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Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis.

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.

Animals↗

[Pharmacological effects of flavonoids from Scutellaria baicalensis].

Scutellaria baicalensis is a plant widely used in Chinese and Japanese herbal medicine. Dry roots of Scutellaria baicalensis are used, especially as alcohol extracts. Flavonoids isolated from Radix Scutellariae have beneficial effects in hepatitis. Flavonoids derived from Scutellaria baicalensis produce antioxidative, antineoplastic, cardiomiocyte-protective activity. They inhibit agregation of platelets, permeability of capillary vessels, have antibacterial and anty-angiogenic effects.

Antineoplastic Agents, Phytogenic↗

Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis.

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.

Animals↗

Comparative study of Scutellaria planipes and Scutellaria baicalensis.

Scutellaria planipes, a species of Scutellaria, was explored by comparing to Scutellaria baicalensis, a pharmacopoeia species. Four principle flavonoids in both the plant roots were analyzed by using a reversed-phase chromatographic system with a chemically bonded ODS silica gel column and phosphate buffer:methanol (68:32 and 1:1) as mobile phase. Their contents were similar in both plant roots. Antiallergic and antibacterial activities in vitro and acute toxicity were compared. The results provided valuable data for S. planipes as a potential medicinal resource.

Animals↗

The nitric oxide-producing activities of Scutellaria baicalensis.

Scutellaria baicalensis (SB) has antibacterial and antiviral activities. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of bacteria, viruses and tumors has received increasing attention. The objective of this study was to determine the effect of SB on the production of NO. Stimulation of mouse peritoneal macrophages with SB after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO production. SB had no effect on NO production by itself. When SB was used in combination with rIFN-gamma, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SB on NO production was shown 6 h after treatment with rIFN-gamma. NO production by SB was inhibited by N(G)-monomethyl-L-arginine. The increased production of NO from rIFN-(gamma) plus SB-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and SB was mainly dependent on SB-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of SB were endotoxin free. These results suggest that the capacity of SB to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of SB-induced TNF-gamma secretion.

Animals↗

Separation methods used for Scutellaria baicalensis active components.

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.

Chromatography, High Pressure Liquid↗

Anticancer activity of Scutellaria baicalensis and its potential mechanism.

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.

Antineoplastic Agents, Phytogenic↗

Effect of processed Scutellaria baicalensis on dextran sulfate sodium-induced colitis in mice.

Scutellaria baicalensis Georgi (Labiatae) has been used in the treatment of inflammatory diseases. Drug processing (Poje) is the process of treating crude drugs by several methods before use. The aim of this study was to determine the effect of processed Scutellaria baicalensis on experimental ulcerative colitis induced by dextran sulfate sodium (DSS). The types of processed Scutellaria baicalensis used in this study were parched Scutellaria baicalensis (PS) and rice wine-baked Scutellaria baicalensis (RWBS). Experimental colitis was induced in mice using a daily treatment of 5% DSS in the drinking water for 7 days. The water extracts of processed Scutellaria baicalensis (1 g/kg) were administered orally once a day for 7 days. The mice were divided in four groups: i) water plus DSS group, ii) crude Scutellaria baicalensis (CS) plus DSS group, iii) PS plus DSS group, and iv) RWBS plus DSS group. RWBS ameliorated all of the inflammatory symptoms, such as body weight loss, rectal bleeding and histological damage, compared to CS. Furthermore, RWBS significantly reduced the mucosal myeloperoxidase activity, and TNF-alpha (tumor necrosis factor-alpha), COX-2 (cyclooxygenase-2), NF-kappaB (nuclear factor-kappa B) and chymase expression more than CS. But these effects were not shown in the PS plus DSS group. Efficacy of Scutellaria baicalensis was increased after rice wine baking, but not after parching. The findings in this study suggest that RWBS may be a useful therapeutic agent for ulcerative colitis.

Animals↗

Antioxidant activity of flavones from Scutellaria baicalensis in lecithin liposomes.

