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Chemical structures of the active components of skullcap: baicalein ( A ), baicalin ( B ), and wogonin ( C ). 

Chemical structures of the active components of skullcap: baicalein ( A ), baicalin ( B ), and wogonin ( C ). 

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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 sens...

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... this study, we investigated the anti-allergic effect of skullcap extract and its known active compounds-baicalein, baicalin, and wogonin (Figure 1), with a focus on the systemic immunity T cell-mediated immune response. The effects of skullcap and its active components were evaluated by immunoglobulin (Ig) and cytokine analyses of an OVA-induced Th2 dominant mouse model. ...

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... Results suggest Alismatis Rhizoma extract is involved in Nrf2 activation and suppression of in ammation so that it represents the anti-in ammatory effect and can be developed as a potential therapeutics for lung in ammation 23 . Scutellaria baicalensis (Skullcap) has been widely used as a traditional herbal medicine owing to its antiin ammatory properties, such as its active compound wogonin can suppress IL-4 production ex vivo 24 . The ovalbumin (OVA)-induced Th2 immune responses, especially IgE and IL-5 production can be downregulated by wogonin from skullcap in vivo, results suggest the wogonin acting as an active component of S. baicalensis can be applied as a therapeutic agent for IgE-or IL-5 mediated allergic disorders 24 . ...
... Scutellaria baicalensis (Skullcap) has been widely used as a traditional herbal medicine owing to its antiin ammatory properties, such as its active compound wogonin can suppress IL-4 production ex vivo 24 . The ovalbumin (OVA)-induced Th2 immune responses, especially IgE and IL-5 production can be downregulated by wogonin from skullcap in vivo, results suggest the wogonin acting as an active component of S. baicalensis can be applied as a therapeutic agent for IgE-or IL-5 mediated allergic disorders 24 . Active compounds isolated from Scutellaria baicalensis include wogonin and baicalin that inhibit the in ammatory response through inhibition of cyclooxygenase-2 (COX-2) gene expression through blockade of CCAAT/Enhancer Binding Protein Beta (C/EBP-Beta) DNA binding activity 24,25 . ...
... The ovalbumin (OVA)-induced Th2 immune responses, especially IgE and IL-5 production can be downregulated by wogonin from skullcap in vivo, results suggest the wogonin acting as an active component of S. baicalensis can be applied as a therapeutic agent for IgE-or IL-5 mediated allergic disorders 24 . Active compounds isolated from Scutellaria baicalensis include wogonin and baicalin that inhibit the in ammatory response through inhibition of cyclooxygenase-2 (COX-2) gene expression through blockade of CCAAT/Enhancer Binding Protein Beta (C/EBP-Beta) DNA binding activity 24,25 . ...
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... Studies have shown that anomalin inhibits the levels of inflammatory cytokines through the inactivation of NF-κB, nuclear factor erythroid 2related factor 2 (Nrf2), and MAPK signaling pathways (Khan et al., 2016). Wogonin produced an antiallergic effect in AR mouse models by reducing eosinophil infiltration and the Th2 cytokines IL-4, IL-5, and IL-13 in the serum and nasal mucosa (Shin et al., 2014;Kim et al., 2018). Wogonin can also reduce allergic airway inflammation in vivo by reducing the number of eosinophils, increasing eosinophil apoptosis, reducing airway mucus production, and reducing airway hyperresponsiveness. ...
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YU-Pingfeng San (YPFS) can regulate inflammatory response to alleviate the symptoms of nasal congestion and runny rose in allergic rhinitis (AR). However, the mechanism of action remains unclear. In this study, 30 active ingredients of three effective herbs included in YPFS and 140 AR/YPFS-related genes were identified by database analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the targets were mainly enriched in immune inflammatory-related biological processes and pathways. Finally, three hub gene targeting epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), and protein kinase B1 (AKT1) related to YPFS and AR were identified by network pharmacology analysis. YPFS treatment decreased the expression of EGFR, MAPK1, and AKT1 in ovalbumin (OVA)-induced AR mice and impaired the production of inflammatory factors interleukin (IL)-4, IL-5, and IL-13, thus alleviating immunoglobulin E (IgE) production and the symptoms of scratching nose in AR. Through molecular docking analysis, we found that the active ingredients decursin, anomalin, and wogonin of YPFS could bind to EGFR, MAPK1, and AKT1 proteins. Moreover, decursin treatment impaired the expression of IL-4 and IL-5 in human PBMCs. These results suggested that YPFS could alleviate the AR inflammatory responses by targeting EGFR, MAPK1, and AKT1, showing the mechanism of action of YPFS in AR treatment.
