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ED50 values and 95% confidence limits of the sedative effect induced by valerian ethanol extract and different central nervous system depressant drugs in mice
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It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to t...
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... 2 shows the dose-response curves for each of the tested drugs. The values of the effective dose 50 (ED50) and 95% confidence limits (CL95) for valerian extract and the other drugs appears in Table 2. The order of sedative effect was (ED50): haloper- idol (0.41 mg kg À1 ) > buspirone (1.04 mg kg À1 ) > diazepam (1.21 mg kg À1 ) > pentobarbital (11.86 mg kg À1 ) > diphenhy- dramine (17.06 mg kg À1 ) >valerian (181.62 mg kg À1 )>etha- nol (1938.83 ...
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Citations
... The number of rearings was counted for 5 min. A rearing was considered when the forelimb contacted the wall [14]. ...
... The CET involves placing a rodent in an unknown environment that induces anxiogenic behavior reflected by rearing. A reduction in the number of rearings reflects anxiolytic-like behavior, whereas an increase in the number of rearings indicates anxiogenic activity [14]. Compound 4 showed anxiolytic-like activity in two in vivo models. ...
Depressive and anxiety disorders constitute some of the most prevalent mental disorders around the world. For years, the development of new lead compounds for drug discovery in this field has been an area of great attention. Recently, a series of tetrahydrocarbazole derivatives have demonstrated important anxiolytic-like activity, associated with their structures and stereochemistry. Here, we present a study of the antidepressant effect and anxiolytic-like activity of a fused thiopyrano-piperidone-tetrahydrocarboline (compound 4). The antidepressant and anxiolytic-like effects of 4 (1–50 mg/kg p.o.) were assessed with the tail suspension test and the hole-board test, respectively. This study determined the possible mechanisms involved in the anxiolytic-like actions of 4 using inhibitors or neurotransmission and evaluated its interaction with 5HT2A receptors using a molecular docking study. As an analog to the tetrahydrocarbazole core, the tetrahydrocarboline derivative showed anxiolytic-like activity (ED50 = 13 mg/kg p.o.) in the hole-board test, with a comparable effect to the reference drug, 1.5 mg/kg clonazepam, with the possible participation of the serotonergic system.
... Garlic and ginger, which inhibit platelets and increase the risk of bleeding in warfarintreated patients, increase bleeding in patients taking herbal drugs with a limited therapeutic window [81]. Other instances of how herbal medicines can combine 1. Ephedrine increases and prolongs the sympathomimetic impact by interacting with beta-blockers and MAO inhibitors (hypertensive crisis) [82] 2. Valerian and sedatives combination, causing more CNS depression [83] 3. Ginseng increases GABA metabolism and dopamine levels and reacts with MAO inhibitors [84] 4. Because of how KAVA (drug) and paracetamol combine, azole antifungals are more toxic to the liver [85] 5 ...
... The number of squares explored in a period of 2 min was considered ambulatory activity [23]. In addition, the number of times the mice stood on their two hind limbs, placing their two forelimbs on the cylinder wall (rearings), was counted for 5 min [24]. A significant reduction in the rearing events was considered an anxiolytic-like response, and a significant reduction in ambulatory activity a sedative effect [25]. ...
