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With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions. [ABSTRACT FROM AUTHOR]

Background: Scutellaria barbata D. Don, also known as "Banzhilian" in China, the diterpenes of Banzhilian (Bzl-D) is a commonly used herbal medicine for treating various tumors including colorectal cancer (CRC). Objectives: This study aimed to examine the function of Bzl-D in inhibiting CRC development and explore its potential targets and mechanisms involving the Hedgehog (HH) pathway. Materials and Methods: To determine the major components in Bzl-D, we performed ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) analysis. The proliferation, migration, invasion, and apoptosis abilities of the CRC HT-29 cell line were examined, and the related protein expression was tested. Tumorigenesis after treatment was detected by in vivo experiments. Results: Nineteen diterpenoids were detected, Bzl-D significantly inhibited the cell proliferation and metastasis and induced the apoptosis of HT-29 cells through binding to Sonic HH (SHH) and down-regulating the key proteins (SHH, patched, smoothened, and glioma-associated oncogene) of the HH pathway, thus. Of note, Bzl-D remarkably suppressed the growth of HT-29 xenografts in nude mice. Conclusion: This research demonstrates that Bzl-D is a promising anti-rectal cancer drug, providing a new entry point for targeted therapy of CRC. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate Scutellaria barbata D. Don and Seleromitrion diffusa (Willd). R. J. Wang (HDSB) in the treatment of chronic atrophic gastritis (CAG) by using network pharmacology and literature research. Methods: TCMSP, Uniprot, Drug Bank, OMIM, and GeneCards were used to obtain the active components, targets of Scutellaria barbata D. Don and Seleromitrion diffusa (Willd). R. J. Wang and the disease targets of CAG. Cytoscape 3.9.1 was used to construct a drug network. STRING platform was used to analyze the PPI network, and Metascape was used for functional enrichment analysis and KEGG pathway enrichment analysis. Results: The study found a total of 34 active compounds of HDSB, 153 predicted targets, 970 disease targets, and 46 intersection targets of CAG. And identified a total of 27 prescriptions or proprietary Chinese medicines containing Scutellaria barbata D. Don and Seleromitrion diffusa (Willd). R. J. Wang through literature research and database search, that consists in a 1:1, 1:2, or 2:1 ratio, with a dose range of 15 g–300 g. Conclusion: The study suggests that Scutellaria barbata D. Don and Seleromitrion diffusa (Willd). R. J. Wang may exert therapeutic effects on chronic atrophic gastritis by acting on JNK, PI3K-Akt, HIF-1, cancer-related and others. [ABSTRACT FROM AUTHOR]

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients’ quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure–activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4′-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4′-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4′-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3′,4′-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL). [ABSTRACT FROM AUTHOR]

Abstract Background Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. Materials and methods CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. Results The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. Conclusions Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients.

Diabetes mellitus has become a pandemic in modern society. Regulation of carbohydrate hydrolysis by inhibition of key-digestive enzymes is currently used to control hyperglycaemia. Therefore, characterization of safe and efficient alternative therapeutic agents has become essential. Herein, the mechanism of α-amylase and α-glucosidase inhibition of 4-(4-hydroxyphenyl)-but-3-en-2-one (4) isolated from Scutellaria barbata D. Don was investigated by in vitro enzymatic kinetics, conformation analysis and molecular docking. The results demonstrated that 4-(4-hydroxyphenyl)-but-3-en-2-one (4) reversibly inhibited α-amylase and α-glucosidase in a mixed-type and competitive manner with IC50 values of 81.2 ± 5.3 and 54.8 ± 2.4 µM, respectively. Analysis of fluorescence spectroscopy showed that the interaction of the compound with both enzymes was primarily influenced by hydrogen bonding and van der Waals forces, and was a spontaneous process. Moreover, computer modelling indicated that the amino acid residues of the enzymes were bound to the compound mainly by hydrogen bonds. The results indicated that the substituents in the molecular structure of the compounds play a crucial role in the inhibition activity of the compounds. 4-(4-Hydroxyphenyl)-but-3-en-2-one (4) with methyl vinyl ketone substitution on the benzene ring was the most potent inhibitor for both enzymes. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aims to investigate the antidepressant properties of Hispidulin, a flavonoid present in Scutellaria barbata D. Don. The selection of Hispidulin stems from its notable inhibitory activity against Xanthine Oxidase (XO), a parameter in the pathophysiology of depression., Material and Methods: Mice were subjected to a rigorous evaluation using a murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression for 21 days and antidepressant properties were rigorously assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Imipramine and fluoxetine were used as standard drugs. Additionally, neurochemical analyses were conducted to quantify serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels in the cortex, hippocampus, and hypothalamus. Further mechanistic insights were sought through the estimation of monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in the brain. Plasma nitrite and corticosterone levels were also measured to delineate the underlying mechanism of action., Results: Hispidulin demonstrated significant antidepressant effects, as evidenced by reduced immobility time in TST and FST and increased exploratory behavior in OFT. Neurochemical analysis revealed restoration of 5-HT, NE, and DA levels in key brain regions. Furthermore, Hispidulin modulated MAO activity and enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were elevated, indicating enhanced nitric oxide synthesis, while corticosterone levels were reduced., Conclusion: Our findings indicate that Hispidulin exerts potent antidepressant effects, potentially mediated through its influence on monoaminergic neurotransmitters, MAO activity, and antioxidant defenses. These results provide valuable mechanistic insights into the antidepressant action of Hispidulin, supporting its potential therapeutic application in depressive disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization., Methods: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells., Results: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4., Conclusion: SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Background Scutellaria barbata D. Don (SB) is a widely used herbal medicine in China, with various pharmacological effects such as anti-oxidation, anti-inflammation, and anti-cancer. This work is aimed to investigate the tumor-suppressive effect of SB in cervical cancer (CC) and to identify its underlying mechanisms. Methods and materials CC cell lines (HeLa and HT-3) were treated with different concentrations of SB chloroform extract (ECSB) (0, 0.2, 0.5 mg/ml). MiR-195-5p and LOXL2 mRNA expression in CC cell lines and tissue samples was detected by quantitative real-time polymerase chain reaction. Cell counting kit-8 experiment was utilized to examine cell viability; TUNEL assay and Transwell experiment was executed to examine cell apoptosis, migration, and invasion. Western blotting experiments were implemented to detect LOXL2 protein expression. Bioinformatics and dual-luciferase reporter gene experiment were executed to examine the binding relationship between miR-195-5p and LOXL2. Results ECSB repressed the viability, migration, and invasion of HeLa and HT-3 cells, and promoted cell apoptosis in a dose-dependent manner. MiR-195-5p was remarkably under-expressed in CC tissues and cells, and ECSB up-regulated miR-195-5p expression. MiR-195-5p inhibitors partially counteracted the suppressive effects of ECSB on the malignant phenotypes of HeLa and HT-3 cells. LOXL2 was a downstream target of miR-195-5p, and ECSB up-modulated LOXL2 expression by specifically repressing miR-195-5p. Conclusion SB restrains CC cell proliferation and metastasis and promotes cell apoptosis via miR-195-5p/LOXL2, which may be a potential therapeutic agent for CC treatment. [ABSTRACT FROM AUTHOR]

