Centella asiatica improves memory and executive function in middle-aged rats by controlling oxidative stress and cholinergic transmission.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (L.) Urban, is a medicinal herb with rich history of traditional use in Indian subcontinent. This herb has been valued for its diverse range of medicinal properties including memory booster, and also as a folk treatment for skin diseases, wound healing and mild diuretic. AIM OF STUDY: Aging is a gradual and continuous process of natural decay in the biological systems, including the brain. This work aims to evaluate the effectiveness of ethanolic extract of Centella asiatica (CAE) on age-associated cognitive impairments in rats, as well as the underlying mechanism. MATERIAL AND METHODS: Rats were allocated into five distinct groups of 5 animals each: Young rats (3 months old rats), middle-aged (m-aged) rats (13-14 months old), and the remaining three groups were comprised of m-aged rats treated with different concentrations of CAE, viz., 150, 300, and 450 mg/kg b. w., orally for 42 days. Y-maze, open field, novel object recognition, and elevated plus maze tests were used to assess animal behavior. The malondialdehyde (MDA), superoxide dismutase (SOD), and acetylcholinesterase (AChE) assays; and H&E staining were done in the rat brain to assess the biochemical and structural changes. CAE was also subjected to HPLC analysis, in vitro antioxidant and anti-cholinergic activity. The active compounds of CAE were docked with AChE and BuChE in molecular docking study. RESULTS: The results showed that CAE treatment improves behavioral performance; attenuates the age-associated increase in MDA content, SOD, and AChE activity; and reduces neuronal loss. In vitro study showed that CAE has concentration-dependent antioxidant and anti-AChE activity. Furthermore, the presence of Asiatic acid and Madecassic acid in CAE and their good binding with cholinergic enzymes (in silico) also suggest the anticholinergic effect of CAE. CONCLUSION: The findings of the current study show that the anticholinergic and antioxidant effects of CAE are attributable to the presence of Asiatic acid and Madecassic acid, which not only provide neuroprotection against age-associated cognitive decline but also reverse it.

New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model.

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.

Systematic review on the anxiolytic and hypnotic effects of flower extracts in in vivo pre-clinical studies published from 2010 to 2020.

Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.

Acacia catechu Willd. and Acacia arabica Willd. decrease the extent of anxiety behavior by reducing oxidative stress and moderating neurochemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety is a very common psychiatric problem. It affects a large group of people in the world population. Acacia genus is well known for phenolic and flavonoid content. Literature showed its potential for various biological activities and is useful in the treatment of chest pain, asthma, bronchitis, wounds, mouth ulcer, colic, vitiligo, sore throat, inflammation, diarrhoea and also used as tonic. AIM OF THE STUDY: The present study was conducted to assess the antianxiety potential of two plants Acacia catechu Willd. and Acacia arabica Willd. from the common family Fabaceae. MATERIALS AND METHODS: The stems of both plants were used for this purpose. Plants were subjected to complete exhaustive successive extraction using petroleum ether, chloroform, ethanol, and water as solvent. After pharmacognostic and phytochemical investigation, antianxiety activity was conducted on Swiss albino mice at different dose levels (100, 200, 300, & 400 mg/kg body weight p.o.) for all successive extracts of both plants. Two active extracts from each plant were further assessed for anxiolytic potential using the open-field test and mirror chamber test. One extract with the maximum response from each plant was further screened using mCPP-induced anxiety test. RESULTS: The stem of ethanol extract of A. catechu showed comparable antianxiety activity at 400 mg/kg to the standard drug diazepam (2.5 mg/kg). Improved SOD, catalase, and LPO levels were noted after administration of A. catechu ethanolic extract at 400 mg/kg. CONCLUSIONS: In conclusion, A. catechu ethanolic extract improved anxiety symptoms at dose-dependent levels in mice.

