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[Baikal skullcap (Scutellaria baicalensis Georgi) and its effects on the nervous system] Šišák bajkalský (Scutellaria baicalensis Georgi) a jeho účinky na nervový systém

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Abstract

Baikal skullcap (Scutellaria baicalensis Georgi) is one of the most widely used medicinal plants in traditional Eastern medicine, especially in Chinese medicine. Its major phytochemicals are flavonoids (aglycones, glycosides and their glucoronides) such as baicalin, baicalein, wogonin, and wogonoside. S. baicalensis and its flavonoids exert several pharmacological activities, including antiallergic, antioxidant, anti-apoptic, anti-inflammatory effects and many more. Recently, Baikal skullcap and its isolated flavonoids have been studied for their neuroprotective effects in a variety of in vitro and in vivo models of neurodegenerative diseases. Results showed significant neuroprotective effect of these natural substances. In this review, we focus on the neuroprotective effects of Baikal skullcap and its flavonoids on the nervous system, in particular its antidepressant, anticonvulsant and anxiolytic effects and their influence on the cognitive functions of the brain.

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Xiaochaihutang (XCHT) has been used in China for thousands of years to treat "Shaoyang syndrome", which involves depressive-like symptoms. However, few studies have investigated its antidepressant effects and pharmacological mechanism of action. The present study was designed to confirm the antidepressant effect of XCHT using a chronic unpredictable mild stress (CUMS) model and explore its potential mechanism of action by investigating the monoamine neurotransmitters (Dopamine and 5-hydroxytryptamine) and neurotrophins (BDNF and NGF). The CUMS model was established in rats, and the antidepressant effect of XCHT (0.6, 1.7 and 5mg/kg/day, given by gastric gavage for four weeks) was investigated using the open field test (OFT), food consumption test and sucrose preference test. The concentrations of 5-HT and DA in the hippocampus were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). The expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and their receptors tyrosine receptor kinase B (TrkB) and tyrosine receptor kinase A (TrkA) in the hippocampus were measured by immunohistochemical staining analysis. CUMS caused a significant decrease in OFT, food consumption and sucrose preference in rats, and these depression-like behaviors were significantly improved by XCHT (1.7 and 5g/kg/day). Moreover, XCHT significantly increased the concentrations of 5-HT (0.6 and 5g/kg/day) and DA (5g/kg/day), and improved the BDNF, NGF, TrkB and TrkA expression in the hippocampus (1.7 and 5g/kg/day), which was reduced in CUMS rats. The results obtained suggested that XCHT may have therapeutic actions on depression-like behavior induced by CUMS in rats possibly mediated by increasing the monoamine neurotransmitter concentration and neurotrophin expression in the hippocampus.
Article
Baicalin, a flavonoid compound purified from plant Scutellaria baicalensis Georgi, has been reported to possess a wide variety of pharmacological properties including anti-oxidative, anti-apoptotic and neuroprotective properties. Oxidative stress can dramatically alter neuronal function and has been linked to status epilepticus (SE). However, the neuroprotective effect of baicalin on epilepsy is unclear. In this study we investigated whether Baicalin could exert anticonvulsant and neuroprotective effects in the pilocarpine-induced epileptic model in rats. To this end, we recorded the latency to first limbic seizure and SE and observed the incidence of SE and mortality. The changes of oxidative stress were measured 24 h after pilocarpine-induced SE. Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Fluoro-Jade B staining were performed to detect the neuronal loss, apoptosis and degeneration in hippocampus 72 h after pilocarpine-induced seizure. Pretreatment with baicalin significantly delayed the onset of the first limbic seizures and SE, reduced the mortality rate, and attenuated the changes in the levels of lipid peroxidation, nitrite content and reduced glutathione in the hippocampus of pilocarpine-treated rats. Furthermore, we also found that baicalin attenuated the neuronal cell loss, apoptosis, and degeneration caused by pilocarpine-induced seizures in rat hippocampus. Collectively, these results indicated remarkable anticonvulsant and neuroprotective effects of baicalin and should encourage further studies to investigate baicalin as an adjuvant in epilepsy both to prevent seizures and to protect against seizure induced brain injury.