Raphanus sativus L. (Brassicaceae), commonly known as radish, is consumed worldwide as a vegetable. However, its benefits on mental health are unknown. The aim of this study was to evaluate its anxiolytic-like effects and safety using different experimental models. An aqueous extract of R. sativus sprouts (AERSS) was pharmacologically evaluated by intraperitoneal route (i.p.) at 10, 30, and 100 mg/kg and orally (p.o.) at 500 mg/kg on behavior by using open-field and plus-maze tests. In addition, its acute toxicity (LD 50) was determined by the Lorke's method. Diazepam (1 mg/kg, i.p.) and buspirone (4 mg/kg, i.p.) were the reference drugs. A significant and anxiolytic-like dosage of AERSS (30 mg/kg, i.p.) resembling the effects of reference drugs was chosen to explore the involvement of GABA A /BDZs site (flumazenil, 5 mg/kg, i.p.) and serotonin 5-HT 1A receptors (WAY100635, 1 mg/kg, i.p.) as a possible mechanism of action. A 500 mg/kg, p.o. dosage of AERSS produced an anxiolytic-like response equivalent to 100 mg/kg, i.p. No acute toxicity was observed since a LD 50 > 2000 mg/ kg, i.p. The phytochemical analysis allowed the identification and quantification of major presence of sulfor-aphene (2500 µM), sulforaphane (15 µM), iberin (0.75 µM), and indol-3-carbinol (0.75 µM), as major constituents. Both the GABA A /BDZs site and serotonin 5-HT 1A receptors were involved in the anxiolytic-like activity of AERSS, depending on the pharmacological parameter or the experimental assay tested. Our results demonstrate that the anxiolytic activity of R. sativus sprouts involves GABA A /BDZs site and serotonin 5-HT 1A receptors supporting its health benefits in the treatment of anxiety beyond the satisfaction of basic nutritional needs.
... [55] 2. Valerian interacts with sedatives -increased CNS depression. [56] 3. Ginseng interacts with MAO inhibitors increased GABA metabolism and increased dopamine levels. [57] 4. KAVA interacts with Acetaminophen, azole antifungals increase hepatic toxicity. ...
Background: Since ancient times natural herbs were extensively used for the treatment
and prevention of various ailments and in past few decades, due to an extensive research
in traditional system of medicine various herbal medicines have been developed for the
prevention and treatment of diseases, which are environmentally, organically safe and
inexpensive. Indian sub-continent has a good capability to tackle the task of meeting the
worldwide demand for such products due to its rich wealth in case of herbal medicine.
Historically, Indian people conventionally played a vital role in the development and management
of these biological sources and also preserve their pertinent data that were accumulated via
trial and error over centuries. Objectives: Due to tremendous global resurgence in traditional
and alternative healthcare systems, the market for herbal medicines has grown at an
impressive rate and therefore has great economic importance. However, the primary barriers
to the expansion of herbal medicine include biodiversity loss, over-exploitation and improper
use of medicinal plants, industrialization, biopiracy, and a lack of regulation and infrastructure.
For the expansion of herbal medicine usage in the twenty-first century, conservation, proper
research based on traditional knowledge, quality control of herbal medicine, and correct
documentation are required. Methods: The desired and encouraging testifying items for
systematically evaluated reviews and meta-analysis (PRISMA) standards were opted. A
literature exploration was accomplished utilizing SCIENCE DIRECT, SCOPUS and GOOGLE
SCHOLAR to locate articles for the present scenario about traditional and herbal medicines.
Conclusion: The availability and type of conventional medicine safety and effectiveness
data are far from sufficient to fulfil the requirements required to support its use globally. This
review paper examines the restrictions and issues associated with conservation, science and
technology, regulatory constraints, potential usage of herbal medicines, the drug production
industry, safety and efficacy, and the prospects for traditional remedies on a nationally and
internationally scale.
... Furthermore, valerian does not potentiate the effects of alcohol or CNS depressants, does not interfere with the ability to drive vehicles or operate machines, and does not cause physical and/or psychological dependence (Ugalde et al., 2005). ...
The aim of this work is to review the literature on the use of herbal medicines to control dental anxiety. For this purpose, articles were searched in the databases ScienceDirect, Pubmed and The Cochrane Library. 57 articles were included in this study. The research evidence points to Valeriana officinalis and Passiflora incarnata as the most studied herbal medicines for the control of anxiety, and their adverse effects are also investigated. Studies prove the relative safety of these medications, as well as their effectiveness, low cost, lower concentration of active ingredients with better effects and fewer side effects when compared to benzodiazepines. The use of these medicinal plants requires further clarification as to their real effectiveness, correct dosage and side effects in conscious sedation in Dentistry.
