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Antidepressant-like Property of Jobelyn®, an African Unique Herbal Formulation, in Mice
Abstract
Objectives:
The purpose of this investigation was to evaluate whether Jobelyn® (JB) possesses anti-depressant-like property in the mouse forced swimming test (FST), tail suspension test (TST) and yohimbine-induced lethality test (YLT) in aggregated mice.
Methods:
Mice were given JB (10-100 mg/kg, p.o.) daily for 7 days and then subjected to FST, TST, YLT and open field test. The parameters assessed in both FST and TST were the time (s) spent in active movement (struggling time), first occurrence of immobility (s) and the duration of immobility (s). In the YLT, the mortality rate was recorded 24 h after yohimbine (35 mg/kg, i.p.) administration. In the open field test, the number of line crosses and total distance travelled (m) were measured for 10 min in the open field chamber.
Results:
JB significantly (p<0.05) decrease the duration of immobility both in the FST and TST, which suggests antidepressant-like property. JB significantly (p<0.05) prolonged the time spent in active swimming and delayed the first occurrence of immobility, indicating endurance promoting effect. It potentiated the toxic effect of yohimbine, which further suggests antidepressant-like activity and facilitation of both serotonergic and noradrenergic neurotransmissions. However, JB did not significantly increase the locomotor activity in the open-field test.
Conclusions:
Jobelyn® has antidepressant-like activity, which may be related to the stimulation of serotonergic and noradrenergic pathways. The ability of Jobelyn® to delay the onset of immobility and to prolong the struggling time support its use as energizer in general body weakness or exhaustion.
Supplementary resource (1)
... The breakdown in adaptive responses, which signals organ pathologies and immune dysfunctions, was coined by Hans Selye as general adaptation syndrome 8,117,118 , who reasoned that human illnesses stemmed from ineffective adaptation 118 . The notion of general adaptation syndrome led to the search during the Second World War by Russian scientists for substances -later called adaptogens -of plant origin that could be used to enhance the capability for physical and mental work, and which can help individuals to survive in challenging situations involving intense/prolonged stress 117,119 . Adaptogens were initially defined as substances that enhance the "state of non-specific resistance" to stress; a physiological condition that is linked with dysregulation of the neuroendocrine-immune system 117,119 . ...
... The notion of general adaptation syndrome led to the search during the Second World War by Russian scientists for substances -later called adaptogens -of plant origin that could be used to enhance the capability for physical and mental work, and which can help individuals to survive in challenging situations involving intense/prolonged stress 117,119 . Adaptogens were initially defined as substances that enhance the "state of non-specific resistance" to stress; a physiological condition that is linked with dysregulation of the neuroendocrine-immune system 117,119 . More recently, adaptogens were defined as a category of herbal medicinal and nutritional products promoting the adaptability, resilience, and survival of living organisms in stressful situations 8 . ...
... Thus, adaptogens are meant to stimulate the intrinsic adaptive mechanisms of the organism, to help it survive in situations of intense/prolonged stress 117 . The most striking features of adaptogens include the capability to mount resistance against varied stressors, such as physical, chemical, biological (pathogens), and psychological noxious factors, thus exerting beneficial healthy effects independent of the nature of the pathological conditions 117,119 . However, in clinical settings, adaptogens are generally reputed for their ability to exert an anti-fatigue effect, increasing mental work capacity against a background of stress and fatigue, particularly concerning tolerance to mental exhaustion and enhanced attention 117 . ...
Globally, across different cultures, humans have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants have been strongly attributed to the presence of secondary metabolites, particularly polyphenols. The potential health benefits of the leaf sheaths of the West African variety of Sorghum bicolor-based Jobelyn Supplement (SBJS) have also been ascribed to its high contents of polyphenols. This systematic review seeks to synthetically harmonize findings from various experimental and clinical studies on the health benefits of SBJS in different disease conditions including arthritis, cancer, chronic viral infections, stroke, anaemia, and premature aging. A systematic search was conducted using three primary databases (PubMed, Europe PMC, and Cochrane Library), to identify published articles on therapeutic potentials of SBJS and ethnomedicinal surveys on the application of the West African variety of S. bicolor using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standard. The inclusion criteria were experimental and clinical studies conducted on SBJS and West African variety of S. bicolor; while ethnomedicinal surveys were on the therapeutic uses of the West African variety of S. bicolor published in the English language. The review provides valuable information suggesting that SBJS possesses pleiotropic therapeutic potentials in diverse pathological conditions through mechanisms relating to antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. The review also showed that SBJS contains several bioactive substances with polyvalent pharmacological potentials including modulation of pathological mechanisms involved in the mediation of aging and age-related diseases, such as arthritis, stroke, memory loss and cancer as well as chronic viral infections. Taken together, these findings further suggest the need for more robust studies (including disease-specific clinical trial programs) in order to replicate and validate the prior insights gleaned from previous investigations on SBJS.
... Thus, the ability of SBSJ to reduce corticosterone is an important finding from the study of Umukoro et al. [120]. The possibility of SBSJ behaving like an adaptogen is also based on findings that it attenuated depression-like symptoms in mice subjected to stressful situations (i.e., forced swimming exercise and tail suspension protocols) [121]. In an in vitro stress model, it has also been reported that SBSJ protected RBCs against hyposaline-induced haemolysis [43], suggesting cyto-protection and increased cellular resistance to stress. ...