Inhibition of α-glucosidase is a therapeutic approach that slows down the hydrolysis of oligosaccharides and disaccharides to glucose. Therefore, delaying the digestion and absorption of carbohydrates by inhibiting α-glucosidase can reduce blood glucose levels. Herein, the methanol extract of Scutellaria barbata D. Don was screened for α-glucosidase inhibitors using an in vitro inhibition assay and chromatographic techniques (column chromatography, TLC, and HPLC). Six known flavonoids were isolated, including chrysin (1), wogonin (2), apigenin (3), hispidulin (4), pinocembrin (5) and 6-methoxyaringenin (6), and their structures were identified by spectroscopic methods (NMR and MS) and by comparing their spectral data to reported values. Compounds 1 – 6 exhibited higher inhibitory activities against α-glucosidase with IC50 values between 17 μM and 192 μM compared to the reference drug acarbose (1463.0 ± 29.5 μM). The kinetic analysis showed that flavonoid 1 was a competitive inhibitor, flavonoids 2 and 4 were mixed-type inhibitors, while flavonoids 3, 5 and 6 were noncompetitive inhibitors of α-glucosidase. Computer modeling showed that the primary amino acid residue interacted with the flavonoids primarily through hydrogen bonding, with binding energies ranging from –5.44 to –1.85 kcal/mol. These results indicate that compounds 1 – 6 are potential α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components—scutellarin and luteolin—which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications. [Display omitted] • Study shows gut microbiota's role in transforming flavonoids like scutellarin and luteolin. • Findings partially uncover SBD's antitumor actions, underlining its therapeutic promise. • Results pave the way for future research to boost SBD's effectiveness in cancer therapy. [ABSTRACT FROM AUTHOR]

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure–activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4′-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4′-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4′-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3′,4′-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

We investigated whether Scutellaria barbata D. Don (Family Lamiaceae) (SBD), a traditional medicine used for heat clearing and detoxification, possesses antiphotoaging properties. Pretreatment of NIH-3T3 skin fibroblast cells with non-toxicological levels of water extract of SBD (WESBD) and ethanol extract of SBD (EESBD) restored the expression of procollagen type-1 (COL1A1), matrix metalloproteinase-1a (MMP-1a), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-3 (MCP-3) genes following abnormal expression induced by ultraviolet B (UVB) irradiation. WESBD/EESBD administration to the dorsal skin area of hairless mice significantly (p < 0.05) inhibited UVB-induced wrinkle formation and epidermal thickness. The WESBD and EESBD treatments also restored the dermal collagen content, which was decreased by the UVB treatment, and normal COL1A1 and MMP-1a expression. Interestingly, both the WESBD and EESBD pretreatments significantly attenuated UVB-induced phosphorylation of protein kinase B (AKT) but not that of mitogen-activated protein kinases (MAPKs). This finding indicates that the antiphotoaging effects of WESBD and EESBD may be related to attenuation of UVB-induced overactivation of AKT phosphorylation. High performance liquid chromatography (HPLC) and mass spectrometry analysis revealed that isorhamentin and scutebarbatine I were major single components of EESBD. These results suggest that WESBD and EESBD may have potential in development as antiphotoaging agents. [ABSTRACT FROM AUTHOR]

Background: Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. Materials and methods: CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. Results: The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. Conclusions: Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients. [ABSTRACT FROM AUTHOR]

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and β -glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro , and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide. [ABSTRACT FROM AUTHOR]

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and β-glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro, and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide.

