scutellarein and scutellarin

Scutellarin is the major effective ingredient of breviscapine, which is widely used in the treatment of cardiovascular diseases and has a remarkable achievement. In recent years, more and more reseaches had focused on the pharmacokinetics of scutellarin and scutellarein. The article summarized the studies on pharmacokinetics of scutellarin and scutellarein have been performed by domestic and oversea scholars.

Topics: Animals; Apigenin; Flavonoids; Glucuronates; Humans

Topics: Acetylcholinesterase; Alzheimer Disease; Amino Acids; Amyloid beta-Peptides; Animals; Antioxidants; Apigenin; Carbamates; Cholinesterase Inhibitors; Drug Design; Glucuronates; Mice; Neuroprotective Agents; Rats; Structure-Activity Relationship

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine

Topics: Antineoplastic Agents; Apigenin; Arsenites; Cell Line, Tumor; Cell Survival; Erigeron; Glucuronates; HCT116 Cells; Humans; Inhibitory Concentration 50; Jurkat Cells; Sodium Compounds; Structure-Activity Relationship

Scutellarin, one of natural flavonoids, is widely and clinically used for treating many diseases in China. Recently, scutellarin has demonstrated a broad spectrum of anti-proliferative activities against multiple cancer cell lines. However, the molecular mechanism of action remains to be investigated. We herein report the design and synthesis of biotinylated scutellareins as probes, which can be applied to discover scutellarein interacting proteins. Finally, we show that scutellarin directly targets pyruvate kinase M2 (PKM2) and inhibits its cytosolic activity to decrease glycolytic metabolism; on the other hand, scutellarin may also participate in regulating cell cycle and apoptotic proteins by activating MEK/ERK/PIN1 signaling pathway to promote the nuclear translocation of PKM2.

Topics: Apigenin; Cell Proliferation; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Glucuronates; Glycolysis; HeLa Cells; Humans; Inhibitory Concentration 50; MAP Kinase Kinase Kinases; Medicine, Chinese Traditional; NIMA-Interacting Peptidylprolyl Isomerase; Pyruvate Kinase; Signal Transduction

Scutellarin (

Topics: Animals; Antioxidants; Apigenin; Biphenyl Compounds; Brain Ischemia; Cerebrovascular Disorders; Chromans; Erigeron; Fibrinolytic Agents; Free Radical Scavengers; Glucuronates; Humans; Male; Picrates; Rabbits; Solubility

Scutellarein (2), which is an important in vivo metabolite of scutellarin (1), was synthesized from 3,4,5-trimethoxyphenol (3) in high yield in four steps. This strategy relies on acetylation, aldolization, cyclization and hydrolysis reactions, respectively.

Topics: Acetylation; Animals; Apigenin; Cardiovascular Agents; Chemistry Techniques, Synthetic; Cyclization; Glucuronates; Humans; Hydrolysis; Neuroprotective Agents; Phenols

The binding abilities of scutellarin (Scu) and scutellarein (Scue) with bovine serum albumin (BSA) were investigated using equilibrium dialysis, high performance liquid chromatography, fluorescence spectroscopy, competitive site marker and molecular docking. The results showed that the average protein binding ratios of Scu and Scue with BSA were (79.85 ± 1.83) and (85.49 ± 1.21) % respectively. Under simulated physiological conditions, the fluorescence data indicated that Scu and Scue bound with BSA through a static mechanism. The thermodynamic parameters indicated that the interactions of Scu-BSA and Scue-BSA mainly occurred by van der Waals forces and hydrogen bonds and it was easier for Scue to bind with BSA than Scu, indicating that the glucuronic acid molecule in Scu decreased the binding affinity. Site competitive marker experiments showed that the binding sites of Scu and Scue mainly located within the sub-domain IIA of BSA. Furthermore, molecular docking studies indicated that one BSA could bind three Scue, while one BSA could carry only two Scu. All these results clearly indicated the interactions of Scu and Scue with BSA, which will lay the foundation for further research to determine the pharmacology and pharmacodynamics of Scu and Scue for treating ischemic cerebrovascular disease.

