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A bioassay-guided approach was employed to identify the active compounds from the whole herb of Spiranthes sinensis (Pers.) Ames, an orchidaceous medicinal plant. As a result, fourteen compounds were obtained from the active fractions. The structures of the isolates were identified as methyl 4-[2-(butoxymethyl)-5-formyl-pyrrol-1-yl] butyrate (1), 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (2), populnin (3), scutellarein (4), quercetin (5), kaempferol (6), stigmasterol-3-O-β-D-glucopyranoside (7), β-daucosterol (8), trans-p-hydroxy cinnamic acid (9), 4-hydroxybenzoic acid methyl ester (10), 3-(4-tolyloxy)-propanoic acid (11), 2-benzothiazolol (12), ethyl ferulate (13) and kumatakenin (14) by comparing the spectroscopic data from the isolated compounds with the data reported in the literature. Compound 1 was a new natural compound. Compounds 2, 4–6 and 9–14 were first reported from the genus Spiranthes. Compound 7 was isolated from S. sinensis for the first time. In addition, compounds 5, 6, 11 and 13 were found to have potent anti-acetylcholinesterase (anti-AChE) activities with IC50 values ranging from 8.63 ± 0.37 to 19.97 ± 1.05 μg/mL, which indicates that S. sinensis has the potential in the development of new anti-Alzheimer’s disease (anti-AD) drugs.

Although α-amylase is the choice of target to manage postprandial hyperglycemia, inhibitors of this enzyme may get absorbed into the systemic circulation and modulate proteins involved in the pathogenesis of diabetes mellitus. Hence, the present study aimed to identify α-amylase inhibitors from Duranta repens via in silico and in vitro and predict their role in the modulation of multiple pathways involved in diabetes mellitus. α-amylase inhibitory activity of hydroalcoholic extract/fractions (s) and pure compounds from D. repens was performed using in vitro enzyme inhibitory assay. Multiple open-source databases and published literature were used to retrieve reported phytoconstituents present in D. repens and their targets. The network was constructed between α-amylase inhibitors, modulated proteins, and expressed pathways. Further, hit molecules were also confirmed for their potency to inhibit α-amylase using in silico molecular docking and in vitro enzyme inhibitory assay. The glucose uptake assay was performed to assess the effect of hydrolcoholic extract/fraction(s) using rat hemidiaphragm. Fraction rich in flavonoids showed the highest α-amylase inhibitory activity with a IC50 of 644.29 ± 4.36 µg/ml compared to other fractions. PI3K-Akt signaling pathway and p53 signaling pathway were predicted to be primarily modulated in the compound-protein-pathway network. Similarly, scutellarein was predicted as lead hit based on α-amylase inhibitory action, binding affinity, and regulated pathways. Further, α-amylase inhibitors were also predicted to modulate the pathways involved in diabetes complications like AGE-RAGE and FoxO signaling pathway. Fraction rich in flavonoids showed the highest glucose uptake in rat hemidiaphragm with an effective concentration of 534.73 ± 0.79 µg/ml. The α-amylase inhibitors from D. repens may not be limited within the gastrointestinal tract to inhibit α-amylase but may get absorbed into the systemic circulation and modulate multiple pathways involved in the pathogenesis of diabetes mellitus to produce synergistic/additive effect.

Hydroalcoholic extract/fraction(s) and scutellarein, a previously reported phytoconstituent from Duranta repens were evaluated for their α-glucosidase inhibitory activity using in vitro method. The reported phytoconstituents were also screened as α-glucosidase inhibitor, probable cytotoxicity, ADMET profile, and side effects via in silico models. Further, probable gene expression profile and pathways involved in diabetes/diabetes complications were also screened. Similarly, network was constructed among α-glucosidase inhibitors, modulated proteins and respective pathways and docking study was performed using autodock4.0. Fraction rich in flavonoids was found to possess the highest α-glucosidase inhibitory activity and the mode of inhibition was uncompetitive. The predicted α-glucosidase inhibitors were less cytotoxic to normal cells with lower side effects compared to acarbose. Similarly, gene-set enrichment analysis identified p53 signaling pathway to be primarily modulated by majority of phytoconstituents. Further, docking study revealed scutellarein to have highest binding affinity with α-glucosidase enzyme. In conclusion, present study identified the fraction rich in flavonoids to possess highest α-glucosidase inhibitory activity and could modulate p53 signaling pathway in diabetic pathogenesis.

