Scute
Selected from ~250 articles

Han J. Ye M. Xu M. Sun J. Wang B. Guo D. Characterization of flavonoids in the traditional Chinese herbal medicine-Huangqin by liquid chromatography coupled with electrospray ionization mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences. 848(2):355-62, 2007. The root of Scutellaria baicalensis, called Huangqin in Chinese, is one of the most commonly used traditional Chinese medicines for the treatment of hepatitis, tumors, diarrhea, and inflammatory diseases. The major chemical constituents of Huangqin are flavonoids. In the present paper, HPLC-DAD-ESI-MS(n) was used to analyze flavonoids in the roots of S. baicalensis. A total of 26 flavonoids were identified or tentatively characterized, including 5 C-glycosides, 12 O-glycosides, and 9 free aglycones. Two C-glycosides, apigenin-6-C-glucyl-8-C-arabinoside and chrysin-6,8-di-C-glucoside, together with some O-glycosides, are reported from S. baicalensis for the first time. This method is simple, reliable and sensitive, and could be used for the quality control of Huangqin and its related preparations. 

Yu K. Gong Y. Lin Z. Cheng Y. Quantitative analysis and chromatographic fingerprinting for the quality evaluation of Scutellaria baicalensis Georgi using capillary electrophoresis. Journal of Pharmaceutical & Biomedical Analysis. 43(2):540-8, 2007. Quantitative analysis and chromatographic fingerprinting for the quality evaluation of a Chinese herb Scutellaria baicalensis Georgi using capillary electrophoresis (CE) technique was developed. The separation was performed with a 50.0cm (42.0cm to the detector window)x75mum i.d. fused-silica capillary, and the CE fingerprint condition was optimized using the combination of central composite design and multivariate analysis. The optimized buffer system containing 15mM borate, 40mM phosphate, 15mM SDS, 15% (v/v) acetonitrile and 7.5% (v/v) 2-propanol was employed for the method development, and the baseline separation was achieved within 15min. The determination of the major active components (Baicalin, Baicalein and Wogonin) was carried out using the optimized CE condition. Good linear relationships were provided over the investigated concentration ranges (the values of R(2): 0.9997 for Baicalin, 0.9992 for Baicalein, and 0.9983 for Wogonin, respectively). The average recoveries of these target components ranged between 96.1-105.6%, 98.6-105.2%, and 96.3-105.0%, respectively. CE fingerprints combined with the quantitative analysis can be used for the quality evaluation of S. baicalensis. 

Lu T. Song J. Huang F. Deng Y. Xie L. Wang G. Liu X. Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats. Journal of Ethnopharmacology. 110(3):412-8, 2007. Huang-Lian-Jie-Du-Tang (HLJDT) is an important "heat-clearing" multiherb remedy of traditional Chinese medicine, and Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae) is a key ingredient herb in it. Baicalin and wogonoside are two main effective ingredients enriched in Radix scutellariae. In the present study, pharmacokinetic differences of baicalin following oral administration of pure baicalin, Radix scutellariae extract, baicalin co-administrated with extract of the other three herbs of HLJDT and HLJDT were investigated in male S.D. rats with approximately the same dose of 200 mg/kg baicalin. The pharmacokinetic comparison of wogonoside was conducted only in Radix scutellariae extract and HLJDT. Plasma concentrations of baicalin and wogonoside were determined using HPLC method. Unpaired Student's t-test was used for statistical comparison. The results indicated that baicalin and wogonoside demonstrated bimodal phenomenon in the plasma profile. Some ingredients in the other three herbs of HLJDT, not in Radix scutellariae itself, had pharmacokinetic interaction with baicalin and wogonoside and hence decreased their systematic exposure level (p<0.01). The absorption site of baicalin was preliminary evaluated in rat using in situ absorption in stomach and different intestinal segments and results revealed the existence of double-site absorption of baicalin. The first absorption site was in upper intestinal, probably via directly absorption of baicalin; while the second absorption site was in colon in the form of aglygon. 

