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Antidepressant activity of Asparagus racemosus in rodent models

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Abstract

Asparagus racemosus Linn. (AR) is an Ayurvedic rasayana used as an adaptogen. Adaptogenic drugs are those which are useful as anti-stress agents by promoting non-specific resistance of the body. Although, the adaptogenic effect of AR is well documented, its use in psychological disorders like depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of methanolic extract of roots of AR (MAR) standardized to saponins (62.2% w/w). Rats were given MAR in the doses of 100, 200 and 400 mg/kg daily for 7 days and then subjected to forced swim test (FST) and learned helplessness test (LH). The results show that MAR decreases immobility in FST and increases avoidance response in LH indicating antidepressant activity. In behavioral experiments, MAR increased the number of head twitches produced by 5-HTP and increased clonidine-induced aggressive behavior indicating facilitatory effect on both serotonergic and adrenergic systems respectively. However, MAR had insignificant effect on l-DOPA-induced aggressive behavior indicating absence of activity on dopaminergic system. MAR also reversed changes to the endogenous antioxidant system induced by FST. Thus, MAR has significant antidepressant activity and this effect is probably mediated through the serotonergic and the noradrenergic systems and augmentation of antioxidant defenses.

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... Methanolic extract of A. racemosus has shown significant antidepressant activity. [40] Further, it has also shown significant antiamnesic and nootropic activity in experiment models. This may be due to its anticholinesterase, antioxidant, and neuroprotective activity of A. racemosus. ...
... Asparagus racemosus Willd. Methanolic extract [40] Antidepressant activity [40] Methanolic extract [41] Antiamnesic and nootropic activity [41] Methanolic extract [43] Anticonvulsant activity. [43] ...
... Asparagus racemosus Willd. Methanolic extract [40] Antidepressant activity [40] Methanolic extract [41] Antiamnesic and nootropic activity [41] Methanolic extract [43] Anticonvulsant activity. [43] ...
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BACKGROUND: Ayurveda Samhita's has documented nootropic drugs, which may play crucial role in brain development during infancy and early childhood. Any deviation in brain development can affect the overall personality and result in low IQ, poor cognitive function, defective learning, impairment in memory, language, speech, and social communication in later life of child. As a result, knowledge of nootropic medicines is critical for dealing with memory-related symptoms in children. OBJECTIVE: The present review is to explore the therapeutic domain of Medhya Rasayana (nootropic drugs) mentioned by Acharya Kashyapa in the light of recently reported contemporary evidence. MATERIALS AND METHODS: Kashyapa Samhita was reviewed in terms of description of Medhya Rasayana or Medhya drugs including single and compound drugs. The electronic database such as PubMed and Google Scholar were searched for relevant literature published from time of their inception to 2020, with results restricted to report in English language and information was extracted from different published articles as per the search criteria. RESULTS: Important nootropic drugs mentioned by Acharya Kashyapa are Brahmi (Bacopa monnieri (L.) Wettst.), Mandukaparni (Centella asiatica (L.) Urb.), Triphala (Phyllanthus emblica L., Terminalia bellirica (Gaertn.) Roxb., Terminalia chebula Retz.), Chitraka (Plumbago zeylanica L.), Vacha (Acorus calamus L.), Trivrut (Operculina turpethum (L.) Silva Manso), Shatavari (Asparagus racemosus Willd.), Shatapushpa (Anethum graveolens L.), Nagabala (Grewia hirsuta Vahl.) and Danti (Baliospermum montanum (Willd.) Müll.Arg.), Brahmi Ghrita, Kalyanaka Ghrita, and Pancha-Gavya Ghrita, etc. These herbs/drugs have a positive effect on memory; improve the intellect, learning, memory, language, and speech of a child. Moreover, these drugs have shown potential therapeutic actions like cognitive function, antiepileptic effect, antianxiety effect, sedative, tranquilizer, antidepressant, antioxidant, antistress, and adaptogenic effect. Specific medicinal herbs like Triphala, O. turpethum, and P. zeylanica under nootropic drugs are found to act through “gut-brain” axis.CONCLUSION: Nootropic drugs mentioned in Kashyapa Samhita is very unique contribution and in recent times these drugs are scientifically validated in pre-clinical and clinical trials, which plays an important role for brain development in pediatric age group. These drugs are clinically tested for promoting mental health since ancient times. Moreover, most of the pre-clinical/clinical studies have proved that nootropic herbs/drugs are useful in many diseases like epilepsy, attention deficit hyperactivity disorder, intellectual disability, autism spectrum disorders, speech disorders, etc. Clinical studies may be planned on pediatric psychological/mental health issues taking leads from the available anecdotal evidence as well as pre-clinical evidence to generate robust empirical evidence which can be used to promote better physical and mental health in a child.CLINICAL SIGNIFICANCE: Nootropic herbs/drugs are unique drugs mentioned by Kashyapa Samhita, which are having evidence for providing better mental health as well as in the treatment of many neurological disorders. Keywords: Ayurveda, Kashyapa Samhita, Medhya Rasayana, memory, nervous system, nootropic drugs
... Since ancient times, A. racemosus roots have been used in "Ayurveda, Unani and Siddha" medicine, with numerous beneficial effects in several diseases (Bopana & Saxena, 2007). Another asparagus variety, Asparagus africanus roots, has been widely used in folk medicine for its antiparasitic activity (Dikasso et al., 2006), antiepileptic (Jalalpure et al., 2009), antilithiatic (Goel et al., 2006), antihepatotoxic (Muruganadan et al., 2000), antidepressant (Singh et al., 2009a) and antineoplastic (Rao, 1981) activities and to treat and cure stomach ulcers (Sairam et al., 2003). It also exhibited neuroprotective activity (Parihar & Hemnani, 2004). ...
... Asparagus roots are also used in treating psychological disorders such as depression. A study by Singh et al. (2009a) evaluated various concentrations of methanolic extracts of A. racemosus roots to relieve depression in rats. Rats were given different concentration of AR extracts (100, 200 and 400 mg kg À1 body weight) for 7 days before undergoing learned helplessness testing (LH) and forced swim testing (FST). ...
... Rats were given different concentration of AR extracts (100, 200 and 400 mg kg À1 body weight) for 7 days before undergoing learned helplessness testing (LH) and forced swim testing (FST). Rats fed methanolic AR extracts had a significantly lower immobility period during FST and escaped failures in LH compared to controls, suggesting that AR possesses antidepressant activity (Singh et al., 2009a). ...
Article
Asparagus roots (AR) contain many bioactive compounds and their use in Chinese and Indian traditional medicines is well documented. Both in vitro and in vivo studies have indicated AR extracts act as antidiabetic, antioxidant and hypolipidaemic and depict anti‐inflammatory, antibacterial, antiviral, anticarcinogenic activities and also improve cardiovascular and oral health. The physiological effects against wide range of pathologies are due to the wide range of phytochemicals found in AR including polyphenols, saponins and polysaccharides. The aim of this review is to present an overview of the functional, medical and physiological properties of AR bioactives. This review considers the roots of several asparagus species and provides up‐to‐date information on Asparagus officinalis that has not been extensively reviewed before.
... Previous reports have also explored the adaptogenic and nootropic properties of A. racemosus (Velavan et al., 2007) in rodents. Thereby, this neuro-nutraceutical has the potential to combat stress-induced anxiety and depression (Bopana and Saxena, 2007;Singh et al., 2009). Besides, the preclinical experiments and clinical investigations have even established the neuroprotective role of A. racemosus. ...
... Analysis of literature shows that A. racemosus has several neurological effects and is an acclaimed nervine tonic in the Ayurvedic system of medicine (Goyal et al., 2003). Relevant clinical and preclinical studies have further reported the beneficial activity of the A. racemosus extracts in CNS against neuronal degeneration (Bhatnagar et al., 2013;Kashyap et al., 2020;Parihar and Hemnani, 2004;Saxena et al., 2010;Venkatesan et al., 2005), stress (Takanari et al., 2016), depression (Bhattacharya et al., 2000;Dhingra and Kumar, 2007b;Singh et al., 2009), anxiety (Dhingra and Kumar, 2007b;Garabadu and Krishnamurthy, 2014) and epilepsy (Amberkar et al., 2011;Jalalpure et al., 2009;Pahwa and Goel, 2016a;Shastry et al., 2015) (Fig. 1). Despite the myriad of scientific evidence available so far, there is no cumulative collection of the neuropharmacology of A. racemosus. ...
... Another series of studies have further investigated and established the adaptogenic property of the extracts of A. racemosus. A study demonstrated the anti-stress property of the methanolic root extracts of A. racemosus (MAR) in the rodent model of depression (Singh et al., 2009), i.e., FST and LH, the validated models for stress-induced behavioral depression (Willner, 1991). The study reported that the pre-treatment of the experimental animals with MAR for 7 days diminished the immobility during FST and elevated avoidance response in the LH, establishing the adaptogenic property. ...
Article
Debilitating neuropsychiatric and neurodegenerative conditions are associated with complex multifactorial pathophysiology. Their treatment strategies often only provide symptomatic relief, delaying disease progression without giving a complete cure. Potent and safer treatment alternatives beyond symptomatic relief are sought. Herbal supplements have surely been explored due to their multiple component nature to enhance the effect of western medications. One such well-documented nutraceutical in the ancient Greek, Chinese, and Ayurvedic medicine system is known for its various medicinal benefits is Asparagus racemosus. Widely used for its lactogenic properties, A. racemosus is also cited in Ayurveda as a nervine tonic. A. racemosus based nutraceuticals have shown to possess adaptogenic, neuroprotective, antioxidant, anti-inflammatory, and nootropic activity under preclinical and clinical settings without posing significant adverse effects. A. racemosus extracts restore the perturbed neurotransmitters and prevent oxidative neuronal damage. From the available neuropharmacological researches, the physiological actions of A. racemosus can ultimately be directed for either augmentation of cognitive ability or in the management of neurological conditions such as stress, anxiety, depression, epilepsy, Parkinson’s, and Alzheimer’s disease. The studies focus on the multi-component extract, and the lack of standardization has been a major hurdle in preventing the allotment of reported neuropharmacological activity to one of the phytoconstituent. Herbal standardization of the plant extract based on a specific biomarker can help elucidate the intricate biomolecular pathway and neurocircuitries being involved. This, followed by rigorous standardized clinical trials, fixing dosages, and determining contraindications would facilitate the translation of A. racemosus to a FDA-approved neuromedicine for neurological disorders.
... Zea mays L.* (Jamara) No data No data Antioxidative, antiapoptotic (13,18) No data Antioxidative (175,176); receptors (176)(177)(178)(179) SAEs: None reported (18) NSAEs: None reported (18) Ipomoea carnea Jacq. (Ajamari jhar [participants called it Ajawane]) Topical (13) No data Antioxidative (180); antiinflammatory (180); other (180) No data. ...
... Zea mays L.* (Jamara) No data No data Antioxidative, antiapoptotic (13,18) No data Antioxidative (175,176); receptors (176)(177)(178)(179) SAEs: None reported (18) NSAEs: None reported (18) Ipomoea carnea Jacq. (Ajamari jhar [participants called it Ajawane]) Topical (13) No data Antioxidative (180); antiinflammatory (180); other (180) No data. ...
Article
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Background In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause. Methods We used data from a cross-sectional, nationwide population-based study, which enquired into headache and use of medicinal plants and allopathic medications. We searched the literature for pharmacodynamic actions of the medicinal plants. Results Of 2100 participants, 1794 (85.4%) reported headache in the preceding year; 161 (7.7%) reported headache on ≥15 days/month, of whom 28 (17.4%) had used medicinal plants and 117 (72.7%) allopathic medication(s). Of 46 with probable medication-overuse headache, 87.0% (40/46) were using allopathic medication(s) and 13.0% (6/46) medicinal plants, a ratio of 6.7:1, higher than the overall ratio among those with headache of 4.9:1 (912/185). Of 60 plant species identified, 49 were pharmacodynamically active on the central nervous system, with various effects of likely relevance in medication-overuse headache causation. Conclusions MPs are potentially a cause of medication-overuse headache, and not to be seen as innocent in this regard. Numbers presumptively affected in Nepal are low but not negligible. This pioneering project provides a starting point for further research to provide needed guidance on use of medicinal plants for headache.
... [5] It is also proven to be an adaptogen [3] and antidepressant. [6] Tila taila is used as a media in the preparation of shatavari taila which has yogvahi and tridosha-shamaka properties. [7] Physical and Chemical Analysis of Trial Drug ...
