Article

Anticonvulsant effect of water extract of Scutellariae radix in mice

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Abstract

Since a previous study indicated that the water extract of Scutellariae radix (SR) had high affinity for the benzodiazepine (BDZ) binding site of GABA(A) receptors, the present study examined whether SR water extract has an anticonvulsant effect in vivo and an enhancing effect on gamma-amino-n-butyric acid (GABA)-stimulated uptake of 36Cl(-) in cortex preparation in vitro in mice. The results showed that SR water extract had little effect on pentylenetetrazol (PTZ, 85 mg/kg, s.c.)-induced clonic seizures but significantly inhibited maximal electroshock-induced tonic seizures with an ED(50) of 3.6 g/kg. The BDZ agonist chlordiazepoxide (10 mg/kg, i.p.) had anticonvulsant activity on both types of seizures. In 36Cl(-) uptake assay, SR water extract (1-500 microg/ml) had no significant effect on 25 microM GABA-stimulated 36Cl(-) uptake, whereas chlordiazepoxide (10 microM) increased the 36Cl(-) uptake to 125% of control. Therefore, the present results showed for the first time that SR water extract had anticonvulsant activity against maximal electroshock-induced tonic seizures, and suggested that this anticonvulsant effect might be not via the activation of the BDZ binding site of GABA(A) receptors, but probably via the prevention of seizure spread.

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... In contrast to diazepam (a classical benzodiazepine), baicalin showed a signifi cant affi nity to α 2 and α 3 containing GABA A receptor subtypes compared to α 1 and α 5 , which may suggest the selective anxiolytic profi le of baicalin. It has been demonstrated that water extract of baicalin produced signifi cant anticonvulsant eff ects in the maximal electroshock (MES)-induced tonic seizures, and little eff ect against pentylenetetrazole (PTZ)-induced clonic seizures in mice [7]. In contrast to the water extract of baicalin, the benzodiazepine agonist chlordiazepoxide had anticonvulsant activity in both models of epilepsy. ...
... As mentioned in the Introduction, the anticonvulsant eff ect of baicalin is diff erent in comparison to chlordiazepoxide (a benzodiazepine agonist). It has been reported that chlordiazepoxide has anticonvulsant activity in both the MES and PTZ seizure models [7]. In 36 Cl-uptake assay, "SR water extract' had no signifi cant eff ect on GABA stimulated 36 Cl-uptake, but chlordiazepoxide increased by 2.25-fold the 36 Cl-uptake, compared to the control. ...
Article
Water extract of Scutellariae radix (SR) was previously reported to display a signifi cant anticonvulsant eff ect on maximal electroshock (MES)-induced seizures, and little anticonvulsant eff ect in pentylenetetrazole (PTZ)-induces clonic seizure model in mice. The aim of this study was to examine whether water extract of SR has any impact on anticonvulsant properties of valproate (VPA) and tiagabine (TGB) in PTZ-induced clonic seizure model in mice and VPA and topiramat (TPM) in the mouse MES test. Results indicated that water extract of SR did not signifi cantly aff ect the anticonvulsant action of VPA and TPM against MES-induced tonic seizures. The experimentally derived median eff ective doses (ED 50 values) for VPA administered alone and in combination with water extract of SR were 219 and 203 mg/kg and for TPM administered alone, and in combinations with water extract of SR were 41.6 and 40.8 mg/kg, respectively. Likewise, no eff ect of water extract of SR was observed on VPA and TGB in PTZ-induced clonic seizure models. The ED 50 values for TGB administered alone and in combination with water extract of SR were 0.84 and 0.71 mg/kg, while those for VPA were 158 and 129 mg/kg, respectively. In conclusion, water extract of SR had no eff ect on the anticonvulsant activity of TPM and VPA in the mouse MES seizure model and on the antiseizure activity of VPA and TGB in PTZ-induced clonic seizures in mice.
... [11][12][13][14] Recent evidence shows that Scutellariae radix has beneficial properties, including antioxidative, antitumor, and anticonvulsant effects. [15][16][17] In addition, it has been demonstrated that the flavonoids isolated from Scutellariae radix inhibit adhesion molecules and plasminogen activator inhibitor-1 (PAI-1) production induced by thrombin, the thrombin receptor agonist peptide, and cytokines in cultured human umbilical endothelial cells. [18][19][20] These findings suggest that Scutellariae radix has a beneficial role in the regulation of endothelial cells. ...