Article
We screened the major bioactive flavones isolated from Scutellaria baicalensis (baicalin, baicalein and oroxylin A) for their convulsion related activities. In electrogenic response score system and the pentylenetetrazole seizure model, baicalein but not oroxylin A and baicalin exhibited anticonvulsant effects. In vitro studies also revealed that baicalein induced intracellular Cl(-) influx, whereas oroxylin A blocked muscimol- and baicalein-induced intracellular Cl(-) influx. The anticonvulsant effect of baicalein was inhibited by flumazenil, a benzodiazepine(BZD) receptor antagonist. Therefore, anticonvulsive effect of baicalein was mediated by the BZD binding site of GABA(A) receptor. The 5, 7-dihydroxyl group is present in the structure of the three flavones. It is postulated that this group played a key role in inducing convulsion-related activities.
Article
Many studies of Parkinson's disease suggest that oxidative stress is involved in the neurodegenerative process. Baicalein has been shown to have antioxidant effects. The present study examines the effect of baicalein on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice. MPTP treatment impaired spontaneous motor activity and rotarod performance, but baicalein improved this deficit. Moreover, baicalein at 280 and 560 mg/kg exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra, demonstrated by the immunohistological, morphological and behavioral outcomes. MPTP treatment also decreased dopamine levels in the striatum. However, treatment with baicalein attenuated these decreases in dopamine levels by changing dopamine catabolism and inhibiting dopamine turnover. The neuroprotective effect of baicalein on dopaminergic neurons may partly be due to its antioxidant properties. Therefore, we speculate that baicalein might be a promising candidate for prevention or treatment of oxidative stress-related neurodegenerative disorders such as Parkinson's disease.
Article
Scutellaria (HUANG QIN) (Lamiaceae), which includes about 350 species commonly known as skullcaps, is widespread in Europe, the United States and East Asia. Some species are taken to clear away the heat-evil and expel superficial evils in traditional Chinese medicine (TCM). The present paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of Scutellaria species. More than 295 compounds have been isolated, among them flavonoids and diterpenes. Studies show that Scutellaria and its active principles possess wide pharmacological actions, such as antitumor, anti-angiogenesis, hepatoprotective, antioxidant, anticonvulsant, antibacterial and antiviral activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activity from Scutellaria in vivo and in vitro. Increasing data supports application and exploitation for new drug development.
Article
Oxidative stress plays an important role in many neurodegenerative disorders. In this study, the effect of baicalein, a natural flavonoid isolated from the root of Scutellaria baicalensis G., on hydrogen peroxide (H2O2)-induced cytotoxicity in PC12 cells were investigated. Exposure of PC12 cells to 0.15 mM H2O2 for 20 min induced a significant decrease in cell viability accompanied by increased oxidative stress, mitochondrial dysfunction, downregulation of Bcl-2, upregulation of Bax, and cell apoptosis. Pretreatment of PC12 cells with baicalein inhibited H2O2-induced cell viability loss, intracellular reactive oxygen species generation, and lipid peroxidation in a dose-dependent manner. Meanwhile, baicalein potentially inhibited H2O2-induced cell apoptosis characterized with the DNA fragment. And the mitochondrial pathway involving the mitochondrial dysfunction associated with cell apoptosis including membrane potential loss, the release of cytochrome c, the downregulation of Bcl-2, upregulation of Bax induced by H2O2 were also abrogated in the presence of baicalein. Taken together, these results suggest that baicalein can block H2O2-induced apoptosis by prevention of oxidative stress as well as regulation of Bcl-2 family members and suppression of mitochondria dysfunction, which might be beneficial for the treatment of oxidative stress in aging and age-associated neurodegenerative diseases.
Article
Baicalein, a flavonoid obtained from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert a protective effect on neurons against several neuronal insults. The aim of this study was to explore the neuroprotective effect of baicalein in 6-hydroxydopamine (6-OHDA)-induced experimental parkinsonism in vitro and in vivo. In in vitro experiments, we found that baicalein (0.5, 5 microg/mL) could significantly ameliorate the 6-OHDA-induced SH-SY5Y cell apoptosis from 31.56% in the 6-OHDA group to 18.90%, 21.61% respectively, and also promote neurite outgrowth of PC12 cell. In in vivo experiments, baicalein had no effect on apomorphine (APO)-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA-lesioned rats. The burst frequency and amplitude are 13.43%, 35.18% compared to 6-OHDA group. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)-positive neurons to 265.52% of the 6-OHDA group. The neuroprotective action of baicalein was coincident with an attenuated astroglial response within the substantia nigra. Neuroprotective effect of baicalein as demonstrated by the increasing the number of dopaminergic neurons may have been, in part, caused by anti-apoptotic, pro-differentiation and anti-inflammatory mechanisms of baicalein. Therefore, baicalein can be a promising candidate for prevention or treatment of Parkinson's disease, owing to its anti-apoptotic, pro-differentiation and anti-inflammatory action.
