Inhibition of intestinal inflammation and fibrosis by Scutellaria Baicalensis georgi and Boswellia serrata in human epithelial cells and fibroblasts.

OBJECTIVE AND RATIONALE: Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach. Previous results suggest that Scutellaria baicalensis Georgi (SBG) and Boswellia serrata (BS) display anti-inflammatory properties. The aim of this study was to investigate in intestinal epithelial cells and fibroblasts the anti-inflammatory and anti-fibrotic potential of SBG and BS, alone or in combination. METHODS: Human colorectal adenocarcinoma cells (HT29), human intestinal epithelial cells (HIEC6) and human colon fibroblasts (CCD-18Co) were used. Cells were pretreated with SBG and BS and then exposed to pro-inflammatory and pro-fibrotic cytokines. RESULTS: SBG and BS extracts significantly decreased pro-inflammatory cytokine expression and improved epithelial restitution in HT29 and HIEC6 cells. Besides, fibrotic marker expression, including SNAIL, ACTA2, ZNF281, was strongly reduced. Colon myofibroblasts treated with SBG and BS showed a significant decrease of fibrotic markers as well. CONCLUSIONS: SBG and BS extracts significantly reduce inflammation and impair fibrosis in intestinal epithelial cells and colon myofibroblasts. No cooperative effect is observed.

Scutellaria baicalensis ameliorates allergic airway inflammation through agonism and transcriptional regulation of TAS2Rs.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SCB, Huangqin) is a traditional medicinal plant used to treat fever and respiratory diseases. SCB has a good therapeutic effect on asthma and anti-inflammation in traditional clinic use. However, the molecular mechanism and targets of SCB in treating asthma are still unclear. AIM OF THE STUDY: Combining transcriptomic analysis and in vitro experimental validation, this study aimed to reveal the molecular mechanism and targets of SCB in treating asthma. MATERIALS AND METHODS: The anti-asthmatic effects of SCB and its active components, scutellarin and oroxylin A, were evaluated in ovalbumin (OVA)-induced rats by analysis of pulmonary function and pathology. The signaling pathways in rat pulmonary tissue were analyzed using transcriptomics and protein interaction network analysis. Calcium mobilization assay and molecular docking were utilized to discover the active compounds from SCB with agonism activity of type 2 taste receptors (TAS2Rs). The anti-asthmatic effect and transcriptional regulation of TAS2Rs regulated by SCB and its active components were analyzed in vitro. RESULTS: Extracts of SCB (ESB), scutellarin, and oroxylin A ameliorated airway function and inflammation in OVA-induced rats. The anti-asthma mechanism of ESB, scutellarin and oroxylin A was highly related to immune and taste transduction pathways based on transcriptomic analysis, especially the TAS2Rs signaling pathway. ESB was the direct agonist of TAS2R4 and TAS2R14 with EC50 of 209.1 and 217.2 µg/mL based on calcium mobilization assay, respectively. Baicalein was the main active component for TAS2R4 agonism activity, and scutellarin and oroxylin A had weak agonism activity of TAS2R4 and TAS2R14 through calcium mobilization assay and molecular docking. However, scutellarin and oroxylin A significantly upregulated the gene expression of Tas2r108 (the mouse ortholog of the TAS2R4) in lung tissue. ESB, scutellarin, and oroxylin A inhibited LPS-induced lactate dehydrogenase release and gene expression of TNF through transcriptional regulation of TAS2R4 and TAS2R14 on bronchial epithelial cells. ESB and oroxylin A ameliorated IgE-induced ß-hexosaminidase release and gene expression of Il4 and Tnf and upregulated gene expression of Tas2r108. CONCLUSION: These results provided new insight into the anti-asthmatic mechanism of SCB and active components, scutellarin and oroxylin A, through agonism and transcriptional regulation of TAS2Rs to ameliorate allergic airway inflammation.

The Effect of the Extraction Conditions on the Antioxidant Activity and Bioactive Compounds Content in Ethanolic Extracts of Scutellaria baicalensis Root.