Kim YH. Jeong DW. Kim YC. Sohn DH. Park ES. Lee HS. Pharmacokinetics of baicalein, baicalin and wogonin after oral administration of a standardized extract of Scutellaria baicalensis, PF-2405 in rats. Archives of Pharmacal Research. 30(2):260-5, 2007. The pharmacokinetics of active components such as baicalein, wogonin and oroxylin A were evaluated after oral administration of a purified extract of Scutellaria baicalensis GEORGI (PF-2405) containing the high contents of baicalein, wogonin and oroxylin A to rats. Following oral administration of PF-2405 at 10, 20 and 40 mg/kg dose (equivalent to 4.5, 9.0 and 18 mg/kg baicalein), a major constituent baicalein and its active metabolite baicalin showed dose-linear pharmacokinetics as evidenced by unaltered dose-normalized AUC, dose-normalized Cmax, Ae(0-30h) and GI(30h) values. Following oral administration of PF-2405 at three doses (equivalent to 0.4, 0.8 and 1.6 mg/kg wogonin), dose-normalized Cmax and dose-normalized AUC were comparable between the 20 and 40 mg/kg PF2405 doses, but plasma concentrations of wogonin at 10 mg/kg of PF-2405 were not measurable as they were below limit of quantitation (LOQ; 18 pmol/mL). Following oral administration of PF-2405 at the three doses (equivalent to 1.5, 3.0 and 6.0 mg/kg oroxylin A), the concentrations of oroxylin A in plasma, urine and gastrointestine samples were below the assay LOQ (18 pmol/mL). Significant differences in AUCs, Ae(0-30h) and GI(30h) values for baicalein and baicalin were observed after oral administration of pure baicalein (18 mg/kg) and PF-2405 (40 mg/kg). The increases in AUCs of baicalein and baicalin after oral administration of PF-2405 may have been due to the significant decrease in GO(30h) values for baicalein. 

Leung HW. Yang WH. Lai MY. Lin CJ. Lee HZ. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis. Food & Chemical Toxicology. 45(3):403-11, 2007. Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins. 

Zhang Y. Wang X. Wang X. Xu Z. Liu Z. Ni Q. Chu X. Qiu M. Zhao A. Jia W. Protective effect of flavonoids from Scutellaria baicalensis Georgi on cerebral ischemia injury. Journal of Ethnopharmacology. 108(3):355-60, 2006. The protective effect of flavonoids extracted from Scutellaria baicalensis Georgi on cerebral ischemia injury has been explored in experimental animals. Scutellaria flavonoid (SF) could significantly prolong gasping time (prolonged ratio, 23.79%) and survival time after carotid artery occlusion, and decrease attenuate malondialdehyde (MDA) content in damaged brain tissues from 118.56+/-47.95 nmol/g in untreated to 199.29+/-24.24 nmol/g. SF could also increase the content of superoxide dismutase (SOD) in brain tissues after ischemic mice from 1486+/-94 NU/g in untreated to 1168+/-76 NU/g, and showed significant protective effect on cerebral hypoxia and reperfusion brain tissues in middle cerebral artery occlusion (MCAO) procedure. Additionally, SF has inhibitory effect on platelet aggregation, with the average inhibition rate of 45.52%, while the aspirin group was 54.96%. These results suggest that SF has a significant protective effect on cerebral ischemia and ischemia-reperfusion induced brain injury. 

Song SH. Wang BL. Feng JK. Wang ZZ. Research on different processings of Scutellaria baicalensis Georgi. Zhong Yao Cai. 29(9):893-5, 2006. Comparing the different processings of S. baicalensis Georgi with fresh herb. METHODS: Watering, cooking and steaming method were adopted and the contents of flavonoids was determined by HPLC. RESULTS: Cooking and steaming method could not only intenerate the slices, but also destroy the activity of enzyme. So different means could be choosen according to practice. CONCLUSION: Among them, cooking method with 1 time volume of water, heating 10 min, drying at 80 degrees C and steaming method taking 20 min, drying at 80 degrees C is proper. 

Sun J. Ma JS. Jin J. Wang HS. Wen QH. Zhang HG. Zhou QL. Qualitative and quantitative determination of the main components of huanglianjiedu decoction by HPLC-UV/MS. Yao Hsueh Hsueh Pao - Acta Pharmaceutica Sinica. 41(4):380-4, 2006. To establish a comprehensive HPLC analytical method of Huanglianjiedu decoction. METHODS: This study was performed by HPLC-UV/MS to identify the chemical constituents of the whole and individual herbs of the "Huanglianjiedu decoction". Zorbax Extend C18 (150 mm x 4. 6 mm ID, 5 microm) column was used; the mobile phase was composed of acetonitrile (A) and water (B, with 0.5% acetic acid) with gradient elution; the flow rate was 1.0 mL x min(-1) and the column temperature was setup at 25 degrees C. The detection wavelength was 254 nm. RESULTS: The chromatogram of Huanglianjiedu decoction showed 21 main peaks. Peaks 1, 2, 5 and 18 were from Gardenia jasminoides Ellis, Peaks 8, 13, 14, 15, 16, 17, 19 and 21 from Scutellaria baicalensis Georgi. While 10 from Coptis chinensis Franch and 20 from Phellodendron amurense Rupr., Peaks 3, 4, 6, 9, 11 and 12 came from them together. Peak 7 presented in the chromatograms of the herbs except Gardenia jasminoides Ellis. By comparison of the retention time, the on-line UV spectra and MS spectra, 11 peaks were identified as 5 (geniposide), 9 (jatrorrhizine), 10 (coptisine), 11 (palmatine), 12 (berberine), 13 (baicalin), 15 (oroxin A), 17 (wogonoside), 19 (baicalein), 20 (obaculactone), 21 (wogonin), then eight of them were quantified by HPLC-UV. CONCLUSION: The method could represent the characteristics of Huanglianjiedu decoction, and it could be used to evaluate the quality and quantity of Huanglianjiedu decoction. It distinguished between Coptis chinensis Franch and Phellodendron amurense Rupr. by HPLC for the first time. 