Article
To study the effects of flavonoid, isolated from aerial parts of Scutellaria baicalensis Georgi (SSF), on memory impairment, neuronal damage, free radicals and energy metabolite disorders in aged rats. Approximately 25-month-old rats were used to establish the ageing model. The cognition of the rats was determined using the Morris water maze, neuronal morphology was observed by light/electron microscope, malondialdehyde (MDA) levels and the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and Na(+)-K(+)-ATPase were measured by spectrophotometry. In the Morris water maze task, the aged rats always took longer latency to find the hidden platform and spent less time swimming in the target quadrant than those of young control rats. The light/electron microscopic observations found significant neuropathological changes in the aged rats' brain. In addition, the production of MDA and the activity of SOD, LDH and Na(+)-K(+)-ATPase in the hippocampus and cerebral cortex of the aged rats showed critical abnormal changes. However, pre-treatment of the aged rats with SSF (35-140 mg kg(-1)) for 16-21 days dramatically improved cognitive dysfunction, neuropathological changes and biochemical abnormalities. These results indicate that the beneficial effects of SSF on memory impairment and neuronal damage in aged rats may be important for the treatment of senile dementia and for delaying the ageing processes.
Article
Scutellaria baicalensis Georgi (Labiatae) extracts have been used as traditional Korean medicine, to treat cerebral ischemia in addition to bacterial infection and inflammatory diseases. The improvement effect on learning and memory by the administration of Scutellaria baicalensis extracts was evaluated and the underlying mechanisms were investigated. Memory behavior was tested by the passive avoidance test and Y-maze test. We also investigated the cells expressing neuronal markers related to memory processes by immunofluorescence staining analysis in memory deficient animal model (Ibo model) rats and in hippocampal progenitor cells. We found neuronal cells immunoreactive to choline acetyltransferase (ChAT), a marker for cholinergic neurons were increased in the hippocampus, while cells producing GABA and glutamate were not after 30 mg/kg Scutellaria baicalensis administration. Futhermore, Scutellaria baicalensis extracts enhanced the survival of a hippocampal progenitor cell line, HiB5 and its differentiation to ChAT immunoreactive cells. The increased expression of memory related neurotransmitter, NMDA receptor and a reduction of activated microglia in the hippocampus were also observed in the Ibo model when administrated Scutellaria baicalensis extracts. These results imply that Scutellaria baicalensis has significant neuroprotective effects in the Ibo model.
Article
Traditional Chinese medicines have been recently recognized as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellaria also possesses potent anticancer activities. The bioactive components of Scutellaria have been confirmed to be flavones. The major constituents of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumor cell lines in vitro and inhibit tumor growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-kappaB activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumor-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation-reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C gamma 1, a key enzyme involved in Ca(2+) signaling, through H(2)O(2) signaling in malignant lymphocytes. This review is aimed to summarize the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.
Article
An in vivo microdialysis sampling method coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for continuous simultaneous monitoring of unbound baicalin in rat blood and brain. Microdialysis probes were inserted into the jugular vein and brain cerebrospinal fluid (CSF) of Sprague-Dawley rats then, following administration of baicalin at doses of 24mg/kg via the candal vein, samples were collected every 20min and injected directly into the UPLC-MS/MS system. In vitro recoveries of the probes were 19.26% and 18.38%, while in vivo recoveries of the probes were 15.0% and 17.52% for blood and brain, respectively. This improved method offers a rapid quantitative procedure for the determination of baicalin with a retention time of only 1.6min. The lower limit of quantification (LLOQ) and the lower limit of detection (LLOD) based on a signal-to-noise ratio of 5 were 2.37 and 0.1ng/ml for anticoagulant citrate dextrose (ACD) solution, and 1.185 and 0.3ng/ml for artificial cerebrospinal fluid (aCSF), respectively. The pharmacokinetics results indicated that baicalin could pass through the blood-brain barrier (BBB) and was detectable in brain dialysate. These in vivo microdialysis-based measurements provide a technique for simple sampling and rapid sensitive analysis of unbound baicalin in rat blood and CSF and for further application in pharmacokinetic studies.