Ethanolic extracts of Baikal skullcap (Scutellaria baicalensis) root were obtained using various techniques, such as maceration, maceration with shaking, ultrasound-assisted extraction, reflux extraction, and Soxhlet extraction. The influence of the type and time of isolation technique on the extraction process was studied, and the quality of the obtained extracts was determined by spectrophotometric and chromatographic methods to find the optimal extraction conditions. Radical scavenging activity of the extracts was analyzed using DPPH assay, while total phenolic content (TPC) was analyzed by the method with the Folin-Ciocalteu reagent. Application of gas chromatography with mass selective detector (GC-MS) enabled the identification of some bioactive substances and a comparison of the composition of the particular extracts. The Baikal skullcap root extracts characterized by both the highest antioxidant activity and content of phenolic compounds were obtained in 2 h of reflux and Soxhlet extraction. The main biologically active compounds identified in extracts by the GC-MS method were wogonin and oroxylin A, known for their broad spectrum of biological effects, including antioxidant, anti-inflammatory, antiviral, anticancer, and others.

Composite Polysaccharide Hydrogel Loaded with Scutellaria baicalensis Extract for Diabetic Wound Treatment.

Diabetic wounds present significant burdens to both patients and the healthcare system due to their prolonged inflammatory phase and adverse microenvironment. Traditional Chinese medicine (TCM), particularly Scutellaria baicalensis extract (SE), has shown promise in wound healing. Herein, sesbania gum (SG) was oxidized and formed hydrogel with carboxymethyl chitosan (CMCS) through the imine bond. Then, SE was loaded into the hydrogel as a wound dressing (CMCS-OSG@SE hydrogel). In vitro experiments demonstrated the mechanical properties and ROS scavenging efficiency of the hydrogel, as well as the release of SE and its biocompatibility. In an vivo study, diabetic mice with S. aureus infection were used, and the CMCS--OSG@SE hydrogel dressing accelerated wound healing by promoting epidermal regeneration and collagen deposition. This composite polysaccharide hydrogel loaded with SE shows great potential for diabetic wound treatment.

Botanical Bioflavonoid Composition from Scutellaria baicalensis- and Acacia catechu-Protected Mice against D-Galactose-Induced Immunosenescence, and Cyclophosphamide Induced Immune Suppression.

Oxidative stress and chronic inflammation create a perpetual cycle in the elderly, where impaired immune function amplifies susceptibility to oxidative damage, and oxidative stress further weakens the immune response. This cycle is particularly detrimental to the respiratory system of the elderly, which is an easy target for constant exogenous harmful attacks during cold/flu season or under heavy air pollution. Herbal medicines that protect respiratory function are seen as safer alternatives to conventional therapies; however, there is limited availability of scientifically validated, safe, and effective natural supplements for these conditions. In this study, we evaluated a standardized bioflavonoid composition, UP446, that contains bioactives from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu as a natural and nutritional supplement for its antioxidative and immunoregulatory effects in oxidative stress-accelerated aging and chemically induced immune suppression mouse models. Immunosenescence was induced through the repeated subcutaneous inoculation of D-galactose (D-Gal) at a dose of 500 mg/kg/day in CD-1 mice. UP446 was administered orally at doses of 100 mg/kg and 200 mg/kg starting in the fifth week of immunosenescence induction. This study lasted a total of ten weeks. All mice received a quadrivalent influenza vaccine 2 weeks before termination. Whole blood, serum, spleen homogenate, and thymus tissues were processed for analysis. Cyclophosphamide (Cy)-induced immunosuppression was triggered by three consecutive injections of cyclophosphamide at 80 mg/kg/day, followed by the oral administration of UP446 for 18 days at doses of 100 mg/kg and 200 mg/kg. Blood was collected from each animal at necropsy, and serum was isolated for IgA and IgG ELISA analysis. UP446 was found to improve immune response, as evidenced by the stimulation of innate (NK cells) and adaptive immune responses (T cells and cytotoxic T cells), an increase in antioxidant capacity (glutathione peroxidase), the preservation of vital immune organs (the thymus), and a reduction in NFκB. UP446 also increased serum levels of IgA and IgG. The findings presented in this report demonstrate the antioxidative, anti-inflammatory, and immune-regulatory activities of UP446, suggesting its potential use in respiratory conditions involving immune stress due to aging, oxidative stress, and/or pathogenic challenges.

Preparative separation of ten flavonoids from Scutellaria baicalensis Georgi roots using two-dimensional countercurrent chromatography with an online-storage, dilution, and mixing interface.