Topics: Apigenin; Binding Sites; Chromatography, High Pressure Liquid; Glucuronates; Hydrogen Bonding; Molecular Docking Simulation; Protein Binding; Serum Albumin, Bovine; Spectrometry, Fluorescence; Thermodynamics

In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4' and C-7 in 2 were selectively protected by chloromethyl methyl ether after the reaction conditions were optimized, then 6-O-methyl-scutellarein (3) was produced in high yield after methylation of the hydroxyl group at C-6 and subsequent deprotection of the two methyl ether groups.

Topics: Apigenin; Biotransformation; Flavones; Glucuronates; Humans; Methyl Ethers; Methylation; Solutions

For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.

Topics: Animals; Apigenin; Brain Ischemia; Drugs, Chinese Herbal; Glucuronates; Male; Metabolome; Metabolomics; Neuroprotective Agents; Rats; Rats, Wistar

Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 μM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components.

Topics: Animals; Apigenin; Enzyme Inhibitors; Flavonoids; Glucuronates; Glucuronosyltransferase; Isoenzymes; Kinetics; Liver; Male; Rats; UDP-Glucuronosyltransferase 1A9

Scutellarin had protective effects against neuronal injury, however, there are few studies on the protective effect of scutellarein, which is the main metabolite of scutellarin in vivo. This study investigated whether the neural injury by ischemia/reperfusion would be influenced by different doses of scutellarin and scutellarein. Male Wistar rats were orally administered with scutellarin and scutellarein at the doses of 0.09, 0.17, 0.35, 0.70, 1.40 mmol/kg, respectively; then after six consecutive days, they were subjected to global ischemia by occlusion of the bilateral common carotid arteries (BCCAO). After reperfusion for about 21 h, neurological and histological examinations were performed. The present results showed that scutellarein attenuated neuronal cell damage, reduced cerebral water content, regulated the expression of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), γ-aminobutyric acid (GABA) and taurine (Tau), and improved the Ca(2+)-ATPase and Na(+),K(+)-ATPase activity. Meanwhile, significant difference was found among various doses of scutellarin and scutellarein. Our studies indicated that scutellarin and scutellarein could improve neuronal injury, and scutellarein had better protective effect than scutellarin in rat cerebral ischemia.

Topics: Amino Acids; Animals; Antioxidants; Apigenin; Brain; Brain Injuries; Brain Ischemia; CA1 Region, Hippocampal; Calcium; Calcium-Transporting ATPases; Glucuronates; Learning; Male; Memory; Neuroprotective Agents; Nimodipine; Potassium; Rats; Rats, Wistar; Reperfusion Injury; Sodium; Sodium-Potassium-Exchanging ATPase

Scutellarin (SG) and its aglycone, Scutellarein (S), are flavonoids of therapeutic cardiocerebrovascular disease. SG was hydrolyzed by bacterial enzyme into S which was absorbed in the intestine. The aim of this study was to determine the effects of the microflora in the intestinal lumen and the efflux transporter of intestinal epithelial cells on the absorption process of SG and S. After oral administration of antibiotics in Sprague-Dawley rats, the reduced bacterial enzyme formation significantly hinders the absorption of SG, whereas scarcely that of S. The absorption study in situ single-pass intestinal perfusion revealed that S could be absorbed throughout the intestine of rats. The effective intestinal permeability of S in the jejunum was much lower than in the other sections of the GI tract. The efflux transporter promoted SG secretion into lumen from enterocytes, which hindered the absorption of both SG and S into the bloodstream. The efflux transporter protein inhibitor (verapamil, probenecid and reserpine) remarkably enhanced the absorption of S and the bioconversion of S into SG in both the rat intestine and Caco-2-monolayer models.