... 6,7,10) Recent evidence has shown that Scutellariae radix has beneficial properties, including antioxidative effects. [15][16][17] However, to the best of our knowledge, the effect of Scutellariae radix extract on apoptosis in high glucose-induced endothelial cells has not been reported. In the present study, Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. ...
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Endothelial cell apoptosis has been postulated as the initial trigger of the progression of microvascular disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [3H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial cell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5 mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.
... On the other hand, it did not show any significant protection against PTZ-induced seizures. The extract had no significant effect on GABA stimulated Cl-uptake leaving mechanism to be revealed (Wang et al., 2000). Valerian pavonii: Fractioning of an extract of Valeriana pavonii, a native species used in Colombian folk medicine as tranquilizer, led to the isolation and identification of isovaleramide, one of the active constituents responsible for its CNS activity as anticonvulsant. ...
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Epilepsy has now become the most serious brain disorder. A number of synthetic antiepileptic drugs are available in practice, however their effectiveness does not grip true with the entire population suffering from epilepsy. Traditional systems of medicine are popular in developing countries and most of the population relies on traditional medicines for their primary health care need. Medicinal plants to be an important source of traditional medicines. Various plants are used for the treatment of epilepsy in traditional system of medicines and various plants are yet to be scientifically investigated. Phyto-constituents have been the basis of treatment of human diseases including epilepsy. Herbal products are extensively used for the treatment of many diseases worldwide and where allopathic fails or has severe side effects. Psycho neural drugs are also have very serious side effects like physical dependence, tolerance, deterioration of cognitive function and effect on respiratory, digestive and immune system. So the treatments through herbal medicines are widely used across the world due to their wide applicability and therapeutic efficacy with least side effects, which in turn has accelerated the research regarding natural therapy. In this review we have summarized some herbal anti-epileptics.
... Scutellaria baicalensis Georgi is one of the flowering plant species in the family Lamiaceae. This family contains numerous species with potential pharmaceutical value due to their anti-inflammatory (Górniak et al., 2019), anti-cancer (Zhao et al., 2016), hepatoprotective (Chen et al., 2014), antibacterial (Wang, 2018), antiviral (Moghaddam et al., 2014), antioxidant (Fox et al., 2012), anticonvulsant (Wang et al., 2000) and neuroprotective (Sowndhararajan et al., 2018) activities. S. baicalensis is indigenous to several East Asian countries and the Russian Federation and has been cultivated in many European countries. ...
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The development of drug-resistant bacteria as a result of the inappropriate use of antibiotics, has led to a study on other sources of drugs for the treatment of bacterial infections. Natural compounds derived from medicinal plants have long been considered a rich source of therapeutic agents. Scutellaria baicalensis has attracted attention as its root extracts are used for a variety of therapeutic purposes. Published papers involving Scutellaria baicalensis in Scopus, PubMed, and Google Scholar databases were collected and annotated for their antimicrobial and antibiofilm application. Baicalin is the most important compound derived from the roots of Scutellaria baicalensis, and it has antimicrobial, antioxidant, anticancer, and anti-inflammatory properties that can be used for the treatment of several diseases. The main active compounds were identified as natural antimicrobial and anti-biofilm agents with clear-cut mechanisms or identified molecular reports. The present review summarizes the mechanisms of biofilm formation and quorum sensing, as well as recent advances in the discovery and identification of plant-derived natural products which are antimicrobial and anti-biofilm agents. In addition, clinical trials involving plant-derived anti-biofilm therapeutics were also discussed. These newly discovered naturally occurring anti-biofilm agents are promising candidates that could provide novel strategies for combating pathogenic bacteria and treating biofilm-associated infections.
... This suggests that the anxiolytic effect is mediated by the GABAergic neurotransmitter system [74]. The water extract was also found to exert anticonvulsant effects against maximal electroshock-induced tonic seizure (MES) in mice [75]. The extract also showed antistress effects in the EPM test in mice when administrated as in combination with equal amounts of the water extract of the fruit of Schizandra chinensis [76]. ...