... This is especially important in a developing African context, where the high cost of conventional therapies hinders drug compliance and contributes to disease-related morbidity and mortality. The results from such clinical trials are necessary, as they are expected to provide the evidential strength that researchers need to significantly reduce some of the barriers to the clinical adoption of validated indigenous phytomedicines [121] in mainstream medical practice. ...
Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.
... Oxidative stress and inflammation are increasingly recognized as significant contributors to the dysregulation of the hypothalamic-pituitary-thyroid (HPT) axis, a critical hormonal control system. Oxidative stress arises when the production of reactive oxygen species (ROS), highly unstable molecules, overwhelms the body's endogenous antioxidant defenses (Udi, 2025;Udi, et al., 2022;Umukoro, et al., 2014). This imbalance leads to a cascade of cellular damage across various tissues, including the delicate structures of the hypothalamus, pituitary gland, and thyroid gland, all essential components of the HPT axis. ...
... This is consistent with other studies showing that VPA induces excitotoxicity and oxidative damage in the mPFC and hippocampus, leading to neurodegeneration. [39][40][41][42][43] The loss of neurons in this region disrupts the mPFC and critical hippocampal circuits, contributing to the memory deficits often seen in autism. In the mPFC and the CA2 region of the hippocampus, theaflavin resulted in an increased neuronal count, indicating a protective effect against VPAinduced neurotoxicity. ...
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by deficits in communication and repetitive behaviors. Its etiology is multifactorial, involving genetic, epigenetic, and environmental factors, complicating diagnosis and treatment. This study explores the neuroprotective effects of theaflavin (TF) in a valproic acid (VPA)-induced murine model of autism, focusing on its impact on anxiety, memory, oxidative-nitric stress, and cholinergic pathways. Pregnant Swiss albino mice were injected with VPA (250 mg/kg) on gestational day 13. Male offspring, confirmed to exhibit autistic-like behaviors through tests such as Y-maze, NORT, EPM, LDT, and HBT, were treated with TF (10 or 20 mg/kg) or 1% DMSO (10 mL/kg) for 30 days. Behavioral assessments were repeated post-treatment, and brain samples were analyzed for oxidative stress markers (NO, GSH) and histological damage in the medial prefrontal cortex and hippocampus. VPA-exposed mice showed impaired memory, increased AChE and NO levels, reduced GSH, and neuronal damage. TF significantly improved memory in the Y-maze [F(3, 16) = 9.448; (p = 0.0008)] and NORT [F(3, 16) = 15.12; (p < 0.0001)] but did not significantly affect anxiety-like behaviors in EPM, LDT, or HBT. TF treatment reduced oxidative stress, mitigated neuronal damage, and enhanced cholinergic activity, highlighting its potential as a therapeutic agent for autism.
... In this test, mice were forced to swim individually following the method modified by Umukoro et al. (18) for 6 min. Total duration of immobility (in seconds) was recorded during the last 4 min of a 6 min observation period. ...
Introduction: Central nervous system (CNS) neuropathologies are the most common effects of insufficient sleep/ prolonged wakefulness. This puts people who undergo sleep deprivation in the course of their daily lives at risk of certain affective disorders such as depression. Minocycline is an antibiotic that can penetrate the CNS, which puts it at the forefront of numerous neuropathologies. This research was therefore intended to investigate into the possible anti-depressant effect of minocycline in mice exposed to chronic sleep deprivation. Methods: Thirty (30) mice were grouped into five (n=6) and treated with either distilled water, minocycline or astaxanthin. Four out of the five groups were exposed to the sleep deprivation setup. After a 7-day treatment, all groups were subjected to behavioural tests. Subsequently, biochemical assays and histology of selected brain regions were carried out. Experimental data were analysed using one-way analysis of variance and another post-hoc test. Results: Results obtained suggest that minocycline attenuated the alterations in mood behaviour caused by sleep deprivation with a concurrent reversal of sleep-deprivation induced oxidative stress in mice. Conclusion: In conclusion, minocycline could be considered a reliable intervention in further studies on depression in sleep deprivation models.
... In the same study, interferon-alpha (IFN-), an antiviral cytokine showed increased expression by 12-fold following treatment with SBLS extract. 29 There seems to be a correlation between high IFN-production capacities and low HIV viral loads as well as high CD4 cell counts and lack of opportunistic infections. 30,31 This effect can be related to the direct anti-viral role of IFN-on infected HIV cells. ...
Abstract
The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a
natural remedy, which has gained international recognition for its anti-anaemic
effect and energy boosting qualities in debilitating diseases. The widespread use of
traditional medicine in the region usually confirms its safety, but not its efficacy
or deep assessment of their pharmacological properties. The other major issue for
herbal-based treatments is the lack of definite and complete information about the
composition of the extracts. Despite limitations, efforts have been made in isolation
and characterisation of active compounds in this specie of Sorghum showing various
subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and
potential fungal growth inhibitor, which accounts for 84% of the total extract. Nonclinical in vitro and in vivo studies support previous indications that this variety
of Sorghum bicolor possesses several biologically active compounds with potent
antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical
studies show that SBLS has the ability to boost haemoglobin concentrations in anaemic
conditions and most remarkably to increase CD4 count in HIV-positive patients. The
multiple effects and high safety profiles of this extract may encourage its development
as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or
in the symptomatic management of HIV infections. This review describes the potential
therapeutic aspects of SBLS extract and its potential benefits.