A poor prognosis, relapse and resistance are burning issues during adverse-risk acute myeloid leukaemia (AML) treatment. As a natural medicine, Scutellaria barbata D. Don (SBD) has shown impressive antitumour activity in various cancers. Thus, SBD may become a potential drug in adverse-risk AML treatment. This study aimed to screen the key targets of SBD in adverse-risk AML using the drug–biomarker interaction model through bioinformatics and network pharmacology methods. First, the adverse-risk AML-related critical biomarkers and targets of SBD active ingredient were obtained from The Cancer Genome Atlas database and several pharmacophore matching databases. Next, the protein–protein interaction network was constructed, and topological analysis and pathway enrichment were used to screen key targets and main pathways of intervention of SBD in adverse-risk AML. Finally, molecular docking was implemented for key target verification. The results suggest that luteolin and quercetin are the main active components of SBD against adverse-risk AML, and affected drug resistance, apoptosis, immune regulation and angiogenesis through the core targets AKT1, MAPK1, IL6, EGFR, SRC, VEGFA and TP53. We hope the proposed drug–biomarker interaction model provides an effective strategy for the research and development of antitumour drugs. [ABSTRACT FROM AUTHOR]

Dear Editor, Scutellaria barbata D. Don (SBD) is a perennial herb and belongs to the “Lamiaceae” family. This is widely used in China for a long time as Traditional Chinese Medicine (TCM). Based on the TCM theory, SBD is in the category of “Heat-Clearing”. Its functions are to remove heat and detoxification, disperse blood stasis and diuresis. [...]

We investigated whether Scutellaria barbata D. Don (Family Lamiaceae) (SBD), a traditional medicine used for heat clearing and detoxification, possesses antiphotoaging properties. Pretreatment of NIH-3T3 skin fibroblast cells with non-toxicological levels of water extract of SBD (WESBD) and ethanol extract of SBD (EESBD) restored the expression of procollagen type-1 (COL1A1), matrix metalloproteinase-1a (MMP-1a), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-3 (MCP-3) genes following abnormal expression induced by ultraviolet B (UVB) irradiation. WESBD/EESBD administration to the dorsal skin area of hairless mice significantly (p < 0.05) inhibited UVB-induced wrinkle formation and epidermal thickness. The WESBD and EESBD treatments also restored the dermal collagen content, which was decreased by the UVB treatment, and normal COL1A1 and MMP-1a expression. Interestingly, both the WESBD and EESBD pretreatments significantly attenuated UVB-induced phosphorylation of protein kinase B (AKT) but not that of mitogen-activated protein kinases (MAPKs). This finding indicates that the antiphotoaging effects of WESBD and EESBD may be related to attenuation of UVB-induced overactivation of AKT phosphorylation. High performance liquid chromatography (HPLC) and mass spectrometry analysis revealed that isorhamentin and scutebarbatine I were major single components of EESBD. These results suggest that WESBD and EESBD may have potential in development as antiphotoaging agents.

Purpose: To investigate the effect of Scutellaria barbata D. Don extract (SBDE) on apoptosis and proliferation in A549 human lung cancer cells. Methods: Inverted microscope was used to observe morphological changes in A549 cells after exposure to SBDE. Trypan blue staining of living cells was applied to construct cell growth curve after treatment with varying concentrations of SBDE. The influence of SBDE on cell proliferation, apoptosis and cell cycle was determined by MTT assay while protein expressions of key apoptosis-related enzymes were evaluated by immuno-cytochemical method. Results: SBDE inhibited the growth of A549 lung cancer cells at a concentration range of 20 - 160 µg/mL. Flow cytometry showed that SBDE induced apoptosis in the A549 cells. The proportion of cells in G0/G1-phase increased significantly (p < 0.01), while the proportion of cells in S-phase and G2/Mphase decreased correspondingly, indicating that the cells were in G0/G1-phase arrest. Cell cycle arrest and apoptosis-inducing effect gradually increased with increase in SBDE concentration. With increasing concentrations of SBDE, there were significant increases in the expressions of caspase-3 (p < 0.05), caspase-8 (p < 0.01) and caspase-9 (p < 0.05), and significant decreases in Ki-67 (p < 0.01) and p21 ras protein (p < 0.01). Conclusion: SBDE exerts significant inhibitory effect on the proliferation of A549 lung cancer cells, which can be developed for the treatment of lung cancer patients. [ABSTRACT FROM AUTHOR]