Chapter
Lamiaceae, also known as the mint family, is a family of plants comprising about 245 genera and 7886 species distributed all over the world. Plants of this family are widely used in folk medicine, cosmetics, spices, and as a flavoring agents in food. With the exception of the coldest polar regions, Lamiaceae species are distributed almost throughout the world, particularly in tropical and temperate areas, including the Mediterranean region and in tropical upland savannas. The Lamiaceae family is known for a wealth of species possessing medicinal properties with a strong history of use since early times and is well known for high essential oil content, for their richness with polyphenolic compounds and terpenoids. All of these classes of compounds are of great interest due to their biological activities. A number of studies conducted on different species of Lamiaceae family and their effects on memory, anxiety, depression, and sleep disorders have been reported. For example, Rosmarinus officinalis has long been known as the herb of remembrance and was proved to boost memory, reduce anxiety and depression, and improve sleep quality. Different salvia species are used to enhance memory, as a sedative and for the treatment of headaches. Evidence for the use of other Lamiaceae species on the central nervous system (CNS), such as Dracocephalum moldavica. Clerodendrum formicarum, Nepeta clarkei has also been reported. Thymol and menthol are examples of the essential oils identified in species from Lamiaceae. It has been reported that thymol and menthol both act as positive modulators on GABAA receptors (the primary inhibitory neurotransmitter in the mammalian CNS acting through a number of pharmacologically and structurally different receptor subtypes). Thymol was reported to have a GABAergic activity and acts as a positive allosteric modulator with a mechanism of action similar to other depressants, such as diazepam. This review aims to survey the current literature on the effect of Lamiaceae family and its use in the treatment of CNS disorders to provide sufficient baseline information that would improve the knowledge and the application of this family as safe therapeutic alternatives.
... In addition to the effects described above, preparations of S. baicalensis can also work as antioxidants, ROS scavengers [53,54] and anticonvulsants [55]. Recently, the neuroprotective effects of S. baicalensis and its component flavones, have been studied using both in vitro and in vivo models of neurodegenerative diseases. ...
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Scutellaria baicalensis Georgi, or Chinese skullcap, has been widely used as a medicinal plant in China for thousands of years, where the preparation from its roots is called Huang-Qin. It has been applied in the treatment of diarrhea, dysentery, hypertension, hemorrhaging, insomnia, inflammation and respiratory infections. Flavones such as baicalin, wogonoside and their aglycones baicalein wogonin are the major bioactive compounds extracted from the root of S. baicalensis. These flavones have been reported to have various pharmacological functions, including anti-cancer, hepatoprotection, antibacterial and antiviral, antioxidant, anticonvulsant and neuroprotective effects. In this review, we focus on clinical applications and the pharmacological properties of the medicinal plant and the flavones extracted from it. We also describe biotechnological and metabolic methods that have been used to elucidate the biosynthetic pathways of the bioactive compounds in Scutellaria. © 2016 Science China Press and Springer-Verlag Berlin Heidelberg
... On the other hand, it did not show any significant protection against PTZ-induced seizures. The extract had no significant effect on GABA stimulated Cl-uptake leaving mechanism to be revealed (Wang et al., 2000). ...
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Epilepsy has now become the most serious brain disorder. A number of synthetic antiepileptic drugs are available in practice, however their effectiveness does not grip true with the entire population suffering from epilepsy. Traditional systems of medicine are popular in developing countries and most of the population relies on traditional medicines for their primary health care need. Medicinal plants to be an important source of traditional medicines. Various plants are used for the treatment of epilepsy in traditional system of medicines and various plants are yet to be scientifically investigated. Phytoconstituents have been the basis of treatment of human diseases including epilepsy. Herbal products are extensively used for the treatment of many diseases worldwide and where allopathic fails or has severe side effects. Psycho neural drugs are also have very serious side effects like physical dependence, tolerance, deterioration of cognitive function and effect on respiratory, digestive and immune system. So the treatments through herbal medicines are widely used across the world due to their wide applicability and therapeutic efficacy with least side effects, which in turn has accelerated the research regarding natural therapy. In this review we have summarized some herbal antiepileptics.
... The number of death and onset of myoclonic jerks, Straub's tail as well as hind limb extension (tonic convulsion) was recorded. Mice that did not convulse within 30 min after PTZ administration were considered protected (Wang et al. 2000). ...