Topics: Administration, Oral; Animals; Apigenin; Caco-2 Cells; Glucuronates; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Male; Membrane Transport Proteins; Microbiota; Rats, Sprague-Dawley

This work addressed solubility and membrane permeability problems of Biopharmaceutics Classification System (BCS) Class IV glycoside scutellarin (SG) by developing a nanosuspension of its aglycone scutellarein (S) as a precursor. An S nanosuspension containing poloxamer 188 was prepared using antisolvent precipitation where hydroxypropyl-β-cyclodextrin was utilized as a lyophilizing protectant. Particle size and polydispersity index after redispersion were 342.6 ± 18.2 and 0.32 ± 0.06 nm, respectively. The dissolution rate of the S nanosuspension was superior compared with the physical mixture. No free S, but SG and SG's isomer were detected in plasma following oral delivery of SG or S, S nanosuspension or physical mixture of S. The Cmax values of SG after dosing with the S nanosuspension were 12.0, 8.0, and 4.5-fold higher than the SG, S, or physical mixture, respectively. The Tmax and mean residence time (MRTlast ) of SG after dosing with the S nanosuspension were significantly shorter than S and SG. Treatments with SG, S, or S nanosuspensions reduced the hemorrhage rate in a zebrafish model, but the S nanosuspension exhibited the strongest rescue effect. This study highlights a new strategy to circumvent BCS Class IV flavonoid glycosides using a formulation of their aglycone as a precursor to accelerate oral absorption and improve bioactivity.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Animals; Apigenin; beta-Cyclodextrins; Biological Availability; Biotransformation; Cerebral Hemorrhage; Chemistry, Pharmaceutical; Disease Models, Animal; Excipients; Freeze Drying; Glucuronates; Nanostructures; Nanotechnology; Particle Size; Poloxamer; Prodrugs; Rats, Sprague-Dawley; Solubility; Technology, Pharmaceutical; Zebrafish

Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by β-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.

Topics: Animals; Anticoagulants; Apigenin; Binding Sites; Cell Survival; Drug Design; Free Radical Scavengers; Glucose; Glucuronates; Hydrogen Peroxide; Molecular Docking Simulation; Neuroprotective Agents; PC12 Cells; Protein Binding; Protein Structure, Tertiary; Rats; Solubility; Thrombin

Scutellarin [scutellarein-7-O-glucuronide (S-7-G)] displayed a unique pharmacokinetic profile in humans after oral administration: the original compound was hardly detected, whereas its isomeric metabolite isoscutellarin [scutellarein-6-O-glucuronide (S-6-G)] had a markedly high exposure. Previous rat study revealed that S-7-G and S-6-G in the blood mainly originated from their aglycone in enterocytes, and that the S-7-G/S-6-G ratio declined dramatically because of a higher hepatic elimination of S-7-G. In the present study, metabolite profiling in human excreta demonstrated that the major metabolic pathway for S-6-G and S-7-G was through further glucuronidation. To further understand the cause for the exposure difference between S-7-G and S-6-G in humans, studies were conducted to uncover mechanisms underlying their formation and elimination. In vitro metabolism study suggested that S-7-G was formed more easily but metabolized more slowly in human intestinal and hepatic microsomes. Efflux transporter study showed that S-6-G and S-7-G were good substrates of breast cancer resistance protein and multidrug resistance-associated protein (MRP) 2 and possible substrates of MRP3; however, there was no preference great enough to alter the S-7-G/S-6-G ratio in the blood. Among the major hepatic anion uptake transporters, organic anion-transporting polypeptide (OATP) 2B1 played a predominant role in the hepatic uptake of S-6-G and S-7-G and showed greater preference for S-7-G with higher affinity than S-6-G (K(m) values were 1.77 and 43.9 μM, respectively). Considering the low intrinsic permeability of S-6-G and S-7-G and the role of OATP2B1 in the hepatic clearance of such compounds, the selective hepatic uptake of S-7-G mediated by OATP2B1 is likely a key determinant for the much lower systemic exposure of S-7-G than S-6-G in humans.