The polyphenolic composition and anti-inflammatory activity of selected Thymus species (T. longicaulis C. Presl, T. praecox Opiz subsp. polytrichus (A. Kerner Ex Borbas) Jalas, T. pulegioides L., T. serpyllum L. subsp. serpyllum and T. striatus Vahl) was studied in comparison with T. vulgaris, as an officinal medicinal plant, to evaluate the biomedical potential of these Croatian wild-growing species. This paper provides a first insight into the polyphenolic profiles of T. praecox subsp. polytrichus and T. striatus. Also, some flavone and hydroxycinnamic derivatives were at first identified in the other studied species by LC-DAD-ESI–MS/MS analysis. Rosmarinic acid and glycosides of scutellarein and luteolin were found to be the most abundant polyphenolic constituents. The Thymus extracts inhibited Src tyrosine kinase activity and they reduced the production of proinflammatory cytokine interleukin-6 in Balb/C mice splenocytes. The obtained results highlighted T. longicaulis as a potential source of herbal drugs with anti-inflammatory properties and/or novel functional food rich in flavonoids and phenolic acids.

Ingredients in traditional Chinese medicine (TCM) can be absorbed into blood and reach and maintain effective concentrations in the target organ, which is the premise of the ingredients taking effect in vivo. Hollow fibre cell fishing (HFCF) based on ACHN human renal tubular cells or HepG2 hepatoma cells using high-performance liquid chromatography with ultraviolet detection (HPLC/UV), coupled with hollow fibre liquid-phase microextraction (HF-LPME) with HPLC/UV, was developed and employed for the first time to study the antitumour activity of scutellarin, a main ingredient in breviscapine, and its metabolite scutellarein after intraperitoneal injection of breviscapine. The antitumour activity of these ingredients was evaluated by combining their activity screening, target tissue distribution and pharmacokinetics (PK). Before application, the cell growth state, survival rate, binding between fibre active centre or nutrient solution and ingredients, positive and negative control and repeatability for HFCF were investigated; validations of the HF-LPME methodology were optimized and evaluated. The study found that scutellarin can be rapidly absorbed into blood and metabolize partly into scutellarein, and both can reach liver or kidney, combine with ACHN or HepG2 cells and maintain effective concentrations. Thus, scutellarin and scutellarein have potential as lead ingredients for treatment of liver or kidney tumours, and breviscapine injection may have potential properties for use in treatment or prevention of liver and kidney tumours, at least. HFCF and HF-LPME coupled with HPLC can contribute to simultaneous investigation of the antitumour activity of multiple ingredients in TCMs by combining activity screening, tissue distribution and PK studies.

A series of 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein was designed and synthesized. Evaluation of physiochemical properties showed that the newly designed compounds had greater chemical stability and aqueous solubility than scutellarin or scutellarein. The permeabilities (P app AP to BL) of compounds 7b and 7e in Caco-2 cells were 5.9-fold and 3.7-fold higher than that of scutellarin, and 3.7-fold and 2.4-fold higher than that of scutellarein. The permeabilities (P app AP to BL) of compounds 7b and 7e in an in vitro model of the blood–brain barrier were 9.7-fold and 5.9-fold higher than that of scutellarin, and 9.2-fold and 5.6-fold higher than that of scutellarein.

Flavonoids are members of polyphenolic compounds, which are naturally presented in fruits, vegetables, and some medicinal plants. Traditionally, the root of Scutellaria baicalensis is widely used as Chinese herbal medicine and contains several major bioactive compounds such as Wogonin, Scutellarein, Baicalein, and Baicalin. Experimental and clinical evidence has been proving that Wogonin exhibits diverse biological activities such as anti-cancer, anti-inflammation, and treatment of bacterial and viral infections. In this review, we summarize and emphasize the benefits of Wogonin as a therapeutic adjuvant for anti-viral infection, anti-inflammation, neuroprotection as well as anxiolytic and anticonvulsant. Moreover, the molecular mechanism(s) how Wogonin mediates the cellular signal pathways and immune responses are also discussed and highlighted valuable properties of Wogonin in multiple therapies.