Keywords: sorghum bicolor leaf extract, SBLS, jobelyn®, antioxidant, immunemodulatory, anti-inflammatory, anti-anemia, HIV
... In the same study, interferon-alpha (IFN-), an antiviral cytokine showed increased expression by 12-fold following treatment with SBLS extract. 29 There seems to be a correlation between high IFN-production capacities and low HIV viral loads as well as high CD4 cell counts and lack of opportunistic infections. 30,31 This effect can be related to the direct anti-viral role of IFN-on infected HIV cells. ...
Abstract
The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anaemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of Sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and
potential fungal growth inhibitor, which accounts for 84% of the total extract. Nonclinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical
studies show that SBLS has the ability to boost haemoglobin concentrations in anaemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development
as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.
Keywords: sorghum bicolor leaf extract, SBLS, jobelyn®, antioxidant, immune modulatory, anti-inflammatory, anti-anemia, HIV
... Moreover, JB has gained international recognition as a remedy for treatment of anaemia, arthritic pains and relief of stress [17]. We have previously reported that JB exhibited anti-depressant and anti-amnesic properties in rodents [18] [19]. In this present study, we report on the effect of Jobelyn ® on unpredictable chronic mild stress-induced memory impairment in mice. ...
About 90% of women have been reported to become anaemic in pregnancy in sub Saharan Africa and India. Sorghum bicolor sheath (SBS) has been scientifically proven to be effective in anaemia treatment, but the safety of its consumption during pregnancy is unknown. Thirty-nine (39) female rats of weight 160 ± 20 g were used for this study. The test group was daily administered 800 mg/kg body weight aqueous extract of SBS. The animals were sacrificed in batches on days 7, 14, and 19. Selected hormonal assay and haematology were carried out, the uteri of the pregnant rats were observed for changes and the organ-body weight ratio calculated. The results showed a significant reduction (p < 0.05) in the weight, progesterone, oestrogen, and number of implantations in the test group by day 14 of the experiment. A significant increase (p < 0.05) was observed in the haematological parameters of the test group. There was also a 50% resorption noticed in the pregnant rats administered the extract compared with the control rats, with no significant difference (p > 0.05) in the organ-body weight ratio of the liver. It was concluded from this study that Sorghum bicolor sheath extract possesses abortifacient activity.
Objectives:
Our study aimed to investigate the antidepressant-like effect of ethyl acetate extract of the flowers of Campsis grandiflora (EFCG) in a mice model of chronic unpredictable mild stress (CUMS).
Methods:
HPLC-Q-TOF-MS was used to identify the chemical constituents of EFCG. The DPPH assay and ABTS radical-scavenging assay were performed to measure the antioxidant properties. The protective properties of EFCG against H2 O2 -induced oxidative damage were analysed in PC12 cells. The changes of behaviour profiles were investigated by using open-field test, sucrose preference test, forced swimming test (FST) and tail suspension test (TST). Brain tissue samples of mice were collected, and antioxidative measure levels were measured.
Key findings:
The result showed that EFCG had the most active anti-oxidative effect and the protective effect against H2 O2 oxidative injury in PC12 cells. Treatment with the EFCG significantly reduced the depressant-like severity and immobility period as compared with untreated CUMS mice in FST and TST. Moreover, EFCG significantly elevated the contents of superoxide dismutase, Glutathione Peroxidase and decreased the contents of Malonaldehyde (MDA) in mice brain.
Conclusions:
Our study found first the antidepressant activity of the EFCG. The results suggested the therapeutic potential of EFCG for depressive disorder.
Jubi Formula® is a herbal preparation made from three medicinal herbs (Parquetina nigrescens, Sorghum bicolor and Harungana madagascariensis). It has been reported to have been successfully used in the treatment of anaemia in humans. A study was therefore carried out to determine the effect of the preparation on packed cell volume (PCV) and haemoglobin (Hb) concentrations in anaemic rabbits. The PCV and Hb concentrations of healthy rabbits infected with Trypanosoma brucei brucei were monitored for 49 days. T. b. brucei produced a significant reduction in PCV and Hb concentrations in all infected rabbits when compared with the controls (p<0.05). These hematological parameters were restored to normal levels in the anaemic rabbits by the herbal preparation. The anaemic rabbits not treated with the herbal preparation presented with a progressive decline in their PCV and Hb concentrations and majority of them died before the end of the study. Healthy rabbits that received daily doses of the herbal preparation showed gradual elevation in PCV and Hb concentrations which were maintained within normal range. Jubi Formula® can restore the PCV and Hb concentrations in anaemic conditions and is a potential substitute for blood transfusion. However, further studies are needed to investigate the potentials of the herbal preparation in reversing anaemia.