Article
Castanopsis indica (Roxb. ex Lindl.) A.DC. (Fagaceae) is commonly known as ‘Dhalne katus’ and ‘Indian chestnut tree’, found throughout the Himalayan region. The purpose of this investigation was to evaluate the effect of methanol extract of C. indica leaves (MECI) on Central Nervous System using a number of neuropharmacological experimental models in Swiss albino mice. The treatment with MECI at doses of 25 and 50 mg/kg, i.p. caused: signs of central nervous system depressant action confirmed by significant inhibitory effect on acetic acid induced writhing as compared with acetic acid control group indicate an analgesic effect. Anticonvulsant activity was seen as there was delays in the onset of pentylenetetrazole (PTZ) induce convulsion as well as decrease in its mortality rate. The MECI roduced a dose-dependent reduction of the onset and potentiated duration of pentobarbitone-induced hypnosis, reduction of locomotor and muscle relaxant activities determining by using actophotometer and rotarod tests. MECI in a dose-dependent manner significantly reduced the immobility time of mice in both forced swim test (FST) and tail suspension test (TST). These results suggest that the MECI has an analgesic effect, behave as a potential anticonvulsant and central nervous system depressant action.
... Besides anti-inflammatory and anticancer effects, a few other pharmacological activities of RS have also been reported. Its water extract showed an anticonvulsant effect by the prevention of seizure spread in mice [21]. The ethanol extract of RS could inhibit high glucose-induced endothelial cell apoptosis, indicating its beneficial effect in preventing diabetes-associated microvascular complications [22]. ...
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Radix Scutellariae is the dried root of the medicinal plant Scutellariae baicalensis Georgi. It exhibits a variety of therapeutic effects and has a long history of application in traditional formulations as well as in modern herbal medications. It has been confirmed that flavonoids are the most abundant constituents and induce these therapeutic effects. Six flavones are proven to be the major bioactive flavones in Radix Scutellariae existing in the forms of aglycones (baicalein, wogonin, oroxylin A) and glycosides (baicalin, wogonoside, oroxylin A-7-glucuronide). All six flavones are pharmacologically active and show great potential in the treatment of inflammation, cancers and virus-related diseases. The current review covers the preparation of the herb Radix Scutellariae, quantification of its major bioactive ingredients, and pharmacological effects of the proposed six bioactive flavones. In addition, this review summarizes the pharmacokinetic profiles of the bioactive flavones reported so far that could be used for further improvement of their pharmacokinetic study. Moreover, due to abundant co-occurring bioactive components in Radix Scutellariae, our review further documents the pharmacokinetic interactions among them.
... Latency for the development of clonic seizure and mortality protection were determined of each group. Mice that did not convulse 30 min after injection of the PTZ were considered protected (Krall et al., 1978; Wang et al., 2000). ...
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Annona senegalensis Pers. is claimed in traditional medical practice, to be useful in the treatment of epilepsy in some parts of Burkina Faso. In the present work, the anticonvulsant property of methanolic extract, n-hexane fraction, ethyl acetate fraction and aqueous fraction were investigated one seizures induced by pentylenetetra-zole (70 mg/kg) or pilocarpine (240 mg/kg). Extracts were administered intraperit-oneally and per os, at the pre-treatment time of 30 minutes at 200 and 400 mg/kg and mice and rats. Extracts and fractions had no significant increased the latency to the first convulsion induced by pentylenelenetetrazole or pilocarpine. The treatment with methanolic extract and aqueous fraction (400 mg/kg) significantly (p< 0.05) protected against pentylenetetrazole or pilocarpine induced seizures. The result obtained in this study suggests that the stem-barks of this plant may possess anti-conv-ulsant property in mice and rats.
... Many medicinal plants contain large amounts of antioxidant and antimicrobial constituents such as phenols and flavonoids. Phenolic compounds exhibit a wide range of physiological properties such as antiinflammatory 7 , anti-mutagenic 8 , antimicrobial 9 , antioxidant 10 , anti-thrombotic, cardioprotective, and vasodilatory effects 11 . Polyphenols have been shown to exert important antioxidant effects against free radicals and lipid peroxidation via several mechanisms 12 . ...
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... Scutellariae Radix has been suggested to have anticonvulsant activity, cytoprotective properties and anti-inflammatory effects [11][12][13] . In traditional Chinese medicine, SHXXT is thought to reduce heat and the effects of toxins and to promote defecation; thus, it is used to treat constipation with high fever, restlessness, thirst, and insomnia. ...