The process of counter-current chromatography (CCC) separation for natural products typically necessitates the use of multiple solvent systems to accommodate constituents with a wide range of polarities. However, the incompatibility between these different solvent systems often results in unsuccessful online 2D successive separations. In this study, a 2D CCC system was developed, featuring an interface for online-storage, dilution, and mixing. It facilitated the implementation of online 2D CCC using different solvent systems. The method was subsequently applied for the preparative isolation of flavonoids from Scutellaria baicalensis Georgi roots. For 1D CCC, n-heptane-ethyl acetate-methanol-water (HepEMWat, 5:5:4:6, v/v) was utilized, while for 2D CCC, ethyl acetate-n-butanol-water (EBuWat, 0:5:5, v/v) was employed. The eluent with low resolution in 1D CCC was stored online, diluted three times using the lower phase of EBuWat (0:5:5, v/v), and subsequently transferred into 2D CCC for further isolation utilizing the same EBuWat (0:5:5, v/v) system. As results, six lipophilic compounds were isolated in 1D CCC in a normal mode, while two major hydrophilic constituents were isolated in a pH-peak-focusing mode in 2D CCC. Additionally, two additional compounds were purified through subsequent semi-preparative HPLC separation in order to resolve co-elution in 2D CCC. The developed 2D CCC system with a multifunctional interface demonstrated to be an exceptionally efficient and promising approach for the high-throughput purification of complex natural products.

Scutellaria baicalensis Polysaccharide-Mediated Green Synthesis of Smaller Silver Nanoparticles with Enhanced Antimicrobial and Antibiofilm Activity.

Silver nanoparticles (AgNPs) have attracted widespread attention in multidrug-resistant bacterial infections. However, the application of AgNPs synthesized by conventional methods is restricted by its high costs, toxicity, and poor stability. Herein, a water-soluble polysaccharide (Scutellaria baicalensis polysaccharide, SBP) rich in reducing sugars was used as both the reductant and stabilizer to greenly synthesize spherical AgNPs@SBP with smaller particle sizes (11.18 ± 2.50 nm) and higher negative zeta potential (-23.05 ± 2.76 mV), which was favorable to enhance its antimicrobial activity and improve pH and thermal stability. Besides, SBP facilitated the adhesion and penetration of AgNPs@SBP to methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli (CREC), thus significantly enhancing its antibacterial activity (increased by 32-fold and 64-fold, respectively). Likewise, AgNPs@SBP at a low concentration (7.8 µg/mL) could effectively penetrate and inhibit nearly 90% of MRSA and CREC biofilm formation. Antimicrobial mechanism studies showed that AgNPs@SBP could lead to more severe cell membrane damage and genetic material leakage by upregulating reactive oxygen species and depolarizing mitochondrial membrane potential, ultimately resulting in the apoptosis of bacteria. Overall, the wrapping of SBP significantly enhanced the antibacterial and antibiofilm activity of AgNPs, which possessed great potential in the prevention and treatment of multidrug-resistant bacterial infections.

Characterization of the 2ODD genes of DOXC subfamily and its members involved in flavonoids biosynthesis in Scutellaria baicalensis.

BACKGROUND: 2-oxoglutarate-dependent dioxygenase (2ODD) superfamily is the second largest enzyme family in the plant genome and plays diverse roles in secondary metabolic pathways. The medicinal plant Scutellaria baicalensis Georgi contains various flavonoids, which have the potential to treat coronavirus disease 2019 (COVID-19), such as baicalein and myricetin. Flavone synthase I (FNSI) and flavanone 3-hydroxylase (F3H) from the 2ODDs of DOXC subfamily have been reported to participate in flavonoids biosynthesis. It is certainly interesting to study the 2ODD members involved in the biosynthesis of flavonoids in S. baicalensis. RESULTS: We provided a genome-wide analysis of the 2ODDs of DOXC subfamily in S. baicalensis, a total of 88 2ODD genes were identified, 82 of which were grouped into 25 distinct clades based on phylogenetic analysis of At2ODDs. We then performed a functional analysis of Sb2ODDs involved in the biosynthesis of flavones and dihydroflavonols. Sb2ODD1 and Sb2ODD2 from DOXC38 clade exhibit the activity of FNSI (Flavone synthase I), which exclusively converts pinocembrin to chrysin. Sb2ODD1 has significantly higher transcription levels in the root. While Sb2ODD7 from DOXC28 clade exhibits high expression in flowers, it encodes a F3H (flavanone 3-hydroxylase). This enzyme is responsible for catalyzing the conversion of both naringenin and pinocembrin into dihydrokaempferol and pinobanksin, kinetic analysis showed that Sb2ODD7 exhibited high catalytic efficiency towards naringenin. CONCLUSIONS: Our experiment suggests that Sb2ODD1 may serve as a supplementary factor to SbFNSII-2 and play a role in flavone biosynthesis specifically in the roots of S. baicalensis. Sb2ODD7 is mainly responsible for dihydrokaempferol biosynthesis in flowers, which can be further directed into the metabolic pathways of flavonols and anthocyanins.