• Six flavonoids were extracted by an ultrasound-assisted supercritical CO 2 procedure. • Baicalein yield decreased with increasing temperature; others showed opposite trend. • The current procedure had a higher extraction efficiency than other processes. • Second-order law indicates that the current procedure has a lower energy barrier. • Higher temperatures might enhance mass transfer and diffusion in the procedure. Six bioactive flavonoids were isolated from Scutellaria barbata D. Don through heat-reflux, ultrasound-assisted, conventional supercritical CO 2 and ultrasound-assisted supercritical CO 2 (USC-CO 2) extractions using different extraction schemes and parameters. The USC-CO 2 extraction method produced higher yields of six flavonoids that were 28.09–29.31, 24.64–27.74 and 18.63–19.03% higher than those of heat-reflux, ultrasound-assisted and conventional supercritical CO 2 extractions, respectively, with time durations that were lower by factors of 2.29, 1.14 and 2 than those of the three other extraction techniques and with less-harsh operating conditions. Therefore, the current procedure is a promising technique for the extraction of various bioactive constituents from a wide variety of raw matrixes. Furthermore, a second-order kinetic model and a mass transfer model based on Fick's second law were successfully correlated with the overall USC-CO 2 dynamic extraction of S. barbata D. Don. The results obtained from the second-order kinetic model indicated that the energy barrier in the USC-CO 2 procedure was lower than that in the traditional extraction techniques. In addition, the mass transfer model revealed that incrementing the operation temperature from 32 to 52 °C at constant pressure might effectively enhance the mass transfer and diffusion in the current procedure and that the current procedure is dominated by intraparticle diffusion. These results provide very helpful information for the design and development of an efficient procedure to extract bioactive flavonoids from a wide variety of matrixes for future applications in industrial extraction processes. [ABSTRACT FROM AUTHOR]

In this study, we purified a water-soluble polysaccharide, SBPW3, from the whole plant of Scutellaria barbata D. Don through ethanol precipitation, deproteinization, lyophilization, dialysis and separation using a DEAE cellulose column and a Superdex 200 gel filtration chromatography column. SBPW3 is a homogeneous polysaccharide with a molecular weight of 10.2 kDa and is composed of rhamnose (2.51%), arabinose (25.68%), xylose (10.94%), mannose (12.56%), glucose (20.59%) and galactose (27.72%). FT-IR spectrum analysis of the polysaccharide showed that SBPW3 contained a pyranose ring. The effects of SBPW3 on TGF-β1-induced epithelial-mesenchymal transition (EMT) were tested in colon cancer cells. These results suggested that SBPW3 significantly suppressed TGF-β1-induced migration and invasion. Additionally, SBPW3 reduced EMT by increasing the expression of epithelial markers and by decreasing the expression of mesenchymal markers by blocking the Smad2/3 signalling pathway in colon cancer cells. Furthermore, to explore the anti-metastatic effect of SBPW3, we established a mouse model of colon cancer metastasis and found that SBPW3 significantly inhibited the metastatic dissemination of the primary tumour to the liver. These findings provide us with a potential chemotherapeutic strategy for the treatment of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria- , caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, cytotoxic chemotherapy, surgical resection, radiation, and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC is relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is imperative to identify or develop efficient lead compounds for the treatment of NSCLC. Here, we report that the herb Scutellaria barbata D. Don (SBD) can effectively treat NSCLC by anti-inflammatory, promoting apoptosis, cell cycle arrest, and angiogenesis. In this work, we analyze the molecular mechanism of SBD for NSCLC treatment by applying the systems pharmacology strategy. This method combines pharmacokinetics analysis with pharmacodynamics evaluation to screen out the active compounds, predict the targets and assess the networks and pathways. Results show that 33 compounds were identified with potential anti-cancer effects. Utilizing these active compounds as probes, we predicted that 145 NSCLC related targets mainly involved four aspects: apoptosis, inflammation, cell cycle, and angiogenesis. And in vitro experiments were managed to evaluate the reliability of some vital active compounds and targets. Overall, a complete overview of the integrated systems pharmacology method provides a precise probe to elucidate the molecular mechanisms of SBD for NSCLC. Moreover, baicalein from SBD effectively inhibited tumor growth in an LLC tumor-bearing mice models, demonstrating the anti-tumor effects of SBD. Our findings further provided experimental evidence for the application in the treatment of NSCLC.

This study compared the use of ultrasound-assisted supercritical CO 2 (USC-CO 2 ) extraction to obtain apigenin-rich extracts from Scutellaria barbata D. Don with that of conventional supercritical CO 2 (SC-CO 2 ) extraction and heat-reflux extraction (HRE), conducted in parallel. This green procedure yielded 20.1% and 31.6% more apigenin than conventional SC-CO 2 extraction and HRE, respectively. Moreover, the extraction time required by the USC-CO 2 procedure, which used milder conditions, was approximately 1.9 times and 2.4 times shorter than that required by conventional SC-CO 2 extraction and HRE, respectively. Furthermore, the theoretical solubility of apigenin in the supercritical fluid system was obtained from the USC-CO 2 dynamic extraction curves and was in good agreement with the calculated values for the three empirical density-based models. The second-order kinetics model was further applied to evaluate the kinetics of USC-CO 2 extraction. The results demonstrated that the selected model allowed the evaluation of the extraction rate and extent of USC-CO 2 extraction. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, 莲甲散结方 in Chinese), where SB works as the “principle” against non-small cell lung cancer (NSCLC) cells. Materials and methods Four different NSCLC cell lines (A549, H460, H1650, and H1975) were used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein expression were analyzed by MTT assay, soft agar assay, real-time PCR, and Western blots, respectively. Results Among the 14 components in LJSJF, SB was the only one to possess cytotoxic effects at its pharmacologically relevant doses. Additionally, we observed synergistically dose-dependent cytotoxic effects of SB in combination with other LJSJF components. After SB or LJSJF treatment, significant reductions in colony number and/or size were observed in A549 and H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and H1650; significant downregulation in EGFR and its downstream signaling targets mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were significantly increased while survivin, cyclin D1, and MDM2 were significantly decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73 was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct apoptotic pathways in different NSCLC cells. Conclusion LJSJF exerts more pronounced cytotoxic effects against NSCLC cells than SB does by synergistically regulating the underlining molecular mechanisms including EGFR and/or p53 signaling pathways. [ABSTRACT FROM AUTHOR]