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To investigate the effects of San-Huang-Xie-Xin-Tang (SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal (GI) motility in mice. The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates (ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT (0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT (0.1-1 g/kg). These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.
... These models are of predictive relevance regarding the clinical spectrum of activity of experimental compounds [13] . Maximal electroshock seizures and pentylenetetrazole tests are assumed to identify anticonvulsant drugs effective against generalized tonic clonic partial seizures and generalized clonic seizures respectively [13,16] . The effect of AS in these tests could therefore suggest anticonvulsant efficacy against the above mentioned types in man. ...
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Pakistan has large variety of medicinal plants distributed throughout the country. Due to the unavailability and high cost of allopathic medicines, herbal therapists, especially in rural areas, prescribe phytomedicine for Epilepsy. The native people consider such treatments most effective for seizures. The data of the effective antiepileptic medicinal plants of Pakistan were collected from the published research articles by exploring article search engines like PubMed, Medline, Web of Science, Google Scholar, and ScienceDirect. Additional information such as mode of preparation and application of medicinal herbs were acquired from folk medicine users, traditional healers, and local people enriched in knowledge of herbal medicines. Total 97 families were uncovered to be used in epileptic and seizure disorders, of which, the foremost use belonged to Lamiacea 19 (18.56%), Asteraceae and Fabaceae 16 (16.5%) each, Fabaceae 11 (11.34%), Rubiaceae, Rutaceae, and Apocynaceae 6 (2.4%) each, Caesalpiniaceae, Solanaceae, Byrtaceae and Anacardiaceae 5 (2%) each, and Liliaceae, Mimosaceae, Ranunculaceae and Combretaceae 4 (1.6%) each. According to the plants habit, of 241 plants, herbs were 102 (42.15%), trees were 72 (29.75%), shrubs were 54 (22.31%), climbers were 12 (4.96%), and bulbs were 2 (0.83%). According to the part used, 105 (43.39%) plants were found to have antiepileptic potentials in leaves, 51 (31.07%) plants in roots, 20 (8.36%) plants in stem, 8 (3.31%) plants in rhizome, 4 (1.65%) plants in bulb, 32 (13.22%) plants in bark, 6 (2.48%) plants in gum, 19 (7.85%) plants in flowers, 18 (7.44%) plants in fruits, 24 (9.92%) plants in seeds, and 29 (11.98%) plants as a whole. This review provides foundation for researchers to understand the pivotal role of certain medicinal plants towards the treatment of epilepsy and seizures.
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Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold. The present study was performed to investigate the anti-obesity and anti-dyslipidemia effect of Scutellaria baicalensis extracts (SBE) in type 2 diabetic db/db mice. Male db/db mice were divided into three groups (n = 5) and orally administrated vehicle (control), SBE 10, and 100 mg/kg body weight/day for 4 weeks everyday. Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice. In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels. In the livers of db/db mice, SBE promoted 5' AMP-activated protein kinase activity and restored metabolic process and insulin signaling pathways. Our data demonstrate that SBE exerts potent anti-obesity and anti-hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia. Copyright
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Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.
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Context: Scutellaria baicalensis Georgi (Lamiaceae) has been used as a traditional herbal preparation for the treatment of neuropsychiatric disorders in Asian countries for centuries. Objective: To evaluate the effects of S. baicalensis on morphine-induced drug dependence in rats. Materials and methods: In order to evaluate the effect of S. baicalensis and baicalin on morphine-induced dependence-like behavior, a water extract of S. baicalensis [500 mg/kg, intraperitoneally (i.p.)] or baicalin (50 mg/kg, i.p., a flavonoid found in S. baicalensis) was administered prior to morphine injection [5 and 2.5 mg/kg, respectively, subcutaneously (s.c.)] to rats for 8 and 4 d, respectively. Morphine-induced conditioned place preference was assessed by measuring the time spent in a drug-paired chamber. The effect of S. baicalensis on dopamine receptor supersensitivity (locomotor activity) and dopamine agonist-induced climbing behavior due to a single apomorphine treatment (2 mg/kg, s.c.) was also measured. Results: At 50 mg/kg, a water extract of S. baicalensis decreased morphine (5 mg/kg)-induced conditioned place preference by 86% in rats. Apomorphine (2 mg/kg)-induced locomotor activity (dopamine receptor supersensitivity) in rats and climbing behavior in mice were attenuated after pretreatment with 500 mg/kg of S. baicalensis water extract by 41% and 56%, respectively. In addition, baicalin-reduced morphine-induced conditioned places preference by 86% in rats at 50 mg/kg. Discussion and conclusion: These results suggest that S. baicalensis can ameliorate drug addiction-related behavior through functional regulation of dopamine receptors.