Topics: Administration, Oral; Adult; Apigenin; Bile; Biotransformation; Drugs, Chinese Herbal; Female; Flavones; Glucuronates; Glucuronides; Glucuronosyltransferase; HEK293 Cells; Humans; Intestinal Absorption; Intestinal Mucosa; Liver; Male; Metabolic Clearance Rate; Metabolomics; Microsomes, Liver; Middle Aged; Multidrug Resistance-Associated Protein 2; Organic Anion Transporters; Permeability; Transfection

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO) with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.

Topics: Animals; Apigenin; Brain Ischemia; Glucuronates; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Rats; Reperfusion Injury

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.

Topics: Administration, Oral; Animals; Apigenin; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Erigeron; Feces; Female; Gastrointestinal Tract; Glucuronates; Half-Life; Injections, Intravenous; Male; Microsomes, Liver; Rats; Rats, Sprague-Dawley; Sex Factors

Scutellarin (SG) is a bioactive flavonoid used to treat cardiovascular disease. Scutellarein (S) is the aglycone form of SG. This study aimed to characterize their intestinal transport and first-pass metabolism by UDP-glucuronosyltransferase-mediated glucuronidation and β-glucuronidase-mediated hydrolysis. Results showed that S is more readily passed through Caco-2 cell monolayers by passive diffusion than SG. SG was the predominant metabolite of S, which was formed during the transportation of S across Caco-2 cell monolayers or following incubation of S with human microsomes. SG was extensively generated in human liver microsomes (HLMs), which was demonstrated by its higher catalyzing efficiency (C(lint)) in liver microsomes than in human intestinal microsomes (HIMs). Enzymatic kinetic analysis indicated that the catalyzing efficiency of UGT1A9 was the highest among the tested UGTs under the present experimental conditions, followed by UGT1A1 and UGT1A3. No significant P450-mediated hydroxylation of S was found. SG may be hydrolyzed into S in both HLMs and HIMs.

Topics: Apigenin; Biological Transport; Biotransformation; Caco-2 Cells; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Glucuronates; Glucuronides; Glucuronosyltransferase; Humans; Hydrolysis; Hydroxylation; Intestinal Mucosa; Isoenzymes; Kinetics; Mass Spectrometry; Microsomes, Liver; NADP; Recombinant Proteins; Ultraviolet Rays

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, it is very difficult to obtain scutellarein in nature compared with scutellarin. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. The in vitro antioxidant activities of scutellarein were evaluated by measuring its scavenging capacities toward DPPH, ABTS(+•), (•)OH free radicals and its protective effect on H(2)O(2)-induced cytotoxicity in PC12 cells using MTT assay method. The results showed that essential point to the synthesis was the implementation of H(2)SO(4) in 90% ethanol in N(2) atmosphere; scutellarein had stronger antioxidant activity than scutellarin. The results have laid the foundation for further research and the development of scutellarein as a promising candidate for ischemic cerebrovascular disease.

Topics: Animals; Apigenin; Benzothiazoles; Biphenyl Compounds; Cell Survival; Cerebrovascular Disorders; Free Radical Scavengers; Glucuronates; Hydrogen Peroxide; Ischemia; PC12 Cells; Picrates; Rats; Sulfonic Acids

To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds' absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP(2)), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp).. By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (P(app)) were calculated.. The P(app) values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its P(app) value was 0.74×10(-6) to 1.58×10(-6) cm/s from BL to AP. The P(app) values of scutellarein were 4.33×10(-6) to 6.79×10(-6) cm/s and 1.32×10(-6) to 2.56×10(-6) cm/s from AP to BL and from BL to AP, respectively. The P(app) value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571.. Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP(2) and BCRP can promote transportation of scutellarin. The inhibitor of MRP(2) can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.