A new flavanone glucoside, (2S)-dihydrobaicalein 7-O-(6″-benzoylglucopyranoside) (1), along with the known compounds scutellarein 4′-methyl ether (2), pectolinarigenin (3), and β-sitosterol-3-O-β-Dglucopyranoside (4), were isolated from the MeOH extract of Oroxylum indicum stem bark. The structure of the new compound was established on the basis of detailed spectroscopic and chemical studies.

Background Glycosylation of flavonoids is a promising approach to improve the pharmacokinetic properties and biological activities of flavonoids. Recently, many efforts such as enzymatic biocatalysis and the engineered Escherichia coli biotransformation have increased the production of flavonoid glucosides. However, the low yield of flavonoid glucosides can not meet the increasing demand for human medical and dietary needs. Saccharomyces cerevisiae is a generally regarded as safe (GRAS) organism that has several attractive characteristics as a metabolic engineering platform for the production of flavonoid glucosides. However, endogenous glucosidases of S.cerevisiae as a whole-cell biocatalyst reversibly hydrolyse the glucosidic bond and hinder the biosynthesis of the desired products. In this study, a model flavonoid, scutellarein, was used to exploit how to enhance the production of flavonoid glucosides in the engineered S.cerevisiae. Results To produce flavonoid glucosides, three flavonoid glucosyltransferases (SbGTs) from Scutellaria baicalensis Georgi were successfully expressed in E. coli, and their biochemical characterizations were identified. In addition, to synthesize the flavonoid glucosides in whole-cell S. cerevisiae, SbGT34 was selected for constructing the engineering yeast. Three glucosidase genes (EXG1, SPR1, YIR007W) were knocked out using homologous integration, and the EXG1 gene was determined to be the decisive gene of S. cerevisiae in the process of hydrolysing flavonoid glucosides. To further enhance the potential glycosylation activity of S. cerevisiae, two genes encoding phosphoglucomutase and UTP-glucose-1-phosphate uridylyltransferase involved in the synthetic system of uridine diphosphate glucose were over-expressed in S. cerevisiae. Consequently, approximately 4.8 g (1.2 g/L) of scutellarein 7-O-glucoside (S7G) was produced in 4 L of medium after 54 h of incubation in a 10-L fermenter while being supplied with ~3.5 g of scutellarein. Conclusions The engineered yeast harbouring SbGT with a deletion of glucosidases produced more flavonoid glucosides than strains without a deletion of glucosidases. This platform without glucosidase activity could be used to modify a wide range of valued plant secondary metabolites and to explore of their biological functions using whole-cell S. cerevisiae as a biocatalyst. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0535-2) contains supplementary material, which is available to authorized users.

To study the metabolic and pharmacokinetic profile of scutellarin, an active component from the medical plant Erigeron breviscapus (Vant) Hand-Mazz, and to investigate the mechanisms underlying the low bioavailability of scutellarin though oral or intravenous administration in rats.HPLC method was developed for simultaneous detection of scutellarin and scutellarein (the aglycone of scutellarin) in rat plasma, urine and feces. The in vitro metabolic stability study was carried out in rat liver microsomes from different genders.After a single oral dose of scutellarin (400 mg/kg), the plasma concentrations of scutellarin and scutellarein in female rats were significantly higher than in male ones. Between the female and male rats, significant differences in AUC, t(max2) and C(max2) for scutellarin were found. The pharmacokinetic parameters of scutellarin in the urine also showed significant gender differences. After a single oral dose of scutellarin (400 mg/kg), the total percentage excretion of scutellarein in male and female rats was 16.5% and 8.61%, respectively. The total percentage excretion of scutellarin and scutellarein in the feces was higher with oral administration than with intravenous administration. The in vitro t(1/2) and CL(int) value for scutellarin in male rats was significantly higher than that in female rats.The results suggest that a large amount of ingested scutellarin was metabolized into scutellarein in the gastrointestinal tract and then excreted with the feces, leading to the extremely low oral bioavailability of scutellarin. The gender differences of pharmacokinetic parameters of scutellarin and scutellarein are due to the higher CL(int) and lower absorption in male rats.