Herein, 13 previously undescribed neo -clerodane diterpenoids (1 – 13) and 27 known analogs (14 – 40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC 50 value of 10.6 μM. Structure–activity relations of these neo -clerodane diterpenoids revealed that the α, β -unsaturated- γ -lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF- κ B signaling by inhibiting IκBα phosphorylation. [Display omitted] • 40 neo -clerodane diterpenoids was isolated from Scutellaria barbata. • Absolute configurations of 13 undescribed compounds were assigned. • Compound 36 showed potent anti-inflammatory activity by inhibiting NF-κB pathway. • Structure–activity relations of 40 neo -clerodane diterpenoids were discussed. [ABSTRACT FROM AUTHOR]

A high performance liquid chromatography-diode array detection-mass spectrometry method with atmospheric pressure chemical ionization mode (HPLC-DAD-MS-APCI) was developed to determine carotenoids in Scutellaria barbata D. Don (Banzhilian). Results showed that a total of 19 carotenoids including internal standard were separated within 37 min by employing a YMC C30 column and a gradient mobile phase composed of methanol–acetonitrile (86:14, v/v) and methylene chloride. The various carotenoids in S. barbata were identified and quantified using internal standard β-apo-8′-carotenal, in which all-trans-lutein and its cis isomers constituted the largest portion, followed by all-trans-β-carotene and its cis isomers. A high recovery of 93.0–100.9% and a high reproducibility were obtained with this method. This would allow determination of carotenoids in herbal samples, and provide a basis for possible production of functional foods with S. barbata D. Don as raw material.

The objectives of this study were to determine the variety and amount of various functional components in Scutellaria barbata D. Don as well as study their anti-inflammatory activity on RAW 264.7 cells. Both ethanol and ethyl acetate extracts were shown to contain the functional components including phenolics, flavonoids, chlorophylls, and carotenoids, with the former mainly composed of phenolics and flavonoids, and the latter of carotenoids and chlorophylls. Both extracts could significantly inhibit (p < 0.05) the production of lipopolysaccharide-induced nitric oxide, prostaglandin E2, interlukin-6, and interlukin-1b, as well as the expressions of phosphor extracellular signal-regulated kinase and phosphor-c-Jun N-terminal kinase (p-JNK), but failed to retard tumor necrosis factor-α expression. Both ethanol and ethyl acetate extracts had a dose-dependent anti-inflammatory activity on RAW 264.7 cells. Furthermore, the anti-inflammatory efficiency can be varied for both ethanol and ethyl acetate extracts, which can be attributed to the presence of different varieties and amounts of functional components, as mentioned above. This finding suggested that S. Barbata extract may be used as an anti-inflammatory agent for possible future biomedical application. [ABSTRACT FROM AUTHOR]

Metastasis is one of the most aberrant behaviors of cancer cells. Patients with cancers, including colorectal cancer (CRC), have a higher risk of tumor recurrence and cancer-related mortality once metastasis is diagnosed. Existing treatment strategies fail to cure cancer mostly due to the onset of metastasis. Therefore, metastasis remains a challenge in cancer treatment. Some complementary and alternative medical therapies using traditional Chinese medicine have been demonstrated to be clinically effective in cancer treatment. Scutellaria barbata D. Don (SB) is a promising medicinal herb. It was previously reported that the ethanol extract of SB (EESB) is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in human colon cancer cells. However, the anticancer effect of SB and the underlying mechanism require further investigation, particularly its role against metastasis. To further elucidate the antimetastatic effect of SB, MTT and Transwell assays were used in the present study to evaluate the effect of EESB on the proliferation, migration and invasion of the CRC cell line HCT-8. In addition, western blot analysis was performed to detect the expression of matrix metalloproteinases (MMPs), cadherins and other metastasis-associated proteins. EESB significantly reduced HCT-8 cell viability and attenuated the migration and invasion ability of HCT-8 cells in a dose-dependent manner. In addition, EESB decreased the expression of MMP-1, MMP-2, MMP-3/10, MMP-9 and MMP-13, and proteins in the phosphoinositide 3-kinase (PI3K)/AKT and transforming growth factor (TGF)-β/Smad pathways, but not the epithelial-mesenchymal transition (EMT)-related factors E-cadherin and N-cadherin. In conclusion, the results suggested that SB inhibits CRC cell metastasis via the suppression of PI3K/AKT and TGF-β/Smad signaling pathways, which may represent a mechanism by which SB exerts an anticancer effect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. Methods: In vivo experiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group ( n=10) and control group ( n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/mL EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay, respectively. The mRNA expression of c-Myc, Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. Results: EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group ( P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues ( P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner ( P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells ( P<0.05). In addition, RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells ( P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells ( P<0.05). Conclusions: EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity. [ABSTRACT FROM AUTHOR]