... Furthermore, valerian does not potentiate the effects of alcohol or CNS depressants, does not interfere with the ability to drive vehicles or operate machines, and does not cause physical and/or psychological dependence (Ugalde et al., 2005). However, Hendriks et al. (1985) and Leuschner;Müller;Rudmann (1993) stated that Valerian-based phytoterapeutic medicine may interact with barbiturates and benzodiazepines, causing an increase in the therapeutic effects of these drugs and potentiating CNS depression. ...
Anxiety in dental patients is a problem for both dental surgeons and patients. Thus, therapies that aim to control this anxiety and thus favor the patient's collaboration during treatment become factors frequently studied in search of the best alternative for this purpose. Therefore, the objective of this work is to review in the literature the use of herbal medicines in the control of dental anxiety. The bibliographic search was carried out in the databases ScienceDirect, Web of Science, Scielo, Pubmed, The Cochrane Library. 57 articles were included in this study. Research evidence points to Valeriana officinalis and Passiflora incarnata as the most studied herbal medicines for controlling anxiety and adverse effects. Studies prove the relative safety in the use of these drugs, as well as their effectiveness, low cost, less concentration of active ingredients with better effects and lesser side effects when compared to benzodiazepines. However, the use of these medicinal plants requires further clarification as to their real effectiveness, correct dosage and side effects in conscious sedation in Dentistry.
... The roots were dried in the shade at room temperature and were hand-milled to pulverize. The powdered root was extracted as previously reported to obtain a syrupy extract (Oliva et al., 2004;Ugalde et al., 2005) (Fig. 1A). ...
... The animals received the same volume of vehicle by the same administration route. The doses of the extract and PTZ were determined according to previous experiments (González-Trujano et al., 2017;Oliva et al., 2004;Ugalde et al., 2005). Valepotriate fraction was obtained and chemically analyzed as previously reported (Navarrete et al., 2006) where the presence of valepotriates such as: isodihydrovaltrate (18.99%), homovaltrate (13.51%), 10-acetoxy-valtrathydrin (4%), and valtrate (1.34%) were identified (Fig. 1B). ...
... There is no available recommended dose of V. edulis for assessing its efficacy in experimental epilepsy. Therefore, according to preliminary studies (Oliva et al., 2004;Ugalde et al., 2005) we first explored the effects of two doses (100 mg/kg and 300 mg/kg), but V. edulis at a dosage of 300 mg/kg produced adverse effects, specifically a proconvulsive response. Thus, the ethanol extract of V. edulis and its valepotriate fraction were explored at a dosage of 100 mg/kg administered i. p. 15 or 30 min before PTZ administration. ...
Ethnopharmacological relevance
For many centuries, Mexican Valerian (Valeriana edulis ssp. procera) has been an important plant in folk medicine. It has been considered useful to control epilepsy; however, electroencephalographic evidence of its anticonvulsant activity is missing in literature.
Aim of the study: In the present study, in situ electroencephalographic (EEG) analysis was performed along with administration of a crude ethanol extract of V. edulis and its valepotriate fraction on the pentylenetetrazole (PTZ)-induced convulsive behavior in rats.
Materials and Methods
Experiments were performed using male Wistar rats with nail-shaped electrodes implanted in the frontal and parietal cortices for EEG recording. All animals received a single dose of PTZ (35 mg/kg, i.p.) to test the anticonvulsant activity of V. edulis crude extract and valepotriate fraction (100 mg/kg, i.p.) 15 and/or 30 min after administration. EEG recordings were obtained from the cortices and were evaluated to assess ictal behavior over 60-75 min. Chromatographic analysis of the valepotriate fraction and in silico predictions of pharmacodynamic properties were also explored. The latency, frequency and duration of seizures evaluated using EEG recordings from the frontal and parietal cortices of rats showed significant changes demonstrating the inhibition of paroxystic activity.
Results
The spectral analysis confirmed the reduction of excitatory activity induced by V. edulis extract, which was improved in the presence of the valepotriate fraction as compared to that induced by ethosuximide (a reference anticonvulsant drug). The presence of valepotriates such as: isodihydrovaltrate (18.99%), homovaltrate (13.51%), 10-acetoxy-valtrathydrin (4%) and valtrate (1.34%) was identified by chromatographic analysis. Whereas, not only GABAA receptor participation but also the cannabinoid CB2 receptor was found to be likely involved in the anticonvulsant mechanism of action after in silico prediction.