This study was designed to examine the effect of scutellarein on high glucose- and hypoxia-stimulated proliferation of human retinal endothelial cells (HREC).HREC were cultured under normal glucose (NG), moderate, and high glucose (NG supplemented with 10 or 25 mmol/L D-glucose) and/or hypoxic (cobalt chloride treated) conditions. Cell proliferation was evaluated by a cell counting kit. The expression of vascular endothelial growth factor (VEGF) was assessed by Western blot analysis.The proliferation of HREC was significantly elevated in response to moderately-high glucose and hypoxic conditions. The combination of high glucose and hypoxia did not have any additive effects on cell proliferation. Consistent with the proliferation data, the expression of VEGF was also upregulated under both moderately-high glucose and hypoxic conditions. The treatment with scutellarein (1x10(-11) to 1x10(-5) mol/L) significantly inhibited high glucose- or hypoxia-induced cell proliferation and VEGF expression.Both hypoxia and moderately-high glucose were potent stimuli for cell proliferation and VEGF expression in HREC without any significant additive effects. Scutellarein is capable of inhibiting the proliferation of HREC, which is possibly related to its ability to suppress the VEGF expression.

The objective of this research was to establish a simple, practical and efficient method for routine quantitative analysis of Erigeron breviscapus and its extract injection to control their qualities. The reversed phase high performance liquid chromatographic method was adopted to determine simultaneously the contents of two major classes of constituents namely phenolic acids and flavonoids, which were usually ignored in previous studies of E. breviscapus. Under the optimum conditions, three flavonoids including scutellarin, scutellarein and apigenin and four phenolic acids including caffeic acid, chlorogenic acid, 3,4-O-dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid were successfully separated on a Zorbax SB-C18 column (250 × 4.6 mm I.D., 5.0 μm particle size) at 25 °C. Of the three flavonoids, scutellatin is a flavone glucuronide. The mobile phase was a mixture of acetonitrile and 1.0% (v/v) aqueous acetic acid employing gradient elution at a flow rate of 1.0 mL min−1 and the detection wavelength was set at 330 nm. Regression equations revealed good linear relationship between the peak areas of the analytes and their concentrations (r 2 > 0.9990). The relative standard deviations of retention time and peak area were less than 0.33 and 1.45%. The intra- and inter-day precisions as determined from sample solutions were below 1.66 and 2.35%. And the recoveries ranged from 96.5 to 101.8%. The proposed method has been successfully applied to the simultaneous quantification of two major classes of constituents in E. breviscapus and its extract injection for the first time.

Scutellarin, a flavonoid glycoside, is the primary active ingredient in breviscapine that is a mixture of flavonoid glycosides extracted from a Chinese herb Erigeron breviscapus (Vant.) Hand.-Mazz. The pharmacokinetics of scutellarin and its aglycone conjugated metabolites after intraperitoneal injection and oral administration of breviscapine was investigated in rats. The plasma concentration of scutellarin and scutellarein conjugates in serial samples was measured by validated high-performance liquid chromatography methods. The pharmacokinetic results indicated that scutellarin underwent rapid and extensive biotransformation in vivo. After intraperitoneal injection, scutellarin was absorbed rapidly. The profiles of scutellarin and scutellarein conjugates were fitted to a two-compartment open model. Scutellarin and scutellarein conjugates showed a similar time course. No significant difference in tmax, t0.5(alpha) and t0.5(beta) was observed between scutellarin and scutellarein conjugates (p>0.05). After oral administration, fluctuations were observed in the concentration-time profiles of both scutellarin and scutellarein conjugates and the pharmacokinetics could not be explained by classical compartment model. The relative bioavailability of oral administration was very low, 10.67 % +/- 4.78% for scutellarin and 7.92% +/- 1.90% for scutellarein conjugates.

A new method combining solid-phase extraction and reversed phase high-performance liquid chromatography was developed for simultaneous isolation and determination of flavones (baicalin, baicalein, chrysin, scutellarein) and some phenolic acids in aerial and underground parts of a medicinal plant—Scutellaria baicalensis Georgi. The application of optimised enrichment conditions, elaborated on octadecyl and quaternary amine BakerBond microcolumns have led to the extraction of both groups of analytes with recoveries >95% and variation coefficients

(±)-5,2′-Dihydroxy-6,7,6′-trimethoxyflavanone, (-)-5,2′-dihydroxy-6,7,8,6′-tetramethoxyflavanone, chrysin, wogonin, apigenin, isoscutellarein, scutellarein, cosmosiin, and the new flavonoid wogonin-7-O-β-D-glucopyranoside, the structure of which was established using chemical transformations and spectral data, were isolated from Scutellaria immaculata roots.