Identification of the Anti-ischemia-reperfusion Injury Effect of Baicalein from Scutellaria Baicalensis Georgi in Liver Transplantation.

BACKGROUND: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT. METHODS: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model. RESULTS: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation. CONCLUSION: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.

Effects of elicitors from culture filtrate of Fusarium solani CL105 on flavonoid production of Scutellaria baicalensis calli.

Introduction: Endophytic fungi can promote secondary metabolite accumulation in medicinal plants. Previously, we observed that the culture filtrate of Fusarium solani CL105 promoted flavonoid production in Scutellaria baicalensis calli. However, the active ingredients and mechanisms associated with this secondary metabolite accumulation remain unclear. Methods: This study evaluates the effects of different elicitors from the culture filtrate of F. solani CL105 namely, exopolysaccharide (EPS), exoprotein (EP), and other parts (OP), on the flavonoid production in S. baicalensis calli by HPLC. Subsequently, the underlying mechanism of EPS induced flavonoid production in S. baicalensis calli was revealed by transcriptomics and RT-PCR. Results and discussion: The results indicated a significant increase in flavonoid production in S. baicalensis calli following treatment with EPS. Baicalin (1.40 fold), wogonoside (1.91 fold), and wogonin (2.76 fold) were most significantly up-regulated compared with the control. Transcriptome analysis further revealed up-regulation of key enzyme genes (CHS, CHI, FNS, and F6H) involved in flavonoid synthesis after 5 days of EPS treatment. Moreover, the expression of GA2ox and CYP707A-genes involved in gibberellin acid (GA) and abscisic acid biosynthesis (ABA), respectively-were significantly up-regulated. The expression levels of certain transcription factors, including MYB3, MYB8, and MYB13, were also significantly higher than in controls. Our results indicated that EPS was a main active elicitor involved in promoting flavonoid production in S. baicalensis calli. We postulated that EPS might stimulate the expression of MYB3, MYB8, MYB13, GA2ox, and CYP707A, leading to markedly upregulated CHS, CHI, FNS, and F6H expression levels, ultimately promoting flavonoid synthesis. This study provides a novel avenue for large-scale in vitro production of flavonoids in S. baicalensis.

Research progress on pharmacological properties and application of probiotics in the fermentation of Scutellaria baicalensis Georgi.

Scutellaria baicalensis Georgi is a medicinal herb with a rich history of use in traditional Chinese medicine. This review concentrates on the chemical constituents of Scutellaria baicalensis Georgi, with a particular emphasis on flavonoids such as baicalin, baicalein, and wogonin. Additionally, it examines the effects of probiotic fermentation on the plant's chemical profile and pharmacological actions. Evidence suggests that probiotic fermentation markedly modifies the bioactive components of Scutellaria baicalensis Georgi, thereby augmenting its medicinal potency. The paper delves into the mechanisms by which the primary active constituents of Scutellaria baicalensis Georgi are altered during fermentation and how these changes influence its pharmacological properties. This review aims to lay a theoretical groundwork for the clinical utilization of Scutellaria baicalensis Georgi and the formulation of innovative therapeutic approaches.

Wogonin Inhibits Colorectal Cancer Proliferation and Epithelial Mesenchymal Transformation by Suppressing Phosphorylation in the AKT Pathway.

