy was within ±14.7%. After validation, this method was successfully applied to a pharmacokinetic study of Radix Scutellariae extract. [ABSTRACT FROM AUTHOR]

Wogonin has recently been shown to possess anti-inflammatory and chondroprotective properties and is of considerable interest due to its broad pharmacological activities. The present study highlights that Wogonin binds DNA and exerts chondroprotective effects in vitro . Wogonin showed strong binding with chondrocytes genomic DNA in vitro . The mode of binding of Wogonin to genomic-DNA was assessed by competing Wogonin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. EtBr fluorescence reduced significantly with increase in Wogonin concentration suggesting possible DNA intercalation of Wogonin. Further, in silico molecular docking of Wogonin on mammalian DNA also indicated possible intercalation of Wogonin with DNA. The denaturation and FRET studies revealed that Wogonin prevents denaturation of DNA strands and provide stability to genomic DNA against a variety of chemical denaturants. The cellular uptake study showed that Wogonin enters osteoarthritis chondrocytes and was mainly localized in the nucleus. Wogonin treatment to OA chondrocytes protects the fragmentation of genomic DNA in response to IL-1β as evaluated by DNA ladder and TUNEL assay. Treatment of chondrocytes with Wogonin resulted in significant suppression of IL-1β-mediated induction of ROS. Further, Wogonin exhibited protective potential through potent suppression of extrinsic and intrinsic apoptotic pathways and induction of anti-apoptotic proteins in IL-1β-stimulated osteoarthritis chondrocytes. Our data thus suggest that DNA intercalation by Wogonin may result in the stabilization of genomic DNA leading to protective activity. [ABSTRACT FROM AUTHOR]

Wogonin and astringin were synthesized from inexpensive chrysin and piceid in short steps. The key feature of these syntheses is site-selective transformation. The target molecules were obtained in 27 and 62% yields from the starting materials, respectively. wogonin and astringin were synthesized from chrysin and piceid in short steps, based on site-selective transformations of acetyl protective groups. [ABSTRACT FROM PUBLISHER]

Wogonin has been reported to attenuate hyperglycemia in diabetic mice via anti-adipogenic effect on adipocytes. The potential therapeutic role of wogonin in nonalcoholic fatty liver disease (NAFLD) remains obscure. The aim of the present study was to explore the protective effect of wogonin on NAFLD mice and cultured NCTC 1469 cells exposed to palmitate. Wogonin supplementation significantly improved metabolic parameters in NAFLD mice, including body weight, blood glucose, insulin resistance, adiponectin, blood lipids, aminotransferases and hepatic histopathology. Further research in liver tissues from NAFLD mice and NCTC 1469 cells stressed by lipotoxicity showed wogonin treatment reduced inflammatory response by lowering interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), alleviated oxidative stress by preventing the accumulation of oxidative product malondialdehyde (MDA) and strengthening the anti-oxidative capacity of glutathione (GSH), Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX). In addition, wogonin repaired the lipotoxicity-induced decline of peroxisome proliferator- activated receptor α (PPARα) and adiponectin receptor 2 (AdipoR2) in hepatocytes, in vivo and in vitro. Knock-down of PPARα abolished the protective effect of wogonin on NCTC 1469 cells, including the up-regulation of AdipoR2. Taken together, the current study demonstrated wogonin might be a potential therapeutic agent for NAFLD via up-regulation of hepatic PPARα/AdipoR2. [ABSTRACT FROM AUTHOR]

Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity, while, wogonin, a naturally O -methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group. In vitro cytotoxicity assay indicated that the resulting compound 8 not only inherited the genotoxicity of DN604 on gastric cancer cells, but also obtained the COX inhibitory property arising from wogonin. Further studies revealed that compound 8 caused the accumulation of ROS production and decreased the mitochondrial membrane potential (ΔΨm). The CK2α kinase activity assay, ChIP and luciferase assays showed that CK2 plays an important role in the blockade of compound 8 on activated NF-κB survival pathways, which were established for sensitivity of cancer cells to platinum drugs. Similarly in vivo , in nude mice with SGC-7901/cDDP xenografts, compound 8 improved the effectiveness of DN604 via reversing tumor resistance and maintaining low toxicity. Overall, compound 8 is a promising Pt(IV) prodrug, which could be used to promote the anticancer activity of its counterpart Pt(II) species and reverse drug resistance via attenuating CK2-mediated NF-κB pathways during platinum-based chemotherapies. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of wogonin on the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes ( ＲAFLS) and the associated molecular mechanisms． Methods FLSs were harvested from ＲA patients and cultured in joint synovial fluid and through 3-5 passages． With different treatments，cells were divided into six groups: control group，low-dose wogonin group ( 20 μg /mL of wogonin) ，middle-dose of wogonin group ( 50 μg /mL of wogonin) ，high-dose of wogonin group ( 100 μg / mL of wogonin) ，100 μg /mL Wogonin + NAC group，and 100 μg /mL Wogonin + SB203580 group． The proliferation of ＲA-FLS was measured with MTT assay． The apoptosis was measured with flow cytometric analysis． Mitochondrial membrane potential ( MMP) was measured with rhodamine 123 staining． The intracellular levels of reactive oxygen species ( ＲOS) were tested with DCFH-DA staining． The expression of proteins in p38 MAPK pathway was examined with Western blotting． Ｒesults Compared to the control group，different concentrations of wogonin inhibited ＲA-FLS growth，induced apoptosis，decreased mitochondrial membrane potential，and promoted p38MAPK phosphorylation and ＲOS production，and was in a concentration-dependent pattern． The apoptotic ratio of wogonin-treated group was markedly decreased by the ＲOS scavenger NAC or the p38MAPK inhibitor SB203580． and pretreatment of ＲA-FLS with 5 mmol /L NAC markedly reversed the wogonin-induced enhancement of p-p38 MAPK． Conclusion Wogonin effectively induces the apoptosis of FLS from rheumatoid arthritis patients through the induction of ＲOS formation and p38 MAPK activation． [ABSTRACT FROM AUTHOR]

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1ß, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells. [ABSTRACT FROM AUTHOR]

The small molecule multi-kinase inhibitor sorafenib has become the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC) and renal cell carcinoma. Similar to other kinase inhibitors, drug resistance hinders its clinical use; thus, combination therapy to improve sorafenib sensitivity is a promising approach. The present study shows for the first time that the combination of sorafenib and wogonin exerts a significant potentiation of cytotoxicity in a number of human HCC cell lines in a dose-dependent manner. Enhanced cell death was due to potentiation of apoptosis, which was demonstrated by increased apoptotic cell populations, caspase activation and suppression of cell death by the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl. Sorafenib induced autophagy activation, which was shown by autophagic flux. Suppression of autophagy with the autophagy inhibitors chloroquine or 3-methyladenine significantly enhanced cytotoxicity, suggesting that sorafenib-induced autophagy is cytoprotective. Notably, wogonin effectively inhibited sorafenib-induced autophagy. Altogether, our results indicate that the combination of wogonin and sorafenib effectively kills human HCC cells. This occurs, at least in part, through autophagy inhibition, which potentiates apoptosis. Thus, wogonin could be an ideal candidate for increasing sorafenib's activity in HCC therapy, which warrants further investigation in vivo. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1β-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE 2 , iNOS and NO in IL-1β-stimulated OA chondrocytes. Further, Wogonin exhibits potent chondroprotective potential by switching the signaling axis of matrix degradation from catabolic towards anabolic ends and inhibited the expression, production and activities of matrix degrading proteases including MMP-13, MMP-3, MMP-9, and ADAMTS-4 in OA chondrocytes, and blocked the release of s-GAG and COL2A1 in IL-1β-stimulated OA cartilage explants. Wogonin also elevated the expression of cartilage anabolic factors COL2A1 and ACAN in chondrocytes and inhibited the IL-1β-mediated depletion of COL2A1 and proteoglycan content in the matrix of cartilage explants. The suppressive effect of Wogonin was not mediated through the inhibition of MAPKs or NF-κB activation. Instead, Wogonin induced mild oxidative stress through the generation of ROS and depletion of cellular GSH, thereby modulating the cellular redox leading to the induction of Nrf2/ARE pathways through activation of ROS/ERK/Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis in OA chondrocytes. Molecular docking studies revealed that Wogonin can disrupt KEAP-1/Nrf-2 interaction by directly blocking the binding site of Nrf-2 in the KEAP-1 protein. Genetic ablation of Nrf2 using specific siRNA, significantly abrogated the anti-inflammatory and chondroprotective potential of Wogonin in IL-1β-stimulated OA chondrocytes. Our data indicates that Wogonin exerts chondroprotective effects through the suppression of molecular events involved in oxidative stress, inflammation and matrix degradation in OA chondrocytes and cartilage explants. The study provides novel insights into the development of Nrf2 as a promising candidate and Wogonin as a therapeutic agent for the management of OA. [ABSTRACT FROM AUTHOR]