Di B. Feng N. Liu W. Pharmacokinetic comparisons of Shuang-Huang-Lian with the different combinations of its constitutional herbs. Journal of Ethnopharmacology. 107(3):401-5, 2006. Shuang-Huang-Lian (SHL) is a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), and is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. The aim of this study is to compare the pharmacokinetics of SHL and the different combinations of its constitutional herbs, and to investigate the influence of compatibility on the pharmacokinetics of the main active ingredient baicalein. Male Sprague-Dawley rats were randomly assigned to four groups and orally administered with SHL, SR, SR+FF and SR+LJF, respectively. At different time points (0, 0.167, 0.333, 0.5, 0.75, 1, 3, 5, 8, 12, 18, 24, 36, 48, 72 h) after administration, the concentrations of baicalein in rat serum were determined by using HPLC, and main pharmacokinetic parameters were estimated. It was found that there were significant differences (p < 0.05) in the parameters, t(1/2) (beta) and C(max) among different combinations of herbs. The results indicate that SHL has delayed the elimination and reduced the bioavailability of baicalein in rat serum. 

Huang WH. Lee AR. Yang CH. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Bioscience, Biotechnology & Biochemistry. 70(10):2371-80, 2006.  

Woo KJ. Lim JH. Suh SI. Kwon YK. Shin SW. Kim SC. Choi YH. Park JW. Kwon TK. Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity. Immunobiology. 211(5):359-68, 2006. To evaluate the possible mechanisms responsible for the anti-inflammatory effects of baicalein or baicalin, lipopolysaccharide (LPS)-induced inflammatory responses in cultured Raw 264.7 cells were studied. In the present study, baicalein and baicalin, a flavonoid present in the root of Scutellaria baicalensis Georgi, were examined for their effects on LPS-induced cyclooxygenase-2 (COX-2) gene expression in Raw 264.7 macrophages. Baicalein, but not baicalin, inhibited COX-2 gene expression in LPS-induced Raw 264.7 cells. However, both polyphenolic compounds inhibited LPS-induced inducible nitric oxide synthase (iNOS) protein expression, iNOS mRNA expression, and NO production in a dose-dependent manner. To investigate the mechanism by which baicalein inhibits COX-2 gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between baicalein- and baicalin-treated cells. Baicalein and baicalin had no effect on LPS-induced nuclear factor-kappaB (NF-kappaB) and cAMP response element binding protein (CREB) DNA binding activity. Baicalein, but not baicalin, significantly inhibited the DNA binding activity of CCAAT/enhancer binding protein beta (C/EBPbeta) These results indicated that differential effects of baicalein and baicalin on COX-2 gene expression in LPS-induced Raw 264.7 cells were mediated through inhibition of C/EBPbeta DNA binding activity. Taken together, these results suggest that baicalein acts to inhibit inflammation through inhibition of COX-2 gene expression through blockade of C/EBPbeta DNA binding activity. 