... It is also an adaptogen. [3] It has significant antidepressant activity, [6] and this effect is probably mediated through the serotonergic and the noradrenergic systems and augmentation of antioxidant defenses. This helps to reduce the stress levels in the body, thus normalizing the imbalance of hormones. ...
Article
Introduction: Heavy and prolonged bleeding during menses is one of the most common complaints encountered by gynecologists across the globe. The word “Atyartava” literally means excessive bleeding during menstruation which is a cardinal feature in a number of menstrual disorders described in the Ayurvedic classics. Atyartava can be correlated to “Menorrhagia” in modern literature. The aim of the present study was to evaluate “the effect of Shatavari Churna and Shatavari Taila Uttarbasti in Atyartava.” Materials and Methods: A total of 40 patients were selected for the present research work and randomly divided into two groups of 20 patients each. In Group A, patients were treated with 3 g of Shatavari (Asparagus racemosus) Churna orally twice daily for 3 months, while in Group B, patients were given 3 g of Shatavari Churna orally twice daily for 3 months along with Shatavari Taila Uttarbasti on 9 th , 10 th , and 11 th days of menses for 3 consecutive months. After conducting the clinical trial on 40 patients, the data were obtained and analyzed statistically. Results: It was observed that both the groups were significantly effective in ameliorating the symptoms of Atyartava. However, on comparison of both Groups A and B, Group B showed better results. Conclusion: It showed that the specific therapy (Uttarbasti Chikitsa with shatavari oil) along with oral administration of Shatavari Churna was more effective in the treatment of Atyartava, in comparison to Shatavari Churna alone. The effects of Shatavari on menorrhagia were attributed mainly to its phytoestrogenic action.
... In the recent past, tremendous progress in the interdisciplinary fields of medicinal science and computeraided high throughput screening of therapeutic targets has accelerated the ominous process of drug discovery (Singh et al., 2009;Igoli et al., 2014;Singla, 2014;Khan et al., 2020). For this, various therapeutic target databases, models, and tools have been constructed that are essential for the management of vast clinical data Liu et al., 2020;Yan et al., 2020;Chen et al., 2021;He et al., 2021). ...
... The methanolic extracts of Asparagus racemosus Willd. (roots) demonstrated in vivo antidepressant effects via MAO (Monoamine oxidases: MAO-A and MAO-B) inhibitory activity and dopaminergic (D2), serotonergic, GABAergic (Gamma-aminobutyric acid), adrenergic (α1), and noradrenergic receptor system interactions (Dhingra and Kumar, 2007;Singh et al., 2009). Similarly, the whole plant extracts of Bacopa monnieri (L.) Wettst. ...
Article
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Depression, a neurological disorder, is a universally common and debilitating illness where social and economic issues could also become one of its etiologic factors. From a global perspective, it is the fourth leading cause of long-term disability in human beings. For centuries, natural products have proven their true potential to combat various diseases and disorders, including depression and its associated ailments. Translational informatics applies informatics models at molecular, imaging, individual, and population levels to promote the translation of basic research to clinical applications. The present review summarizes natural-antidepressant-based translational informatics studies and addresses challenges and opportunities for future research in the field.
... Shatavari has been mentioned in Ayurvedic texts like the Charak Samhita, Susruta Samhita and Astanga Samgraha. 3,4 Shatavari possesses nutritive, antistress, adaptogenic, immunomodulatory, galactogogue, anabolic and performance enhancing properties and are used in various medicinal preparations. [5][6][7][8][9] According to recent chemical investigations, shatavari contains four steroid saponins: Shatavarins 1 to 4. Shatavarin 1 is the major glycoside of sarsasapogenin, the sugar moieties being 3 glucose and 1 rhamnose. ...
... Shatavari has been mentioned in Ayurvedic texts like the Charak Samhita and Susruta Samhita, and Astanga Samgraha. 3,4 Kashyap Samhita has evidently stated that Shatavari promotes maternal health and noted its meticulous use as a galactagogue (enhances breast milk secretion in lactating mothers). Ayurveda has called Shatavari the Queen of herbs and is the primary herb recommended for female health. ...
... The learned helplessness (LH) model is well established and has been widely used to induce behavioral disorders, despair in particular [8,9]. In this paradigm, animals are exposed to inescapable and unpredictable footshock stress and finally develop depressive-like behaviors [10][11][12]. The behavioral characteristics of susceptible LH animals are very similar to clinical depression [13]. ...
... Numbers of studies have suggested that chronic injury of peripheral nerve results in behavioral abnormalities and then induces mental disorders [31,32]. It is also widely known that stresses such as chronic unpredictable stress, chronic mild stress, social stress, and LH result in mental disorders [11,12,[33][34][35][36][37]. LH studies have repeatedly reported that inescapable electrical stimulation drives the initiation of depression in rodent models [11,38,39]. ...
Article
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To investigate the behavioral and biomolecular similarity between neuralgia and depression, a trigeminal neuralgia (TN) mouse model was established by constriction of the infraorbital nerve (CION) to mimic clinical trigeminal neuropathic pain. A mouse learned helplessness (LH) model was developed to investigate inescapable foot-shock-induced psychiatric disorders like depression in humans. Mass spectrometry was used to assess changes in the biomolecules and signaling pathways in the hippocampus from TN or LH mice. TN mice developed not only significant mechanical allodynia but also depressive-like behaviors (mainly behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis demonstrated common and distinctive protein changes in the hippocampus between groups. Many protein function families (such as cell-to-cell signaling and interaction, and cell assembly and organization,) and signaling pathways (e.g., the Huntington’s disease pathway) were involved in chronic neuralgia and depression. Together, these results demonstrated that the LH and TN models both develop depressive-like behaviors, and revealed the involvement of many psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and LH.
... The extract also inverted alterations to the endogenous antioxidant system produced by FST. Therefore, A. racemosus extract has a remarkable antidepressant effect and this property is likely mediated via the noradrenergic and serotonergic systems and increment of antioxidant defenses (Singh, Garabadu, Muruganandam, Joshi, & Krishnamurthy, 2009) (Table 1). The methanolic extract of A. racemosus exhibited considerable antidepressant-like property perhaps by inhibition of monoamine oxidase (MAO)-A and MAO-B; and by fundamental interaction with serotonergic adrenergic, GABAergic, and dopaminergic systems. ...
... Asparagus racemosus -Modifying alterations to the endogenous antioxidant system produced by FST -Interaction with the noradrenergic and serotonergic systems -Increasing antioxidant defenses -Inhibiting MAO-A and MAO-B enzymes Singh et al. (2009) -Interaction with adrenergic, GABAergic, and dopaminergic systems Dhingra and Kumar (2007) Bacopa monnieri -Interacting with the serotonergic and noradrenergic systems -Renormalizing the amounts of ACTH and corticosterone -Improving the expression of BDNF, DCX, and BrdU/NeuN -Elevating the activity of antioxidant enzymes Kumar and Mondal (2016) -Regulating level of BDNF, total and phospho-CREB, and total and phospho-Akt in the hippocampus Hazra, Kumar, Saha, and Mondal (2017) Berberis aristata -Inhibition of MAO-A -Interaction with NO pathway and/or sigma receptors Kulkarni and Dhir (2008) -Increasing brain serotonin, noradrenaline, and dopamine amounts Kulkarni and Dhir (2007) Camellia sinensis -Increasing dopamine and serotonin secretion in the brain Jalali and Hashemi (2018) -Promoting phosphorylation of CREB in rat cerebellum Asrari et al. (2018) induced by menopause (Mohammad-Alizadeh-Charandabi, Shahnazi, Nahaee, & Bayatipayan, 2013; Patel, 2015). ...
Chapter
Depression is one of the most prevalent psychiatric disorders affecting several people worldwide. The synthetic medicines that are available as the standard treatment for depressed patients have various side effects that can impair their therapeutic properties. Therefore, there is an increment in demand for alternative and complementary drugs. A search of English articles in PubMed, Scopus, Google Scholar, and Web of Science databases was carried out on probable mechanisms of action of herbal antidepressants. Herbal medicines stated in folk medicine face acceptance concerns by the medical community because of the lack of scientific documents regarding their neurochemical mechanisms. Henceforth, there has been increased attention to reveal the underlying mechanisms of herbal psychotropics. In this chapter, the antidepressant mechanisms of several medicinal plants such as Curcuma longa, Rosmarinus officinalis L., Crocus sativus, and Ginkgo biloba have been reviewed to show their potential physio-pharmacological effects including affecting the action of the hypothalamic–pituitary–adrenal axis, interaction with dopaminergic, serotonergic, and noradrenergic systems, and attenuating monoamine oxidase A and B activities. In the main body of this chapter, the most frequently used herbs (24 cases) being assessed for the treatment of depression have been discussed. However, the safety and efficacy of these herbal remedies for depression have to be confirmed by more clinical studies.
... Due to destructive harvesting, combined with habitat destruction, and deforestation, the plant is now considered endangered in its natural habitat. The tuberous root is experimentally proven as antioxidant, anticancer, anti-infl ammatory, antiageing (Hayes 2008a , b ) and antidepressant (Singh et al. 2009 ). Two novel compounds were isolated from the tuber extract: shatavarins and sarsasapogenin (Sidiq et al. 2011 ). ...
Chapter
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Arunachal Pradesh is a treasure house of biodiversity as well as traditional knowledge. The state harbours over 800 medicinal plants. Rising demands of signifi cant medicinal plants such as Taxus baccata , Paris polyphylla , Swertia chirayita , Neopicrorhiza scrophulariifl ora , etc. for developing pharmaceutical drugs have drastically reduced the wild population of these species. Some important medicinal plants of the state, their bioactive effi cacy and conservation status are mentioned in this paper. This paper also describes the traditional use of 13 ethnomedicinal plants used by the Monpa tribe of Arunachal Pradesh as antidote against food poisoning, snake bite, scorpion bite and insect bites. Some of the potent antidote plants claimed by the Monpa tribe are Aconitum heterophyllum , Asparagus racemosus , Ligularia amplexicaulis , Rhododendron hodgsonii , Swertia hookeri and Verbascum thapsus. Out of the 13 traditional antidote plants, six are new to science as traditional medicine and are yet to be pharmaceutically validated for their bioactivity. Given the strong traditional cultural use of the plants, it is expected that biochemical and pharmacological studies would reveal the bioactive compounds, which could be further developed as holistic evidence-based drugs to cure some complicated ail-ments/diseases.
... The total duration of immobility induced by tail suspension was recorded for the period of 6minutes of 10mins period by using stopwatch. Animal was considered to be immobile when it did not show any movement of the body, hanged passively and completely motionless [27,28] . Test group2 PERC(500mg/kg p.o) 118.33 ±18.949* *Values are expected as mean ± SEM (no=6) *** p< 0.001 statistically significant as compared to control group ** p< 0.01 statistically significant as compared to control group. ...
Article
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Background: Worldwide epidemiological rate of psychiatric disorders has been on an increased count among which Depression stands more common than others. Research under this sector is always a choice of interest which is on progress. Aim: The present study is carried out to study the antidepressant activity with aqueous extract of Rosa centifolia. Materials and methods: The extract was primarily subjected for preliminary phytochemical investigation and for Maximum Tolerance Dose (MTD). Antidepressant activity was evaluated in various animal models like Swiss Albino, Mice etc with whom Tail suspension test, Acto-photometer were performed. Result and Discussion: The aqueous extract of Rosa centifoliawas positively identified with carbohydrates, tannins, proteins, amino acids, alkaloids, flavonoids, flavanone, glycosides and phenolic compounds. The extract was subjected for maximum tolerance dose upto the dose level of 2000mg/kg has not produced any mortality. Conclusion:The extract of Rosa centifoliashowed significant antidepressant activity at high dose (100 mg/kg) in Tail suspension test, Acto-photometer. The extract didn’t antagonize the hypothermia induced by apomorphine.
... Saponin fraction of methanolic root extract of Asparagus racemosus showed anti-depressant activity in forced swim test model of depres- sion, which was indicative of its effect through the serotonergic and adrenergic systems [69]. Abbas et al. showed the anti-depressant ac- tivity of nut extract of Areca catechu and its aqueous fraction to be via increasing serotonin and norepinephrine levels in rat hippocampus [70]. ...