Antidepressant- and anxiolytic-like actions of Cajanus cajan seed extract mediated through monoaminergic, nitric oxide-cyclic GMP and GABAergic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Cajanus cajan (L) Millsp, are used in Traditional medicine for the treatment of anxiety and other neurological disorders. Hence, this study is designed to investigate the antidepressant- and anxiolytic-like properties of ethanol seed extract of Cajanus cajan (CC) in mice. MATERIALS AND METHODS: CC (50, 100 or 200 mg/kg, p.o.) was administered 1h before subjecting the animals to different behavioral models: forced swim test (FST) and tail suspension test (TST) (depressive-like behaviour), open field test (OFT), elevated plus maze (EPM), light-dark test (LDT) and hole-board test (HBT) for anxiety-like behaviour. To ascertain the pharmacodynamic of CC mice were pretreated with monoaminergic, nitrergic and GABAergic receptors antagonists. As well as molecular docking analysis of about 19 flavonoids present in CC on GABAA, α2 adrenoceptors and 5-HT2A receptors. RESULTS: CC (50, 100 or 200 mg/kg, p.o.) treatment significantly reduced immobile time in both FST and TST when compared with vehicle-treated control. However, the pretreatment of mice with prazosin/yohimbine (α1/2 adrenoceptor antagonists, respectively), WAY100635 (5-HT1A receptor antagonist), ketanserin (5-HT2A receptor antagonist), sulpiride (dopamine D2 receptor antagonist), L-NG-Nitro arginine methyl ester (L-NAME), or methylene blue reversed the antidepressant-like effect of CC. In anxiety model, CC produced significant (p < 0.05) increase in open arms exploration and head dipping behavior which was reversed by flumazenil (benzodiazepine receptor antagonist) in the EPM. Docking analysis showed significant binding affinity of orientin, vitexin, pinostrobin and quercetin with 5HT2A, α2-adrenoceptor and GABAA receptors. CONCLUSION: Findings from this study showed that C.cajan seeds extract exerts antidepressant-like effect through participation of monoaminergic systems (5-HT2 receptor, α1/α2-adrenoceptors, and dopamine D2-receptors), nitric oxide-cyclic GMP pathway and anxiolytic-like effect via GABAA benzodiazepine receptors. Moreso, presence of flavonoids with significant binding energies with monoaminergic and GABAergic systems support the potential of the extract in the management of mixed anxiety-depressive illness.

Anxiolytic Effect of Satureja montana Dry Extract and its Active Compounds Rosmarinic Acid and Carvacrol in Acute Stress Experimental Model.

BACKGROUND: Anxiety disorders are an important not only medical, but also social problem, affecting approx. 300 million people worldwide in 2019. Medications used in the treatment of anxiety are associated with many adverse reactions, which explains the increased use of herbal products as anxiolytics. METHODS: An anxiolytic activity of Satureja montana, rosmarinic acid and carvacrol after 14-day long administration on an animal model of acute stress was studied. For measurement of anxiolytic effect elevated plus maze, social interaction and Vogel tests were provided as well as examination of locomotor activity. RESULTS: The dry extract of Satureja montana at both tested doses significantly increased locomotor activity as well as the time spent in the social recognition, compared to the control groups. The extract reduced the time in the closed arms and the proportion of entries into open arms to total entries and increased the time in the open arms of elevated plus maze compared to the positive control group. Likewise, rosmarinic acid and carvacrol increased significantly the time spent with a new congener in the social interaction test. Both compounds reduced the ratio of entries into open arms to total entries similarly to the dry extract of Satureja montana. Only rosmarinic acid increased the time in the open arms and reduced the time in the closed arms. CONCLUSIONS: Satureja montana at both experimental doses exerted a significant anxiolytic activity in almost all the tests employed for evaluating anxious behavior. Carvacrol and rosmarinic acid showed a moderate anxiolytic effect.

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Neuropharmacological evaluation and HPTLC fingerprint profile of phytocompound-enriched chloroform fraction of methanolic extract of Lagenaria siceraria (Molina) Standley fruits - a potent Asian ethno-medicinal vegetable plant.