Zhao Y. Li H. Gao Z. Gong Y. Xu H. Effects of flavonoids extracted from Scutellaria baicalensis Georgi on hemin-nitrite-H2O2 induced liver injury. European Journal of Pharmacology. 536(1-2):192-9, 2006. Hemin-nitrite-H2O2 system may play a role in liver oxidative injury in some pathological events. In this paper, the effects of the three active components of the root of Scutellaria baicalensis Georgi, i.e. baicalin, baicalein and wogonin, on hemin-nitrite-H2O2 induced liver injury were studied in liver homogenate, liver microsome and human hepatoblastoma cell line HepG2 cells. It was found that hemin-nitrite-H2O2 could induce liver homogenate protein nitration, lipid peroxidation and liver microsome protein oxidation; it also caused a decrease of HepG2 cells viability. Baicalein, baicalin and wogonin could inhibit protein nitration and lipid peroxidation in liver homogenate as well as in HepG2 cells in a dose-dependent manner, the inhibition order was baicalein>baicalin>>wogonin. These three flavonoids also inhibited the oxidation of protein in liver microsome, the decrease of cell viability and the content of GSH in HepG2 cells, among which baicalin represented the most inhibitory effect. Besides, hemin-H2O2 induced cell injury could be augmented with the existence of nitrite, indicating protein nitration involved in hemin-nitrite-H2O2 induced liver injury. These results demonstrated hemin-nitrite-H2O2 could induce liver injury through oxidizing or nitrating different biomolecules. Baicalein, baicalin and wogonin could inhibit hemin-nitrite-H2O2 induced liver injury in dose-dependent manners by inhibiting oxidation and nitration. 

Wang JY. Chuang HN. Chiu JH. Fu SL. Tsai TH. Tsou AP. Hu CP. Chi CW. Yeh SF. Lui WY. Wu CW. Chou CK. Effects of Scutellaria baicalensis Georgi on macrophage-hepatocyte interaction through cytokines related to growth control of murine hepatocytes. Experimental Biology & Medicine. 231(4):444-55, 2006. The aim of this study is to elucidate the effects of Scutellaria baicalensis Georgi (SbG) extract and its constituents on macrophage-hepatocyte interaction in primary cultures. By using trans-well primary Kupffer cell culture or conditioned medium (CM) from murine macrophage RAW264.7 cell line (RAW cells), effects of SbG on hepatocyte growth were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and trypan blue exclusion assay. Cytokine production, antibody-neutralization studies, and molecular mechanisms of transforming growth factor (TGF)-beta1 gene expression were elucidated on SbG-treated RAW264.7 cells. In addition, recombinant human TGF-beta1 (r-human TGF-beta1) was added to elucidate the mechanisms of SbG effects on cultured hepatocytes. Immunohistochemistry using anti-NF-kappaB antibody was used to determine the possible signal transduction pathways in primary hepatocyte culture. The results showed that SbG stimulated the proliferation of cultured hepatocytes, possibly through NF-kappaB, but not of Toll-like receptor 4 activation; whereas SbG-RAW-CM and SbG in trans-well significantly suppressed the proliferation of hepatocytes. Antibody-neutralization studies revealed that TGF-beta1 was the main antimitotic cytokine in SbG-treated RAW cells CM. The growth stimulation effect of SbG on cultured hepatocytes was inhibited by exogenous administration of r-human TGF-beta1. Furthermore, SbG induced NF-kB translocation into the nuclei of cultured cells. In the RAW264.7 line, SbG and baicalin stimulated TGF-beta1 gene expression via NF-kappaB and protein kinase C activation. We conclude that SbG stimulates hepatocyte growth via activation of the NF-kappaB pathway and induces TGF-beta1 gene expression through the Kupffer cell-hepatocyte interaction, which subsequently results in the inhibition of SbG-stimulated hepatocyte growth. 

Huang Y. Tsang SY. Yao X. Chen ZY. Biological properties of baicalein in cardiovascular system. [Review] [76 refs] Current Drug Targets - Cardiovascular & Haematological Disorders. 5(2):177-84, 2005. The dried roots of Scutellaria baicalensis (S. baicalensis) Georgi (common name: Huangqin in China) have been widely employed for many centuries in traditional Chinese herbal medicine as popular antibacterial and antiviral agents. They are effective against staphylococci, cholera, dysentery, pneumococci and influenza virus. Baicalein, one of the major flavonoids contained in the dried roots, possesses a multitude of pharmacological activities. The glycoside of baicalein, baicalin is a potent anti-inflammatory and anti-tumor agent. This review describes the biological properties of baicalein (Table 1), which are associated with the prevention and treatment of cardiovascular diseases. Baicalein is a potent free radical scavenger and xanthine oxidase inhibitor, thus improving endothelial function and conferring cardiovascular protective actions against oxidative stress-induced cell injury. Baicalein lowers blood pressure in renin-dependent hypertension and the in vivo hypotensive effect may be partly attributed to its inhibition of lipoxygenase, resulting in reduced biosynthesis and release of arachidonic acid-derived vasoconstrictor products. On the other hand, baicalein enhances vasoconstricting sensitivity to receptor-dependent agonists such as noradrenaline, phenylephrine, serotonin, U46619 and vasopressin in isolated rat arteries. The in vitro effect is likely caused by inhibition of an endothelial nitric oxide-dependent mechanism. The anti-thrombotic, anti-proliferative and anti-mitogenic effects of the roots of S. baicalensis and baicalein are also reported. Baicalein inhibits thrombin-induced production of plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis factor-alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. The pharmacological findings have highlighted the therapeutic potentials of using plant-derived baicalein and its analogs for the treatment of arteriosclerosis and hypertension.  