A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amitriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are (1) the use of a simple, objective test situation, (2) the concordance of the results with the validated "behavioral despair" test from Porsolt and, (3) the sensitivity to a wide range of drug doses.
Roots of Ptychopetalum olacoides Bentham (Olacaceae), known as Marapuama, are prepared in alcoholic infusion for treating “nervous weakness” by Amazonian Caboclos. “Nervous weakness” can be described as a syndrome having several symptoms, among which the following are emphasized: lassitude, depression, sexual impotence and tremors. Based on ethnopharmacological data, we have considered the hypothesis that PO may have psychopharmacological effects, by interacting with different neurotransmitter systems: (i) the dopaminergic system, considering its use as an appetite modulator and to counteract tremors, as well as for its alleged sexual arousing properties; (ii) the noradrenergic system, again for its use against tremors and/or depression; and/or (iii) the serotonergic system, also related to depression and sexual arousal. This paper reports that P. olacoides hydroalcoholic extract potentiated yohimbine-induced lethality, rever sed reserpine-induced ptosis and prevented apomorphine-induced stereotypy. The data indicates that P. olacoides has central nervous system effects and supports the hypothesis of its interaction with dopaminergic and/or noradrenergic systems.
Since clinical and biochemical observations point to much overlap between depression and aggression, both characterised by intolerance to frustration, a questionnaire was developed to test if different patterns of depressive and aggressive reactions elicited by exposure to negative events and deprivation from expected positive ones in human and nonhuman conditions, respectively, would result in specific response patterns in depressive and aggressive persons. The questionnaire was tested for internal consistency in a pilot healthy sample and for correlations of responses with the personality factors of Aggression and Depression in 60 abstinent male alcoholics. Aggressive and depressive responses were highly correlated across all stimulus conditions, and not specifically but rather equally associated with the personality factors of Aggression and Depression, confirming the close association between these dimensions.
A herbal mixture of herbs code named African Herbal Formula (AFH) influenced the state of anaemia in trypanosome infected rats. Observations showed that the formula has an effect on the haemopoietic system manifested by a positive increase in the levels of haemoglobin, packed cell volume and red blood cell while the white blood cell and lymphocyte levels were decreased. AHF also delayed the proliferation of the parasites and improved the level of the characteristic weight loss associated with trypanosomiasis.
The use of complementary and alternative medicine (CAM) is on the increase globally with a high prevalence in children and adults with chronic illnesses. Many studies have evaluated the epidemiology of medicine use for children in developing countries but none has evaluated the use of CAM for children with chronic illnesses. The aim of this study was therefore to determine the prevalence, pattern of use, parental sources of information, perceived benefits, cost, and adverse effects of CAM in children with epilepsy, sickle cell anaemia and asthma in Lagos, Nigeria.
Parents of children with epilepsy (122), asthma (78) or sickle cell anaemia (118) who presented consecutively to the paediatric neurology, respiratory and haematology clinics of the Lagos State University Teaching Hospital (LASUTH), Ikeja were interviewed with a structured open- and close-ended questionnaire. The information obtained comprised the demography of both the patients and their parents; past and present treatments received by the patients; the type of CAM, if any, used by the patients; and the sources, cost, benefits and adverse effects of the CAM used.
A total of 303 CAMs were used by the patients, either alone or in combination witother CAM. CAM was reportedly used by 99 (31%) patients (epilepsy--38%, sickle cell anaemia--36% and asthma--25%). The majority (84%) of these patients were currently using CAM. The use of CAM was stopped six months prior to the study by 16 patients (16%). Biological products were the most frequently used CAMs (58%), followed by alternative medical systems (27%) and mind-body interventions (14%). Relations, friends and neighbours had a marked influence on 76% of the parents who used CAM for their children. Eighty-five (86%) parents were willing to discuss the use of CAM with their doctors but were not asked. CAM use was associated with adverse reactions in 7.1% of the patients.
Parental use of CAMs to treat their children with epilepsy, asthma and sickle cell anaemia is common in Nigeria. Efforts should be made by doctors taking care of these patients to identify those CAM therapies that are beneficial, harmless and cheap for possible integration with conventional therapy.
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.
The dorsal raphe nucleus (DR)-serotonin (5-HT) system has been implicated in depression and is dramatically affected by swim stress, an animal model with predictive value for antidepressants. Accumulating evidence implicates the stress-related neuropeptide corticotropin-releasing factor (CRF) in the effect of swim stress on this system. This study investigated neural circuits within the DR that are activated by swim stress as revealed by neuronal expression of the immediate early gene, c-fos. Swim stress increased c-fos expression in the dorsolateral subregion of the DR. The majority of c-fos-expressing neurons were doubly labeled for GABA (85 +/- 5%), whereas relatively few were immunolabeled for 5-HT (4 +/- 1%), glutamate (0.5 +/- 0.3%) or calbindin (1.5 +/- 0.3%). Dual immunohistochemical labeling revealed that c-fos-expressing neurons in the dorsolateral DR were enveloped by dense clusters of CRF-immunoreactive fibers and also contained immunolabeling for CRF receptor, suggesting that c-fos-expressing neurons in the DR were specifically targeted by CRF. Consistent with this, the CRF receptor 1 antagonist, antalarmin, prevented swim-stress-elicited c-fos expression in the dorsolateral DR. Together with previous findings that both swim stress and CRF decrease 5-HT release in certain forebrain regions, these results suggest that swim stress engages CRF inputs to GABA neurons in the dorsolateral DR that function to inhibit 5-HT neurons and 5-HT release in the forebrain. This circuitry may underlie some of the acute behavioral responses to swim stress as well as the neuronal plasticity involved in long-term behavioral changes produced by this stress.