Colorectal cancer is the third leading cause of cancer-related death worldwide. Hence, there is a need to identify new therapeutic agents to improve the current repertoire of therapeutic drugs. Wogonin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antitumor activity. Our study aimed to further explore the inhibitory effects of wogonin on colorectal cancer and its specific mechanism. The results showed that wogonin significantly inhibited the proliferation of colorectal cancer cells as well as their ability to invade and metastasize. We detected phosphorylation of tumor-associated signaling pathways using a phosphorylated protein microarray and found that wogonin intervention significantly inhibited the phosphorylation level of the AKT protein in colorectal cancer cells. Through in vitro and in vivo experiments, it was confirmed that wogonin exerted its antitumor effects against colorectal cancer by inhibiting phosphorylation in the AKT pathway. Our discovery of wogonin as an inhibitor of AKT phosphorylation provides new opportunities for the pharmacological treatment of colorectal cancer.

Scutellaria Root extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Baicalin and baicalein from Scutellaria baicalensis Georgi alleviate aberrant neuronal suppression mediated by GABA from reactive astrocytes.

AIMS: γ-aminobutyric acid (GABA) from reactive astrocytes is critical for the dysregulation of neuronal activity in various neuroinflammatory conditions. While Scutellaria baicalensis Georgi (S. baicalensis) is known for its efficacy in addressing neurological symptoms, its potential to reduce GABA synthesis in reactive astrocytes and the associated neuronal suppression remains unclear. This study focuses on the inhibitory action of monoamine oxidase B (MAO-B), the key enzyme for astrocytic GABA synthesis. METHODS: Using a lipopolysaccharide (LPS)-induced neuroinflammation mouse model, we conducted immunohistochemistry to assess the effect of S. baicalensis on astrocyte reactivity and its GABA synthesis. High-performance liquid chromatography was performed to reveal the major compounds of S. baicalensis, the effects of which on MAO-B inhibition, astrocyte reactivity, and tonic inhibition in hippocampal neurons were validated by MAO-B activity assay, qRT-PCR, and whole-cell patch-clamp. RESULTS: The ethanolic extract of S. baicalensis ameliorated astrocyte reactivity and reduced excessive astrocytic GABA content in the CA1 hippocampus. Baicalin and baicalein exhibited significant MAO-B inhibition potential. These two compounds downregulate the mRNA levels of genes associated with reactive astrogliosis or astrocytic GABA synthesis. Additionally, LPS-induced aberrant tonic inhibition was reversed by both S. baicalensis extract and its key compounds. CONCLUSIONS: In summary, baicalin and baicalein isolated from S. baicalensis reduce astrocyte reactivity and alleviate aberrant tonic inhibition of hippocampal neurons during neuroinflammation.

Scutellaria baicalensis water decoction ameliorates lower respiratory tract infection by modulating respiratory microbiota.

BACKGROUND: The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis, a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. PURPOSE: To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. METHODS: A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae. Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. High-performance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were determined by hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRT-PCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. RESULTS: Seven main components, including scutellarin, baicalin, oroxylin A-7-O-ß-d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae-induced LRTI mice, as evidenced by the dose-dependent reductions in the levels of serum inflammatory cytokines, IL-6 and TNF-α. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL-17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae, and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae-induced LRTI mice. CONCLUSION: SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.

Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role of Scutellaria baicalensis in Alzheimer's Disease.

Aim: Scutellaria baicalensis, a traditional Chinese medicinal herb renowned for its anti-inflammatory, antioxidant, and anti-tumor properties, has shown promise in alleviating cognitive impairment associated with Alzheimer's disease. Nonetheless, the exact neuroprotective mechanism of Scutellaria baicalensis against Alzheimer's disease remains unclear. In this study, network pharmacology was employed to explore the possible mechanisms by which Scutellaria baicalensis protects against Alzheimer's disease. Methods: The active compounds of Scutellaria baicalensis were retrieved from the TCMSP database, and their corresponding targets were identified. Alzheimer's disease-related targets were obtained through searches in the GeneCards and OMIM databases. Cytoscape 3.6.0 software was utilized to construct a regulatory network illustrating the "active ingredient-target" relationships. Subsequently, the target genes affected by Scutellaria baicalensis in the context of Alzheimer's disease were input into the String database to establish a PPI network. GO analysis and KEGG analysis were conducted using the DAVID database to predict the potential pathways associated with these key targets. Following this, the capacity of these active ingredients to bind to core targets was confirmed through molecular docking. In vitro experiments were then carried out for further validation. Results: A total of 36 active ingredients from Scutellaria baicalensis were screened out, which corresponded to 365 targets. Molecular docking results demonstrated the robust binding abilities of Baicalein, Wogonin, and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone to key target proteins (SRC, PIK3R1, and STAT3). In vitro experiments showed that the active components of Scutellaria baicalensis can inhibit STAT3 expression by downregulating the PIK3R1/SRC pathway in Neuro 2A cells. Conclusion: In summary, these findings collectively suggest that Scutellaria baicalensis holds promise as a viable treatment option for Alzheimer's disease.