Hu Z. Yang X. Ho PC. Chan SY. Heng PW. Chan E. Duan W. Koh HL. Zhou S. Herb-drug interactions: a literature review. [Review] [505 refs] Drugs. 65(9):1239-82, 2005. Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations. Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers. 

Li HB. Chen F. Isolation and purification of baicalein, wogonin and oroxylin A from the medicinal plant Scutellaria baicalensis by high-speed counter-current chromatography. Journal of Chromatography. A. 1074(1-2):107-10, 2005. The medicinal plant Scutellaria baicalensis Georgi has been used widely in traditional Chinese medicine for anti-inflammation, anticancer, antiviral and antibacterial infections, reducing the total cholesterol level and decreasing blood pressures. A high-speed counter-current chromatography (HSCCC) method was developed for the preparative separation and purification of three bioactive flavonoids, namely, baicalein, wogonin and oroxylin A, from S. baicalensis Georgi. Preparative HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-n-butanol-water (1:1:8:10, v/v/v/v) was successfully performed by increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml min(-1) after 4 h. The components purified and collected were analyzed by high-performance liquid chromatography. The method yielded 144.8 mg of baicalein at 95.7% purity, 50.2 mg of wogonin at 98.5% purity, and 12.4 mg of oroxylin A at 93.2% purity from 500 mg of the crude extract in a one-step separation. The recoveries of baicalein, wogonin and oroxylin A were 92.7%, 91.6% and 92.5%, respectively. 

Tang W. Sun X. Fang JS. Zhang M. Sucher NJ. Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95 (PSD-95)/disc large/zonula occludens-1 (PDZ) domain of PSD-95. Phytomedicine. 11(4):277-84, 2004. Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and subsequent production of nitric oxide by neuronal nitric oxide synthase (nNOS) contribute to neuronal damage resulting from hypoxic and ischemic insults. NMDARs and nNOS are coupled together at the postsynaptic membrane through their interaction with postsynaptic density protein (PSD) 95 via PSD-95/disc large/zonula occludens-1 (PDZ) domains. We used NMR (nuclear magnetic resonance) spectroscopy to screen medicinal herbs used in traditional Chinese medicine (TCM) stroke therapy for compounds binding to the second PDZ domain (PDZ2) of PSD-95, the domain linking nNOS and PSD-95. Aqueous extract of Huangqin, the root of Scutellaria baicalensis Georgi (Labiatae), showed significant binding to PDZ2 of PSD-95. The binding site of the active components in the extract overlapped with the nNOS/NR2B-binding pocket of PDZ2 of PSD-95. Four flavones, baicalin, norwogonoside, oroxylin A-glucuronide (oroxyloside), and wogonoside were isolated and found to account for the PDZ-binding activity of the extract. NMR titration experiments showed that baicalin and norwogonoside displayed the highest PDZ2 binding affinity, while oroxylin A-glucuronide and wogonoside showed 4-5 fold less potency in binding to the PDZ domain. Identification of the PDZ binding activity of these compounds will allow investigating whether or not it contributes to the observed clinical effects of Radix Scutellariae. Furthermore, these molecules might provide leads for the development of drugs targeting the signaling pathways mediated by PDZ domains. 

Li HB. Jiang Y. Chen F. Separation methods used for Scutellaria baicalensis active components. Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences. 812(1-2):277-90, 2004. Scutellaria baicalensis Georgi is one of the most widely used traditional Chinese herbal medicines. Its roots have been used for anti-inflammation, anticancer, antiviral and antibacterial infections of the respiratory and the gastrointestinal tract, cleaning away heat, moistening aridity, purging fire, detoxifying toxicosis, reducing the total cholesterol level and decreasing blood pressures. Baicalin, baicalein, wogonin and oroxylin A are its main active components. This review provides an overview of various separation, detection, and identification techniques employed for the quantitative and qualitative determination of these active components. Applications of high-performance liquid chromatography, high-speed counter-current chromatography, thin layer chromatography, capillary electrophoresis, and micellar electrokinetic capillary chromatography to the separation and determination of these active components are described. Examples of identification of these active components and their metabolites in complex matrices by high-performance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry are also presented. The advantages and limitations of these separation and identification methods are assessed and discussed. 