This study was performed to identify safe and more effective acetylcholinesterase (AChE) inhibitors in the treatment of Alzheimer's disease. The total methanol extract of Citrus junos had a significant inhibitory effect on AChE in vitro. By sequential fractionation of C.junos, the active component was finally identified as naringenin. Naringenin inhibited AChE activity in a dose-dependent manner. In this study, we also evaluated the anti-amnesic activity of naringenin, a major flavanone constituent isolated from C. junos, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight). Naringenin, when administered to mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance and the Y-maze test. These results suggest that naringenin may be a useful chemopreventive agent against Alzheimer's disease.
The dorsal raphe nucleus (DR)-serotonin (5-HT) system has been implicated in depression and is dramatically affected by swim stress, an animal model with predictive value for antidepressants. Accumulating evidence implicates the stress-related neuropeptide corticotropin-releasing factor (CRF) in the effect of swim stress on this system. This study investigated neural circuits within the DR that are activated by swim stress as revealed by neuronal expression of the immediate early gene, c-fos. Swim stress increased c-fos expression in the dorsolateral subregion of the DR. The majority of c-fos-expressing neurons were doubly labeled for GABA (85 +/- 5%), whereas relatively few were immunolabeled for 5-HT (4 +/- 1%), glutamate (0.5 +/- 0.3%) or calbindin (1.5 +/- 0.3%). Dual immunohistochemical labeling revealed that c-fos-expressing neurons in the dorsolateral DR were enveloped by dense clusters of CRF-immunoreactive fibers and also contained immunolabeling for CRF receptor, suggesting that c-fos-expressing neurons in the DR were specifically targeted by CRF. Consistent with this, the CRF receptor 1 antagonist, antalarmin, prevented swim-stress-elicited c-fos expression in the dorsolateral DR. Together with previous findings that both swim stress and CRF decrease 5-HT release in certain forebrain regions, these results suggest that swim stress engages CRF inputs to GABA neurons in the dorsolateral DR that function to inhibit 5-HT neurons and 5-HT release in the forebrain. This circuitry may underlie some of the acute behavioral responses to swim stress as well as the neuronal plasticity involved in long-term behavioral changes produced by this stress.
One widely accepted explanation of bullying, known as the aggressive-motive thesis, assumes that bullying is a form of aggressive behaviour triggered by external stress. However, recent evidences have suggested a different explanation, known as the frustration-aggression thesis, which asserts that bullying is a psychological defense triggered by external stress to reduce anxiety. The present investigation is an attempt to compare school bullying in Japan and Hong Kong and to find out whether the frustration-aggression thesis is applicable in the schooling context of both societies. Data analysis using structural equation modeling was based on 703 girls selected from 13 primary and 6 junior secondary schools in Japan and 2,477 girls selected from 21 primary and 19 secondary schools in Hong Kong. Results of the analysis suggest that girl bullying in Japan can be explained by the frustration-aggression thesis but that girl bullying in Hong Kong can be explained by the aggressive-motive thesis. The reasons behind the different bullying mechanisms are suggested, but further investigations are needed to uncover the underlying causes.
1.A new subtype of depression is proposed, named: anxiety/aggression-driven depression.2.The psychopathological, psychopharmacological and biochemical evidence on which this construct is based, is being discussed.3.Selective postsynaptic 5-HT1A agonists together with CRH and/or cortisol antagonists are hypothesized to be a specific biological treatment for this depression type, in conjunction with psychological interventions to raise the stressor-threshold and to increase coping skills.4.The development of this depression construct has been contingent on the introduction of two new diagnostic procedures, called functionalization and verticalization of psychiatric diagnosis.5.These procedures are explained and it is stressed that they are essential to psychiatric diagnosing, in order to put this process on a scientific footing.
The ability of antidepressant agents to potentiate the lethal or toxic effects of yohimbine in mice was evaluated. With very few exceptions, the antidepressants were the only agents that significantly enhanced yohimbine-induced lethality. All of the clinically effective antidepressants, both typical (e.g., amine reuptake inhibitors, monoamine oxidase inhibitors) and atypical (e.g., mianserin, iprindole, bupropion, quipazine) drugs, produced a dose-related potentiation of yohimbine in mice. Representative anxiolytics and antipsychotics failed to potentiate yohimbine over a wide range of doses. Although several possible “false positives” (e.g., atropine, chlorpheniramine, and d-amphetamine) would be detected in this procedure, these same agents would be detected in other models (e.g., tetrabenazine antagonism, behavioral despair) considered predictive of antidepressant potential. Thus, the potentiation of yohimbine-induced lethality test in mice appears to represent a useful screening procedure for discovering potential antidepressant drugs.