INTRODUCTION: Lagenariasiceraria (Molina) Standley (Cucurbitaceae) is a traditional vegetable plant, popularly known as bottle gourd (English) and lauki (Hindi). It is a climbing herb characterized with a number of therapeutic properties. Traditionally Lagenariasiceraria (LS) fruits were used for their cardioprotective, hepatoprotective, diuretic, and purgative effects, but there is very little scientific data available on its neuroprotective potential.

Monoaminergic system involvement in the antidepressant-like and anxiolytic-like properties of novel ß-dihydroagarofuran sesquiterpene alkaloid and triterpenes isolated from Gymnosporia heterophylla aerial parts in mice.

Gymnosporia heterophylla (synonym Maytenus) is widely used in folk medicine for the treatment of various illness including neurological diseases. This study presents the antidepressant-like and anxiolytic-like effects of novel bioactive constituents; 3,4-seco-1-hydroxy-21-oxoolean-3,11-olide (A2), 1ß,2ß-diacetoxy-9ß-benzoyloxy-6α-nicotinoyloxy-ß-dihydroagarofuran (A5) as well as known 3-acetoxy-1ß-hydroxyLupe-20(29)-ene (selective COX-2; A4) from the aerial parts of G. heterophylla. The antidepressant-like effect was studied using the forced swim test (FST) while the elevated plus maze test (EPMT) and open field test (OFT) were employed for anxiolytic-like effect. Acute treatment with A4 and A5 (0.5, 5 or 10 mg/kg) significantly reduced the duration of immobility and immobile episodes with prolongation of immobility latency in the FST with peak effects observed at 10 and 0.5 mg/kg, respectively. Moreover, antidepressant-like effect of A4 and A5 were relatively better than that of fluoxetine. Conversely, the pretreatment of mice with prazosin (1 mg/kg, α1-adrenoceptor antagonist), yohimbine (1 mg/kg; α2-adrenoceptor antagonist), or sulpiride (50 mg/kg; dopamine D2-receptor antagonist) reversed antidepressant-like effect of A4 and A5 but not WAY 100635 (10 mg/kg, i.p., selective 5-HT1A receptor antagonist), GR 127935 (5 mg/kg, i.p., selective 5-HT1B receptor antagonist), metergoline (4 mg/kg, i.p, non-selective 5-HT2 receptor antagonist), ketanserin (5 mg/kg, i.p., a selective 5-HT2A receptor antagonist) or p-chlorophenylalanine (pCPA) (100 mg/kg, i.p., tryptophan hydroxylase inhibitor) in the FST. Interestingly, A2, A4 and A5 significantly increased the time spent in the open arms of the EPM suggestive of anxiolytic-like action. Findings from this study showed that the novel ß-dihydroagarofuran sesquiterpene alkaloid and triterpenes possesses antidepressant-like and anxiolytic-like effects through enhancement of monoaminergic signaling.

Stress-Relieving Effects of Sesame Oil Aroma and Identification of the Active Components.

(1) Sesame oil aroma has stress-relieving properties, but there is little information on its effective use and active ingredients. (2) Methods: ICR male mice were housed under water-immersion stress for 24 h. Then, the scent of sesame oil or a typical ingredient was inhaled to the stress groups for 30, 60, or 90 min. We investigated the effects of sesame oil aroma on mice behavior and the expression of the dual specificity phosphatase 1 (DUSP1) gene, a candidate stress marker gene in the brain. (3) Results: In an elevated plus-maze test, the rate of entering into the open arm of a maze and the staying time were increased to a maximum after 60 min of inhalation, but these effects decreased 90 min after inhalation. As for the single component, anxiolytic effects were observed in the 2,5-dimethylpyrazine and 2-methoxy phenol group, but the effect was weakened in the furfuryl mercaptan group. The expression levels of DUSP1 in the hippocampus and striatum were significantly decreased in 2,5-dimethylpyrazine and 2-methoxy phenol groups. (4) Conclusions: We clarified the active ingredients and optimal concentrations of sesame oil for its sedative effect. In particular, 2,5-dimethylpyrazine and 2-methoxy phenol significantly suppressed the stress-induced changes in the expression of DUSP1, which are strong anti-stress agents. Our results suggest that these molecules may be powerful anti-stress agents.