Article
Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options. Medicinal plants have long been used in discovering novel treatment strategies and compounds with promising roles in treating various disease conditions. There has been an increase, worldwide, in the use of medicinal plants and herbs for developing nutraceuticals for treatment of depression and other psychiatric disorders. Medicinal plants in their natural forms are valuable as they are rich in various phytochemical compounds. These phytochemical compounds have pharmacological roles in treating various diseases conditions; apart from being widely available in nature and commercially beneficial. The phytochemical compounds in plants are constantly being explored through various experimental studies to determine the molecular basis of how medicinal plants work in relation to drugs and diseases and to develop neutraceuticals for improving conditions. This review summarizes 110 medicinal plants and their phytochemical constituents that have been shown to possess anti-depressant activity. This review also highlights the various mechanisms of anti-depressant action of some of these plants and their plant parts like roots, stem, leaves, flowers, fruit or whole plant; phytochemical compounds showing anti-depressant activity such flavanoids, steroids, saponins, sugars, lectins, alkaloids, etc.; and various anti-depressant screening models used such as tail suspension test, forced swim test, chronic unpredictable stress test, sucrose preference test, monoamine oxidase inhibition assay, learned helplessness test, open field test, hole board test, etc. However, mechanistic evaluation of many of these plants still needs to be investigated and explored.
... The young edible shoots of green asparagus is considered a delicacy, while the roots of green asparagus can be used as a remedy for edema due to its diuretic effect (Negi et al., 2010). Asparagus racemosus, another asparagus species whose roots have been used for traditional medicines, has been receiving more interest as a result of its important pharmacological actions including anti-depressant, anti-hepatotoxic and anti-neoplastic (Muruganandan et al., 2000;Singh et al., 2009). Major bioactive compounds of A. officinalis L root (AR) include steroidal saponins, flavonoids (mainly rutin) and dietary fibre (Huang and Zhang, 2006;Huang and Kong, 2006;Huang et al., 2008;Negi et al., 2010). ...
Article
Optimisation of the antioxidant activity of asparagus root extract (ARE) and inosine from New Zealand and Chinese asparagus root cultivars was carried out using a response surface methodology (RSM) using Box-Behnken design (BBD). The determination of inosine was carried out using HPLC under optimal extraction conditions. The independent parameters variables combination (extraction temperature 51 °C, extraction time 73.02 min, ethanol 75.23% and solid: liquid ratio 1:50) produced maximum total flavonoids content (TFC) (9.2–17.1 mg RE/g dry root), total phenolic content (TPC) (14.7–35.2 mg GAE/g dry root) and total saponin content (TSC) (9.2–17.1 mg RE/g dry root). Extraction at temperature 50 °C for 78.5 min, using 70% ethanol at solid: liquid ratio of 1:40 for maximum 2,2-diphenyl-1-picrylhydracyl (DPPH) (38.9–78.1%), 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulfonate) (ABTS) (36.6–61.2%), ferric reducing antioxidant power assay (FRAP) (0.54–1.69 μmol/g), β-carotene bleaching assay (51.2–76.0%) and superoxide anion radical (O²⁻) scavenging capacity (42.5–70.2%). For methanol, extraction conditions viz. extraction temperature at 51 °C for 75 min, using 75% methanol at solid: liquid ratio of 1:50 resulted in maximum TFC (12.0–13.4 mg RE/g dry root), TPC (25.1–26.2 mg GAE/g dry root) and TSC (5.9–6.4 mg SE/g dry root). Extraction temperature at 50 °C for 76.5 min using 80% methanol at solid: liquid ratio of 1:50 produced maximum%DPPHsc (55.8–69.9%), %ABTSsc (43.0–52.0%), FRAP (0.54–0.59 μmol/g dry root), %βsc (49.2%–71.2%) and%O²⁻sc (34.4–41.6%). The content of inosine from ARC ranged from 1.3 to 6.0 mg/g with ethanol and from 0.9 to 4.1 mg/g with methanol extraction.
... These chemicals present in the plant extracts are expected to be safer and more cost effective than the existing antidepressants. Different ethno-pharmaceutical properties of various plant extracts and their effects are summarised in Table 7. Behavioural Despair [47] Allium sativum Garlic Rhizome Ethanolic Extract, dose25,50 and 100 mg/kg [48] Aloysia polystachya Lemon Verbena Aerial Part Hydroethanolic Extract Effect on Depression [49] Apocynum venetum Dogbane Aerial Part Dose-30-125 mg/kg [50] Areca catechu Betel Nut Fruit Ethanolic Extract, dose4-80 mg/kg Effect on Motor Activity [51] Asparagus racemosus Satavari Root Methanolic Extract, dose-100,200 and 400 mg/kg Effect on Serotonergic And Noradrenergic System And Augmentation Of Antioxidant Defences [52] Bacoba monnieri Brahmi Aerial Part Methanolic Extract, dose-20 and 40 mg/kg Significant Antioxidant Effect, Anxiolytic Activity And Improve Memory Retention [53] Berberis aristata Indian Barberry Root Berberine, (An Alkaloid), dose-5,10 and 20 mg/kg. Effect on CNS, Inhibit Monoamine Oxidase-A [54] Bupleurum falcatum Chai Hu, Hare's Ear Root Root Methanolic Extract Psycho stimulant Effect [55] Cimicifuga racemosa Black Bugbane Roots And Rhizomes Ethanolic And Isopropanolic Aqueous Extracts Effect on heraprutical Responses In Climacteric Women [56] Citation: Khushboo, Sharma B (2017) Antidepressants: Mechanism of Action, Toxicity and Possible Amelioration. ...
... This may enhance resistance to physical, biological and mental stress. Asparagus racemosus (Shatavari) has been used historically as a tonic and adaptogenic herb 14 and antidepressant 15 , anxiolytic 16 and adaptogenic 17 effects have been recently demonstrated in animal studies. Investigations exploring the mechanism of action of Shatavari have shown physiological modulation of the HPA axis and the sympathetic-noradrenergic system in animals 16 . ...
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A significant proportion of patients who present with skin disorders have concomitant psychopathology. It has been suggested that besides its primary physiological roles, the skin may also be an organ of expression or outlet for anxiety and emotional issues, and psychological stress may manifest on the skin in the absence of any identifiable skin disease. This case study describes the treatment of skin pathology of unknown aetiology where the manifestation corresponds with periods of emotional and psychosocial stress. It demonstrates the importance of a naturopathic treatment strategy that incorporates emotional health considerations and treatment with herbal formulations. The skin condition in this case was successfully treated and the beneficial effects of herbal medicine extended to improved nervous system function, with better sleep and emotional health and digestive tract function with reduced bloating. This case illustrates a naturopathic approach for the successful treatment of a perplexing skin condition.
... In the present research, the sedative and anxiolytic effects of P. roseum EO were examined in mice by using open field, elevated plus maze, and forced swimming test, which are validated models to test the effects of a given drug on CNS. Our findings showed that P. roseum Hil., and L. angustifolia (Blanco et al., 2009;Chioca et al., 2013;Galdino et al., 2012;Lopes Campêlo et al., 2011). in the FST test (Costa et al., 2013;de Almeida Costa et al., 2011 has been demonstrated that this activity is mediated through the serotonergic and noradrenergic systems (Singh, Garabadu, Muruganandam, & Krishnamurthy, 2009). ...
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The anxiolytic and antidepressant activities of the Reunion Geranium (Pelargonium roseum Willd) essential oil (EO) were evaluated in male Swiss albino mice by intraperitoneal administration of 10, 20, and 50 mg/kg bw using elevated plus maze (EPM), open‐field test (OFT), and forced swim- ming test (FST). Moreover, we evaluated whether the 5‐HT1A and GABAA–benzodiazepine recep- tor systems are involved in the anxiolytic effects through the coadministration of WAY‐100635 (a selective 5‐HT1A receptor antagonist) and flumazenil (an antagonist of benzodiazepine). GC–MS revealed the monoterpene alcohols citronellol (35.9%) and geraniol (18.5%) as the main compo- nents of the P. roseum EO. EO was effective in increasing the total number of entries and time spent in the open arms of EPM whereas number of rearing in OFT was significantly decreased in comparison with the control. In the FST, immobility time decreased in EO treated mice. Pre- treatment with WAY‐100635, but not Flumazenil, was able to reverse the effects of the EO in the EPM and FST, indicating that the EO activity occurs via the serotonergic but not GABAergic transmission. Overall, results of this work showed significant anxiolytic and antidepressant activ- ity of P. roseum EO and confirmed the traditional uses of Pelargonium species as calming agents
... Medicinal plants are considered as an important source of herbal drugs in the management of depression. They are comparatively better than that of synthetic anti-depressants in terms of safe and lesser unwanted side effects (Schulz 2006;Singh et al. 2009). Calotropis procera Linn (Family: Asclepiadaceae) is an Ayurvedic plant with important medicinal properties. ...
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Calotropis procera (CP; Apocynaceae) is reported to have several neuroprotective activities however it’s anti-depressant activity yet to be established. Therefore, the present study was proposed to evaluate the anti-depressant activity of the standardized ethanolic extract of CP (ECP) in chronic unpredictable mild stress (CUMS) paradigm exposed male rats. Animals were exposed to CUMS from day-1 (D-1) to D-28 except control group animals of the experimental schedule. ECP (50, 100 and 200 mg/kg, p.o.) and Imipramin (15.0 mg/kg, p.o.) were administered for seven consecutive days after CUMS paradigm. On D-35, ECP (200 mg/kg) significantly attenuated immobility period of the animals in both forced-swim and tail suspension and improved behavioural parameters in open-field and anhedonia in sucrose feeding tests. ECP (200 mg/kg) attenuated CUMS-induced hyperactivity of HPA-axis function. Further, ECP (200 mg/kg) mitigated CUMS-induced decrease in serotonin (5-HT), increase in 5-hydroxy indole acetic acid (5-HIAA) and increase in the ratio of 5-HIAA/5-HT in hippocampus and pre-frontal cortex. The CUMS-induced decrease in the level of expression of BDNF was significantly reversed with ECP (200 mg/kg) treatment. Moreover, ECP (200 mg/kg) significantly reduced the CUMS-induced decrease in the mitochondrial function and integrity in terms of level of formazan formed and intensity of tetramethyl rhodamine methylester dye in both the brain regions respectively. Therefore, ECP (200 mg/kg) mitigates CUMS-induced alterations in the behaviours, HPA-axis function, serotonergic activity, neurogenesis and mitochondrial function in the rodents. Thus, it can be assumed that ECP could be a potential alternative candidate in the management of depression.
... The traditional Indian medicinal practice known as Ayurveda is widely used in Asia and recognized by the WHO as a medical science. 13 In Europe, Ayurvedic medicine has become increasingly popular and recognized over the last years, particularly in the treatment of chronic 14,15 and psychosomatic 14,16 diseases. Multi-component and individualized Ayurvedic treatment strategies for burnout-syndrome include various non-pharmacological measures and are based on the assumption that combinations of various treatment elements may exert synergistic therapeutic effects. ...
Article
Objectives Ayurveda claims to be effective in the treatment of psychosomatic disorders by means of lifestyle and nutritional counseling. Design In a randomized controlled study mothers with burnout were randomized into two groups: Ayurvedic nutritional counseling (according to tradition), and conventional nutritional counseling (following the recommendations of a family doctor). Patients received five counseling sessions over twelve weeks. Main outcome measures Outcomes included levels of burnout, quality of life, sleep, stress, depression/anxiety, and spirituality at three and six months. It also included a qualitative evaluation of the communication processes. Results We randomized thirty four patients; twenty three participants were included in the per protocol analysis. No significant differences were observed between the groups. However, significant and clinically relevant intra-group mean changes for the primary outcome burnout, and secondary outcomes sleep, stress, depression and mental health were only found in the Ayurveda group. The qualitative part of the study identified different conversational styles and counseling techniques between the two study groups. In conventional consultations questions tended to be category bound, while counseling-advice was predominantly admonitory. The Ayurvedic practitioner used open-ended interrogative forms, devices for displaying understanding, and positive re-evaluation more frequently, leading to an overall less asymmetrical interaction. Conclusions We found positive effects for both groups, which however were more pronounced in the Ayurvedic group. The conversational and counseling techniques in the Ayurvedic group offered more opportunities for problem description by patients as well as patient-centered practice and resource-oriented recommendations by the physician. Trial Registration: NCT01797887.