Dietary flavonoids possess a multiplicity of neuroprotective actions in various central nervous pathophysiological conditions including depression. In this study, the neuropharmacological mechanism of the dietary flavonoid naringenin was investigated in the mouse behavioral models of depression. For this purpose, we investigated the influence of pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester or α-methyl-p-tyrosine, respectively in the anti-immobility effect of naringenin. Compared to the control group, naringenin significantly decreased the immobility time after acute treatment in the mouse tail suspension test (10, 20 and 50 mg/kg), but not in the forced swimming test, without producing locomotor alteration in the open-field test. In addition, pretreatment of mice with p-chlorophenylalanine methyl ester (100 mg/kg) or α-methyl-p-tyrosine (100 mg/kg) prevented the anti-immobility effect of naringenin (20 mg/kg) in the tail suspension test. Taken together, this data demonstrated that naringenin possessed potent antidepressant-like property via the central serotonergic and noradrenergic systems. Thus, our findings suggest the therapeutic potential of this dietary flavonoid in central nervous system disorders especially depression where monoaminergic systems are involved.
The concept of a 5-HT related, anxiety and/or aggression-driven, stressor-precipitated depression is formulated and discussed. It comprises the following elements. The 5-HT ergic disturbances found in some depressed individuals - and of them particularly lowered CSF 5-HIAA - are linked to the anxiety- and the aggression-components of the depressive sydrome. In this type of depression - called 5-HT related depression - dysregulation of anxiety and/or aggression are primordial and mood lowering is a derivative phenomenon. In other words this is a group of anxiety/aggression-driven depressions. The 5-HT ergic impairment in certain types of depression is a trait-phenomenon, ie, persists during remission. This disturbance makes the individual susceptable for perturbation of anxiety- and aggression-regulation. Anxiety and (overt or suppressed) anger, are core constituents of the stress-syndrome. Thus, the 5-HT ergic disturbance will induce a heightened sensitivity for stressful events, ie, the latter will induce more readily than normal, stress phenomena , among which anxiety and anger. The latter psychological features induce lowering of mood and thus "drive" the patient into a fullblown depression. Furthermore it is predicted that anxiolytics and serenics (ie, anti-aggressive drugs) that act via normalisation of 5-HT ergic circuits, will exert a antidepressant effect in 5-HT related depression, in addition to their therapeutic actions in anxiety disorders and states of increased aggressiveness, respectively. The exact nature of the 5-HT ergic impairment in 5-HT related depression has yet to be elucidated.
Psychopathy is a developmental disorder marked by emotional hyporesponsiveness and an increased risk for instrumental and reactive aggression. The increased risk for reactive aggression is the focus of the current paper. It will be argued that the increased risk for reactive aggression does not relate to an increased sensitivity to threatening stimuli since psychopathy is associated with a reduced sensitivity to threat. Instead, it is argued that the increased risk for reactive aggression relates to an increased risk for frustration; i.e., the emotional state following the performance of an action in the expectation of a particular reward and not receiving this reward. Two impairments seen in psychopathy would increase the risk for frustration and consequent potential reactive aggression; impairments in stimulus-reinforcement learning and reversal learning. It is argued that both are known consequences of impairment in ventromedial prefrontal cortex, one of the regions principally implicated in psychopathy.
The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.
Yohimbine, 5 or 20 mg/kg given intraperitoneally, increased the concentration of brain serotonin and decreased that of 5-HIAA, in the rat. The changes occurred in 2–4 hr after administration of the alkaloid. Changes in the same direction as brain were observed for serotonin in the intestine. Tryptophan in the blood was slightly increased at 2 hr, but no change was detected in the brain. MAO activity in vitro was inhibited only by the higher concentration of yohimbine; no inhibition was observed in vivo in the brain and the liver. Yohimbine induced also a dose-dependent decrease of spontaneous locomotion and of body temperature. Corynanthine, an isomer of yohimbine, did not cause any of the above changes at the same dose levels. The results are discussed in terms of inhibition of tryptophan pyrrolase by yohimbine as well as the possible stimulation of serotonin receptors by yohimbine. This drug could be considered as a potential tool to test the involvement of serotoninergic processes in endogenous depression.
In recent years the plant alkaloid, yohimbine, has been studied as a selective α2-adrenoreceptor antagonist in many species, in vivo and in vitro, and has been used in many of these studies as a sole criterion for classifying the receptor activated by a given drug or mediating a specified physiological response. Although yohimbine has been studied for over 100 years, a comprehensive summary of the pharmacology of this compound has not been compiled and the relative certainty with which one can attribute effects of yohimbine to blockade of α2-adrenoreceptors has not been critically evaluated. The pupose of this review is to summarize the known effects of yohimbine and to relate them to the physiology of α2-adrenoreceptors.
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.