Anxiolytic effect of the heartwood of Haematoxylum campechianum L. and sappanchalcone in an in vivo model in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Haematoxylum campechianum L., is a well-known plant in the southeast region of Mexico, where it is named as "palo tinto" or "palo de Campeche", in English there are vernacular names such as "redwood", "bloodwood tree" or "campeachy wood". Traditional medicine refers its use for the treatment of different disorders including depression. AIM OF THE STUDY: Considering the traditional use of this plant for the alleviation of depression, the aim of this study was the evaluation of the anxiolytic effect of the methanolic and hydroalcoholic extracts from the heartwood of Haematoxylum campechianum L., and the sappanchalchone (Sapp). Additionally, it is presented the characterization of the new compound 4-hydroxyhematoxylol (2) isolated from the hydroalcoholic extract. MATERIAL AND METHODS: The anxiolytic effect of the extracts and Sapp was evaluated by using the Elevated Plus Maze (EPM) additionally the sedative effect was assessed with the Open Field Test (OFT). The chemical characterization of Sapp and 2 was performing by 1D and 2D NMR experiments. RESULTS: The EPM test showed that the administration of the plant extracts increased the percentage of time spent in open arms (76.32 ± 6.35 and 66.68 ± 20.64%, respectively for the methanolic and hydroalcoholic extracts), whereas the administration of Sapp increased the percentage of time spent in open arms by 60.07 ± 14.28%, these results are similar to Diazepam (DZP, positive control) which caused an increment of 74.06 ± 23.42%. For the OFT, all of the doses evaluated for both extracts and Sapp diminished the number of rearing (R) and total corssing (TC) behavior in a similar way to the positive control (DZO) and statistically different with respect to the vehicle. CONCLUSION: The results obtained showed that the polar extracts from the heartwood of Haematoxylum campechianum L. possess both anxiolytic and sedative effect and that the chalcone-type compound Sapp, isolated from the methanolic extract, is partially responsible of these activities.

Anxiolytic-like and antidepressant-like effects of ethanol extract of Terminalia chebula in mice.

Terminalia chebula (T.chebula) fruit is referred as "King of Medicines" in Tibet and is listed as a key plant in "Ayurvedic Materia Medica" due to its diverse pharmacological activity. The present study was aimed to investigate the comorbid antidepressant-like and anxiolytic-like effects of ethanol extract from T.chebula fruit using experimental behavioral tests in mice. In addition, the study explored the effects of extract on monoamine oxidase -A (MAO-A) levels in mouse brain. Two doses of the T.chebula extract (100 or 200 mg/kg, p.o.) were treated continuously for fifteen days to mice. Regarding antidepressant-like effects, the treatment of T.chebula extract at both dose (100 or 200 mg/kg, p.o.) levels resulted with significant (p < 0.001) reduction in duration of immobility time and increase in swimming time as compared to control group in forced swimming test. Moreover, both doses declined the duration of immobility time in the tail suspension test and increased the number of crossing in the center area using open-field test. Additionally, the dose 200 mg/kg treatment showed a significant reduction (p < 0.05) in MAO-A activity in mouse brain. For anxiolytic activity, both doses significantly (p < 0.001) improved the time spent in open arm and the number of head dips in elevated plus maze test. The higher duration of time spent in light chamber and higher number of crossing between the light and dark chambers by extract treatment in light-dark box test also supported the anxiolytic behavior. The obtained results supported the antidepressant-like and anxiolytic-like effects of ethanol extract of T.chebula in mice.

Antidepressant and anxiolytic compounds isolated from Salvia elegans interact with serotonergic drugs.