Cho J. Lee HK. Wogonin inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion. Biological & Pharmaceutical Bulletin. 27(10):1561-4, 2004. The present study evaluated the effect of wogonin, a flavonoid originated from the root of Scutellaria baicalensis GEORGI, on focal ischemic brain injury in rats. Focal brain ischemia was induced by the permanent occlusion of middle cerebral artery (pMCAO) for 24 h with a silicone rubber cylinder inserted through the right internal carotid artery. We found that wogonin, intraperitoneally administered at a dosage of 20 mg/kg at 30 min before and 4 h after the surgery, reduced the pMCAO-induced infarct areas in the cerebral cortex as well as in the striatum. The total volume of infarction was significantly reduced by the treatment with wogonin. In addition, wogonin was found to significantly improve the pMCAO-induced behavioral deficits at 24 h after the surgery. Taken together, these results demonstrate that wogonin inhibits ischemic brain injury and improves behavioral dysfunction caused by pMCAO. These findings, along with previous reports demonstrating the neuroprotective effects of wogonin, provide strong pharmacological basis for the use of wogonin or Scutellaria baicalensis in the treatment of stroke. 

Heo HJ. Kim DO. Choi SJ. Shin DH. Lee CY. Potent Inhibitory effect of flavonoids in Scutellaria baicalensis on amyloid beta protein-induced neurotoxicity. Journal of Agricultural & Food Chemistry. 52(13):4128-32, 2004. The free radical scavenging activities of two major flavonoids (baicalein and baicalin) in Scutellaria baicalensis were determined. The antioxidant capacities of baicalein and baicalin were determined by the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(*)(-) scavenging assay and showed about 110 and 70% vitamin C equivalent antioxidant capacity, respectively. Because amyloid beta (Abeta) protein is known to increase free radical production and lipid peroxidation in PC12 nerve cells, leading to apoptosis and cell death, treatment with baicalein and baicalin may result in the prevention of cellular damage by the Abeta-induced reactive oxygen species. We found that baicalein and baicalin resulted in a dose-dependent anti-Abeta toxicity by means of three different assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, lactate dehydrogenase release, and trypan blue exclusion assays]. These results suggest that baicalein as well as baicalin can reduce the cytotoxicity of Abeta protein in PC12 cells, possibly by a reduction of oxidative stress, and these flavonoids may be useful in the chemoprevention of Alzheimer's disease Shao ZH. Vanden Hoek TL. Li CQ. Schumacker PT.

Becker LB. Chan KC. Qin Y. Yin JJ. Yuan CS. Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on scavenging reactive oxygen species in vitro. American Journal of Chinese Medicine. 32(1):89-95, 2004. Scutellaria baicalensis (SbE) is a commonly used Chinese herb medicine and grape seed proanthocyanidins is a popular herbal supplement in the United States. Both herbs have been shown to possess potent antioxidant effects. Using an in vitro model to produce the reactive oxygen species (ROS) generation (H2O2/FeSO4 for hydroxyl radicals, xanthine/xanthine oxidase for suproxide), we observed that Scutellaria baicalensis and grape seed proanthocyanidins acted synergistically to scavenge ROS. Our data suggest that a combination of these two herbs can potentially enhance their antioxidant efficacy, allowing lower dosages of each drug to be used. This has the advantage of avoiding possible side effects that may arise when higher doses of a single herb are used in an attempt to achieve a maximum degree of antioxidant activity. 

Lai MY. Hsiu SL. Hou YC. Tsai SY. Chao PD. Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis. Planta Medica. 70(2):132-7, 2004. Scutellariae Radix (SR), the root of Scutellaria baicalensis (Labiatae), is widely used in clinical Chinese medicine. In order to investigate the effect of SR on the absorption and disposition of cyclosporine, rats were administered with cyclosporine orally (in the form of the microemulsion Neoral and intravenously with and without coadministration of SR decoction in randomized cross-over designs, respectively. Furthermore, the effects of the major constituents, e. g., baicalin and its aglycone baicalein on cyclosporine pharmacokinetics were also investigated in rats. A specific monoclonal fluorescence polarization immunoassay was used to determine the blood concentration of cyclosporine. Our results indicated that coadministration of SR decoction at doses of 1 g/kg and 2 g/kg significantly decreased the C (max) of cyclosporine by 62.9 % and 79.6 % and reduced the AUC (0 - 540) by 55.2 % and 82.0 %, respectively. On the contrary, coadministration of baicalin and baicalein at doses of 112 micromol/kg markedly elevated the C (max) of cyclosporine by 408.1 % and 87.5 % and increased the AUC (0 - 540) by 685.3 % and 150.2 %, respectively. Nevertheless, SR decoction did not alter the pharmacokinetics of intravenous cyclosporine. These results indicate that a profound interaction between SR decoction and cyclosporine occurred at the absorption site. In order to ensure the efficacy and safety of cyclosporine, the coadministration of SR and its preparations with oral cyclosporine should be avoided. 