... 7 In spite of the availability of many anti-depressant drugs, depression continues to be a major medical problem. 8,9 Newer generations of antidepressants have provided pharmacologic interventions that are effective and better tolerated than older agents. Even though, there is always a need for the development of new drugs for the treatment of depression as the existing classes of antidepressants are associated with several limitations like adverse effects, delay in the onset of antidepressant action, poor response in certain individuals, etc. 10 The development of newer and safer therapeutic agents would benefit the treatment modalities of depression. ...
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Background: Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. Many drugs are available as effective antidepressants. But still there is necessity of developing novel compounds with minimized side effects. Hence this study was aimed to investigate the antidepressant activity of novel furan compound in albino mice. Methods: Antidepressant activity of novel furan compound was investigated by using forced swimming test (FST) and tail suspension test (TST) models. Fluoxetine was used as standard drug in this study. Results: It has been observed from our study that medium dose of test compound (10 mg/kg) reduced duration of immobility time to 35 seconds when compared to control group (147 seconds) in FST model. In TST model, the test compound of medium dose (10 mg/kg) had produced 83% protection against passive behaviour which is almost similar to standard drug fluoxetine (100%). Conclusions: The results of the specifies that compared to other two doses of test compound (5 mg/kg and 20 mg/kg), medium dose of test compound found as an effective dose for treating depression produced due to stress. However, further expansion of the study is needed for this compound to prove as a novel effective antidepressant compared to other drugs available for treating depression.
... Due to destructive harvesting, combined with habitat destruction, and deforestation, the plant is now considered endangered in its natural habitat. The tuberous root is experimentally proven as antioxidant, anticancer, anti-infl ammatory, antiageing (Hayes 2008a , b ) and antidepressant (Singh et al. 2009 ). Two novel compounds were isolated from the tuber extract: shatavarins and sarsasapogenin (Sidiq et al. 2011 ). ...
Chapter
Arunachal Pradesh is a treasure house of biodiversity as well as traditional knowledge. The state harbours over 800 medicinal plants. Rising demands of signifi cant medicinal plants such as Taxus baccata , Paris polyphylla , Swertia chirayita , Neopicrorhiza scrophulariifl ora , etc. for developing pharmaceutical drugs have drastically reduced the wild population of these species. Some important medicinal plants of the state, their bioactive effi cacy and conservation status are mentioned in this paper. This paper also describes the traditional use of 13 ethnomedicinal plants used by the Monpa tribe of Arunachal Pradesh as antidote against food poisoning, snake bite, scorpion bite and insect bites. Some of the potent antidote plants claimed by the Monpa tribe are Aconitum heterophyllum , Asparagus racemosus , Ligularia amplexicaulis , Rhododendron hodgsonii , Swertia hookeri and Verbascum thapsus. Out of the 13 traditional antidote plants, six are new to science as traditional medicine and are yet to be pharmaceutically validated for their bioactivity. Given the strong traditional cultural use of the plants, it is expected that biochemical and pharmacological studies would reveal the bioactive compounds, which could be further developed as holistic evidence-based drugs to cure some complicated ail-ments/diseases.
... Further, the roots of this plant have been used to treat diseases related to spleen, liver, and other internal organs as well as for miscarriage threats 9 . The ethnopharmacological research in the last decade on A. racemosus revealed their immunomodulatory potential 10 , phytoestrogenic effects 11 , anti-diarrheal action 6 , anti-dyspepsia action 12 , anti-depressant action 13 , anti-tussive action 14 , immunoadjuvant 15 , anti-bacterial action 16 , antiulcerogenic action 7,17 , anti-stress action 18 , hypolipidemic potential 19 and cardio-protective ability 20 . Further, the extract of fresh roots of A. racemosus has been reported to have anti-neoplastic potential in female rats treated with 2,4-Dimethoxybenzaldehyde (DBMA) 21 . ...
... 7 It also demonstrates antitussive, antibacterial antihepatotoxic, immunomodulatory antioxidant, antidepressant and anti-inflammatory properties. [8][9][10][11][12][13][14][15][16][17] Though extract of Asparagus racemosus roots has several therapeutic properties, it has not been tested for it's cardioprotective activity against doxorubicin induced cardiotoxicity. ...
Article
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Background: Cardiotoxicity is one of the most feared side effects of anticancer agents like Doxorubicin. Asparagus racemosus is a widely used medicinal plant in Indian system of medicine known for its antioxidant activity. In certain studies ethanol extract of Asparagus racemosus has shown to possess cardioprotective activity in experimental animals while in some other studies cardioprotective potential of Asparagus racemosus has not been demonstrated. Therefore, due to the controversial action, the present study was designed to explore the cardioprotective effect of aqueous effect of Asparagus racemosus against doxorubicin induced cardiotoxity.Methods: Following approval from Institutional Animal Ethics Committee of L.L.R.M Medical College registered under CPCSEA, India, this study was conducted in which 30 rats were randomized into five groups of six rats each. Group I received 2 ml/kg b.w. normal saline p.o for 21 days, group II apart from receiving pellet diet and normal saline for 21 days were treated with Doxorubicin in a single dose of 20 mg/kg intraperitoneally on the 21st day, group III and group IV received aqueous extract of Asparagus racemosus in doses of 250 mg/kg/day and 500 mg/kg/day respectively p.o. for 21 days followed by administration of Doxorubicin (20 mg/kg i.p.) on the 21st day, Group V received Carvedilol in doses of 30 mg/kg/day p.o. for 21 days followed by administration of Doxorubicin (20mg/kg i.p) on the 21st day. Then they were anaesthetized and blood sample was collected from abdominal aorta for performing blood test i.e. Creatinine kinase MB fraction (CK-MB), Lactate dehydrogenase (LDH), Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruvate transaminase (SGPT). After blood collection the animals were sacrificed and heart was dissected out for histopathological study. The data obtained was organized and analysed by suitable statistical methods i.e. ANOVA followed by Post Hoc test.Results: CK-MB, LDH, SGOT and SGPT levels were found to be significantly raised (p<0.001) in Doxorubicin treated group. Asparagus racemosus pretreated groups exhibited significant limitation (p<0.001) in rise in levels of CK-MB,LDH,SGOT and SGPT levels in a dose dependent manner following Doxorubicin administration which were comparable to the group treated with the standard cardioprotective drug Carvedilol. Histopathological changes further corroborated cardioprotective potential of Asparagus racemosus.Conclusions: The present study concluded that aqueous extract of Asparagus racemosus possess cardioprotective potential against Doxorubicin induced cardiotoxicity.
... Many studies have demonstrated that plants having antioxidant activities have shown antidepressant-like effects in rodents (Singh et al., 2009;Prakash et al., 2018). A. blazei has proven itself as an excellent antioxidant herb (Hakime-Silva et al., 2013) this antioxidant potential of the herb might have played a role in the antidepressant-like activity of this magic mushroom. ...
Article
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The aim of this study was to investigate the antidepressant activity of hydroalcoholic extract Agaricus blazei (273 and 819 mg/kg; orally) in stressed and unstressed Swiss albino mice. Mice were immobilized to induce stress. Fluoxetine 20 mg/kg orally was given to stressed and unstressed animals and immobility time was noted by using forced swim test and tail suspension test. The concentration of plasma nitrite was also evaluated in stressed and unstressed mice. The effect of prazosin (α1-adrenoceptor antagonist), p-CPA (parachlorophenylalanine–tryptophan hydroxylase inhibitor) and 7-nitro-indazole (nNOS inhibitor) on the antidepressant activity of A. blazei was also evaluated. A. blazei and fluoxetine significantly decreased the duration of immobility time in stressed and unstressed mice, showing significant antidepressant activity. No substantial change was found in the locomotor activity. However, a significant reduction in the level of plasma nitrite was also noted in stressed mice. Hydroalcoholic extract showed prominent antidepressant activity in mice.
... Then all these rodents were inspected for the antidepressant effect of the extract by performing two major tests that are forced swim test (FST) and learned helplessness test (LH). The outcome of the tests showed diminished immobility in FST and amplification of avoidance response in LH demonstrating antidepressant activity because Asparagus racemosus provides assistance to both serotonergic and adrenergic systems [23]. The same dose-dependent antidepressant effect was observed when the methanolic extract The Pharmaceutical and Chemical Journal (50,100 and 200 mg/kg p.o.) was received by mice for 14 days and there was a noteworthy difference in test groups as compared to control groups. ...
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Asparagus racemosus is commonly known as Shatavari having a place in the family Asparagaceae that is extensively present in tropical and subtropics of Asia, Australia, and Africa. Traditionally it was used as a galactagogue, aphrodisiac, Rasayana, antiepileptic, adaptogenic, general health tonic, and in numerous female reproductive system problems. Now a day's extensive research has been done for phytochemical investigation and to explore its effects to treat and manage different diseases. It has specific steroids, flavonoids, phenolic compounds, and glycosides. Extract of different parts of the plant has been approved for its both in vitro and in vivo activities. It has an immunomodulatory, antidiabetic, antioxidant, anticancer, hepatic, and neuroprotective effect, antimicrobial, antiurolithiatic, aphrodisiac, memory-enhancing the property, antitussive effect, etc. This review elaborated on all of its pharmacological effect, active constituents that are more responsible for multi-facet actions of Asparagus racemosus.
... It is a main drug for improving female reproductive health, and so only it is also known as the 'Queen of herbs' [76]. Various animal and clinical studies have demonstrated that Asparagus racemosus is having antileishmanial [77], antitumoUr [78], immunomodulatory [79], antidepressant [80], antihyperglycaemic [81] and anti-infertility [82] activities. Costus speciosus (Koenig) Sm. is used as vegetables in many Indian states and also widely used in traditional medicines in the management of several ill health conditions such as jaundice, diabetes, pneumonia, rheumatism and skin diseases. ...
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Chhattisgarh state is situated in the central part of India and is also known as the ‘Bowl of rice’. Paddy is the principal crop of this state, and rice is the staple diet of the people. The state largely maintains its ethnic food culture as most of its population continues to live within rural and tribal areas. The state has nearly 44% of forest cover which serves as a decent source of food. People here prefer a vegetarian diet, and over 70 varieties of leaves, 25 varieties of tubers and roots are used here as vegetables. The present article is an attempt to explore the ethnic food culture of Chhattisgarh and to provide information about rice and non-rice-based traditional recipes, sweet dishes, leafy vegetables, tubers and roots which are consumed here. Irrespective of all the modern changes in food habits, the people of Chhattisgarh still preserve their traditional food culture.
... The high progesterone levels observed in A. racemosus -treated animals may contribute to its antidepressant effects, since progesterone has been reported to have similar antidepressant effects when chronically administered [61][62][63]. The A. racemosus treatment also restored monoamine levels and reduced nitrosative stress, also reported previously [64]. These changes have been reported to be associated with depression in various clinical and preclinical studies [27][28][29][30][65][66][67][68][69][70][71][72]. ...
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Asparagus racemosus Willd. (Family Liliaceae), also known as female reproductive tonic, is traditionally used across the Sub-Himalayan region in Uttarakhand, India for treatment of epilepsy and disorders of female reproductive system. Therefore, in this study, we investigated the anticonvulsant effect of A. racemosus in a mouse model of catamenial epilepsy. We artificially increased progesterone and neurosteroid levels (a state of pseudo-pregnancy) in adult Swiss albino female mice by injecting pregnant mares' serum gonadotropin (PMSG) (5 IU s.c.), followed by human chorionic gonadotropin (HCG) (5 IU s.c.) after 46 h. In the following 10 days, A. racemosus treatment was given along with measurement of progesterone, estradiol, and corticosterone levels in the blood. Neurosteroid withdrawal was induced by finasteride (50 mg/kg, i.p.) on treatment day 9. Twenty-four hours after finasteride administration (day 10 of treatment), seizure susceptibility was evaluated with the sub-convulsant pentylenetetrazole (PTZ) dose (40 mg/kg i.p.). Four hours after PTZ, animals were assessed for depression like phenotypes followed by euthanasia and separation of brain parts (cortex and hippocampus). The results showed that PMSG and HCG treatment elevated progesterone and estradiol levels. Treatment with finasteride increased seizure susceptibility and depression due to decreased progesterone and elevated estrogen levels coupled with decreased monoamine and elevated corticosterone levels. A. racemosus treatment, on the other hand, significantly decreased seizure susceptibility and depression like behaviors, possibly because of increased progesterone, restored estradiol, corticosterone, and monoamine levels. We concluded that herbal formulations using A. racemosus root extracts may be used as monotherapy or adjuvant therapy along with available AEDs for the better and safe management of catamenial epilepsy as well as comorbid depression.