Salvia elegans belongs to a genus plants with biological activities in central nervous system. In this work, the purpose was to evaluate the anxiolytic and antidepressant effects of fractions and compounds isolated from S. elegans and its interaction with serotoninergic drugs by using behavioral tests in mice. Fractions from aerial parts of S. elegans were obtained by column chromatography, SeF1, SeF2, SeF3, and SeF4. Each of them was administered to 25 mg/k in ICR mice subject to forced swimming test (FST), or elevated plus maze test (EPM), or open field test (OFT). The most active fractions were chemically separated until compounds, which were analyzed as anxiolytic or antidepressant and the coadministration of these treatments with 5-HT1A and 5-HT2 drugs was measured in the different biological tests. All fractions were anxiolytic and antidepressant, oleanolic acid (OA) was found in SeF2, and from SeF3, a mixture of terpenes was found; a GC-MS analysis confirmed the presence of two main compounds: rosifoliol and agaraspirol (TM, mixture of terpenes). TM (doses-response curve, 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg) and OA (5 mg/kg) were also evaluated demonstrating an antidepressant and anxiolytic effect, respectively. The combination of TM (0.5 mg/kg) with 8-OH (selective 5-HT1A receptor agonist) induced an increment of antidepressant activity, while with the antagonist WAY-100635, the effect diminished. But with DOI (5-HT1c/5-HT2 receptor agonist), there was no change, and with KET (5-HT2 receptor antagonist), the activity was increased. When OA is co-administered with 8-OH or with DOI, the anxiolytic activity of this terpene, diminished; but with the combination with antagonists, the effect of OA shows no change. TM and OA were antidepressant and anxiolytic, respectively, on mice exposed to different tests, and these are able to interact with serotoninergic drugs.

In vivo anxiolytic and in vitro anti-inflammatory activities of water-soluble extract (WSE) of Nigella sativa (L.) seeds.

The WSE is a highly polar, gummy and mucilaginous bioactive content of the Nigella sativa (L.) seeds. This study reports the anxiolytic and anti-inflammatory effects of WSE investigated using Elevated Plus Maze (EPM) and Hole-Board Test (HBT) in adult mice and human RBCs haemolysis inhibition and protein denaturation respectively. The oral WSE treatment (100 & 200 mg/kg b.w/day) for 72 hours has exhibited slightly better anxiolytic effect (p < 0.05) through the time span (92.33 & 93.33 s) spent in the opened arms of EPM vs. diazepam (1 mg/kg b.w i.p/day; 69.33 s). In HBT, only WSE (200 mg/kg b.w/day) has shown a promising number of mean head pokes (13.27 times/min) vs. diazepam (12.87 times/min). The WSE (62.5-500 µg/mL) exposure has exhibited 40.14-72.18% protection against lysis of RBCs vs. aspirin (57.04-71.48%) whilst 62.67-67.66% inhibition of protein denaturation vs. diclofenac sodium (43.11-80.64%). The current findings suggested WSE has promising anxiolytic and anti-inflammatory activities.

Anxiolytic effect of an extract of Salvia miltiorrhiza Bunge (Danshen) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has demonstrated in modern studies for its pharmacological activities in treatments of CNS disorders like insomnia, dysphoria. However, its application on anxiolytic effect from the ethanol extract of Salvia miltiorrhiza Bunge (SMEtOH) has not yet been reported. MATERIALS AND METHODS: This study investigated the anxiolytic effect of the SMEtOH using the elevated plus-maze test (EPM) and the hole-board test (HBT) with diazepam and buspirone as positive controls. Also, the spontaneous locomotor activity of mice had been investigated in the open field. Further, we have illustrated the anxiolytic mechanisms of SMEtOH with its influencing upon GABAergic and/or serotonergic nervous systems via a method that SMEtOH was co-administered with flumazenil, a benzodiazepine (BZD) antagonist, or a drug (WAY-100635), a selective 5HT1A receptor antagonist. RESULTS: In hole-board test, results presented that SMEtOH increased head-dip counts and duration time. On the other hand, a decrease in spontaneous locomotor activity was observed. In the EPM test, SMEtOH increased the percentage of open-arm entries and the percentage of time spent in open arms. However, when SMEtOH co-administered with flumazenil or WAY-100635, the anxiolytic effect of SMEtOH was significantly counteracted. CONCLUSION: From these results, we can conclude that the anxiolytic mechanism of SMEtOH is exerted through an activation of the BZD and 5HT1A receptors.