Topics: Adenocarcinoma; Apigenin; Biological Transport; Caco-2 Cells; Colonic Neoplasms; Glucuronates; Humans; Multidrug Resistance-Associated Protein 2

A specific, precise and accurate high-performance liquid chromatography (HPLC) method for the determination of aglycone conjugated metabolites of scutellarin in plasma after enzymolysis to scutellarein (the aglycone of scutellarin) was developed and validated. The chromatographic separation was performed on a Lunar C18(2) reversed-phase column at a column temperature of 40 degrees C. The mobile phase, delivered at 1.0 ml/min, consisted of acetonitrile-KH2PO4 buffer (40 mM, pH 2.5) (33:67, v/v). The detection wavelength was set at 335 nm. Scutellarein and I.S. (quercetin) were isolated by a liquid-liquid extraction after incubating the plasma samples with beta-glucuronidase/sulfatase. The method was validated using scutellarin spiked plasma as standards. Linearity was confirmed in the concentration range of 0.2165-4.329 nmol/ml, R.S.D.s were within 8.32%, and the recoveries of scutellarein ranged from 101.2 to 108.6%. The method is applicable to the pharmacokinetic study of aglycone conjugated metabolites of scutellarin in rats after oral administration of scutellarin.

Topics: Acetonitriles; Animals; Apigenin; Chromatography, High Pressure Liquid; Drug Stability; Drugs, Chinese Herbal; Flavonoids; Glucuronates; Glucuronides; Male; Phosphates; Potassium Compounds; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Temperature

A HPLC-ECD method was established to determine scutellarin in rat bile.. The analytical column was Prontosil C18 (4.6 mm x 250 mm, 5 microm), and the mobile phase was consisted of methanol, 50 mmol x L(-1) phosphate buffer (adjusted by phosphoric acid to pH 2. 6), and tetrahydrofuran (40: 60: 10) , the flow rate was 1.0 mL x min(-1); the potential electrode voltage was 100 mv.. Concentration profile of scutellarin in rat bile was shown in this paper after oral administration of scutellarein.. Only scutellarin was detected in rat bile, while both of scutellarin and scutellarein were detected in rat plasma.

Topics: Animals; Apigenin; Bile; Chromatography, High Pressure Liquid; Erigeron; Glucuronates; Male; Plants, Medicinal; Rats; Rats, Sprague-Dawley

The present study investigated the protective actions of the antioxidant scutellarin against the cytotoxicity produced by exposure to H2O2 in PC12 cells. This was done by assaying for MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide) reduction and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) and Ca2+ in cells were evaluated by fluorescent microplate reader using DCFH and Fura 2-AM, respectively, as probes. Lipid peroxidation was quantified using thiobarbituric acid-reactive substances (TBARS). Mitochondrial membrane potential (MMP) was assessed by the retention of rhodamine123 (Rh123), a specific fluorescent cationic dye that is readily sequestered by active mitochondria, depending on their transmembrane potential. The DNA content and percentage of apoptosis were monitored with flow cytometry. Vitamin E, a potent antioxidant, was employed as a comparative agent. Preincubation of PC12 cells with scutellarin prevented cytotoxicity induced by H2O2. Intracellular accumulation of ROS, Ca2+ and products of lipid peroxidation, resulting from H2O2 were significantly reduced by scutellarin. Incubation of cells with H2O2 caused a marked decrease in MMP, which was significantly inhibited by scutellarin. PC12 cells treated with H2O2 underwent apoptotic death as determined by flow cytometric assay. The percentage of this H2O2-induced apoptosis in the cells was decreased in the presence of different concentrations of scutellarin. Scutellarin exhibited significantly higher potency compared to the antioxidant vitamin E. The present findings showed that scutellarin attenuated H2O2-induced cytotoxicity, intracellular accumulation of ROS and Ca2+, lipid peroxidation, and loss of MMP and DNA, which may represent the cellular mechanisms for its neuroprotective action.