The antioxidant effect of a trihydroxyflavone extract from Scutellaria baicalensis on oxidation induced by ultraviolet light, was studied with phosphatidylcholine liposome membrane. Also, as standards, the antioxidative activity of baicalin, wogonin, baicalein and butylated hydroxytoluene (BHT) was investigated. Comparison of the protective effects of the compounds studied against photoinduced lipid peroxidation in lecithin liposome membranes showed that: (1) the inhibitory effect of those compounds (at 1.2 mol% antioxidant content in liposomes) on TBA reactive materials from lipid peroxidation decreased in the order of baicalin > BHT approximately equal to Scutellaria baicalensis. These were found much greater than wogonin and baicalein; (2) the depressed effect of those compounds (at 1.1 mol% compounds content in liposomes) on the production of conjugated dienes (proportional to oxidation index) could be classified as follows: Scutellaria baicalensis approximately equal to baicalin > BHT, these three were found more active much greater than baicalein and wogonin. Results obtained by ESR measurement confirm that Scutellaria baicalensis extract and the BHT compound significantly depressed the effect of liposome oxidation. It was found that the new trihydroxyflavones of Scutellaria baicalensis, ensured a very satisfactory concentration-dependent protection of the liposome membrane against UV-induced oxidation. These findings suggest that some of the beneficial effects of the extract of the Scutellaria baicalensis can be mediated in certain diseases (for example in skin diseases) by their ability to scavenge free radicals and by their protective effect on lipid peroxidation caused by sunlight irradiation.

Antioxidants↗

Baicalein, an alpha-glucosidase inhibitor from Scutellaria baicalensis.

Methanol extracts of Scutellaria baicalensis, Rheum officinale, and Paeonia suffruticosa showed potent inhibitory activity against rat intestinal sucrase. The active principles were identified as baicalein from the first and methyl gallate from the last two plants. In addition to its activity against the rat enzyme, baicalein also inhibited human intestinal sucrase expressed in Caco-2 cells.

Animals↗

Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes.

Extract from Scutellaria baicalensis Georgi Attenuates Oxidant Stress in Cardiomyocytes. Journal of Molecular and Cellular Cardiology (1999) 31, 1885-1895. Scutellaria baicalensis Georgi is a Chinese herbal medicine used to treat allergic and inflammatory diseases. The medicinal effects of S. baicalensis root may result, in part, from its constituent flavones reported to have antioxidant properties. Since oxidants play multiple roles in cells, we tested whether S. baicalensis could confer protection in a cardiomyocyte model of ischemia and reperfusion. The intracellular fluorescent probes 2',7'-dichlorofluorescin diacetate (DCFH-DA, sensitive to H(2)O(2) and hydroxyl radicals) and dihydroethidium (DHE, sensitive to superoxide) were used to assess intracellular reactive oxygen species (ROS), and propidium iodide (PI) was used to assess viability in cultured embryonic cardiomyocytes. S. baicalensis extract (SbE) quickly attenuated levels of oxidants generated during transient hypoxia and during exposure to the mitochondrial site III inhibitor antimycin A, as measured by DCFH oxidation or by DHE oxidation. These attenuated oxidant levels were associated with improved survival and function. Cell death after ischemia/reperfusion decreased from 47+/-3 % in untreated to 26+/-2 % in S. baicalensis treated cells (P<0.001). After antimycin A exposure, S. baicalensis decreased cell death from 49+/-6 % in untreated to 23+/-4 % in treated cells. Return of contraction occurred in S. baicalensis-treated cells but was not observed in control cells. Other in vitro studies revealed that baicalein, a major flavone component of SbE can directly scavenge superoxide, hydrogen peroxide, and hydroxyl radicals. Collectively, these findings indicate that SbE and its constituent flavones such as baicalein can attenuate oxidant stress and protect cells from lethal oxidant damage in an ischemia-reperfusion model.

Animals↗

[Quality evaluation of seed of Scutellaria baicalensis from different habitats].

OBJECTIVE: To study the seed quality of Scutellaria baicalensis Georgi. METHOD: Collecting seeds from different habitats and studying the thousand-seeds weight, plumpness rate and germination percentage. RESULT: The seeds from Ningxia and Juxian (Shandong province) are better than those from other habitats. Its plumpness rate is above 95%, thousand-seeds weight is 2.2 g and germination percentage is above 90%. CONCLUSION: There are obvious differences in quality of seeds of Scutellaria baicalensis from different habitats.

Climate↗

Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on scavenging reactive oxygen species in vitro.

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.

Drug Synergism↗

[Separation and determination of baicalin in prescriptions containing Scutellaria baicalensis Georgi by HPCE].