Effects of Sesame Oil Aroma on Mice after Exposure to Water Immersion Stress: Analysis of Behavior and Gene Expression in the Brain.

(1) Background: Sesame has been popular as a healthy food since ancient times, and effects of the aroma component of roasted sesame are also expected. However, little research has been reported on its scent; (2) Methods: Jcl:ICR male mice were housed under water immersion stress for 24 h. Then, the scent of saline or sesame oil was inhaled to stress groups for 90 min. We investigated the effects of sesame oil aroma on the behavior and brains of mice; (3) Results: In an elevated plus maze test, the rate of entering to open arm and the staying time were decreased by the stress. These decrements were significantly enhanced by sesame oil aroma. Stress had a tendency to increase the serum corticosterone concentration, which was slightly decreased by the aroma. Expression of Kruppel-like factor-4 (Klf-4) and Dual-specificity phosphatase-1 (Dusp-1) in the striatum were increased by water immersion stress, and the level of Klf-4 and Dusp-1 in the striatum and hippocampus were significantly attenuated by sesame oil aroma (4) Conclusions: The present results strongly suggest that the odor component of sesame oil may have stress suppressing effects. Moreover, Klf-4 and Dusp-1 may be sensitive stress-responsive biomarkers.

Bacopa monnieri alleviates aluminium chloride-induced anxiety by regulating plasma corticosterone level in Wistar rats.

Objectives Aluminium is present in food preparations, antacids and many medications. It causes neurodegeneration thereby resulting in a spectrum of neurological disorders such as dementia, Alzheimer's disease and anxiety. Bacopa monnieri (BM) is widely used in ayurvedic medicine to improve memory functions. Its anxiolytic property was investigated in this study by using elevated plus maze (EPM) and plasma corticosterone level. Methods Thirty rats were assigned into five groups. Control group received distilled water, and 0.5% tween 80, AlCl3 group received Aluminium Chloride (AlCl3), Protective groups (BM100 + AlCl3 group and BM200 + AlCl3 group) received AlCl3 and BM at two different doses, and the BM200 group received BM. The EPM experiment was performed at the end of the 4th week of oral administration of BM and AlCl3 followed by the measurement of plasma corticosterone. Results Oral administration of AlCl3 to rats increases the levels of anxiety as seen in a decrease in the percentage of entries into the open arms of EPM, an increase in grooming frequency and defecation index. However, the rats in the protective groups shown an increase in the percentage of open arm entries and rearing frequency, and decreased grooming frequency and defecation index. AlCl3 alone treated group showed a significant increase in the plasma corticosterone levels compared to the control group. Whereas the protective groups have shown a significant decrease in the plasma corticosterone levels than the AlCl3 alone treated group. Conclusions Hence the BM has potential role in reverting the anxiogenic effect of AlCl3 in the amygdala as it is evident from the plasma corticosterone levels and the EPM parameters of different groups under study.

Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Differentially Effects Meal Patterns and Cardiovascular Parameters in Mice.

Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a popular nutraceutical used for weight management and appetite control. We sought to determine the physiological benefits of RK on the meal patterns and cardiovascular changes associated with an obesogenic diet. In addition, we explored whether the physiological benefits of RK promoted anxiety-related behaviors. Male and female C57BL/6J mice were administered a daily oral gavage of RK 200 mg/kg, RK 400 mg/kg, or vehicle for 14 days. Commencing with dosing, mice were placed on a high-fat diet (45% fat) or low-fat diet (10% fat). Our results indicated that RK 200 mg/kg had a differential influence on meal patterns in males and females. In contrast, RK 400 mg/kg reduced body weight gain, open-field total distance travelled, hemodynamic measures (i.e., reduced systolic blood pressure (BP), diastolic BP and mean BP), and increased nocturnal satiety ratios in males and females. In addition, RK 400 mg/kg increased neural activation in the nucleus of the solitary tract, compared with vehicle. RK actions were not influenced by diet, nor resulted in an anxiety-like phenotype. Our findings suggest that RK has dose-differential feeding and cardiovascular actions, which needs consideration as it is used as a nutraceutical for weight control for obesity.