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Genus Scutellaria belongs to the family Lamiaceae and is known to possess different pharmacological properties. S. litwinowii is a species from this genus that is endemic to Iran. In this work, antioxidant activities of methanol, dichloromethane, and ethyl acetate extracts of S. litwinowii were evaluated using thiobarbituric acid reactive species (TBARS) and 2, 20-diphenyl-1- picrylhydrazyl (DPPH) radical scavenging assays. In addition, antimicrobial activities of the mentioned extracts were screened against standard strains of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The minimum inhibitory concentrations and minimum bactericidal concentrations were determined by broth microdilution method and tetrazolium chloride salt. The highest antioxidant index (AI) was observed from the methanolic extract in both TBARS (41.6% at 32 mg/ml) and DPPH (92.29% at 16 mg/ml) assays. The AI of the methanolic extract in DPPH assay was significantly higher than those of other extracts (p < 0.001). However, the AI of all extracts were significantly lower than those of the reference compounds, namely vitamin E and butylated hydroxytoluene (p < 0.001). The results of this investigation indicated that extracts obtained from the aerial parts of S. litwinowii possessed antioxidant and antimicrobial properties. Further research is required to identify the active phytochemicals responsible for these biological activities.
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Anticonvulsant effect of the leaf extracts of Emilia sonchifolia is reported for the first time. The ethanol, chloroform and aqueous extracts, especially the aqueous extract, showed marked anticonvulsant effect (ED 50 of 4 mg/kg and 8 mg/kg in chicks and mice, respectively). This research finding gives scientific justification to the traditional healers in Nigeria for the use of aqueous leaf extract of the plant for treating infantile convulsion. The extracts of E. sonchifolia showed concentration-dependant protective effect against maximal electroshock (MES) and strychnine-induced seizures (SIS). The potent anticonvulsant effect exhibited by the extracts of E. sonchifolia (especially the aqueous extract) is an indication of its promising anticonvulsant application as a possible new clinical drug. Further studies on the principal anticonvulsant compounds of the aqueous extract are in progress.
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Radix Scutellariae is the dried root of Labiatae plant, Scutellariae baicalensis Georgi. It has broad therapeutic effects such as purging fire, moistening aridity, stoppage of bleeding and preventing miscarriage, and has been extensively applied in traditional medicine as well as modern pharmaceutics. Flavonoids are the major components in Radix Scutellariae, exhibiting low oral bioavailability due to the extensive first pass metabolism during intestinal absorption. This paper reviews the research progress of the pharmacokinetics studies on the Radix Scutellariae extract and co-existing components and proposes the aspects which call for attention in its future research.
Article
Objective: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. Methods: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1β and TNF-α were then determined. Results: In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1β and TNF-α expression. In hippocampal neurons exposed to PTZ, p-mTOR and p-70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa. Conclusion: SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway.
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Epilepsy is a neurological disorder affecting a large scale of the population, which accounts for about 1% of the world's burden of diseases. A large number of agents called antiepileptic drugs are available to treat various types of seizures with the objective to reduce seizure frequency and severity within a framework of an acceptable level of side effects. There are number of drugs available for treatment of epilepsy in modern therapy. But the major disadvantage being faced is their chronic side effects. Treatment of epilepsy with herbal drugs as adjuvant seems to be more beneficial and is gaining more popularity due to their fewer side effects. Herbal drugs are acting at target site having same mechanism of action as that of synthetic drugs. There is still a need for new antiepileptic drugs (AEDs), may be derived from natural sources, as the clinical efficacy tolerability, toxicity properties of existing synthetic AEDs may not be satisfactory. This review focuses on the use of natural products for control of epilepsy.