... Formononetin, a phytoestrogen extracted from Huangqi, has been demonstrated to ameliorate IL-13-induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1/Nrf2 signaling pathway [40]. With regard to wogonin, it has been proved to reduce allergic airway inflammation by inducing eosinophil apoptosis and regulating T lymphocyte differentiation [41][42][43]. On the whole, YPFP is a compound with a multitarget therapeutic effect. ...
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Objective: To explore the potential mechanisms of Yupingfeng Powder (YPFP) in the treatment of allergic diseases by using network pharmacology and molecular docking technology. Methods: The active components and targets of YPFP were screened by the TCMSP database. The targets associated with atopic dermatitis, asthma, allergic rhinitis, and food allergy were obtained from GeneCards and OMIM databases, respectively. The intersection of the above disease-related targets was identified as allergy-related targets. Then, allergy-related targets and YPFP-related targets were crossed to obtain the potential targets of YPFP for allergy treatment. A protein-protein-interaction (PPI) network and a drug-target-disease topology network were constructed to screen hub targets and key ingredients. Next, GO and KEGG pathway enrichment analyses were performed separately on the potential targets and hub targets to identify the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between key ingredients and hub targets. Results: In this study, 45 active ingredients were identified from YPFP, and 48 allergy-related targets were predicted by network pharmacology. IL6, TNF, IL1B, PTGS2, CXCL8, JUN, CCL2, IL10, IFNG, and IL4 were screened as hub targets by the PPI network. However, quercetin, kaempferol, wogonin, formononetin, and 7-O-methylisomucronulatol were identified as key ingredients by the drug-target-disease topological network. GO and KEGG pathway enrichment analysis indicated that the therapeutic effect of YPFP on allergy involved multiple biological processes and signaling pathways, including positive regulation of fever generation, positive regulation of neuroinflammatory response, vascular endothelial growth factor production, negative regulation of cytokine production involved in immune response, positive regulation of mononuclear cell migration, type 2 immune response, and negative regulation of lipid storage. Molecular docking verified that all the key ingredients had good binding affinity with hub targets. Conclusion: This study revealed the key ingredients, hub targets, and potential mechanisms of YPFP antiallergy, and these data can provide some theoretical basis for subsequent allergy treatment and drug development.
... Th2-dominant responses, with increased Th2 (IL-4, IL-5, and IL-13) cytokines and IgE production, are characteristic immune responses in patients with allergic diseases such as food allergy, asthma, and AD [42][43][44]. We previously reported a few strategies to treat allergic diseases [45][46][47]. The first involves regulating the Th1/Th2 immune balance by suppressing excessively induced Th2-mediated immune responses or increasing Th1-related immune responses [48][49][50]. ...
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Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.
... Likewise, Shin et al. assert that Wogonin suppresses the production of the IgE and IL-5 in ovalbumin-induced allergic Th2 response. [38]. Ex vivo experiments show that Wogonin suppresses the production of IL-4 and IFN-γ in splenocytes from mice sensitized with ovalbumin. ...
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Flavonoids are members of polyphenolic compounds, which are naturally presented in fruits, vegetables, and some medicinal plants. Traditionally, the root of Scutellaria baicalensis is widely used as Chinese herbal medicine and contains several major bioactive compounds such as Wogonin, Scutellarein, Baicalein, and Baicalin. Experimental and clinical evidence has been proving that Wogonin exhibits diverse biological activities such as anti-cancer, anti-inflammation, and treatment of bacterial and viral infections. In this review, we summarize and emphasize the benefits of Wogonin as a therapeutic adjuvant for anti-viral infection, anti-inflammation, neuroprotection as well as anxiolytic and anticonvulsant. Moreover, the molecular mechanism(s) how Wogonin mediates the cellular signal pathways and immune responses are also discussed and highlighted valuable properties of Wogonin in multiple therapies.
... Most of these studies concerning the effect of Baikal skullcap on the immune system focused on lymphocytes and their activity. Some authors concluded that Baikal skullcap and its active flavonoids predominantly inhibit Th2 lymphocyte response (especially through decreasing Th2 cytokine production) and stimulate Th1-mediated response (Shin et al. 2014a, Jung et al. 2017. However, other researchers demonstrated SB-derived inhibition of both Th1 and Th2-mediated response (Liu et al. 2015). ...