... Divine therapy and psycho-supportive therapy are the two components of Ayurveda that address the psychological component of the individual, reinforcing their belief system toward the divine and elevating their morale to face the unseen and unknown with a positive approach. Divine [17,18] 3 ...
... Asparagus racemosus decreased immobility in the FST and increased the avoidance response in the LHT, which is indicative of antidepressant-like activity. The authors concluded that this activity could be mediated through the serotonergic and the noradrenergic systems, as well as an increase in antioxidant defenses [84,85]. Moreover, A. racemosus is a nonselective competitive inhibitor for both AChE and MAO enzymes and thus may produce some interactions with other drugs and food [86]. ...
Article
Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. Johnʼs wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.
... AC extracts reportedly provide neuroprotective, antipsychotic, and anti-depressant effects [30][31][32], as well as improved memory protection against amnesia in rodent models [33]. In addition, extracts from a related species, Asparagus, have been reported to possess anti-inflammatory properties [34,35]. ...
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Background Depression is a serious and common psychiatric disorder generally affecting more women than men. A woman’s risk of developing depression increases steadily with age, and higher incidence is associated with the onset of menopause. Here we evaluated the antidepressant properties of Asparagus cochinchinensis ( AC) extract and investigated its underlying mechanisms in a rat menopausal depression model. Methods To model this menopausal depression, we induced a menopause-like state in rats via ovariectomy and exposed them to chronic unpredictable mild stress (CUMS) for 6 weeks, which promotes the development of depression-like symptoms. During the final 4 weeks of CUMS, rats were treated with either AC extract (1000 or 2000 mg/kg, PO), which has been reported to provide antidepressant effects, or with the tricyclic antidepressant imipramine (10 mg/kg, IP). Results We report that CUMS promotes depression-like behavior and significantly increases serum corticosterone and inflammatory cytokine levels in the serum of ovariectomized (OVX) rats. We also found that CUMS decreases the expression of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomyosin receptor kinase B (TrkB), in OVX rats, and treatment with AC extract rescues both BDNF and TrkB expression levels. Conclusion These results suggest that AC extract exerts antidepressant effects, possibly via modulation of the BDNF-TrkB pathway, in a rat model of menopausal depression.
... The attributes of many herbs, including species of Asparagus (Asparagaceae), have received much attention, because they are reported to have neuroprotective (Xiong et al., 2011), anti-inflammatory, anti-amnestic (Ojha et al., 2010), antipsychotic (Zhang, 2004), and antidepressant effects (Singh et al., 2009 a tonic and anti-inflammatory (Kim et al., 1998;Park et al., 2011) herbal medicine in Asian countries. Pharmacological studies of AC have demonstrated its antitumor (Park et al., 2011), anti-inflammatory (Lee et al., 2009, and immunostimulant activities (Xiong et al., 2011). ...
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Extracts of Asparagus cochinchinensis (AC) have antitumor, anti-inflammatory, and immunostimulant effects. The neurobiological mechanisms underlying the effects of AC have not been sufficiently explored. Thus we performed in vivo and in vitro experiments to further characterize potential therapeutic effects and to clarify the underlying mechanisms. In the tail suspension test immobility time was significantly reduced after administration of AC which suggests antidepressant-like activity without effect on body core temperature. Moreover, in animals pretreated with AC infarct size after occlusion of the middle cerebral artery was reduced. In vitro experiments confirmed neuroprotective effects. Total saponin obtained from AC significantly inhibited H2O2-induced cell death in cultured cortical neurons. The survival-promoting effect by AC saponins was partially blocked by inhibitors for extracellular signal-regulated kinase (ErK) and phosphoinositide 3-kinase Akt (PI3K/Akt) cascades, both of which are known as survival-promoting signaling molecules. Furthermore, phosphorylation of Scr homology-2 (SH2) domain-containing phosphatase 2 (Shp-2) was induced by AC, and the protective effect of AC was abolished by NSC87877, an inhibitor for Shp-2, suggesting an involvement of Shp-2 mediated intracellular signaling in AC saponins. Moreover, AC-induced activation of pShp-2 and ErK1/2 were blocked by NSC87877 indicating that activation of these signaling pathways was mediated by the Shp-2 signaling pathway. These effects appear to be associated with activation of the Shp-2, ErK1/2 and Akt signaling pathways. Our results suggest that AC has antidepressant-like and neuroprotective (reducing infarct size) effects and that activation of pShp-2 and pErK1/2 pathways may be involved in the effects.
... Depression is a common, chronic and recurrent mental disorder which is one of the leading cause of disability and suicide (Singh et al., 2009). It is a complex disease whose etiology is not yet fully explained, but the occurrence of the disease is thought to be related to psychosocial, biological and genetic risk factors (Yemez and Alptekin, 1998). ...
Article
Ethnopharmacological relevance Ethnobotanical surveys revealed that X. orientale subsp. italicum (Moretti) Greuter has been used against central nervous system disorders in Turkish folk medicine. The aim of the present study is to verify the folkloric assertion on this plant. The compounds responsible for the activity were investigated using bioassay-guided fractionation procedures. Materials and methods The antidepressant activity of the aqueous, n-hexane, ethyl acetate (EtOAc), methanol (MeOH) extracts; fractions and isolated compounds from active MeOH extract were evaluated by using the in vitro MAO inhibition assay and three different in vivo models namely forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with control and reference groups, and active compounds of the plant have been determined. Through the bioassay-guided fractionation procedures, two compounds were isolated from the active fraction and their structures were elucidated by spectroscopic methods. Results The MeOH extract of the plant was found to possess antidepressant-like activity. This extract was then subjected to chromatographic techniques. Isolated sesquiterpene lactones were elucidated as xanthatin (1) and xanthinosin (2), which were responsible for the antidepressant-like activity. Conclusions This study discovered the antidepressant potential of X. orientale subsp. italicum. Using bioassay-guided fractionation and isolation techniques, xanthatin (1) and xanthinosin (2) were determined as the main active components of the leaves.
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DEPRESSION Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and sense of well-being. 1 Depressed people may feel sad, anxious, empty, hopeless, worried, helpless, worthless, guilty, irritable, hurt, or restless. They may lose interest in activities that once were pleasurable, experience loss of appetite or overeating, have problems concentrating, remembering details, or making decisions, and may contemplate or attempt suicide. Insomnia, excessive sleeping, fatigue, loss of energy, or aches, pains, or digestive problems that are resistant to treatment may also be present. 2 Depression can happen to anyone-and does happen to one in four of us over our lifetimes. Different factors that make it more likely to happen, include biological make-up, upbringing, or reaction to life events. Depression is an extreme low mood that lasts a long time and makes a person feel sad, irritable or empty. Many people, including many teens, have suffered in this way. A depressed person 3 :  has much less energy to do activities  feels like nothing matters.  sees life in a negative way.  feels like it will never get better W WO OR RL LD D J JO OU UR RN NA AL L O OF F P PH HA AR RM MA AC CY Y A AN ND D P PH HA AR RM MA AC CE EU UT TI IC CA AL L S SC CI IE EN NC CE ES S V Vo ol lu um me e 2 2, , I Is ss su ue e 4 4, , 2 22 27 79 9-2 22 29 90 0.. R Re ev vi ie ew w A Ar rt ti ic cl le e I
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OBJECTIVE Asparagus adscendens Roxb. (Liliaceae), a traditional herbal medicine, has been used as an aphrodisiac and brain tonic in Asian countries. The aim of the present study is to investigate the antidepressant-like effect of standardized hydroethanolic extract of A. adscendens root and its possible mechanisms. MATERIALS AND METHODS Mice administered with vehicle, imipramine (15 mg/kg/day; i.p.), and A. adscendens extract (AAE) (25, 50, and 100 mg/kg/day; i.p.) for 14 days were subjected to behavioral tests including forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) on the 14th day. In order to explore the underlying mechanism behind an antidepressant effect of AAE, the brain monoamine levels, oxidative stress parameters, and serum corticosterone levels were monitored. RESULTS Our results indicated that pretreatment of AAE (25, 50, and 100 mg/kg) for 14 days statistically significantly (P < 0.01) demonstrated antidepressant-like effect as evidenced by reduced immobility time in both FST (105, 78.6, and 53.6 s) and TST (97.6, 73.5, and 54.67 s), with no significant change in spontaneous locomotor activities as observed in OFT. Further, the behavioral improvement was supported by the statistically significantly (P < 0.05) enhanced levels of monoamines and reduced corticosterone level along with amelioration of oxidative stress in AAE-treated animals as compared to vehicle control group. Conclusion Our findings clearly demonstrated the antidepressant-like effect of AAE, which might have been mediated through the modulation of monoaminergic system and by regulating hypothalamic–pituitary–adrenal axis with amelioration of oxidative stress.
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Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities.
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Childbirth is a critical period of life and behavior towards childbirth varies from culture to culture. In many Southeast Asian cultures, postpartum period is considered important from point of view of recovery by offering a period of confinement. This study aimed to describe the plants used in diet therapy after childbirth in postpartum period, their importance and tried to assess the potential effects of the practices on the health of new mother and baby. The study shows that medicinal plants play a significant role in the recovery of new mother as they possess many biological properties and their molecular targets cover vast area. Therefore, the above mentioned plant species should be further explored for their other pharmacological characteristics for human welfare. Formulations can be prepared using these plants for the better healthcare of women.
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In this study, the herbal formulation containing nanophytosomes of Mucuna prureins extract (MPE) was engineered to ameliorate its rate of drug release, in vivo antidepressant profile, and stability. The Mucuna prureins nanophytosomes (MPP) were designed by using a full factorial design approach, taking into consideration various variables that could give optimized formulation. Then, pure extract and optimized formulation showing higher entrapment efficiency were studied for in vitro dissolution and in vivo antidepressant activity in depression models like forced swimming test (FST) and tail suspension test (TST) in Swiss albino mice. The physicochemical characterization was carried out using particle size analysis and zeta potential, Fourier transformation infrared spectroscopy, differential scanning calorimetry, proton nuclear magnetic resonance, powder X-ray diffractometer, scanning electron microscopy, and solubility studies. Moreover, the stability of nanophytosomes was assessed by subjecting optimized formulation to freeze–thaw cycle stability testing and calculating entrapment efficiency at the end of the cycle. PXRD and SEM revealed a decrease in the crystalline nature of nanophytosomes. 1H NMR, DSC, and FTIR asserted the formation of the phyto-phospholipids complex. The rate and extent of dissolution were also found enhanced and sustained in nanophytosomes as compared to pure extract. In vivo antidepressant activity depicted a significant reduction of immobility in mice treated with nanophytosomes as compared to those treated with the pure extract. Moreover, optimized formulation was found stable as entrapment efficiency values were not reduced significantly. Thus, nanophytosomes drug delivery could be the best strategy to improve physicochemical properties of extract and thus could be exploited for the extracts having poor solubility, poor permeability, and poor stability.
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Major depression is a debilitating disorder, predicted to be the second most prevalent human malady by the year 2020. Although a variety of chemical antidepressant remedies like tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors are available, yet approximately 30% of depressed patients are resistant to the existing drugs and remaining 70% do not achieve full remission. Therefore, a constant urge continues for discovery of newer, better-tolerated and more efficacious treatments of depression, which include search for discovery of medicinal plants with potential antidepressant activity. The present paper discusses anti-depression potential of 70 medicinal plants with emphasis on their pre-clinical and clinical reports. Majority of plants shows antidepressant activity through serotonergic, noradrenergic and dopaminergic systems.