Scutellaria barbata D. Don has been used as a traditional Chinese medicine for antitumor and anti-inflammatory. However, there were just a few investigations about S. barbata D. Don according to bioactivity-directed isolation and online identification for the chemical constituents. In this work, eight compounds were isolated from S. barbata D. Don. The three flavonoids indicated the cytotoxic activity against human leukemic Reh cell lines. In addition, the constituents of S. barbata D. Don were further characterized and identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The UHPLC-Q-TOF-MS method was in negative ion mode. HPLC separation was performed on a Tosoh TSK gel ODS-100V (4.6 × 150 mm, 3.0 μm) column by gradient elution using water containing 0.3% formic acid and acetonitrile as mobile phase at a flow rate of 0.8 mL min-1. A total of 18 compounds, including 4 phenolic acids and 14 flavonoids were tentatively characterized and identified by means of the retention time, accurate mass, and characteristic fragment ions. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Scutellaria barbata D. Don is a widely used medicinal herb in China. It possess various medicinal properties including antioxidative, anti-inflammatory and anti-cancer effects. The aim of this study was to explore whether Scutellaria barbata D. Don could inhibit the growth of ovarian cancer cells in vitro and further investigate the underlying mechanisms. Materials and methods Effects of Scutellaria barbata D. Don on the viability of ovarian cancer A2780 cells were measured by MTT assay. Apoptosis was measured by cell morphologic observation through DAPI staining and Annexin V-FITC staining assay for apoptosis analysis. The migration of ovarian cancer cells which exposed to Scutellaria barbata D. Don were measured by wound healing and transwell chamber assays. The protein levels of caspase 3/9, Bcl-2 and MMP-2/9 in human ovarian cancer cells treated with Scutellaria barbata D. Don were assessed by western blotting analysis. The potential bioactive compounds were characterized by HPLC-Q-TOF-MS. Results The present study was to investigate the anticancer effects of crude extracts from Scutellaria barbata D. Don on ovarian cancer A2780 cells by MTT, DAPI staining, wound healing assay, transwell migration assay and western blotting analysis. Our study showed that Scutellaria barbata D. Don reduced the viability of A2780 cells and induced apoptosis by down-regulated Bcl-2 protein and increased Caspase 3/9 proteins. Furthermore, migration of A2780 cells were significantly inhibited by Scutellaria barbata D. Don and the underlying mechanism may be related to the decrease of MMP-2/9. The main constituents from Scutellaria barbata D. Don were identified to be thirteen flavonoids. A HPLC-Q-TOF-MS analysis of Scutellaria barbata D. Don indicated the presence of 14 flavonoids compounds, which may contribute to the anticancer activity of the Scutellaria barbata D. Don. Conclusions Scutellaria barbata D. Don could inhibit proliferation and induce apoptosis in A2780 cells through mitochondrial pathway. Moreover, the inhibitory effect of Scutellaria barbata D. Don on the migration of ovarian cancer cells was associated with the down-regulation of MMP-2/9 expression. These findings could shed a light on the therapy of ovarian cancer. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the 70% acetone extract of the whole plant of Scutellaria barbata D. Don afforded six new neo- clerodane diterpenoids, scubatines A–F ( 1 – 6 ), and four known analogues ( 7 – 10 ). Their structures were elucidated on the basis of extensive spectroscopic analyses. Cytotoxic activity against the HL-60 and A549 cell lines was assessed for all isolated compounds. Compound 9 exhibited moderate activity against HL-60 with an IC 50 value of 5.6 μM. Compound 6 showed weak cytotoxic activity against A549 and HL-60 with IC 50 values of 10.4 and 15.3 μM, respectively. [ABSTRACT FROM AUTHOR]

One of the most critical cellular signal transduction pathways known to malfunction in colorectal cancer is the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway. Scutellaria barbata D. Don (SB) is well-known traditional medicine in China that targets STAT3 signaling, and it has long been used to treat various types of cancer; however, the precise mechanism of its anti-tumor activity remains largely unclear. In order to further elucidate this underlying mechanism, an ethanol extract of SB (EESB) in cancer treatment. The aim of the present study was to evaluate the effects of EESB on the IL-6-inducible STAT3 pathway. We tested the dose-response association between EESB, IL-6-induced proliferation and apoptosis using an MTT assay, colony formation and low cytometry analysis in vitro. In addition, caspase-9 and caspase-3 activation was determined using a colorimetric assay, the activity of IL-6-induced STAT3 pathway was evaluated using western blot analysis, and the expression levels of cyclin D1, cyclin-dependent kinase 4, Bcl2 and Bcl2-associated X were determined using reverse transcription-polymerase chain reaction and western blot analysis. In the present study it was found that EESB could significantly inhibit the IL-6-mediated increase in STAT3 phosphorylation levels and transcriptional activity in HT-29 human colon carcinoma cells, resulting in the suppression of cell proliferation and the induction of apoptosis. In addition, treatment with EESB markedly inhibited the IL-6-induced upregulation of cyclin D1 and B-cell lymphoma-2, two key target genes of the STAT3 pathway. These results suggest that treatment with EESB could effectively inhibit the proliferation and promote the apoptosis of human colon carcinoma cells via modulation of the IL-6/STAT3 signaling pathway and its target genes. [ABSTRACT FROM AUTHOR]