A mechanism of antidepressant activity of beta-amyrin palmitate was studied using the forced swimming method in mice. Beta-amyrin palmitate (10 mg/kg) reduced the increase in the duration of immobility induced by tetrabenazine (100 and 200 mg/kg), but showed no effect on that in mice treated with alpha-methyl-para-tyrosine (500 mg/kg). Beta-amyrin palmitate (5 and 10 mg/kg) decreased the duration of immobility in mice treated with desipramine plus 6-hydroxy-dopamine (50 micrograms/mouse), but did not affect that induced by nomifensine plus 6-hydroxydopamine. The decreased immobility produced by desipramine (15 mg/kg) was not affected by beta-amyrin palmitate. A study of norepinephrine release in mouse brain synaptosomes indicated that beta-amyrin palmitate caused a release of [3H]norepinephrine. The results of the present study suggest that beta-amyrin palmitate might release norepinephrine from newly synthesized pools, and thus, it might activate noradrenergic activity.
The alpha 2-adrenoceptor antagonist yohimbine has in several previous studies been found to produce anticonflict effects comparable to those produced by the benzodiazepines (BDZ) in rat punished conflict models. In this and a following paper we have tried to elucidate the neurochemical mechanisms underlying these effects in a modified Vogel's drinking conflict test. Since yohimbine previously has been demonstrated to interfere both with noradrenaline (NA) and serotonin (5-HT) neurochemistry, and, in addition, shows affinity for the BDZ binding site, we have focused on the putative involvement of these neuronal systems in the yohimbine-induced anticonflict effect. The alpha 2-adrenoceptor agonist clonidine (10 micrograms/kg, i.p.) completely antagonized the anticonflict effect of yohimbine (4.0 mg/kg, i.p.), whereas the alpha 1-adrenoceptor agonist ST 587 (1.0 mg/kg, i.p.) had no effect. The anticonflict effect of yohimbine was totally abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high dose of the mixed beta 1 and beta 2 adrenoceptor antagonist propranolol (8.0 mg/kg, i.p.) caused a partial blockade of the yohimbine-induced effect in intact animals, whereas the selective beta 1-adrenoceptor antagonist metoprolol (4.0 mg/kg, i.p.) had no significant effect and the alpha 1-adrenoceptor antagonist prazosin instead potentiated the anticonflict action. The anticonflict effect of yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5-hydroxytryptophan (25-100 mg/kg, i.p.). The BDZ receptor antagonist flumazenil (10 mg/kg, p.o.), as well as Ro 15-4513 (1.0 mg/kg, p.o.), a partial inverse agonist at BDZ receptors, partly, but significantly, counteracted the yohimbine-induced anticonflict effect, whereas low doses of both the chloride channel blocker picrotoxin and the GABAA antagonist bicuculline only tended to counteract the yohimbine effect. Taken together, the results in the present behavioral paper indicate that the anticonflict effect of yohimbine involves both increased NA and decreased 5-HT activity, and that direct or indirect activation of BDZ receptors may also be involved. Neurochemical findings related to these behavioral results are presented in a following paper.
The clinical efficacy of selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) is normally attributed to their ability to increase brain 5-HT function although recent preclinical findings indicate that their selectivity for 5-HT over noradrenaline may be less evident in vivo. The present study investigated the effects of the SSRI, paroxetine, on extracellular levels of noradrenaline. Microdialysis was carried out in the hippocampus of the awake rat. In rats treated twice daily for 14 days with paroxetine (5 mg/kg s.c.), dialysate levels of noradrenaline showed a maintained two-fold increase compared to saline-injected controls. Paroxetine (5 mg/kg s.c.) administered once daily for 14 days did not cause a sustained increase in noradrenaline but levels showed a moderate (+58%) increase in response to a paroxetine challenge. Acute injection of paroxetine (5 mg/kg s.c.) did not elevate noradrenaline levels. Paroxetine (5 mg/kg s.c.) elevated dialysate 5-HT after both acute and repeated (twice daily for 14 days) treatment. The paroxetine-induced increase in noradrenaline (and 5-HT) was positively correlated with plasma concentrations of the drug, which were around the therapeutic range. In comparison to paroxetine, desipramine (10 mg/kg s.c.) caused a four-fold increase in dialysate noradrenaline (but did not change 5-HT) following repeated (once daily for 14 days) treatment and a two-fold increase at for acute treatment. In summary, despite its selectivity as a 5-HT reuptake inhibitor, paroxetine increased extracellular levels of noradrenaline in rat hippocampus following repeated administration. We discuss the possibility that a facilitation of noradrenaline function might be involved in the antidepressant effect of paroxetine, and possibly other SSRIs.
The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite conclusions are difficult to establish. A reliable method for assessing individual studies and generating combined results is provided by systematic reviews using meta-analytical techniques. In this study, we carried out a systematic review of studies investigating 5-HT receptors and the 5-HTT in suicidal behavior. Studies were identified by means of MEDLINE database searches and by scanning reference lists. More than 190 articles were reviewed and 26 met the inclusion criteria. In all, 14 studies investigated six different 5-HT receptor loci and 12 studies investigated the 5-HTT promoter 44 bp insertion/deletion polymorphism. Two specific meta-analyses were carried out, pooling studies investigating the 5-HT2A 102 T/C and the 5-HTT promoter loci that included, respectively, a total of 1599 and 2539 subjects. The combined evidence was significant for association with the 5-HTT locus (Mantel-Haenszel weighted odds ratio (M-H(w) OR)=1.17 CI : 1.04-1.32, P=0.009), but not for the 5-HT2A 102 T/C variant (M-H(w) OR)=1.09 CI : 0.93-1.27, P=0.319). The 5-HTT result was robust and remained significant following sensitivity analysis, suggesting that 5-HTT may play a role in the predisposition to suicide.