... Some showed that skullcap and its active compounds, e.g. wogonin, suppress cytokine production by Th2 lymphocytes (IL-4, IL-5, IL-10, IL-13), hereby inhibiting Th2-mediated immune (Lim 2004, Shin et al. 2014a,b, Jung et al. 2017. Moreover, they were supposed to increase Th1 cytokine synthesis: IFN-γ, IL-2, IL-12 (Lim 2004, Chu et al. 2015, Jung et al. 2017. ...
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The aim of this study was to investigate the effect of aqueous extract from Scutellaria baical-ensis Georgi roots (SB) on blood parameters and immune response during an experimental trich-inellosis. A total of 60 mice infected with 200 Trichinella spiralis larvae were assigned into two groups. One of them served as a control and the second received SB extract orally from day 5 before infection to day 28 after infection (dpi). Blood was sampled at 7, 14, 21 dpi. Lymphocytes obtained from the spleen and mesenteric lymph nodes (MLN) at 7, 14, 21, and 28 dpi were counted, CD4 + and CD8 + subpopulations were analyzed by flow cytometry, and lymphocyte proliferation was estimated with colorimetric (MTT) assay. The intensity of intestinal and muscle invasion was also studied. SB caused a remarkable elevation of banded neutrophils in the blood at 7 dpi. SB increased ConA-stimulated splenocyte proliferation and CD4 + and CD8 + splenocyte subsets at 14 and 21 dpi, whereas MLN lymphocyte subset stimulation involved only CD4 + at 14 dpi. After administration of SB a downward trend in the number of T. spiralis larvae in the muscle was observed. These results suggest that Scutellaria baicalensis root extract stimulates murine cellular immune response during intestinal phase of T. spiralis infection.
... Th2-dominant responses, showing increased Th2 (IL-4, IL-5, and IL-13) cytokines and IgE production, are characteristic immune responses in patients with allergic diseases such as food allergy, asthma, and AD [42][43][44] . We previously reported some strategies to treat allergic diseases [45][46][47] . The first involves regulating the Th1/Th2 immune balance by suppressing excessively induced Th2-mediated immune responses or increasing Th1-related immune responses [48][49][50] . ...
... Dried extracts of the root of Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, have been found to enhance functioning of the immune system [20,38]; have anti-androgenic and growth-inhibitory actions in prostate cancer [5]; have anti-proliferative and apoptotic activity in acute lymphocytic leukaemia, lymphoma and myeloma cell lines [27]; induce cell cycle arrest and apoptosis in human lung cancer cells [19]; reduce gingivitis and dental plaque [3]; reduce body mass and blood triglycerides in diabetic mice [39]; and have been used for many other conditions, such as the treatment of diarrhoea, dysentery, hypertension, insomnia and respiratory infections [46]. Many active flavonoids have been discovered in the dried root extract of Scutellaria baicalensis including baicalein (5,6,7-trihydroxyflavone), wogonin (5,7-dihydroxy-8-methoxyflavone), norwogonin (5,7,8-trihydroxyflavone), baicalin and oroxylin A (5,7dihydroxy-6-methoxy-2-phenylchromen-4-one) [26,36,43,11]. ...
Article
The dried root of the angiosperm Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, is widely used in traditional Chinese medicine, Korean traditional medicine and as a nutritional supplement; several studies have indicated that both the supplement and some of its ingredients may have clinically beneficial actions. However, the National Institutes of Health official guidance states that the use of Scutellaria "has been implicated in rare instances of clinically apparent liver injury" and that "the onset of symptoms and jaundice occurred within 6-24 weeks of starting skullcap, and the serum enzyme pattern was typically hepatocellular", with marked increases in serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Careful perusal of all such published case reports showed that in each case the patient was concurrently taking at least one other supplement which had an established association with hepatic dysfunction. The authors hypothesised that long-term supplementation with Scutellaria baicalensis does not lead to hepatic dysfunction. The aim of this study was to test this hypothesis by assessing liver function before and after starting supplementation with Scutellaria baicalensis. Pre- and post-supplementation serum assays of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin were carried out in 17 patients (16 female) of average age 38.6 (standard error 4.4) years who had each taken 1335 mg dried root daily for an average of 444 (71) days. The mean baseline versus follow-up values for each liver function test were: alanine transaminase: 25.7 (2.6) IU/L v. 25.1 (1.7) IU/L; aspartate transaminase: 22.1 (1.1) IU/L v. 23.5 (1.3) IU/L; alkaline phosphatase: 63.7 (4.6) IU/L v. 63.3 (3.9) IU/L; and bilirubin: 6.1 (0.6) μM v. 6.0 (0.7) μM. None of these changes was statistically significant; indeed, three of the four parameters showed a non-significant decrease over time. Furthermore, none manifested clinical symptoms or signs of hepatic dysfunction during Scutellaria supplementation. These results suggest that daily intake of a relatively high level of Scutellaria baicalensis for over a year is not associated with any biochemical or clinical evidence of hepatic dysfunction. Indeed, Scutellaria baicalensis has been shown in murine experiments to have hepatoprotective actions.