Platinum-based complexes like cisplatin and oxaliplatin are well known the mainstay of chemotherapy regimens on clinic. Wogonin, a natural product that possesses wide biological activities, is now in phase I clinical test as an anticancer agent in China. Herein reported are a series of novel Pt(IV) complexes that conjugated a wogonin derivative (compound 3 ) to the axial position via a linker group. After being tethered to the platinum(IV) complexes, the wogonin derivative provided multiple anticancer effects, especially in compound 10 , a fusion containing wogonin and cisplatin units. Compound 10 not only inherited the genotoxicity from cisplatin, but also obtained the COX inhibitory property from the wogonin derivative. Further mechanistic investigation revealed that compound 10 caused the accumulation of ROS, decreased the mitochondrial membrane potential ( ΔΨ m ) and then activated the p53 pathway. Overall, the research demonstrates that the “integrative” prodrug can be an effective strategy to promote the anticancer potency of Pt-based drugs for cancer treatment. [ABSTRACT FROM AUTHOR]

Inflammation in the retinal pigment epithelium is an important contributor to the pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated from the root of Scutellaria baicalensis a nd has multiple pharmacological effects, including anti-inflammatory effects. The present study sought to determine if the pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE-19 cells were pre-conditioned with different concentrations of wogonin (0-50 µM) prior to induction of inflammation with LPS (2 µg/ml). Transepithelial electrical resistance analysis demonstrated that 24 h treatment with 10 and 50 µM wogonin ameliorated LPS-induced changes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence analyses revealed that wogonin restrained LPS-induced tight junction proteins, claudin-1 and ZO-1. LPS-induced upregulation of inflammatory mediators in ARPE-19 cells, including IL-1β, IL-6, IL-8, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and TNF-α was reduced after pre-treatment with wogonin. In addition, RT-qPCR and western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS-stimulated ARPE-19 cells. This is a novel mechanism indicating that pre-treatment with wogonin could attenuate the TLR4/NF-κB-mediated inflammatory response in LPS-stimulated ARPE-19 cells, and thus could be a potential therapy for the treatment of AMD. [ABSTRACT FROM AUTHOR]

During the ongoing search for new monoamine oxidase (MAO) inhibitors, five coumarin derivatives and eight flavonoids were isolated from the roots of Angelica gigas Nakai and Scutellaria baicalensis Georgi, respectively. Of the phytochemicals, decursin ( 4 ) was found to potently and selectively inhibit human MAO-A (IC 50 = 1.89 μM). The IC 50 value of 4 for MAO-A belonged to the lowest group in herbal sources and was similar to that of toloxatone (1.78 μM), a marketed drug. Wogonin ( 11 ) effectively inhibited MAO-A and MAO-B (IC 50 = 6.35 and 20.8 μM, respectively). Furthermore, compounds 5 (decursinol angelate) and 10 (baicalein) were observed to selectively and moderately inhibit MAO-A. In addition, compound 4 reversibly and competitively inhibited MAO-A with a K i of 0.17 μM. Compound 11 also competitively inhibited MAO-A and MAO-B (K i = 0.56 and 1.96 μM, respectively). Molecular docking simulation revealed that 4 interacts with Asn181 residue of MAO-A or Asn116 residue of MAO-B by formation of hydrogen bond. The findings suggest compounds 4 and 11 be considered as new potent and reversible MAO-A inhibitors or useful lead compounds for the developments of MAO inhibitors for the treatment of disorders like depression, Parkinson’s disease and Alzheimer disease. [ABSTRACT FROM AUTHOR]