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Ethnopharmacological relevance Cognitive symptom is a “core” symptom of major depressive disorder (MDD) patients with clear deficit in memory, social and occupational function, and may persist during the remitting phase. Therefore, the remission of cognitive symptom has been considered as one of the main objectives in the treatment of MDD. Herbal antidepressants have been used to treat MDD, and there has been great advances in the understanding of the ability of these herbs to improve cognitive deficit linked to brain injury and various diseases including depression, Alzheimer disease, diabetes and age-related disorders. This systematic review summarizes the evidence from preclinical studies and clinical trials of herbal antidepressants with positive effects on cognitive deficit. The potential mechanisms by which herbal antidepressants prevent cognitive deficit are also reviewed. This review will facilitate further research and applications. Materials and methods We conducted an open-ended, English restricted search of MEDLINE (PubMed), Web of Science and Scopus for all available articles published or online before 31 December 2019, using terms pertaining to medical herb/phytomedicine/phytochemical/Chinese medicine and depression/major depressive disorder/antidepressant and/or cognitive impairment/cognitive deficit/cognitive dysfunction. Results 7 prescriptions, more than 30 individual herbs and 50 phytochemicals from China, Japan, Korea and India with positive effects on the depressive state and cognitive deficit are reviewed herein. The evidence from preclinical studies and clinical trials proves that these herbal antidepressants exhibit positive effects on one or more aspects of cognitive defect including spatial, episodic, aversive, and short- and long-term memory. The action mode of the improvement of cognitive deficit by these herbal antidepressants is mediated mainly through two pathways. One pathway is to promote hippocampal neurogenesis through activating brain derived neurotrophic factor-tropomyosin-related kinase B signaling. The other pathway is to prevent neuronal apoptosis through the inhibition of neuro-inflammation and neuro-oxidation. Conclusion These herbal antidepressants, having potential therapy for cognitive deficit, may prevent pathological processes of neurodegenerative diseases. Furthermore, these herbal medicines should provide a treasure trove, which will accelerate the development of new antidepressants that can effectively improve cognitive symptom in MDD. Studies on their molecular mechanisms may provide more potential targets and therapeutic approaches for new drug discovery.
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Ayurveda is an ancient Indian medical system with unique approaches for the treatment of various brain disorders. Ashtanga Ghrita, a cow Ghrita-based polyherbal classical formulation, has been well defined in ancient Ayurvedic texts Ashtanga Hridya to enhance speech, intellect, and memory. The formulation contains eight potent neuroprotective herbs along with clarified cow butter and milk. The review is aimed to come up with comprehensive scientific evidence regarding the plant ingredients of Ashtanga Ghrita so that it can be used for further clinical studies as well as to treat a variety of neurological diseases. The plant ingredients have been practiced since ancient times for various disorders in India as well as worldwide. The plants contain various phytochemicals including terpenes, steroids, glycosides, flavonoids, alkaloids, amino acids, fatty acids, aryl esters, and carbohydrates. The collected pharmacological evidence suggests that all the plant ingredients have neuroprotective, anxiolytic, antidepressant, antioxidant, immunomodulatory, sedative, antiproliferative, and anticonvulsant activity. Based on the collected evidence, Ashtanga Ghrita may prove to be an effective neuroprotective drug and might be useful in various neurological disorders. Further, well-designed multicentric clinical trials are required to elucidate and comprehend the therapeutic potential of the formulation.
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Background of research Ficus religiosa L. (Moraceae) has been indicated for a range of ailments including disorders of the central nervous system (CNS) like convulsion, anxiety and amnesia. Its fruits/figs have been reported for high serotonergic content. Moreover, depression is a common mental disorder of dysfunctional monoamines (serotonin, noradrenaline and dopamine) level in CNS. Objective The current study was aimed at investigating the antidepressant effects of hydroalcoholic extract of Ficus religiosa L. fruits (EFR) in rodent models of depression. Material and Method The rodents were pre-treated orally with suspension (DMSO 1: CMC 9) of EFR for 7 days, daily at the doses of 30, 100 or 300 mg/kg/day and screened with validated depression models viz., force swim test (FST), tail suspension test (TST) and 5- hydroxytryptophan (5-HTP) induced head twitches. The antidepressant effect of EFR was compared to that of imipramine (15 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.). Result and discussion The EFR significantly (p<0.05) decreases the duration of immobility time in rats of both FST and TST in a dose-dependent manner. Further, the extract also shows a dose-dependent increase in head twitches in mice. The efficacy of tested EFR was found to be comparable to that of imipramine and fluoxetine. Conclusion Results of the study establish the potential of the hydro-alcoholic extract of Ficus religiosa L. fruits (EFR) against behavioural depression. Furthermore, the EFR possess antidepressant activity possibly via modulating serotonergic neurotransmission. Keywords: Moraceae, Force swim test, Tail suspension test, Serotonin.
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Tuberous plants are the vital source of medicinal drugs. Among these Asparagus racemosus is an important herb which is well known for its pharmacological applications. A lot of medicinally importance attributes have been assigned to this herb. It has been used by tribes located in distinct area of India from primeval time. Key component of this herb is saponins. Recent developments in transgenic research have opened up the possibility of the metabolic engineering of biosynthetic pathways to produce these high-value secondary metabolites. The present review is a pragmatic approach to accrue the findings on this very important herb.
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Background of research Ficus religiosa L. (Moraceae) has been indicated for a range of ailments including disorders of the central nervous system (CNS) like convulsion, anxiety and amnesia. Its fruits/figs have been reported for high serotonergic content. Moreover, depression is a common mental disorder of dysfunctional monoamines (serotonin, noradrenaline and dopamine) level in CNS.
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Medicinal plant plays a crucial role in the socioeconomic development and maintaining the human health and culture. Naturally, plant-derivative drugs have an imperative position in both traditional and modern medicine. Jharkhand is rich in biodiversity of medicinal plants. The forest area covers about 30.29% of the total area of Jharkhand. The extensive use of such medicinal plants is nowadays being adopted by almost all the developing and developed countries as therapeutic purpose. It is used to heal various diseases and also prevents the ill effects of synthetic drugs. The main objectives of this article are to identify selected native medicinal properties found in the native forest of Jharkhand and maintain the plants under ex-situ conservation Park for socioeconomic development of the tribal which has been used for multipurpose curative applications and their value addition for different diseases. In the current article a total of 41medicinal plants have been selected for study and documented to their therapeutic use against various types of diseases frequently occurred in tribal dominating mining areas at coal capital of the country located at CSIR-CIMFR, Dhanbad in Jharkhand state of India.
Chapter
Central nervous system disorders such as anxiety, depression, and Alzheimer’s occur as a result of the imbalance of neurotransmitters such as acetylcholine (Ach), dopamine (DA), serotonin (5-HT), and/or γ-aminobutyric acid (GABA). Such disorders may lead to emotional changes as well as impaired cognitive functions. Plants have been the predominant source of medicines throughout the vast majority of human history and remain so today outside of industrialized societies. Many plants are known for their anxiolytic, antidepressant, and memory-enhancing properties. Moreover, phytoconstituents, particularly alkaloids, have proven effectiveness as psychoactive lead drugs. In this chapter, we will have an overview of the most important psychoactive, neuroprotective, and antidepressant plants and phytoconstituents with emphasis on their mechanism of action.
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DEPRESSION Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and sense of well-being. 1 Depressed people may feel sad, anxious, empty, hopeless, worried, helpless, worthless, guilty, irritable, hurt, or restless. They may lose interest in activities that once were pleasurable, experience loss of appetite or overeating, have problems concentrating, remembering details, or making decisions, and may contemplate or attempt suicide. Insomnia, excessive sleeping, fatigue, loss of energy, or aches, pains, or digestive problems that are resistant to treatment may also be present. 2 Depression can happen to anyone-and does happen to one in four of us over our lifetimes. Different factors that make it more likely to happen, include biological make-up, upbringing, or reaction to life events. Depression is an extreme low mood that lasts a long time and makes a person feel sad, irritable or empty. Many people, including many teens, have suffered in this way. A depressed person 3 :  has much less energy to do activities  feels like nothing matters.  sees life in a negative way.  feels like it will never get better W WO OR RL LD D J JO OU UR RN NA AL L O OF F P PH HA AR RM MA AC CY Y A AN ND D P PH HA AR RM MA AC CE EU UT TI IC CA AL L S SC CI IE EN NC CE ES S V Vo ol lu um me e 2 2, , I Is ss su ue e 4 4, , 2 22 27 79 9-2 22 29 90 0.. R Re ev vi ie ew w A Ar rt ti ic cl le e I
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Climbers are plants with weak stems that require support to grow upright. This group of plants develops various climbing mechanisms, classified as tendrillar, twiners, scramblers, clinging, adhesive and woody climbers (lianas). Although climbers are predominantly angiosperms, some are ferns, and one gymnosperm member Gnetum is included in this category. The angiosperm families mainly composed of climbers include Cucurbitaceae, Convolvulaceae and Dioscoreaceae. India’s biodiversity includes two regions, the Western Ghats and the Eastern Himalayas. According to the Botanical Survey of India, of approximately 18,000 species of angiosperms in India, 8000 of them are medicinal plants and several of them are climbers. Many climbers are medicinally important and used as herbal remedies in traditional systems of Indian medicine, including Ayurveda, Sidha and Unani. Several active phytochemicals from different parts of these plants are isolated and used as medicine either alone or in combination with other compounds. Unfortunately, many of these plants are under the threat of extinction due to habitat depletion and overexploitation and conservation efforts are required to ensure their long-term stability. In this review, we discuss in vitro propagation and conservation strategies for Indian medicinal climbers from diverse families including Fabaceae, Aristolochiaceae, Asparagaceae, Caesalpiniaceae, Sapindaceae, Asclepiadaceae, Vitaceae, Ranunculaceae, Menispermaceae, Colchicaceae, Apocynaceae, Rubiaceae, Passifloraceae, Stemonaceae, Euphorbiaceae and Cucurbitaceae due to their high medicinal value.
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The present study deals with validation of adaptogenic potential of different extracts (petroleum ether, dichloromethane, chloroform, ethanol and aqueous) of an Ashtavarga plant, Polygonatum cirrhifolium (Wall.) Royle by in vitro, in vivo and in silico studies. In vitro adaptogenic potential was determined by evaluating in vitro antioxidant activity using ABTS, DPPH, and total antioxidant capacity assays. Anoxia stress tolerance (AST), forced swimming endurance test (FST), tail suspension test (TST) and chronic cold restraint stress (CCRS), models have been used for in vivo adaptogenic study. Docking study of selected chemical constituents (from GC/MS analysis of different extracts) with glucocorticoid protein (PDB 5NFP) and c-Jun N-terminal kinase 3 protein (PDB 2P33) was carried out for analyzing in silico adaptogenic activity. Ethanol extract showed highest antioxidant power among all the extracts. Swimming time in FST and tolerance time in AST increased significantly by petroleum ether (PE) and ethanol (EE) extract treatment compared to stress control animals. PE and EE treatment significantly reduced the immobility time in TST over stress control animals. Further, pre-treatment with PE and EE significantly decreased the stress induced elevated levels of various biochemical parameters such as blood glucose, total protein, triglycerides, corticosterone and blood urea nitrogen. Docking study revealed good interaction of sitosterol with PDB5NFP (docking score of 7.66 kcal/mol). 3,5-Dicyclohexyl-4-hydroxy-benzoic acid-methyl ester and 6,7-Dichloro-5-[(1-ethylpyrrolidin-2-yl)methylami-no]-1,3-dimethyl-pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione showed excellent interaction with PDB2P33. On the basis of the present findings, it can be perceived that P. cirrhifolium possessed noteworthy adaptogenic activities which might be due to antioxidant property of different secondary metabolites of the plant.
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There is enough data available now to believe that nature has provided cure of almost every ailment through herbal medicine or management. Therefore, now there is lot of emphasis on identification, evaluation, development and characterization of numerous plants and their active constituents against several diseases including depression. Depression is not only one of the most common ailments but also a highly complex condition to study. Even though several antidepressant drugs are available now, yet their effectiveness and usefulness are highly questionable especially because of their side effects. As herbal remedies are generally associated with favourable safety profiles therefore they have the possible potential to deliver effective replacements to currently available synthetic antidepressants. More recently, efforts have been focused on characterization of pharmacologically active ingredients and to identify the mode of action of herbal antidepressant medicines. This review describes a brief introduction of different animal models for depression and discusses the advantages and disadvantages for each approach. Then we have summarized possible plant phytochemicals as antidepressant drug and the underlying mechanisms. In the main body of the review, we have discussed in detail the most frequently used plants (21) being investigated for the treatment of depression. Additionally, we have provided the list of medicinal plants (92) representing their origin, parts used, extraction method, evaluation method and possible active ingredient. In the final part of the review we have presented the summary of clinical trials on the use of medical plants for depression and their active constituents.