As a famous Chinese herb having good inhibitory effects on numerous human cancers both in vitro and in vivo, Scutellaria barbata D. Don attracts extensive attention worldwide. In this work, four flavonoids named scutellarin, baicalin, luteolin, and apigenin were simply and rapidly prepared from S. barbata by microwave-assisted extraction coupled to countercurrent chromatography. Extraction conditions including irradiation time, extraction temperature, liquid/solid ratio, and microwave power were optimized using an orthogonal array design method. The extract of S. barbata was separated and purified with a two-phase solvent system composed of hexane/ethyl acetate/methanol/acetic acid/water (1:5:1.5:1:4, v/v/v/v/v) and 4.5 mg of scutellarin, 4.6 mg of baicalin, 1.1 mg of luteolin, 2.1 mg of apigenin were obtained from 2.0 g original sample in a single run. The purities of scutellarin, baicalin, luteolin, and apigenin determined by HPLC were 93.6, 97.3, 97.6, and 98.4%, respectively. The targeted compounds were identified by LC with MS and 1H NMR spectroscopy. The total time including extraction, separation, and purification was <300 min. Compared to traditional methods, microwave-assisted extraction coupled to countercurrent chromatography method is more simple and rapid for the extraction, separation, and purification of flavonoid compounds from natural products. [ABSTRACT FROM AUTHOR]

Highlight: [•] An HPLC-DAD-MS-APIC method was developed to determine the carotenoids in S. barbata. [•] A total of 19 carotenoids including internal standard were separated within 37 min. [•] A high accuracy and precision was attained with this method. [•] All-trans-lutein and its cis isomers was present in largest amount. [Copyright &y& Elsevier]

A modified ultrasound-assisted extraction (MUAE) method and an HPLC technique were developed to identify and quantify simultaneously the amount of oleanolic acid (OA) and ursolic acid (UA) inScutellaria barbataD. Don. The optimal conditions for MUAE were observed when the particle size was 0.2–0.5 mm, the duty cycle was 75%, the extraction temperature was 55°C, the ratio of solvent to raw material was 12.0:1 (mL:g), the ethanol concentration was 60%, and the extraction time was 25 min. Compared to the traditional extraction method, MUAE reduced the extraction time, extraction temperature, and solvent consumption and achieved superior yields of OA and UA. Furthermore, the combined MUAE-HPLC method was successfully applied for the first time to investigate and compare the amounts of OA and UA in samples obtained from different geographical regions. [ABSTRACT FROM PUBLISHER]

Scutellaria barbata D. Don (SB) has long been used as a major component in numerous Chinese medical formulas to clinically treat various types of cancer. Previously, we reported that the extracts of SB were able to suppress colon cancer growth in vivo and in vitro, possibly by inducing cancer cell apoptosis and inhibiting cell proliferation and tumor angiogenesis. However, the anticancer mechanisms of its bioactive ingredients remain largely unclear. In the present study, using three human colon cancer cell lines SW620, HT-29 and HCT-8, the antitumor effect of different solvent fractions of SB were evaluated and the potential underlying molecular mechanisms were investigated. Using an 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was revealed that the chloroform fraction of SB (ECSB) exhibited the most potent inhibitory effect on the growth of all three colon cancer cell lines and SW620 cells exhibited the most sensitive response to ECSB treatment (IC50=65 μg/ml). In addition, by performing fluorescence-activated cell sorting, transmission electron microscopy and colony formation assays, it was observed that ECSB significantly induced apoptosis and inhibited proliferation in SW620 cells in a dose-dependent manner. Furthermore, ECSB treatment resulted in the upregulation of the pro-apoptotic Bax/Bcl-2 ratio and a decrease in the expression of the pro-proliferative cyclin D1 and cyclin-dependent kinase 4. The results from the present study may provide a scientific foundation for the development of novel anticancer agents from the bioactive ingredients in the ECSB. [ABSTRACT FROM AUTHOR]