Article
Accumulation of amyloid beta peptide (Abeta) has been suggested to contribute to neurodegeneration in Alzheimer's disease (AD). Since chronic inflammation occurs in AD pathogenesis and lipoxygenases are important mediators of inflammatory processes, we evaluated the effect of lipoxygenase inhibitors on apoptosis induced by Abeta on rat cortical cells. The 12-lipoxygenase inhibitor baicalein attenuated both neuronal apoptosis and c-jun protein over-expression induced by Abeta(25- 35), whereas no protection was found with the broad spectrum lipoxygenase inhibitor nordihydroguaiaretic acid or the 5-lipoxygenase inhibitor caffeic acid. These results suggest that 12-lipoxygenase participates in a c-jun-dependent apoptosis pathway triggered by Abeta(25-35), and that specific 12-lipoxygenase inhibitors might be of interest in AD.
Article
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.
Article
A previous receptor binding assay indicated that baicalein, one of the active principles of the Chinese herbal drug, Huangqin (Scutellariae Radix), interacts with the benzodiazepine binding site of GABA(A) receptors in mouse cortex membrane preparations with a K(i) value of 13.1 microM. Therefore, the present study examined whether baicalein and its 7-glucuronide, baicalin, have anxiolytic-like effects in a Vogel conflict test adapted for ICR mice. The results showed that both baicalein (10 mg/kg, i.p.) and baicalin (20 mg/kg, i.p.) significantly increased the number of shocks accepted in the Vogel lick-shock conflict paradigm over 9 min, as did a benzodiazepine receptor agonist, chlordiazepoxide (5.0 mg/kg, i.p.) and a 5-HT(1A) receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (0.5 mg/kg, i.p.). Since the total volume of water intake and the shock sensitivity of mice were not significantly changed after drug treatment, the effect of baicalein or baicalin was not due to an enhancement of thirst or shock tolerance. Furthermore, this anxiolytic-like effect of baicalein or baicalin was antagonized by co-administration with a benzodiazepine receptor antagonist, flumazenil (2 mg/kg, i.p.), but not with a 5-HT(1A) receptor antagonist, pindolol (10 mg/kg, i.p.). It is concluded that the anxiolytic-like effect of baicalein or baicalin may be mediated through activation of the benzodiazepine binding site of GABA(A) receptors.
Scutellaria lateriflora is an herbal medicine with long-standing traditional use as a relaxing nervine. There has been controversy in the literature with regards to its efficacy, and this study was designed to clarify its effectiveness in reducing anxiety, one of the phytotherapeutic indications. A double blind, placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects. The use of phytomedicines for the treatment of anxiety is reviewed, as is the published literature on S. lateriflora and its putative toxicity.
Article
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. The pathology of PD is typified by the presence of cytoplasmic inclusions (Lewy bodies) containing alpha-synuclein and ubiquitin. The pathogenesis of PD is not completely understood but environmental and genetic factors are thought to play important roles. To understand the pathophysiology of PD, and to develop novel therapies for improved symptomatic management, it is important to have relevant disease models. In this review, we summarize the available in vivo and in vitro models of PD and discuss their value.
Article
Baicalein may act on the benzodiazepine binding sites to exert an anxiolytic-like effect in mice. Since many benzodiazepine drugs have amnesic side-effect and baicalein can protect cultured cortical neurons from beta-amyloid peptide-(25-35)-induced toxicity, this study examined the amnesic effect of baicalein and its effects on beta-amyloid peptide-(25-35) (3 nmol/mouse, i.c.v.)-induced amnesia in mice. Using the step-through passive avoidance test, the results showed that baicalein (10-100 mg/kg, i.p.), unlike the benzodiazepine drug chlordiazepoxide (10 mg/kg, i.p.), had no significant amnesic effect. Baicalein (10-50 mg/kg, i.p.) also had no facilitating effect on the learning and memory. However, one dosage pretreatment, but not post-treatment, of baicalein (5 or 10 mg/kg, i.p.) attenuated beta-amyloid peptide-(25-35)-induced amnesia. Interestingly, post-treatment for 7 or 13 days of baicalein (10-15 mg/kg/day, i.p.), like melatonin (10 mg/kg/day, i.p.), also attenuated beta-amyloid peptide-(25-35)-induced amnesia. Therefore, this study demonstrated that baicalein has protective effect on beta-amyloid peptide-(25-35)-induced amnesia.