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Ethnopharmacological relevance Cross-cultural comparison of plants used during lactation and the postpartum period offers insight into a largely overlooked area of ethnopharmacological research. Potential roles of phytochemicals in emerging models of interaction among immunity, inflammation, microbiome and nervous system effects on perinatal development have relevance for the life-long health of individuals and of populations in both traditional and contemporary contexts. Aim of the study Delineate and interpret patterns of traditional and contemporary global use of medicinal plants ingested by mothers during the postpartum period relative to phytochemical activity on immune development and gastrointestinal microbiome of breastfed infants, and on maternal health. Materials and Methods Published reviews and surveys on galactagogues and postpartum recovery practices plus ethnobotanical studies from around the world were used to identify and rank plants, and ascertain regional use patterns. Scientific literature for 20 most-cited plants based on frequency of publication was assessed for antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, antidepressant, analgesic, galactagogic and safety properties. Results From compilation of 4418 use reports related to 1948 species, 105 plant taxa were recorded ≥ 7 times, with the most frequently cited species, Foeniculum vulgare, Trigonella foenum-graecum, Pimpinella anisum, Euphorbia hirta and Asparagus racemosus, 81, 64, 42, 40 and 38 times, respectively. Species and use vary globally, illustrated by the pattern of aromatic plants of culinary importance versus latex-producing plants utilized in North Africa/Middle East and Sub-Saharan Africa with opposing predominance. For 18/20 of the plants a risk/benefit perspective supports assessment that positive immunomodulation and related potential exceed any safety concerns. Published evidence does not support a lactation-enhancing effect for nearly all the most-cited plants while antidepressant data for the majority of plants are predominately limited to animal studies. Conclusions Within a biocultural context traditional postpartum plant use serves adaptive functions for the mother-infant dyad and contributes phytochemicals absent in most contemporary diets and patterns of ingestion, with potential impacts on allergic, inflammatory and other conditions. Polyphenolics and other phytochemicals are widely immunologically active, present in breast milk and predominately non-toxic. Systematic analysis of phytochemicals in human milk, infant lumen and plasma, and immunomodulatory studies that differentiate maternal ingestion during lactation from pregnancy, are needed. Potential herb-drug interaction and other adverse effects should remain central to obstetric advising, but unless a plant is specifically shown as harmful, considering potential contributions to health of individuals and populations, blanket advisories against postpartum herbal use during lactation appear empirically unwarranted.
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Experiments were conducted to determine if the actions of antidepressant drugs in a pharmacological screen would be localized to specific brain regions. Rats were infused in discrete brain regions with drugs of different pharmacological properties and processed in the forced swim test. Infusion of imipramine and pargyline into the amygdala produced behavioral responses similar to i.p. injections of the drugs. The regions of the amygdala from which positive responses could be elicited were highly selective. From cannula placements and diffusion studies with autoradiography it appears that a locus of action of imipramine and pargyline is confined to the central, basolateral and/or lateral nuclear regions of the amygdala. Behavioral responses of rats in which imipramine was infused into the anterior amygdala or caudate-putamen did not differ from saline controls. When infused into regions of the amygdala in which imipramine was active, iprindole, an "atypical" antidepressant, did not produce a behavioral response in the forced swim test. Two "false positives" in the forced swim test, atropine and amphetamine, were also not active when infused into the amygdala. These results indicate that the amygdala is a critical site of action for certain antidepressant drugs in the forced swim test, and that behavioral activation in the test induced by iprindole, amphetamine and atropine involve brain regions other than the amygdala.
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We used in vivo microdialysis to examine extracellular levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum and the lateral septum during the forced swimming test, (FST) a behavioral test conducted in rats that is commonly used to predict the effect of antidepressant drugs. The forced swimming test consisted of a 15-min pretest swim and a 5-min test swim 24 hr later. The antidepressant fluoxetine (20 mg/kg s.c.) or saline was administered 23.5, 5 and 1 hr before the test swim. In the striatum, the pretest swim increased 5-HT in both treatment groups. On the second day, the test swim had no effect on 5-HT in saline-treated rats but slightly decreased striatal 5-HT in fluoxetine-treated rats. In the lateral septum, the pretest swim decreased 5-HT in both treatment groups. On the second day, the test swim had no effect on 5-HT in saline-treated rats but decreased lateral septum 5-HT in fluoxetine-treated rats. Ratings of behavior showed that fluoxetine treatment increased swimming behavior and decreased immobility during the test swim. Immobility was positively correlated and swimming was negatively correlated with changes in extracellular 5-HT in the lateral septum but not in the striatum. Therefore, fluoxetine treatment altered adaptation of the regional response of extracellular 5-HT ordinarily produced in the FST, reversing the 5-HT response to the initial swim in the striatum and restoring the response to the initial swim in the lateral septum.
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The forced swimming test (FST) predicts the efficacy of clinically effective antidepressants. In the present study, using the FST we examined the antidepressant potential of three novel tropane analogs: 8-methyl-2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicy clo[3.2.1] (WF-31) and 2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1 ]octane (WF-50), selective inhibitors of serotonin uptake, and 8-methyl-2beta-propanoyl-3beta-(4-(1-methylphenyl)-8-azabicyclo[3. 2.1] octane (PTT, WF-11), a selective inhibitor of dopamine uptake. Fluoxetine and GBR 12909 were used as controls for selective inhibitors of serotonin and dopamine, respectively. Drugs were administered three times in a 24-hr period between pretest and test sessions. Intraperitoneal administration of WF-31 (0.1-10.0 mg/kg), WF-50 (0.3-10.0 mg/kg) and fluoxetine (0.3-10.0 mg/kg) dose-dependently decreased immobility while increasing swimming. In contrast, WF-11 (0.3-3.0 mg/kg) dose-dependently decreased immobility and increased both swimming and climbing, whereas GBR 12909 (3.0-30.0 mg/kg) decreased immobility, increased climbing but did not affect swimming. In a separate experiment, WF-11 (1.0 mg/kg) increased locomotor activity, whereas a higher dose of WF-11 (3.0 mg/kg) and GBR-12909 (30.0 mg/kg) produced stereotypic behaviors, suggesting that the effects in the FST may have been attributable to increases in general activity. However, the effects of WF-11 on swimming in the FST indicate that WF-11 produces antidepressant-like effects in addition to motor stimulation. These results confirm previous results that behavioral patterns manifested in the FST are characteristic of specific monoamine uptake inhibitors. In addition, these results demonstrate that WF-31 and WF-50 produce behavioral patterns similar to fluoxetine in the FST without accompanying decreases in motor activity, suggesting a potential antidepressant action. Based on comparisons with fluoxetine, the data suggest WF-31 and WF-50 may be therapeutically useful as potential antidepressant medications.
Article
Abstract1.The degree to which organisms can exert control over events to which they are exposed has a strong impact on behavior and physiological functioning. Effects caused by the uncontrollability of events that are beyond the organism's control rather than by the events perse have been called learned helplessness effects.2.The present paper reviews such learned helplessness effects. At a behavioral level, uncontrollable aversive events result in associative, motivational, and emotional deficits. At a neurochemical level, uncontrollable but not controllable aversive events have been reported to lead to disturbances in cholinergic, noradrenergic, dopaminergic, serotonergic, and GABAergic systems. However, there are interpretive difficulties in this literature, and these are discussed.3.The controllability/uncontrollability of aversive events has a role in producing stress-induced analgesia and the activation of endogenous opiate systems. These relationships are reviewed. It is proposed that the learning that aversive events cannot be controlled activates an opiate system.4.The research reviewed is related to depression, and the general issue of animal models of depression is discussed. It is concluded that no experimental paradigm can be a model of depression in some general sense, but can only model a particular aspect. Learned help-lessness may model “stress and coping”.
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The pathophysiology of major affective illness is poorly understood. However, several lines of preclinical and clinical evidence indicate that an enhancement of 5-HT-mediated neurotransmission might underlie the therapeutic effect of most antidepressant treatments. This net effect would, however, be obtained via different mechanisms. A better understanding of the neurobiological basis for the delayed onset of action of antidepressant treatments has led to the elaboration of strategies that could accelerate the antidepressant response. These strategies are discussed in this article by Pierre Blier and Claude de Montigny.
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1. Three sets of criteria are proposed for assessing animal models of human mental disorders: predictive validity (performance in the test predicts performance in the condition being modelled), face validity (phenomenological similarity) and construct validity (theoretical rationale).2. The problems inherent in each of these validation procedures are discussed, and their application to the learned helplessness model of depression is examined.3. It is concluded that whilst the model has good predictive validity, important questions about face validity remain unanswered, and construct validity has not yet been established.4. The distinctions between animal models and some related experimental procedures are also discussed.
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A new scoring technique is described that measures active behaviors of rats in the forced swimming test, a test that predicts antidepressant drug effects. The technique distinguishes the effects of selective serotonin reuptake inhibitors, which reduce immobility and increase swimming behavior, from selective norepinephrine reuptake inhibitors, which reduce immobility and increase climbing behavior. The magnitude of behavioral effects described for each drug (i.e., reduced immobility for both drugs, increased swimming for fluoxetine, increased climbing for desipramine) was greater when testing was conducted at the deeper 30-cm rather than the shallow 15-cm water depth. Results obtained with the technique demonstrate that selective serotonin reuptake inhibitors are not false negatives in the rat forced swimming test, as previously thought.
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High doses of 2-(2, 6-dichlorphenylamino)-2-imidazoline hydrochloride (ST 155) were found to induce biting attacks in mice. Among several CNS drugs tested, neuroleptic agents were the most effective in antagonizing such aggressive behavior. The aggressiveness induced by ST 155 appears to be independent of the sympathomimetic effects.
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The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
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Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
Article
The phenomenon of “learned helplessness” was evaluated as a potential animal model of depression. Imipramine, but not chlorpromazine or lorazepam, had a delayed protective effect on the development of this behavior although lorazepam was effective after a single dose. Dose-response curves related either to concentration of imipramine in drinking water or to free drug levels in brain were linear with higher drug levels associated with a lowered degree of learned helplessness following chronic administration. The effects of imipramine on the development of learned helplessness were seen following four days of access to drug in drinking water, but not after 1, 2 or 3 days. This model, although clearly not a perfect fit with depression in humans, has many characteristics which suggest its utility in further studies of the mechanism of action of antidepressants.
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Exposure to random, uncontrollable shock produced a deficit in escape performance in rats tested 1-5 days later. In saline-injected controls, this deficit would last 12-13 days. But in animals injected with multiple doses of imipramine, it could be reversed in four days. Even high doses of imipramine were ineffective in reversing this performance deficit after a single dose. This delayed onset of action of imipramine parallels its clinical effectiveness as an antidepressant.
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Effects of acute administration of LiCl on aggressive behavior and alterations in brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents induced by nialamide plus L-DOPA and by clonidine were examined in mice. Effects of LiCl on turnover and metabolism of brain NE were also investigated. LiCl potentiated the aggressiveness induced by both nialamide plus L-DOPA and by clonidine. Increase in levels of brain NE, DA and 5-HT by nialamide plus L-DOPA was not affected by LiCl. The potentiating effect of LiCl on clonidine aggression was not observed in mice pretreated with disulfiram. Although LiCl did not alter the steady state levels of brain NE, DA and 5-HT, it increased the turnover of NE and decreased the content of endogenous normetanephrine. These results favour the assumption that lithium reduces the ability of nerve terminal vesicles to store NE leading to an increased turnover and decreased concentration of NE at receptor sites.
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Chronic treatment with imipramine increased the locomotor response to quinpirole, a selective D2 receptor agonist. This effect was blocked by minute doses of prazosin (0.1-1 mg/kg), a selective alpha 1 receptor blocker, in a dose-dependent manner. Conversely, in control rats the locomotor response to quinpirole was enhanced by the stimulation of alpha 1 receptors with the selective agonist St 587. The results suggest that alpha 1 receptor stimulation plays a permissive role in the supersensitivity of D2 receptors following chronic treatment with imipramine.