Purpose: Scutellaria barbata D. Don (SB), mainly containing flavonoids, has been frequently used for cancer treatment. However, little research has investigated the antitumor activity of flavonoids from SB (FSB). The current study aimed to assess the antitumor effect of TFSB and elucidate the probable underlying mechanism in vivo and in vitro.Study Design: FSB was prepared, and its chemical composition was characterized by HPLC-MS. Colorectal HCT116 cells were treated with various concentration of FSB. The viability, proliferation, apoptosis, migration, and autophagy of HCT116 cells were studied, as were further confirmed in tumor xenografts.Methods: Cell viability and proliferation were respectively examined by MTT and EdU staining. ROS was determined with DCFH-DA, and cell apoptosis was detected using flow cytometry. Transwell and wound-healing assays were performed to evaluate cell migration. Immunofluorescence was employed to evaluate sestrin2 and ATF4 level. The protein expressions of p-AMPK, p-ULK1, p-mTOR, 4E-BP1, LC3-I/II, cleaved-caspase-3, Bax, and bcl-2 were investigated by western blot. ATF4 was overexpressed in experiments to explore the role of ATF4/sestrin2 pathway in FSB-mediated efficacy.Results: FSB clearly reduced the cell viability, promoted ROS generation, and induced apoptosis in HCT116 cells by down-regulated Bcl-2, and increased cleaved-caspase-3 and Bax. Furthermore, FSB significantly inhibited migration of colorectal cells in a dose-dependent manner. Further mechanistic study indicated that FSB upregulated p-mTOR protein level, and reduced p-AMPK, p-ULK1, p-mTOR, p-4E-BP1 and LC3-I/II expression, which were major autophagy-related genes. In addition, FSB could cause downregulation of endogenous mTOR inhibitor sestrin2 and ATF4 expression. Transient overexpression of ATF4 resulted in mTOR and sestrin2 inhibition, and significantly compromised the effects of FSB on apoptosis and autophagy in HCT116 cells.Conclusion: Our results reveal, for the first time, that FSB exerts antitumor activity through autophagy inhibition and apoptosis induction via ATF4/sestrin2 pathway in colorectal cancer cells. Scutellaria barbata D. Don may have great potential in the application for the prevention and treatment of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Highlights: [•] A heat-reflux extraction hyphenated with ultrasound (HUAE) was used to extract three flavonoids from Scutellaria barbata D. Don. [•] HUAE process provides a superior extraction yield and saves time, energy, raw materials and solvent consumption. [•] Contents of flavonoids in samples from different geographical regions were varied significantly. [•] The HUAE may serve as a very promising green technology for pharmaceutical and food industry. [ABSTRACT FROM AUTHOR]

Highlights: [⿢] The extraction of PA from S. barbata using SC⿿CO2 technique with water is described for the first time. [⿢] Solubility data of PA in SC⿿CO2 correlated well using the Chrastil model. [⿢] Optimized conditions resulted in high yield without the use of organic solvents. [⿢] The SC⿿CO2 method dramatically reduced time and energy consumption. [⿢] The SC⿿CO2 extract process is an environmentally friendly technology for pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Highlights: [•] UA–SC–CO2–HPLC was developed to evaluate the contents of UA and OA in S. barbata. [•] The efficient HPLC technique has good linearity, sensitivity, precision and accuracy. [•] The optimal UA–SC–CO2 extraction saves time, solvent, energy and raw materials. [•] The UA–SC–CO2–HPLC serves as a very promising technology in separation processing for herbs. [ABSTRACT FROM AUTHOR]

Angiogenesis, which plays a critical role during tumor development, is tightly regulated by the Sonic Hedgehog (SHH) pathway, which has been known to malfunction in many types of cancer. Therefore, inhibition of angiogenesis via modulation of the SHH signaling pathway has become very attractive for cancer chemotherapy. Scutellaria barbata D. Don (SB) has long been used in China to treat various cancers including colorectal cancer (CRC). Our published data suggested that the ethanol extract of SB (EESB) is able to induce apoptosis of colon cancer cells and inhibit angiogenesis in a chick embryo chorioallantoic membrane model. To further elucidate the precise mechanisms of its anti-tumor activity, in the present study we used a CRC mouse xenograft model to evaluate the effect of EESB on tumor growth and angiogenesis in vivo. Our current data indicated that EESB reduces tumor size without affecting on the body weight gain in CRC mice. In addition, EESB treatment suppresses the expression of key mediators of the SHH pathway in tumor tissues, which in turn resulted in the inhibition of tumor angiogenesis. Furthermore, EESB treatment inhibits the expression of vascular endothelial growth factor A (VEGF-A), an important target gene of SHH signaling and functioning as one of the strongest stimulators of angiogenesis. Our findings suggest that inhibition of tumor angiogenesis via suppression of the SHH pathway might be one of the mechanisms by which Scutellaria barbata D. Don can be effective in the treatment of cancers. [ABSTRACT FROM AUTHOR]

Abstract: Gas chromatography fingerprint of Scutellaria barbata D. Don (SB) from different origins was studied by gas chromatography–mass spectrometry (GC–MS) and related Chemometrics methods. The constituents of essential oil of Scutellaria barbata D. Don (SB) and its two adulterants Oldenlandia diffusa (OD) and Lobelia chinensis Lour (LCL) were analyzed and compared, 50, 36 and 38 components were identified from SB, OD and LCL, respectively, there were 16 and 18 common components between SB and OD, SB and LCL. Nine different samples collected from different producing areas of SB were studied. The relative standard deviations (RSDs) of retention time and peak area of each component were less than 0.2% and 6%, respectively. The number of common peaks was up to 52 and the un-common peak area was less than 10%. The similarity and difference among SB and its adulterants were also evaluated by correlation coefficient similarity analysis and principal component analysis, the result showed that developed fingerprint characterize the SB from different producing areas and it is useful and feasible for the discrimination of its adulterants. [Copyright &y& Elsevier]

Two new neo-clerodane diterpenoids have been isolated from the whole plant of Scutellaria barbata D. Don, and their structures were established by detailed spectral analyses as scutehenanine H (1) and 6-(2,3-epoxy-2-isopropyl-n-propoxyl)barbatin C (2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer lines, and gave IC50 values in the range OF 2.0-4.2μΜ. [Copyright &y& Elsevier]