Kang BY. Chung SW. Kim SH. Cho D. Kim TS. Involvement of nuclear factor-kappaB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis. Planta Medica. 69(8):687-91, 2003. Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing development and progression of disease in experimental models of autoimmunity. In this study we investigated the effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Baicalein potently inhibited the LPS-induced IL-12 production from both primary macrophages and RAW264.7 monocytic cell-line in a dose-dependent manner (the IC50 values were 43.7 and 17.4 microM, respectively). The effect of baicalein on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect mapped to a region in the IL-12 gene promoter containing a binding site for NF-kappaB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-kappaB site, which significantly decreased upon addition of baicalein, indicating that baicalein inhibited IL-12 production in LPS-activated macrophages via inhibition of NF-kappaB binding activity. 

Chi YS. Lim H. Park H. Kim HP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochemical Pharmacology. 66(7):1271-8, 2003. Flavonoids from plant origin show anti-inflammatory activity in vitro and in vivo. In addition to inhibition of inflammation-associated enzymes, such as cyclooxygenases (COX) and lipoxygenases, they have been found to regulate the expression of inflammation-associated proteins from in vitro experiments. In order to prove in vivo behavior and the potential for beneficial use against inflammatory skin disorders, the effect of wogonin (5,7-dihydroxy-8-methoxyflavone) on in vivo expression of several inflammation-associated genes was examined in the intact as well as in the inflamed mouse skin by reverse transcriptase-polymerase chain reaction analysis. When applied topically on the intact skin, only a high dose treatment of wogonin (1000 microg/ear/3 days) slightly increased COX-1 and fibronectin mRNA. On the other hand, wogonin at the doses of 250-1000 microg/ear/3 days potently lowered mRNA levels of COX-2 and tumor necrosis factor-alpha with less effect on intercellular adhesion molecule-1 and interleukin-1beta in a sub-chronic skin inflammation model of tetradecanoylphorbol-13-acetate-induced ear edema (multiple treatment). The decrease of prostaglandin E(2) concentration (27.3-34.3%) was concomitantly observed in the wogonin-treated groups. A similar effect was also observed in an acute inflammation model of arachidonic acid-induced ear edema. From the present study, wogonin was proved to differentially regulate the expression of inflammation-associated genes in vivo and to become a useful therapeutic agent for skin inflammatory diseases mainly due to its modulation of the expression of proinflammatory molecules. 

Zhang DY. Wu J. Ye F. Xue L. Jiang S. Yi J. Zhang W. Wei H. Sung M. Wang W. Li X. Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Research. 63(14):4037-43, 2003. Scutellaria baicalensis is a widely used Chinese herbal medicine that has been used historically in anti-inflammatory and anticancer therapy. The purpose of this study is to verify its anticancer activity on head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E(2) (PGE(2)) and is highly expressed in HNSCC. Two human HNSCC cell lines (SCC-25 and KB) and a nontumorigenic cell line (HaCaT) were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with Scutellaria baicalensis extract. Its effects were compared with those of baicalein (a flavonoid isolated from Scutellaria baicalensis), indomethacin (a nonselective COX inhibitor), and celecoxib (a selective COX-2 inhibitor). Four nude mice with s.c. inoculation of KB cells were tested for its anticancer activity in vivo by oral administration of Scutellaria baicalensis at a dose of 1.5 mg/mouse (75 mg/kg), five times/week for 7 weeks. Scutellaria baicalensis and other agents demonstrated a strong growth inhibition in both tested human HNSCC cell lines. No growth inhibition of HaCaT cells was observed with Scutellaria baicalensis. The IC(50)s were 150 micro g/ml for Scutellaria baicalensis, 25 micro M for celecoxib, and 75 micro M for baicalein and indomethacin. Scutellaria baicalensis, as well as celecoxib and indomethacin, but not baicalein, suppressed proliferation cell nuclear antigen expression and PGE(2) synthesis in both cell types. Scutellaria baicalensis inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. A 66% reduction in tumor mass was observed in the nude mice. Scutellaria baicalensis selectively and effectively inhibits cancer cell growth in vitro and in vivo and can be an effective chemotherapeutic agent for HNSCC. Inhibition of PGE(2) synthesis via suppression of COX-2 expression may be responsible for its anticancer activity. Differences in biological effects of Scutellaria baicalensis compared with baicalein suggest the synergistic effects among components in Scutellaria baicalensis. 