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We studied the immunocytochemical distribution of catecholaminergic fibers in the hippocampal formation from two cynomolgus monkeys by using phenylethanolamine-N-methyltransferase, dopamine-beta-hydroxylase, and tyrosine-hydroxylase antibodies. There were no phenylethanolamine-N-methyltransferase immunoreactive fibers suggesting the lack of epinephrine containing fibers. In order to compare the distributions of tyrosine-hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers, we counted fibers in four hippocampal regions, the dentate gyrus, CA3, CA1, and the subiculum at three different rostrocaudal levels. The distributions of dopamine-beta-hydroxylase and tyrosine-hydroxylase immunoreactive fibers were overlapping but clearly different, suggesting that the hippocampus receives both noradrenergic and dopaminergic inputs in primates. Dopamine-beta-hydroxylase-immunoreactive fibers were present in moderate density and roughly evenly distributed throughout the hippocampus. Tyrosine-hydroxylase immunoreactive fibers were found in high density in the dentate gyrus, in the stratum lacunosum-moleculare, and in the molecular layer of the subiculum. There were only minor side-side and rostrocaudal differences in the distribution of tyrosine-hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers. The identification of a putative dopaminergic projection to primate hippocampus, which is more dense and widely distributed than in the rodent, parallels similar increases in dopaminergic projections reported for primate cerebral neocortex.
Article
The effect of chronic treatment with antidepressants (ADs) on the behavioral responses to LY 171555, a selective D2 receptor agonist, SKF 38393, a selective D1 receptor agonist, and B-HT 920, a selective DA autoreceptor agonist, was studied in rats. In normal rats small, intermediate and high doses of LY 171555 produced hypomotility, hyperactivity and stereotypies, respectively. Chronic but not acute pretreatment with imipramine (IMI) greatly potentiated the motor stimulant effect of LY 171555, but failed to modify its stereotypic and sedative effect. The potentiation of the motor stimulant effect of LY 171555 was observed also after chronic, but not acute, treatment with desmethylimipramine (DMI), mianserin (MIA) or repeated electroconvulsive shock (ECS). Chronic treatment with IMI failed to modify the effect of SKF 38393 (motor stimulation, grooming and penile erection), but reversed the sedative effect of B-HT 920 into a motor stimulant response. The motor stimulant response to LY 171555 in IMI-pretreated animals was suppressed by L-sulpiride, a D2 antagonist, and by a combination of reserpine with alpha-methyltyrosine (alpha-MT), but it was only partially antagonized by high doses of SCH 23390, a selective D1 antagonist. The results indicate that chronic treatment with ADs potentiates the behavioural responses mediated by the stimulation of postsynaptic D2 receptors in the mesolimbic system and suggest that this behavioural supersensitivity is due to enhanced neurotransmission at the D1 receptor level.
Article
The most familiar usage of animal models of depression is as antidepressant screening tests. Paul Willner reviews their usage in a different context--as simulations of depression. The behavioural features of animal models of depression are compared with clinical symptomatology, and the contribution of animal models to understanding the following aspects of depression are reviewed: sources of population variability, natural history, psychological aspects, symptomatology and mechanisms of antidepressant action. Finally, the role of animal models of depression is considered as a critical interface between basic behavioural neuroscience and the clinic.
Article
The present study was undertaken to investigate in rats the role of the noradrenergic innervation of the hippocampus in the reversal by antidepressant drugs of escape failures caused by previous exposure to inescapable shocks (learned helplessness design). Rats were either sham-operated or given a bilateral infusion of 6-hydroxydopamine (6-OHDA, 8.1 micrograms of free base in 0.8 microliter saline containing 0.02% ascorbic acid) into the dorsal hippocampus. Three weeks later, sham and lesioned rats were exposed (experimental rats) or not exposed (control rats) to 60 randomized, inescapable footshocks (0.8 mA, 15 s duration) and, 48 h later, experimental and control rats were subjected to daily consecutive shuttle-box sessions (30 trials/day; intertrial interval = 30 s). Separate groups of experimental animals were given twice daily injection (i.p.) of clomipramine (total daily dose: 16 or 32 mg/kg), desipramine (24 mg/kg), imipramine (32 mg/kg), nialamide (16 mg/kg) or saline. After behavioral testing, animals were sacrificed and [3H]noradrenaline uptake was assayed in synaptosomal preparations from the hippocampus, the cerebral cortex and the septum, [3H]serotonin uptake being assessed in hippocampal synaptosomes. We found that hippocampal 6-OHDA infusion resulted in a mean 70% reduction in local [3H]noradrenaline uptake and a marked delay in the response to antidepressants (reversal of escape failures over consecutive shuttle-box sessions). The 6-OHDA infusion was found not to alter hippocampal [3H]serotonin uptake but to decrease (30%) [3H]noradrenaline uptake in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The forced swimming test is reviewed. This test appears to be suitable for detecting antidepressant activity in rats but not in mice. Difference in experimental procedure may account for the different sensitivity to drugs of the two animal species.
Article
Eighty-nine consecutive admissions with primary depressive illness were prospectively ascertained and diagnosed in 1965-66 by R. E. Kendell, who also allocated each a position on a neurotic-psychotic continuum on the basis of previous discriminant function analysis. In 1983-84, 94% of the survivors were personally interviewed by a psychiatrist blind to index admission data. Operational outcome criteria were employed and longitudinal data were established for 98% of the series. Mortality risk was doubled overall, and increased sevenfold for women under 40 years at index admission. Less than one-fifth of the survivors had remained well, and over one-third of the series suffered unnatural death or severe chronic distress and handicap. Patients whose index episode marked their first psychiatric contact had a 50% chance of readmission within their lifetime, but those with previous admissions had a 50% chance of readmission within three years. Readmissions occurred even after 12 years of being symptom-free, and conversely patients recovered after as long as 15 years of illness. There was a high incidence of other disorders (schizoaffective disorder, alcoholism, schizophrenia), and only four patients showed pure recurrent unipolar histories. Patients at the psychotic end of the continuum were more likely to be readmitted and to have very poor outcomes.
Article
The present study was aimed at testing the hypothesis (based mainly on biochemical evidence) of the implication of brain serotonergic neurons in the induction of learned helplessness (escape deficit) and its reversal by antidepressants in rats. After desipramine (25 mg/kg IP)-pretreatment rats were either sham-operated or infused with 5,7-dihydroxytryptamine (5,7-DHT, 3 micrograms of free base in 0.4 microliter saline containing 0.02% ascorbic acid) into the midbrain raphe area. Three weeks later, experimental animals were exposed to 60 randomized inescapable shocks (0.8 mA; 15 sec duration), control rats being not shocked, and 48 hr later, they were subjected to daily shuttle-box sessions (30 trials/day; ITI = 30 sec) on 3 consecutive days in order to assess escape deficits. After inescapable shock pretreatment separate groups of rats were given twice daily injections of clomipramine (total daily dose: 32 mg/kg), desipramine (24 mg/kg), imipramine (32 mg/kg), nialamide (32 mg/kg) or saline. After behavioral testing, animals were sacrificed, and tryptophan hydroxylase activity was assayed in the cerebral cortex, the hippocampus and the striatum. We found that damage to serotonergic neurons associated with a 70% loss of tryptophan hydroxylase activity altered neither escape deficits produced by prior exposure to inescapable shock, nor the ability of either antidepressant studied to reverse escape failures in the shuttle-box paradigm. These findings cast some doubts on the hypothesized crucial role of serotonergic neurons in helpless behavior and its reversal by antidepressants.
Article
The chronic (10 mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice. An analogous potentiation of clonidine-induced aggressiveness was obtained with chronic administration (the schedule as above) of levomepromazine (2 mg/kg) or thioridazine (5 mg/kg) but not of spiperone (0.2 mg/kg). Fluoxetine (10 mg/kg), atropine (5 mg/kg), propranolol (10 mg/kg) or metergoline (0.5 mg/kg) given chronically (the schedule as above) also had no effect. The enhancement of clonidine aggressiveness induced by prolonged treatment with imipramine (10 mg/kg) was prevented by cycloheximide, an inhibitor of protein synthesis. The results supply further evidence for the previously proposed hypothesis that chronic administration of antidepressants enhances the responsiveness of central postsynaptic noradrenaline receptors.
Article
The learned helplessness model of depression was tested for its responsiveness to several types of antidepressant therapies, and to a number of psychoactive drugs which are not effective in treating depression in humans. Chronic administration of tricyclic antidepressants (imipramine, desipramine, amitryptyline, nortryptyline, or doxepin), atypical antidepressants (iprindole or mianserin), monoamine oxidase inhibitors (iproniazid or pargyline), or electroconvulsive shock was effective in reversing learned helplessness. Chronic treatment with anxiolytics (diazepam, lorazepam, or chlordiazepoxide), neuroleptics (chlorpromazine or haloperidol) stimulants (amphetamine or caffeine), or depressants (phenobarbital or ethanol) was not. Thus, this model provides a reasonable degree of specificity toward therapies which are successful in humans.
Article
The noradrenaline (NA)-containing innervation of the hippocampal formation arises exclusively in the brainstem nucleus locus coeruleus. The projection is 75--90% ipsilateral, originating predominantly in the large, multipolar cells of the compact component of the nucleus. The axons course into the hippocampal formation by three pathways. Ammon's horn receives its NA innervation principally through the ventral amygdaloid bundle-ansa peduncularis, with smaller contributions from the fornix and ipsilateral fasciculus cinguli. The innervation of the area dentata is to a larger extent bilateral, with the greatest contribution arising from the ipsilateral fasciculus cinguli and approximately equal proportions of fibers traveling via the contralateral cingulum, fornix, and the ventral path. In general, the endogenous content of NA is greater in the area dentata than in Ammon's horn, and in both structures is greater in the temporal than in the septal ends. The pattern of NA innervation is similar at all septotemporal levels, however. The dense plexuses of preterminal and terminal elements appear in the infragranular hilus of the area dentata, stratum lucidum of CA3, and in the molecular layer of the subiculum. Fluorescent varicosities often appear in perisomatic clusters, or, closely apposed to dendrites of granule and pyramidal cells.
Article
The effect of the antipsychotic agents chlorpromazine (CPZ) and Li2CO3 on superoxide dismutase (SOD, EC 1.15.1.1) and glutathione peroxidase (GPx, EC 1.11.1.9) activities of brain, liver and erythrocyte of rats was investigated. The short-term treatment (7 days) either with CPZ (10 mg/kg body weight) or with Li2CO3 (2 mEq Li/kg body weight) did not affect enzymatic activities. In contrast, the long-term administration of CPZ (1 month) decreased the SOD activity in brain and erythrocytes while Li2CO3 had no effect. GPx activity and lipid peroxidation of brain and liver homogenates were not affected by either acute or chronic administration of these agents.
Article
In this study, the involvement of serotonergic and dopaminergic receptors in the modulation of the head-twitch (HTW) response to the 5-hydroxytryptamine (5-HT)2A/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, was characterized in rats using novel and selective ligands at 5-HT2A, 5-HT2C, D1, D2 and 5-HT1A receptors. HTW were dose-dependently inhibited by the 5-HT2A/2C antagonists, ritanserin, metergoline, mesulergine, mianserin, ICI 169,369 and LY 58,537, by the preferential 5-HT2A antagonist, ketanserin and by the novel, selective 5-HT2A antagonist, SR 46349B. A further selective 5-HT2A antagonist, MDL 100,907, very potently abolished HTW (ED50 = 0.005 mg/kg). The order of relative potency correlated highly with their affinity at 5-HT2A (r = 0.83) but not 5-HT2C receptors (r = 0.06). In addition, the novel, selective 5-HT2C antagonist, SB 200,646A, failed to abolish HTW and the 5-HT2C agonists/5-HT2A antagonists, 1-(3-chlorophenyl)piperazine and 1-(3-trifluoromethylphenyl)piperazine, blocked, rather than elicited, HTW. The D1 antagonists, SCH 23390, NNC 112, NNC 756, SCH 39166 and A 69024, in this order of relative potency that correlated with their affinity at D1 receptors (r = 0.98), blocked HTW. The D2 antagonists, raclopride, eticlopride and haloperidol also blocked HTW. The 5-HT1A agonists, S 14671, S 14506, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone and (+)-flesinoxan, abolished HTW. The action of 8-hydroxy-2-(di-n-propylamino)tetralin was blocked by (-)-tertatolol (ID50 = 4.5 mg/kg), a novel 5-HT1A receptor antagonist. Similarly, (-)-tertatolol attenuated the action of S 14506 and abolished that of S 14671, buspirone and ipsapirone. A role of postsynaptic 5-HT1A receptors in the action of 5-HT1A agonists was suggested by the finding that parachlorophenylalanine (3 x 300 mg/kg, i.p.), which depleted cerebral pools of 5-HT, did not modify the activity of ipsapirone. The present data demonstrate that 5-HT2A receptors mediate HTW in rats and that both D1 and D2 receptors as well as (postsynaptic) 5-HT1A receptors play a role in their expression.