Background: Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future.Methods: Cell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules.Results: In vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1.Conclusions: Wogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted therapeutic agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1. [ABSTRACT FROM AUTHOR]

A novel series of 49 wogonin derivatives were synthesized by introducing group at 7-, 8- or B ring of wogonin. The cytotoxic activities against HepG2, A549 and BCG-823 cancer cell lines were also investigated in vitro . Several of them showed obvious cytotoxic activities and compound 3h possessed the highest potency against HepG2, A549, and BCG-823 with IC 50 values of 1.07 μM, 1.74 μM and 0.98 μM, respectively. A quantitative structure-activity relationship (QSAR) study of these synthetic derivatives as well as wogonin indicated that high solubility and low octanol/water partition coefficient are favorable, and excessive electrostatic properties and refractivity are unfavorable for the cytotoxic activities of these wogonin derivatives. These findings and results provide a base for further investigations. [ABSTRACT FROM AUTHOR]

ABSTRACT Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)−2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017. [ABSTRACT FROM AUTHOR]

Wogonin exerts anti-tumour activities via multiple mechanisms. We have identified that high-dose wogonin (50 or 100 mg/kg) could inhibit the growth of transplanted tumours by directly inducing tumour apoptosis and promoting DC, T and NK cell recruitment into tumour tissues to enhance immune surveillance. However, wogonin (20-50 μM) ex vivo prevents inflammation by inhibiting NF-κB and Erk signalling of macrophages and epithelial cells. It is elusive whether high-dose wogonin promotes or prevents inflammation. To investigate the effects of high-dose wogonin on murine colitis induced by dextran sodium sulphate ( DSS), mice were co-treated with DSS and various doses of wogonin. Intraperitoneal administration of wogonin (100 mg/kg) exacerbated DSS-induced murine colitis. More CD4+ CD44+ and CD8+ CD44+ cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4+ CD25+ CD127− and CD4+ CD25+ Foxp3+ cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high-dose wogonin (50-100 μg/ml equivalent to 176-352 μM) could synergize with IL-2 to promote the functions of CD4+ and CD8+ cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF-κB and Erk but down-regulated STAT3 phosphorylation in the CD4+ T cells. Wogonin down-regulated Erk and STAT3-Y705 phosphorylation in the regulatory T cells but promoted NF-κB and STAT3-S727 activation. Our study demonstrated that high-dose wogonin treatments would enhance immune activity by stimulating the effector T cells and by down-regulating regulatory T cells. [ABSTRACT FROM AUTHOR]

Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis (Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anti-cancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt (also known as protein kinase B) and AMP-activated protein kinase (AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity. Furthermore, wogonin also decreases DNA adduct formation with a carcinogenic compound 2-Aminofluorene and inhibits growth of drug resistant malignant cells and their migration and metastasis, without any side effects. Recently, newly synthesized wogonin derivatives have been developed with impressive anti-tumor activity. This review is the succinct appraisal of the pertinent articles on the mechanisms of anti-tumor properties of wogonin. We also summarize the potential of wogonin and its derivatives used alone or as an adjunct therapy for cancer treatment. Furthermore, pharmacokinetics and side effects of wogonin and its analogues have also been discussed. [ABSTRACT FROM AUTHOR]