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Quassinoids are secondary metabolites that characteristically belong to the Simaroubaceae family. These compounds have called attention because they are responsible for a wide range of biological activities, many of which are extremely promising. The great majority of isolated quassinoids have basic skeleton C20. Therefore, this review aims to discuss the biological activities and compile the ¹³C NMR spectra data of quassinoids isolated after 1985, skeletal-type C20. The conclusion is that many C20 quassinoids appear to be promising antitumor and antimalarial agents. Besides that, different studies report several other biological activities of these compounds, as insecticidal, larvicidal, antileishmanial, antiviral, antiinflammatory activities, among others. From data compilation, it is concluded that 154 quassinoids were isolated and identified between 1985 and the present time and that there are eight types of skeletons that are more frequent for the ring A of quassinoids, and also eight different ring C skeletons. As far as the rings B and D are concerned, variation in C-15 was observed, which usually has no substituents oxidated by a free hydroxyl group, as well as esterification of the hydroxyl group.
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This study investigates pharmacological activities of crude hydroalcoholic extract and fractions of Qualea grandiflora Mart. leaves employing different experimental models using mice. The treatment with crude hydroalcoholic extract (EH) in a dose of 500 mg/kg, i.p. caused: signs of central nervous system depressant action in the Hippocratic screening test, confirmed by the potentiation of sodium pentobarbital sleeping time. Increasing in the latency time of hot plate assay that indicate an analgesic effect; significantly delaying of the onset of clonic PTZ convulsions, increasing in the time for death, suppressing of the tonic PTZ convulsion, and decreasing of severity and number of convulsions. The median lethal dose of EH was 1.321 mg/kg. The convulsions induced by PTZ, ethyl ether fraction (300 mg/kg, i.p.) was more active in increasing the latency time for first convulsion, moreover, the hexane fraction, at the same dose, was more active in increasing the time for death and/or avoiding the death. Both did not cause disturbance in motor coordination at the dose of 500 mg/kg, assessed by rotarod test. These results suggest that the crude extract of leaves of Qualea grandiflora Mart. has a central nervous system depressant action, an analgesic effect and behave as a potential anticonvulsant.
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Gouteng, Ramulus Uncariae cum Uncis, is the dry branches bearing hooks of Uncaria rhynchophylla (Miq.) Jacks., U. macrophylla Wall., U. hirsuta Havil., U. sinensis (Oliv.) Havil., or U. sessilifructus Roxb. (Rubiaceae), which are collected in the fall and winter. It is officially listed in the Chinese Pharmacopoeia and is used as an antipyretic and anticonvulsant for the treatment of headache, vertigo, and epilepsy.
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Antiepileptic drugs (AEDs) vary in their efficacy against generalized tonic-clonic, myoclonic, and absence seizures, suggesting different mechanisms of action. Phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) reduced the ability of mouse central neurons to sustain high-frequency repetitive firing of action potentials (SRF) at therapeutic free serum concentrations. Phenobar-bital (PB) and the benzodiazepines (BZDs), diazepam (DZP), clonazepam (CZP), and lorazepam (LZP), also reduced SRF, but only at supratherapeutic free serum concentrations achieved in treatment of generalized tonic-clonic status epilepticus. These AEDs interact with sodium channels to slow the rate of recovery of the channels from inactivation. The BZDs and PB enhanced γ-aminobutyric acid (GABA) responses evoked on mouse central neurons by binding to two different sites on the GABAA receptor channel. BZDs increased the frequency of GABA receptor channel openings. In contrast, barbiturates increased the open duration of these channels. VPA enhanced brain GABA concentration and may enhance release of GABA from nerve terminals. Ethosuximide (ESM) reduced a small transient calcium current which has been shown to be involved in slow rhythmic firing of certain neurons. Reduction of SRF, enhancement of GABA-ergic inhibition, and reduction of calcium current may be, in part, the bases for A ED action against generalized tonic-clonic, myoclonic, and absence seizures, respectively.
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By means of the maximal electroshock seizure (MES) test, the subcutaneous pentylenetetrazol (PTZ) seizure threshold test, and the Rotorod minimal neurotoxicity test, the Anticonvulsant Screening Project has evaluated the activity of 1,495 experimental compounds accessioned in the first 2 years. A three-screen protocol for appraising these compounds has proved reliable, fast, and inexpensive. Preliminary data show that 430 of these compounds have good anticonvulsant activity. Completed evaluations of 352 identified 16 that have anticonvulsant activity at doses less than 75 mg/kg and protective indices greater than 5.0.