Ye F. Xui L. Yi J. Zhang W. Zhang DY. Anticancer activity of Scutellaria baicalensis and its potential mechanism. Journal of Alternative & Complementary Medicine. 8(5):567-72, 2002. OBJECTIVE: Scutellaria baicalensis is a widely used Chinese herbal medicine that historically is used in anti-inflammatory and anticancer therapy. The aim of the study is to determine its ability to inhibit human cancer cells in vitro and to determine whether its anticancer activity is because of the inhibition of prostaglandin E(2) (PGE(2)) production that is derived from arachidonic acid through cyclooxygenase-2 (COX-2) pathway. METHODS: Cell lines from the most common human cancers, including squamous cell carcinoma (SCC-25, KB), breast cancer (MCF-7), hepatocellular carcinoma (HepG2), prostate carcinoma (PC-3 and LNCaP), and colon cancer (KM-12 and HCT-15) were tested. The cells were treated with various concentrations of Scutellaria baicalensis (0.1-100 mg/mL) for 72 hours. Percentage of viable cells after treatment was assessed using a trypan blue dye exclusion assay and the level of PGE(2) production was determined by enzyme immunoassay (EIA). RESULTS: Scutellaria baicalensis demonstrated a strong dose-dependent growth inhibition in all cell lines. Inhibition concentration at 50% (IC(50)) for HepG2, MCF-7, PC-3, LNCaP, KM-12, HCT-15, KB and SCC-25 cells was 1.1, 0.9, 0.52, 0.82, 1.1, 1.5, 1.0, and 1.2 mg/mL, respectively. Three cell lines (KB, SCC-25, and HepG2) were assessed for the production of PGE(2) and a high level of extracellular (KB and SCC-25) and intracellular PGE(2) (HepG2) was noted. In the presence of Scutellaria baicalensis extract, there was a significant decrease of PGE(2) in a dose-dependent fashion. CONCLUSIONS: Scutellaria baicalensis strongly inhibits cell growth in all cancer cell lines tested. However, prostate and breast cancer cells (PC-3, LNCaP, and MCF-7) are slightly more sensitive than other type of cancer cells. It also inhibits PGE(2) production, indicating that suppression of tumor cell growth may be due to its ability to inhibit COX-2 activity. This study supports the notion of using Scutellaria baicalensis as a novel anticancer agent to treat various cancers. 

Hui KM. Huen MS. Wang HY. Zheng H. Sigel E. Baur R. Ren H. Li ZW. Wong JT. Xue H. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochemical Pharmacology. 64(9):1415-24, 2002. The search for novel anxiolytics devoid of undesirable side-effects typical of classical benzodiazepines (BDZs) has been intense, and flavonoids, as a relative new class of ligands, have been shown to possess anxiolytic effects in vivo. The present study evaluated the pharmacological properties of a naturally occurring monoflavonoid, 5,7-dihydroxy-8-methoxyflavone or wogonin. The affinity (K(i)) of wogonin for the benzodiazepine site (BZD-S) on the gamma-aminobutyric acid(A) (GABA(A)) receptor complex was 0.92 microM. Using electrophysiological techniques, we showed that wogonin enhanced the GABA-activated current in rat dorsal root ganglion neurons, and in Xenopus laevis oocytes expressing recombinant rat GABA(A) receptors, the enhancement was partially reversed by the co-application of a 1 microM concentration of the BZD-S antagonist anexate (Ro15-1788). Acute toxicity and behavioral effects were examined in mice. Acute lethal activity was low, with an LD(50) of 3.9 g/kg. Oral administration of wogonin (7.5 to 30 mg/kg) elicited an anxiolytic response that was similar to that elicited by diazepam in the elevated plus-maze; a dose-dependent increase in open arm entries and time spent in open arms was observed. More importantly, its anxiolytic effect was blocked by the co-administration of Ro15-1788. In the holeboard test, not only did wogonin-treated mice experience an increased number of head-dips but they also spent more time at it, showing no signs of sedation. Furthermore, wogonin did not cause myorelaxant effects in the horizontal wire test. Taken together, these data suggest that wogonin exerts its anxiolytic effect through positive allosteric modulation of the GABA(A) receptor complex via interaction at the BZD-S. Its anxiolytic effect was not accompanied by sedative and myorelaxant side-effects typical of BDZs.