In mice, yohimbine appears to accentuate the normal "alarm" reactions (alerting, flight) to external stimuli. Imipramine increases this effect and at the same time converts a non-lethal dose of yohimbine into a lethal one. The effect of imipramine is greatly reduced by adrenalectomy or by treatment with reserpine, syrosingopine, ganglion-blocking drugs or adrenaline antagonists acting on sympathetic beta-receptors. Hypnotic, anti-convulsant or anaesthetic agents, tetrabenazine or antagonists of 5-hydroxytryptamine do not reduce the imipramine effect. A variety of drugs which, like imipramine, are known to interfere with the tissue binding of noradrenaline also increase the toxicity of yohimbine. Yohimbine significantly reduces brain noradrenaline content; adrenal catechol amines are slightly reduced. The results suggest that yohimbine releases noradrenaline from stores or nerves as a consequence of increased central sympathetic activity. Imipramine increases the actions and toxicity of yohimbine by increasing the effects of the released noradrenaline on beta-receptors. The lethal effects of a high dose of yohimbine alone are not reduced by any of the treatments tested, and appear not to result from activation of sympathetic mechanisms.
Sorghum is a rich source of various phytochemicals including tannins, phenolic acids, anthocyanins, phytosterols and policosanols. These phytochemicals have potential to significantly impact human health. Sorghum fractions possess high antioxidant activity in vitro relative to other cereals or fruits. These fractions may offer similar health benefits commonly associated with fruits. Available epidemiological evidence suggests that sorghum consumption reduces the risk of certain types of cancer in humans compared to other cereals. The high concentration of phytochemicals in sorghum may be partly responsible. Sorghums containing tannins are widely reported to reduce caloric availability and hence weight gain in animals. This property is potentially useful in helping reduce obesity in humans. Sorghum phytochemicals also promote cardiovascular health in animals. Such properties have not been reported in humans and require investigation, since cardiovascular disease is currently the leading killer in the developed world. This paper reviews available information on sorghum phytochemicals, how the information relates to current phytonutrient research and how it has potential to combat common nutrition-related diseases including cancer, cardiovascular disease and obesity.
Existing antidepressant treatments exhibit limited efficacy and a slow onset of action. Several neurobiological adaptive mechanisms might delay the clinical effects of antidepressants, whose therapeutic action is primarily triggered by an increase of serotonergic and noradrenergic neurotransmission. Here, we review several potential mechanisms that could be useful to increase the speed of current antidepressant drugs, such as additional blockade of aminergic autoreceptors or antagonism of certain postsynaptic (5-HT2A, 5-HT2C) receptors. The potential use of strategies not based on monoaminergic transmission, such as CRF and NK1 receptor antagonists, or more novel strategies, based on glutamatergic or GABAergic transmission or on intracellular messengers, are also reviewed.
Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen 'depressed' mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.
Putrescine, a polyamine present at high concentrations in the mammalian brain, was suggested to play a role in the modulation of depression. Thus, this study investigated the effect of putrescine in the mouse forced swimming test (FST) and in the tail suspension test (TST), two models predictive of antidepressant activity. Putrescine significantly reduced the immobility time both in the FST and in the TST (dose range of 1-10 mg/kg, i.p.), without changing locomotion in an open-field. I.c.v. injection of putrescine (0.1-10 nmol/site) also reduced the immobility time in the FST and in the TST. The pretreatment of mice with arcaine (1 mg/kg, i.p., an antagonist of the polyamine-site of NMDA receptor) completely blocked the anti-immobility effect of putrescine (10 mg/kg, i.p.). A subeffective dose of putrescine (0.1 mg/kg, i.p.) produced a synergistic antidepressant-like effect with agmatine (0.001 mg/kg, i.p.) in the FST. Moreover, a subeffective dose of putrescine (0.01 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect with arcaine (50 microg/site, i.c.v.). The results indicate that putrescine produces antidepressant-like effects in the FST that seems to be mediated through its interaction with the polyamine-site of NMDA receptors.
To isolate the compound(s) responsible for the MAO-inhibitory activity.
Six extracts of varying polarity of Mentha aquatica L. were tested in a photometric peroxidase linked MAO bioassay. The 70% ethanol extract had highest inhibitory activity. (S)-Naringenin was isolated from the extract by bioassay guided fractionation on VLC and preparative TLC. The structure of the compound was determined by (1)H, (13)C and (13)C-DEPT NMR and optical rotation.
The IC(50) values for MAO inhibition by naringenin were 342+/-33 microM for the rat liver mitochondrial fraction, 955+/-129 microM for MAO-A and 288+/-18 microM for MAO-B.
The content of naringenin in Mentha aquatica might explain its use in traditional medicine for depression-like conditions.
Behavioral despair in rats: a new animal model sensitive to antidepressant treatments
- R D Porsolt
- Anton G Deniel
Porsolt R D, Anton G, Deniel M et al. Behavioral despair in rats: a new
animal model sensitive to antidepressant treatments. Eur J Pharmacol
1978 ; 47 : 379 -391