The herb low cudweed has yielded for the first time a new acylated flavone glycoside, for which the structure of 3′,4′,5,7-tetrahydroxy-6-methoxyflavone 7-O-(6″-O-caffeyl-β-D-glucopyranoside) has been established. In addition, 6-methoxyluteolin, 6-hydroxyluteolin 7-O-β-D-glucopyranoside, and scutellarein 7-O-β-D-glucopyranoside have been isolated. Identification was made on the basis of UV, IR, PMR, and mass spectra, the products of alkaline and acid hydrolyses, and the results of elementary analyses, melting points, and specific rotations.

1. From the leaves ofSorbaria sorbifolia (L.) A. Br. a new glycoside sorbifolin, has been isolated, and its structure has been established as scutellarein 7-O-α-L-rhamnopyranosyl-(4»1)-O-β-D-xylopyranoside. 2. The enzymatic and stepwise acid hydrolyses of sorbifolin have yielded a new monoside, desxylosorbifolin (scutellarein 7-O-α-L-rhamnopyranoside).

The epigeal part ofScutellaria przewalskii has been shown to contain apigenin, luteolin, scutellarein, dinatin, hispidulin, pectolinarigenin; the 7-glucosides and 7-glucuronides of apigenin, luteolin, scutellarein, and dinatin; and also the 7-glucobiosides of scutellarein, dinatin, and hispidulin; and these substances have been isolated. It has been established that the glucuronides of the flavonoids are present in the salt form.

Apigenin does not undergo persulphate oxidation satisfactorily. But acacetin, its monomethyl ether and analogous higher members do so. By the methylation of the products (quinols) the fully methylated ethers of isoscutellarein, 8-hydroxyluteolin and 8-hydroxytricetin could be readily obtained. Demethylation of the quinols or their methyl ethers with aluminium chloride is not successful. Boiling with hydriodic acid produces isomeric change yielding conveniently scutellarein and the higher members. 6-Hydroxy-tricetin and its derivatives are newly described.

THE glycoside pectolinarin which was isolated from the flowers of Linaria vulgarise yielded on hydrolysis an aglycone, pectolinarigenin, having the molecular formula C 17H, 406 . It was a dimethyl ether of scutellarein. The position of one of the methoxyl groups could be easily located since it yielded anisic acid by alkali fission. The other methoxyl was considered to be in the 6-position since the compound was found to be identical with the 6: 4'dimethyl ether of scutellarein (II) obtained synthetically by Wessely and Moser. 2 The sugar residue could be allotted the position 7 because the glycoside was unchanged when treated with diazomethane and hence had the free hydroxyl group in the resistant 5-position. Subsequently the synthesis of the glycoside itself has been effected using the aglycone and hexa-acetyl-rutinosidyl bromide. 3

A simple and at the same time unambiguous method of synthesis of the 5∶6∶7-hydroxyflavones, baicalein and scutellarein and their derivatives is described. It starts from phloracetophenone which is partially methylated to the 4∶6-dimethyl ether. Oxidation of this ether with potassium persulphate yields the 2∶5-dihydroxy compound which on partial methylation produces 2-hydroxy-4∶5∶6-trimethoxyacetophenone. Using the benzoyl and anisoyl derivatives of this ketone and adopting the Baker-Venkataraman procedure, the trimethyl ether of baicalein and the tetramethyl ether of scutellarein have been prepared and from them the hydroxyflavones and their acetates.

6∶7∶8-Trihydroxy and 6∶7∶8∶4′-tetrahydroxyflavones and their derivatives (methyl ethers and acetates) have been prepared starting with 2-hydroxy-3∶4∶5-trimethoxyacetophenone and adopting the Baker-Venkataraman procedure. Their properties and reactions have been studied and compared with those of the isomeric compounds, baicalein and scutellarein.