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A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
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gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, is believed to act by increasing membrane conductance of chloride ions. In this study it was found that GABA agonists increased the uptake of chloride-36 by cell-free membrane preparations from mouse brain. This influx was rapid (less than 5 seconds), and 13 micromolar GABA produced a half-maximal effect. The GABA antagonists (bicuculline and picrotoxin) blocked the effect of GABA, whereas pentobarbital enhanced the action. This may be the first demonstration of functional coupling among GABA and barbiturate receptors and chloride channels in isolated membranes. The technique should facilitate biochemical and pharmacological studies of GABA receptor-effector coupling.
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Effects of ethanol and pentobarbital on the GABA receptorchloride channel complex were evaluated in mice selected for differential sensitivity to the hypnotic effects of ethanol (long sleep and short sleep lines). 36Cl- influx, [35S]tbutylbicyclophosphorothionate (TBPS) and [3H]muscimol binding were measured in a membrane vesicle suspension (microsacs) from cerebellum or forebrain. Muscimol was found to be a more potent stimulator of 36Cl- flux in the LS cerebellum, as compared to the SS cerebellum, but a similar maximal level of uptake was achieved in the two lines. Muscimol displaced [35S]TBPS (a ligand for the convulsant site) from cerebellar microsacs, and LS mice were also more sensitive than SS mice to this action of muscimol. However, the number or affinity of high affinity [3H]muscimol binding sites did not differ between the lines. Physiologically relevant concentrations of ethanol (15-50 mM) potentiated muscimol stimulation of 36Cl- uptake in LS cerebellum but had no effect in SS cerebellum. Ethanol failed to alter stimulated chloride flux hippocampal microsacs from either line. Both the LS and SS lines responded similarly to pentobarbital potentiation of muscimol stimulated chloride uptake regardless of brain region. The demonstrated difference between the LS and SS mice in muscimol stimulated chloride uptake as well as in muscimol displacement of [35S]TBPS binding offers a biochemical explanation for the line differences in behavioral responses to GABAergic agents. Moreover, the findings suggest that genetic differences in ethanol hypnosis are related to differences in the sensitivity of GABA-operated chloride channels to ethanol.
In the present study, we established receptor binding assays to evaluate the water extracts of ten central nervous system (CNS)-active Chinese herbal drugs. These ten herbal drugs are Chaihu (Radix Bupleuri), Chuanxiong (Rhizoma Chuanxiong), Danggui (Radix Angelicae sinensis), Danshen (Radix Salviae miltiorrhizae), Duhuo (Radix Angelicae pubescentis), Hangqin (Radix Scutellariae), Qinjiao (Radix Gentianae macrophyllae), Shengma (Rhizoma Cimicifugae), Suanzaoren (Semen Zizphi spinose), and Yangjihua (Flos Daturae). The results indicated that these water extracts contained the principles acting on the dopamine (D1 & D2), muscarinice acetylcholine (M1), or 5-HT (5-HT1A & 5-HT2) receptors, or the benzodiazepine and the gamma-amino-n-butyric acid (GABA) binding sites of GABAA receptors as determined by receptor binding assays. The receptors or binding sites which predominantly acted by each water extract are listed as follows: Chaihu: D2, 5-HT1A, GABA; Chuanxiong: GABA, 5-HT1A; Danggui: GABA, 5-HT1A; Danshen: BDZ; Duhuo: GABA, 5-HT1A, D2, D1; Hangqin: BDZ, D1, 5-HT1A; Qinjiao: GABA, BDZ, 5-HT1A, D2; Shengma: 5-HT1A; Suanzaoren: 5-HT1A, 5-HT2, GABA; Yangjihua: M1, 5-HT1A, 5-HT2. These results provided evidence to explain the CNS effects of these herbal drugs at the receptor level. Furthermore, these results provided information to direct the isolation and purification of receptor-interactive compounds from these herbal drugs.
Article
A benzodiazepine binding assay directed separation led to the identification of 3 flavones baicalein (1), oroxylin A (2), and skullcapflavone II (3) from the water extract of Scutellaria baicalensis root. Compounds 1, 2, and 3 interacted with the benzodiazepine binding site of GABAA receptors with a Ki value of 13.1, 14.6 and 0.36 micromol/L, respectively.