Qingkailing Oral Tonic and Shuanghuanglian Oral Tonic are two kinds of complex formlae of Chinese traditional patent medicine, and both contain Scutellaria baicalensis Georgi. Baicalin is referred to the main active component with functions of dispelling wind-heat to reduce fever and detoxicating, and takes effect on uppering respiratory tract infection and tonsillities. In this work a high performance capillary electrophoresis (HPCE) method was established for separation and quantitative analysis of baicalin in prescriptions containing Scutellaria baicalensis Georgi, based on the mode of capillary zone electrophoresis. Electrophoretic conditions are as follows: uncoated fused silica capillary (34.8/39.5 cm x 50 microns i.d.), 40 mmol/L borax buffer(pH 9.0), applied voltage 17 kV, polarity anode (inlet) to cathode (outlet), temperature 25 degrees C, detection wavelength 285 nm, injection 68.95 kPa x s. Under the optimum conditions, baicalin was separated successfully from other components within 15 minutes. The relative peak area of baicalin increased linearly with the increase of its concentration in the range of 10-640 mg/L. The recoveries were (100.31 +/- 1.98)% for Qingkailing Oral Tonic and (100.60 +/- 2.36)% for Shuanghuanglian Oral Tonic. The analytical results demonstrate the method is simple, rapid and well reproducible, and can be used as a reliable tool for the quality control of Chinese traditional medicines containing Scutellaria baicalensis Georgi.

Anti-Infective Agents↗

[The modulating effects of preparations of Baikal skullcap (Scutellaria baicalensis) on erythron reactions under conditions of neurotic exposures].

Preparations of Scutellaria baicalensis, namely its dry extract and the bioflavonoid baicalin stimulate erythropoiesis depressed in deprivation of the paradoxical phase of sleep. After a conflict situation, when hemopoiesis is activated, both drugs normalize it. The modulating effect of drugs on hemopoiesis in exposure to neurotic factors is a consequence of their influence on the functional state of the cell elements of the hemopoiesis-inducing microenvironment. The capacity of the Scutellaria baicalensis drugs for reducing the effect of psychoemotional stress on the blood system is apparently related to their influence on the adrenergic structures.

Animals↗

Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells.

BACKGROUND: Flavonoid-rich extracts from the mature roots of Scutellaria baicalensis have been shown to exhibit antiproliferative effects on various cancer cell lines. We assessed the ability of an ethanolic extract of S. baicalensis root to inhibit the proliferation of malignant glioma cells. METHODS: Cell lines derived from primary and recurrent brain tumors from the same patient and cells selected for resistance to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were used to identify antiproliferative effects of this extract when used alone and in conjunction with BCNU. RESULTS AND DISCUSSION: Results indicated that Scutellaria baicalensis not only inhibits cellular growth in recurrent and drug resistant brain tumor cell lines, but also demonstrates an increased inhibitory effect when used in conjunction with BCNU. CONCLUSION: The results of this study support the efficacy of S. baicalensis as an anticancer agent for glioblastomas multiforme and a potential adjuvant treatment to current chemotherapeutic agents used in the treatment of both primary and recurrent GBMs. Further studies of the effects of individual flavonoids alone and in combination with each other and with currently used therapies are needed.

Antineoplastic Agents↗

Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines.

Scutellaria baicalensis (S.B.) is a widely used Chinese herbal medicine. We initially investigated its in vitro anti-tumor activities. S.B inhibited the growth of ALL, lymphoma and myeloma cell lines by inducing apoptosis and cell cycle arrest at clinically achievable concentrations. The anti-proliferative effect was associated with mitochondrial damage, modulation of the Bcl family of genes, increased level of the CDK inhibitor p27(KIP1) and decreased level of c-myc oncogene. HPLC analysis of S.B. showed it contains 21% baicalin and further studies confirmed it was the major anti-cancer component of S.B. Thus, Scutellaria baicalensis should be tested in clinical trials for these hematopoietic malignancies.

Antineoplastic Agents, Phytogenic↗

[The Baikal scullcap (Scutellaria baicalensis Georgi)--a potential source of new drugs].

The scullcap (Scutellaria baicalensis Georgi) is a medicinal plant of traditional Chinese medicine and the drug--Scutellariae radix--is, because of its antioxidant, antiviral, antibacterial, antiinflammatory, antiallergic, and sedative properties, the subject of intensive development. This paper reports the results of pharmacological-toxicological studies of this drug and its flavonids approximately from the year 1990 till the year 2001. The results confirm the validity of traditional use and at the same time indicate that some flavonoids have more utilizable therapeutic effects. Mainly baicalein seems to be a prospective medicine for the treatment of some kinds of cancer.

Animals↗