The effect of scutellaria baicalensis and its active ingredients on major depressive disorder: a systematic review and meta-analysis of literature in pre-clinical research.

Background: Scutellaria baicalensis, the dry root of scutellaria baicalensis georgi, is a traditional Chinese medicine with long. In clinic, scutellaria baicalensis is commonly used in prescription for the treatment of depression. Additionally, numerous pre-clinical studies have shown that Scutellaria baicalensis and its active constituents are effective for depression. In this study, we aims to systematically review the roles of scutellaria baicalensis in depression and summarize the possible mechanism. Methods: A systematic review and meta-analysis were conducted to analyze the existing studies on the effects of scutellaria baicalensis on depression in animal models. Briefly, we searched electronic databases including Pubmed and Embase for preclinical trial studies from inception to September 2023. The items in each study were evaluated by two independent reviewers, and meta-analyses were performed on scutellaria baicalensis-induced behavioral changes in the study. Finally, random effects model is used to collect data. Results: A total of 49 studies were identified, and 13 studies were included in the final analysis. They all reported the different antidepressant effects of scutellaria baicalensis and the underlying biological mechanisms. Among the included 13 studies, the results of eight articles SPT[SMD = -2.80, 95%CI(-4.03, -1.57), p < 0.01], the results of the nine articles OFT[SMD = -2.38, 95%CI(-3.53, -1.23), p < 0.01], and the results of two articles NSFT[SMD = -2.98, 95%CI(-3.94, -2.02), p < 0.01] were significantly different from the control group. The risk of bias was moderate in all studies, however, there was a significant heterogeneity among studies. Conclusion: These results preliminarily suggest that scutellaria baicalensis can alleviate depressive behaviors and modulate underlying mechanisms, which is expected to be a promising antidepressant.

Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis.

BACKGROUND: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. METHODS: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. CONCLUSION: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

Scutellaria baicalensis Georgi alleviates Clostridium difficile associated diarrhea and its modulatory effects on the gut microbiota.

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.

Pharmacokinetic analysis of antiviral drug ritonavir across the blood-brain barrier and its interaction with Scutellaria baicalensis using multisite microdialysis in rats.

Ritonavir, an excellent inhibitor of CYP3A4, has recently been combined with nirmatrelvir to form Paxlovid for the treatment of severe acute respiratory syndrome coronavirus 2 infections. The root of Scutellaria baicalensis Georgi (S. baicalensis), a traditional Chinese medicinal (TCM) herb commonly used to treat heat/inflammation in the lung and digestive tracts, which are major organs targeted by viral infections, contains flavones that can influence the CYP3A metabolism pathway. To investigate the ability of ritonavir to cross the bloodbrain barrier (BBB) and its potential herb-drug interactions with an equivalent TCM clinical dose of S. baicalensis, multisite microdialysis coupled with an LCMS/MS system was developed using rat model. Pretreatment with S. baicalensis extract for 5 days, which contains less flavones than those used in previous studies, had a significant influence on ritonavir, resulting in a 2-fold increase in the total concentration of flavones in the blood and brain. Treatment also boosted the maximum blood concentration of flavones by 1.5-fold and the maximum brain concentration of flavones by 2-fold, all the while exerting no noticeable influence on the transfer ratio across the bloodbrain barrier. These experimental results demonstrated that the use of a typical traditional Chinese medicinal dose of S. baicalensis is sufficient to influence the metabolic pathway and synergistically increase the concentration of ritonavir in rats.