Article
The search for flavonoids with novel therapeutic effects has been intense. Wogonin, as a naturally existing monoflavonoid, has been shown to have therapeutic potential in vitro and in vivo. Methods for its extraction from herbs and its chemical synthesis have been developed. Pharmacokinetic studies have shown a rapid tissue distribution and prolonged plasma elimination phase of wogonin. It has been shown experimentally that wogonin exerts anti-oxidant activity, which may, in part, underlie its antiinflammatory, anti-cancer, antiviral and neuroprotective actions. The recent discovery of its anxiolytic activity suggests a new mechanism of action, involving interaction with the benzodiazepine (BZD) binding site of the GABA(A) receptor and modulation of this receptor activity. Although the safety record of wogonin is remarkable and voluminous literature about its pharmacological effects is available, it has not been used in Western medicine in the form of a pure chemical. In this article we review its therapeutic effects, its sources and pharmacokinetic profile to highlight its therapeutic potential.
Article
The present study evaluated effects of wogonin (5,7-dihydroxy-8-methoxyflavone) on excitotoxic and oxidative stress-induced neuronal damage in primary cultured rat cortical cells. Wogonin was shown to inhibit the excitotoxicity induced by glutamate or N-methyl-D-aspartic acid, whereas it showed no effects on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- or kainate-induced toxicity. In addition, wogonin inhibited the oxidative neuronal damage induced by H(2)O(2), xanthine/xanthine oxidase, and by a glutathione depleting agent D,L-buthionine [S,R]-sulfoximine. Furthermore, wogonin dramatically inhibited lipid peroxidation initiated by Fe(2+) and L-ascorbic acid in rat brain homogenates. It also exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate that wogonin exhibits neuroprotective actions in cultured cortical cells by inhibiting excitotoxicity and various types of oxidative stress-induced damage, and that its antioxidant actions with radical scavenging activity may contribute, at least in part, to the neuroprotective effects.
Article
It has been suggested that baicalein, a flavonoid obtained from the Scutellaria root, exerts a protective role on neurons against several neuronal insults. However, the protective mechanisms underlying this protective effect remain largely unknown. Our results indicate that baicalein protects SH-SY5Y cells, a dopaminergic neuronal cell line, from 6-hydroxydopamine (6-OHDA)-induced damage by the attenuation of reactive oxygen species (ROS). In order to determine the effects of baicalein on mitochondrial events, mitochondrial membrane potentials (deltapsim) and caspase cascades downstream of mitochondria were assessed. Baicalein inhibited the collapse of deltapsim, suggesting that baicalein reduces the mitochondrial dysfunction associated with 6-OHDA treatment. Baicalein also inhibited caspase-9 and caspase-3 activation, which can be triggered by mitochondrial malfunctions. Furthermore, baicalein induced a significant reduction in the level of phospho-JNK, which is known as an apoptotic mediator in 6-OHDA-induced neuronal cell death. Our results indicate that baicalein protects neurons from the deleterious effects of 6-OHDA via the attenuation of oxidative stress, mitochondrial dysfunction, caspase activity, and JNK activation.
Article
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.