Neuroprotective effect of Reinwardtia indica against scopolamine induced memory-impairment in rat by attenuating oxidative stress.

Reinwardtia indica belongs to Linaceae family and used as a folk medicine in Asian countries. Traditionally, it has been used in the treatment of paralysis and anti-microbial in wound healing, etc. The current study was undertaken in order to investigate the antioxidant and memory protective effect of the alcoholic (99.90%) (AERI) and hydro-alcoholic (70:30) leaves extract (HAERI) of Reinwardtia indica, against scopolamine-induced memory impairment in animals and also tried to determine the possible mechanism of action. In addition, phytochemical profiling of alcoholic leaves extract was also conducted through gas chromatography-mass spectrometry (GC-MS/MS). Rats were pretreated with AERI, HAERI (dose 250 and 500 mg/kg) and Donepezil (standard drug) along with scopolamine (1 mg/kg) for a period of 14 days followed by different test like elevated plus maze, passive avoidance, and Morris water maze to assess learning and memory ability. Acetylcholine levels, acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT & GSH), histopathology of the brain and biochemical test were also performed at the end of the treatment period. The scopolamine treatment resulted in learning and memory deficits which were partially and significantly ameliorated by the AERI at higher dose among other doses of extracts. The AERI at higher dose also counteracted the scopolamine-induced decrease in acetylcholine levels, increase in AChE activity, and decrease in antioxidant enzymes activities. No significant changes observed in the biochemical estimation of all dose of extracts. Histology of brain tissue showed the marked cellular changes in only scopolamine treated group while the standard, AERI and HAERI treated group were showing less damage at hippocampus region of the brain. The phytochemicals found after chemical profiling through GC-MS also supported the activity because of the presence of chemicals already reported for the neuroprotective, memory-enhancing and antioxidant activity, etc. The results demonstrated that the ability of the AERI at higher dose among all doses of extracts has more potential to revert the scopolamine-induced learning and memory deficits in rats by attenuating the decreased level of acetylcholine and antioxidant enzymes.

Murine's amygdala microstructure and elevated plus maze activities following R. vomitoria root bark and G. latifolium leaf extracts administration.

R. vomitoria (RV), a plant used locally in the management of psychotic disorders, adversely affects the brain functionally and structurally. Such adverse reports, as well as the potential of G. latifolium (GL) to mitigate same warranted this investigation on the combined actions of RV and GL on the amygdala. Twenty-four male CD-1 mice weighing 22-27 g were divided into four groups (n = 6): Control (20 ml/kg body weight, b.w., distilled water); RV (200 mg/kg b.w.), GL (200 mg/kg b.w.), and RV (200 mg/kg b.w.) and GL (200 mg/kg b.w.) combination orally, and for 14 days. On day 15, the elevated-plus maze test was carried out and the animals sacrificed, and processed for histological and immunohistochemical studies. Neurobehavioural results showed significant decrease (p[Formula: see text] 0.001) in stretch-attend posture, time spent in closed arms, grooming frequency, protected head-dip, as well as significantly (p [Formula: see text] 0.01) increased time spent in the open arms and unprotected head-dips of the RV group. The combined RV and GL groups showed no such differences in these parameters. Histologically, the amygdala showed hypertrophied cells, with pyknotic and karyorrhectic nuclei, and reduced expression of Nissl substance in the RV group, while the combined RV and GL group showed less degenerative features. Glial fibrillary acidic protein expression (GFAP) was increased in the RV group, while the combined RV and GL group showed reduced expression. In conclusion, RV root bark extract has adverse effects on the microstructure of murines' amygdala and their behaviour, which may be ameliorated by GL.