Topics: Animals; Antioxidants; Apigenin; Apoptosis; Calcium; Cytoprotection; DNA, Neoplasm; Dose-Response Relationship, Drug; Flavonoids; Glucuronates; Hydrogen Peroxide; L-Lactate Dehydrogenase; Lipid Peroxidation; Membrane Potentials; Mitochondria; PC12 Cells; Rats; Reactive Oxygen Species; Tetrazolium Salts; Thiazoles; Vitamin E

Scutellarin is the major active constituent of Scutellaria barbata D. The metabolism of scutellarin has been investigated in rats. The solid-phase extraction and HPLC-DAD methods were established to separate and analyse metabolites. Five metabolites (M1-M5) were identified by enzymatic hydrolysis, HPLC-DAD, HPLC-MS and HPLC-NMR. M1 and M3 were conjugates of scutellarin with two sulfate groups, which have not been reported in natural plants. M2 was scutellarin; M4 was 6-methyl-scutellarin; and M5 was 6-methyl-scutellarein. The metabolic pathway was proposed.

Topics: Administration, Oral; Animals; Apigenin; Bile; Flavonoids; Glucuronates; Liver; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Scutellaria

The flavonoid profiles of two monotypic genera, Teucridium and Tripora, have been studied by analytical methods. These genera were formerly placed in the Verbenaceae, but are now classified in the Lamiaceae, subfamily Ajugoideae. The major flavonoids of both genera were identified as glycosides of scutellarein 4'-methyl ether (5,6,7-trihydroxy-4'methoxyflavone) and acacetin (5,7-dihydroxy-4'-methoxyflavone). The new flavone glycoside, scutellarein 4'-methyl ether 7-O-rutinoside, was isolated from Teucridium parvifolium and the rare scutellarein 4'-methyl ether 7-O-glucuronide from Tripora divaricata. The latter compound has only been reported previously in the related genus Clerodendron. The potential of these flavonoids as taxonomic markers for the tribe Ajugoideae is discussed.

Topics: Apigenin; Carbohydrate Conformation; Carbohydrate Sequence; Flavonoids; Glucuronates; Glycosides; Lamiaceae; Spectrum Analysis

Twenty-six flavonoids were isolated from Scutellaria baicalensis. Their affinities for the benzodiazepine (BDZ) binding site of GABA A receptor have been studied using [ 3H]flunitrazepam binding to rat cortical membranes in vitro. The structure-activity relationships suggested that 2'-OH flavones exhibited the most potent binding affinity, which could lead to the design and discovery of new BDZ receptor ligands.

Topics: Animals; Apigenin; Binding Sites; Flavanones; Flavonoids; Flunitrazepam; GABA Modulators; Glucuronates; Molecular Structure; Plant Extracts; Quantitative Structure-Activity Relationship; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Scutellaria baicalensis

To study the antioxidative effects and its mechanism of scutellarin.. Scavenging effects of scutellarin on hydroxyl radical (OH.) produced from 0-phenathroline-ascorbic acid system, super oxide anion radical (O2-.) produced from xanthine-xanthine oxidase-luminol system and hydrogen peroxide was studied by a chemiluminescence assay.. Scutellarin has a significant effect on scavenging hydroxyl radicals, super oxide anion radicals, hydrogen peroxide, their IC50 are 66 micrograms/ml, 1.3 micrograms/ml and 1.6 micrograms/ml respectively.. Scutellarin is an efficiency antioxidant.

Topics: Apigenin; Asteraceae; Flavonoids; Free Radical Scavengers; Glucuronates; Hydrogen Peroxide; Hydroxyl Radical; Luminescent Measurements; Plants, Medicinal; Reactive Oxygen Species; Superoxides

To study the chemical constituents of Erigeron breviscapus.. The constituents were separated and purified by column chromatography with silica gel, and identified by IR, MS, NMR and physical data.. Five compounds were isolated and identified as 3, 5, 6, 4'-tetrahydroxy-7-methoxy flavonoid(I); 5, 7, 4'-trihydroxy flavonoid(II); 3, 5, 6, 7, 4'-pentahydroxy flavonoid(III); scutellarein (IV) and 5, 7, 4'-trihydroxy flavanone(V).. Compounds I, III and V were isolated from this plant for the first time.

Topics: Apigenin; Asteraceae; Flavonoids; Glucuronates; Plants, Medicinal