Article
In the present study, baicalein (BE) but not its glycoside, baicalin (BI), induced heme oxygenase-1 (HO-1) gene expression at both the mRNA and protein levels, and the BE-induced HO-1 protein was blocked by adding cycloheximide (CHX) or actinomycin D (Act D). Activation of ERK, but not JNK or p38, proteins via induction of phosphorylation in accordance with increasing intracellular peroxide levels was detected in BE-treated RAW264.7 macrophages. The addition of the ERK inhibitor, PD98059, (but not the p38 inhibitor, SB203580, or the JNK inhibitor, SP600125) and the chemical antioxidant, N-acetyl cysteine (NAC), significantly reduced BE-induced HO-1 protein expression by respectively blocking ERK protein phosphorylation and intracellular peroxide production. Additionally, BE but not BI effectively protected RAW264.7 cells from hydrogen peroxide (H(2)O(2))-induced cytotoxicity, and the preventive effect was attenuated by the addition of the HO inhibitor, SnPP, and the ERK inhibitor, PD98059. H(2)O(2)-induced apoptotic events including hypodiploid cells, DNA fragmentation, activation of caspase 3 enzyme activity, and a loss in the mitochondrial membrane potential with the concomitant release of cytochrome c from mitochondria to the cytosol were suppressed by the addition of BE but not BI. Blocking HO-1 protein expression by the HO-1 antisense oligonucleotide attenuated the protective effect of BE against H(2)O(2)-induced apoptosis by suppressing HO-1 gene expression in macrophages. Overexpression of the HO-1 protein inhibited H(2)O(2)-induced apoptotic events such as DNA fragmentation and hypodiploid cells by reducing intracellular peroxide production induced by H(2)O(2), compared with those events in neo-control (neo-RAW264.7) cells. In addition, CO, but not bilirubin and biliverdin, addition inhibits H(2)O(2)-induced cytotoxicity in macrophages. It suggests that CO can be responsible for the protective effect associated with HO-1 overexpression. The notion of induction of HO-1 gene expression through a ROS-dependent manner suppressing H(2)O(2)-induced cell death is identified in the present study.
Article
In previous studies, we identified sedative effects of Scutellaria baicalensis extracts and found that these extracts or their constituents may also have anticonvulsive effects. Wogonin is a natural product isolated from S. baicalensis, which possesses central nervous system effects such as anxiolytic and neuroprotective activities. In this study, we investigated the effects of wogonin on convulsion related behaviors, such as myorelaxation, motor coordination, and anticonvulsant effects of wogonin on chemical induced seizure and electroshock seizure in mice or rats. The effect of wogonin on membrane potential was also observed. Wogonin was intraperitoneally injected into mice or rats 30 min prior to testing. Animals treated with wogonin did not change locomotor activities as well as endurance times on the rota-rod, which indicates that wogonin did not cause a sedative and myorelaxation effect. Wogonin significantly blocked convulsion induced by pentylenetetrazole and electroshock but not convulsion induced by strychnine. Wogonin also significantly reduced the electrogenic response score, but flumazenil treatment reversed this decrease to the level of the control group. The wogonin treatment increased Cl(-)influx into the intracellular area as dose increased. Flumazenil and bicuculline treatment, however, inhibited the Cl(-) influx induced by wogonin. These results indicate that the anticonvulsive effects produced by wogonin were mediated by the GABAergic neuron.
Article
Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. The aim of this study was to characterize the effects of oroxylin A on the memory impairments and pathological changes induced by Aβ25-35 peptide in mice. The ameliorating effect of oroxylin A on memory impairment was investigated using passive avoidance and Y-maze tasks and pathological changes were identified by immunostaining and western blotting. Aβ25-35 peptide (5 nmol) was administered by intracerebroventricular injection. In the acute treatment study, a single dose of oroxylin A (5 mg/kg, p.o.) treated 1 h before behavioral tests was found to significantly reverse Aβ25-35-induced cognitive impairments based on passive avoidance and Y-maze task findings (P < 0.05). Moreover, these acute effects of oroxylin A were blocked by diazepam (1 mg/kg, i.p.), a GABAA/benzodiazepine binding site agonist (P < 0.05). On the other hand, our subchronic studies revealed that oroxylin A (1 or 5 mg/kg/day, p.o.) for 7 days ameliorated the memory impairment induced by Aβ25-35 peptide. Moreover, Aβ25-35-induced increases in GFAP (an astroglia marker) and OX-42 (a microglia marker), and increases in iNOS positive cells in the hippocampus were found to be attenuated by subchronic oroxylin A (1 or 5 mg/kg/day, i.p., P < 0.05). In addition, reductions in the immunoreactivity and protein level of ChAT (a cholinergic neuronal cell marker) in the CA3 hippocampal area induced by Aβ25-35 peptide were also attenuated by oroxylin A. Furthermore, lipid peroxidation induced by Aβ25-35 was also reduced by oroxylin A. These results suggest that the amelioration of Aβ25-35 peptide-induced memory impairment by oroxylin A is mediated via the GABAergic neurotransmitter system after a single administration, or by reductions in Aβ25-35 peptide-induced astrocyte and microglia activations, iNOS expression, lipid peroxidation, and increased cholinergic neurotransmission after subchronic administration.
Šišák bajkalský (Scutellaria baicalensis Georgi) -potenciální zdroj nových léčiv
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