Conclusions
Our data support the anticonvulsant properties attributed to this plant in folk medicine, due to the presence of valepotriates.
... The cytoprotective, antioxidant, and anti-inflammatory profile of numerous compounds isolated from medicinal plants makes them suitable candidates for therapy against gastric damage by NSAIDs (Borrelli and Izzo 2000;Rozza and Pellizzon 2013;Hafez et al. 2019). Despite the use of mixtures of medicinal plants as a common practice in traditional medicine (Schmeda-Hirschmann and Yesilada 2005;Farzaei et al. 2015), only a few studies have evaluated the interactions between natural compounds, and rarely has experimental evidence endorsed the pharmacological effects of these compounds (Ugalde et al. 2005;Rozza and Pellizzon 2013;Rodríguez-Ramos et al. 2016). Our research group has studied the gastroprotective effects of 3αhydroxymasticadienoic acid (3α-OH MDA), a triterpenoid isolated from Amphipterygium adstringens (Schtdl.), ...
The co-administration of 3α-hydroxymasticadienoic acid (3α-OH MDA) and diligustilide (DLG) generates a synergist gastroprotective effect on indomethacin-induced gastric damage. However, the related protective activities of the compounds alone (or in combination) remain unclear. In the present study, we evaluated the anti-inflammatory and antioxidative activities, as well as the potential modulation of important gasotransmitters of each compound individually and in combination using the indomethacin-induced gastric damage model. Male Wistar rats were treated orally with the 3α-OH MDA, DLG, or their combination (at a fixed ratio of 1:1, 1:3, and 3:1) 30 min before the generation of gastric mucosal lesions with indomethacin (30 mg/kg, p.o.). Three hours later, the gastric injury (mm2) was determined. Results from these experiments indicate, in addition to maintaining basal levels of PGE2, the gastroprotective effect of the pre-treatment with 3α-OH MDA (70%), DLG (81%), and their combination (72%) which was accompanied by significant decreases in leukocyte recruitment, as well as decreases in TNF-α and LTB4 gastric levels (p < 0.05). We also found that the pre-treatment maintains the basal antioxidant enzyme activities (SOD) and gastric NO and H2S production even in the presence of indomethacin (p < 0.05). In conclusion, when 3α-OH MDA-DLG is given at a 1:1 combination ratio, the gastroprotective effect and the inflammatory, antioxidant, and gaso-modulation properties are not different from those of treatments using the maximum doses of each compound, revealing that this combination produces promising results for the treatment of gastric ulcers.
... Each mouse was introduced in the cylinder (45 cm in height, 20 cm in diameter, with wall of 3 mm) and the amount of rearings were documented with a camera for 5 min (Ugalde et al., 2005). In additional experiments, groups of mice were intraperitoneally pretreated with 0.5 mg/kg prazosin (an α1-adrenoceptor antagonist), 2 mg/kg flumazenil (a selective GABA antagonist), and 100 mg/kg 4-chloro-DL-phenylalanine methyl ester hydrochloride (an inhibitor of serotonin synthesis). ...
... The EPM estimates the intrinsic fear of mice to evade open and elevated spaces (Dawson & Tricklebank, 1995) which displays anxiety conduct. The light-dark box test assesses the repugnance of mice to luminously zones (Takao & Miyakawa, 2006), and the exploratory cylinder test estimates the distress of mice to novel surroundings (Ugalde et al., 2005). The forced swimming test and the tail suspension test, established on a behavioral desperation in an inescapable condition, assess antidepressant actions (Cryan et al., 2005;Porsolt et al., 1977). ...