Although baicalein and wogonin contents in Scutellaria baicalensis , a traditional Chinese herb, are known to be regulated by jasmonic acid, the exact mechanism by which jasmonic acid regulates the accumulation of baicalein and wogonin remains unclear. In this study, we discovered SbLOX3, a gene encoding 13-lipoxygenase from the roots of S. baicalensis , which plays an important role in the biosynthesis of jasmonic acid. The contents of methyl jasmonate, baicalin, wogonin, and three metabolic intermediates of methyl jasmonate, 13-HPOT, OPDA, and OPC-8, were downregulated in the hair roots of the SbLOX3 RNAi lines. We confirmed that SbLOX3 was induced by drought stress simulated by PEG and Fusarium oxysporum , which subsequently led to changes in the content of MeJA, baicalin, and wogonin. Taken together, our results indicate that a 13-LOX is involved in the biosynthesis of jasmonic acid, and regulates the accumulation of baicalein and wogonin in S. baicalensis roots., Competing Interests: Author YZ was employed by the company Shandong Hongjitang Pharmaceutical Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Geng, Wang, Zhang, Lu, Dong, Liu, Guo and Wang.)

Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells. The mechanism of wogonin-related autophagy was investigated, and the antioxidant N-acetyl-L-cysteine (NAC) was used to assess the role of reactive oxygen species (ROS) in wogonin-related autophagy. The results demonstrated that wogonin may induce autophagy by activating the Beclin-1/phosphatidylinositol-3-kinase and ROS pathways in HPCCs, and may enhance ROS generation, followed by the activation of the AKT/ULK1/4E-BP1/CYLD pathway and inhibition of the mammalian target of rapamycin signaling pathway. The incubation of HPCCs with wogonin and the antioxidant NAC, revealed that the effects of wogonin-enhanced ROS generation on autophagy-related molecules were inhibited, contributing to the inhibition of autophagy and increasing the cell death ratio through apoptosis activation in HPCCs. These studies suggest that autophagy activation, via the ROS pathway, by the antitumor drug wogonin in HPCCs may partially reduce the antitumor effects of the drug, and that the antioxidant NAC may enhance the antitumor effectiveness of wogonin via the inhibition of ROS-enhanced autophagy and the subsequent promotion of apoptosis. Therefore, the present research suggests that wogonin combined with NAC may be a novel combination therapy for clinical pancreatic cancer therapy trials. [ABSTRACT FROM AUTHOR]

Context:Scutellaria havanensisJacq. (Lamiaceae) is a native medicinal herb with a history of use in Cuba. Objective:This study screens the antiprotozoal activity ofS. havanensis. Materials and methods:Chloroform and methanol extracts from leaves and stems were evaluatedin vitroat doses between 0.015 and 200 μg/mL against protozoan parasites:Plasmodium berghei,Trichomonas vaginalisandLeishmania amazonensis.Chloroform and methanol extracts were characterized by GC/MS. Cytotoxicity against mouse peritoneal macrophages was tested in parallel. Results:Scutellaria havanensisextracts exhibited IC50values between 7.7 and 32.2 μg/mL against trophozoites ofP. bergheiandT. vaginalis; while the extracts were inactive againstL. amazonensispromastigotes. Trichomonicidal activity of methanol extract exhibited the best selectivity but chloroform extract showed the highest antiplasmodial, trichomonicidal and cytotoxic activity. The majority of compounds in the chloroform extract were hydroxy and/or methoxyflavones (77.96%), in particular, wogonin (48.27%). In methanol extract, wogonin (5.89%) was detected. Trichomonicidal effect of wogonin was moderate (IC50 = 56 μM) and unspecific with respect to macrophages (SI = 2). On the contrary, antiplasmodial activity of wogonin were particularly active (IC50 = 15 μM) demonstrating a higher selectivity index (SI = 7.4). Conclusions:Wogonin is an active principle compound of the chloroform extract ofS. havanensisagainstP. bergheiandT. vaginalistrophozoites, whereas the methanol extract ofS. havanensisshould be investigated more deeply as a trichomonicide. Our findings suggest that wogonin is potentially useful for the development of antimalarial alternative treatments. [ABSTRACT FROM AUTHOR]