... Chemical structures of Daidzein and KaemferolInterestingly, another plant-derived bioflavonoid, baicalein (5,6,7-trihydroxyflavone), originally isolated from Scutellaria baicalensis root, displays a potent antiviral effect against JEV replication in Vero cells. Furthermore, it not only possesses viral anti-adsorption activity, but also has a direct extracellular virucidal action on JEV as well (figure 3)[96,131]. Chemical structure of 5, 6,7-trihydroxyflavone (Balcalein). ...
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Background and Objective Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections. Method A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar and Web of Science. The relevant key words used as search terms were: “myelitis”, “encephalitis”, “meningitis”, “meningoencephalitis”, “encephalomyelitis”, “central nervous system”, “brain”, “spinal cord”, “infection”, “virus”, “medicinal plants” and “biological compounds”. Results The most significant viruses involved in central nervous system infections are: Herpes simplex virus (HSV), Varicella zoster virus (VZV), West Nile virus (WNV), Enterovirus 71 (EV71), Japanese encephalitis virus (JEV) and Dengue virus (DENV). The inhibitory activity of medicinal plants against CNS viruses are mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive oxygen species (ROS) and reduction of plaque formation. Conclusion Due to the increased resistance of microorganisms (bacteria, viruses and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.
... [51] Moreover, many previous works have demonstrated that Scutellaria baicalensis has significant antiallergic effects, but the detailed functions and mechanisms have not been elucidated so far. Shin et al. [52] demonstrated that wogonin, an active ingredient of Scutellaria baicalensis, could downregulate the OVA-induced Th2 immune response, strongly inhibit the production of IL-5 and indirectly reduce IgE levels without reduction in cell viability. This finding might suggest that wogonin can be used as a therapeutic agent for IgE and IL-5-mediated allergic diseases. ...
... This finding might suggest that wogonin can be used as a therapeutic agent for IgE and IL-5-mediated allergic diseases. Meanwhile, they had an interesting finding that oral administration of 1 mg/kg BW of wogonin was equivalent to the administration of Scutellaria baicalensis extract at 25 mg/kg BW. [52] In 2017, Bui et al. showed that the EESB (100, 200 and 400 mg/kg, p.o.), baicalein (10 mg/kg, p.o.) and wogonin (10 mg/kg, p.o.) may have potential preventive and therapeutic effects on Th2 type or mast cell-mediated allergic asthma through a mechanism possibly associated with the regulation of Th1/Th2 imbalance and histamine release. [53] Liver protection Scutellaria baicalensis is a traditional Chinese herbal medicine which is used to treat liver diseases. ...
... In vivo [52] EESB 100, 200 and 400 mg/ kg, (p. o.) ...
Article
Objectives: Scutellaria baicalensis Georgi. (Lamiaceae) is a plant of the genus Lamiaceae, and its root is the main part used as a medicine. In China, Scutellaria baicalensis is still an important traditional Chinese medicine with the functions of clearing away heat and dampness, purging fire and detoxification. This medicinal plant is widely distributed in China, Russia, Mongolia, North Korea and Japan. The purpose of this paper was to provide a systematic and comprehensive overview on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics and toxicology of this plant. Furthermore, the possible development trends and perspectives for future research on this medicinal plant are also discussed. Key findings: So far, over 40 compounds have been isolated and identified from Scutellaria baicalensis, including flavonoids, terpenoids, volatile oils and polysaccharides. The compounds and extracts isolated from Scutellaria baicalensis exhibit a wide range of pharmacological activities, including the effects on the nervous system, effects on the immune system, liver protection, antitumour effects, antibacterial and antiviral effects, antioxidant effects and other pharmacological effects. Summary: As a traditional Chinese herbal medicine, Scutellaria baicalensis has shown significant effects on the treatment of various diseases, especially hepatitis, diarrhoea, vomiting and high blood pressure. Numerous traditional uses of Scutellaria baicalensis have been confirmed by current investigations. However, it is also necessary to further study the drug-forming properties and pharmacokinetics of the active constituents of Scutellaria baicalensis, as well as to establish quality control standards for different areas of Scutellaria baicalensis, and to carry out the research at the cellular and molecular levels.