Salvia tiliifolia is used in folk medicine as a relaxant agent and for the treatment of diarrhea and neurodegenerative diseases. Tilifodiolide (TFD) is a diterpene obtained from this plant. The purpose of this work was to evaluate the antidiarrheal, vasorelaxant, and neuropharmacological actions of TFD. These effects were selected based on the folk medicinal use of S. tiliifolia. The antidiarrheal activity of 1–50 mg/kg p.o. TFD was assessed with the castor oil related tests. The vasorelaxant effect of TFD (0.9–298 μM) was performed with smooth muscle tissues from rats, and its mechanism of action was evaluated using different inhibitors. The sedative, anxiolytic, and antidepressant effects of 1–100 mg/kg TFD were assessed. The possible mechanisms of action of the anxiolytic and antidepressant effects of TFD were evaluated using inhibitors. TFD exhibited antidiarrheal (ED50 = 10.62 mg/kg) and vasorelaxant (EC50 = 48 ± 3.51 μM) effects. The coadministration of TFD with N(ω)-nitro-L arginine methyl ester (L-NAME) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), reverted the vasorelaxant action showed by
TFD alone. TFD exerted anxiolytic actions (ED50 = 20 mg/kg) in the cylinder exploratory test, whereas TFD (50 mg/kg) showed antidepressant actions in the tail suspension test by 44%. The pretreatment with 2 mg/kg flumazenil partially reverted the anxiolytic actions of TFD, whereas the pretreatment with 1 mg/kg yohimbine abolished the antidepressant effects of TFD. In summary, TFD exerted antidiarrheal activity by decreasing the intestinal fluid accumulation and vasorelaxant effects mediated by nitric oxide and cyclic guanosine monophosphate. TFD showed anxiolytic and antidepressant effects by
the partial involvement of gamma-Aminobutyric acid (GABA) receptors and the possible participation of α2-adrenoreceptors, respectively.
... The mix of traditional herbal remedies is frequently used in several countries, mainly for the treatment of gastrointestinal diseases (Farzaei, Abdollahi, & Rahimi, 2015;Schmeda-Hirschmann & Yesilada, 2005). In the evaluation of newly isolated compounds, the interaction studies are an important aspect to evaluate, especially in those with a pharmaceutical potential (Balderas et al., 2008;Ugalde et al., 2005). However, there are few studies that evaluate interactions with natural compounds ; Rodríguez-Ramos, Andrade-Moreno, Alfaro-Romero, Balderas-López, & Navarrete, 2016;Ugalde et al., 2005). ...
... In the evaluation of newly isolated compounds, the interaction studies are an important aspect to evaluate, especially in those with a pharmaceutical potential (Balderas et al., 2008;Ugalde et al., 2005). However, there are few studies that evaluate interactions with natural compounds ; Rodríguez-Ramos, Andrade-Moreno, Alfaro-Romero, Balderas-López, & Navarrete, 2016;Ugalde et al., 2005). ...
... In these models, the significant anti-ulcer effect was achieved at doses above 10 mg/kg for 3αhydroxymasticadienonic acid and, doses above of 3 mg/kg for DLG The gastroprotection exerts by natural products and crude extract mixtures in the traditional medicine plays an important role, because the mix of traditional herbal remedies is frequently used in several countries, mainly for the treatment of gastrointestinal diseases (Farzaei et al., 2015;Schmeda-Hirschmann & Yesilada, 2005). In the evaluation of newly isolated compounds, the interaction studies are an important aspect to evaluate, especially in those with a pharmaceutical potential (Balderas et al., 2008;Ugalde et al., 2005). Nonetheless, few studies have evaluated natural product-natural product interactions, especially in those that come from plants with an important traditional use Rodríguez-Ramos et al., 2016;Ugalde et al., 2005). ...
The aims of the study were to evaluate the pharmacodynamic interaction between 3α‐hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacin‐induced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α‐hydroxymasticadienonic acid, DLG or the mixture of 3α‐hydroxymasticadienonic acid‐DLG (at a fixed‐ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm2) was determined. 3α‐hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin‐induced gastric damage (p < .05). The effective dose (ED50) values for each compound were 6.96 ± 1.25 mg/kg for 3α‐hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super‐additive interaction as the experimental ED50 values (Zexp) were lower than theoretical additive dose values (Zadd; p < .05). Our results identify the super‐additive (synergist) interaction between 3α‐hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin—induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti‐inflammatory drugs (NSAIDs).
