Estrogenic and anti-amnesic potential of Millettia griffoniana Baill. (Fabaceae) ethanolic extract on scopolamine-induced memory impairment in ovariectomized Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia. AIM: Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats. MATERIALS AND METHODS: The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD50) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus. RESULTS: No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD50 was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract. CONCLUSION: M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.

From the Mother to the Child: The Intergenerational Transmission of Experiences of Violence in Mother-Child Dyads Exposed to Intimate Partner Violence in Cameroon.

Intimate partner violence (IPV) is a widespread social problem with serious consequences for the health of both women and their children. However, little is known about the combined effect of maternal childhood abuse and current exposure to IPV with respect to the psychopathological symptoms of the mother-child dyad. In a Cameroonian cultural setting, where IPV affects more than half of women, we aimed to better understand how mother's childhood abuse and current IPV co-occur to lead to psychopathological symptoms in the mother-child dyad. With the help of a non-governmental organization in Cameroon, we recruited 49 mother-child dyads exposed to IPV, along with 25 mother-child dyads who had not been exposed, and who functioned as a control group. All mothers completed a set of questionnaires, including the Revised Conflict Tactics Scale to assess IPV; the Child Trauma Questionnaire to examine their childhood trauma; the Child Behavior Checklist to assess their children's psychopathological traits; the Hospital Anxiety and Depression Scale; and the Symptom Checklist. We found that physical abuse experienced by mothers during childhood was associated with IPV in adulthood, and specifically sexual abuse, p = .001. In addition, we found that the accumulation of maternal childhood abuse and current IPV was related to anxiety and depression symptoms in mothers, all R2 ≥ .18, all ps ≤ .015, as well as to externalized symptoms in children, all R2 ≥ .27, all ps ≤ .017. Our results suggest the intergenerational transmission of experiences of childhood abuse and current IPV, which calls for the development of interventions and care strategies for the mother-child dyad.

HPA-axis activity and the moderating effect of self-esteem in the context of intimate partner violence in Cameroon.

Background: The experience of intimate partner violence (IPV) is stressful. One objective way to monitor it is to assess victims' stress response by measuring the concentration of their salivary cortisol, the major stress hormone released by the hypothalamic-pituitary-adrenal axis. Objective: We investigated how the IPV experienced by women in Cameroon affects their stress levels and those of their children. Method: We recruited 50 mother-child dyads exposed to IPV and a control group of 25 mother-child dyads. All mothers completed questionnaires, including the Revised Conflict Tactics Scale to assess IPV, the Sense of Coherence Scale, and the Self-Esteem Scale, to assess their psychological resources. Mothers were asked to collect 3 saliva samples from themselves and 3 from their children on a single weekday: immediately after waking up, 30 minutes after waking up, and 45 minutes after waking up. The total cortisol secretion over the first hour after awakening was determined by calculating the area under the curve with respect to the ground (AUCg). Results: Mothers exposed to IPV exhibited higher total post-awakening cortisol concentrations compared with those in the control group. However, no significant difference was found between exposed and non-exposed children. In addition, higher IPV, specifically injuries, was significantly and positively associated with greater AUCg among mothers exhibiting lower self-esteem. When self-esteem was high, however, no significant effect of IPV on AUCg was observed. Conclusions: Of particular clinical significance is that self-esteem can modulate the stress levels of women exposed to IPV, a valuable insight into the development of effective psychosocial interventions to support IPV victims in sub-Saharan Africa.

Antecedentes: La experiencia de violencia de pareja (VIP) es estresante. Una forma objetiva de monitorearla es evaluar la respuesta al estrés de las víctimas midiendo la concentración de su cortisol salival, la principal hormona del estrés liberada por el eje hipotalámico-pituitario-adrenal.Objetivo: Investigamos cómo la VIP que experimentan las mujeres en Camerún afecta sus niveles de estrés y la de sus hijos.Método: Reclutamos 50 díadas madre-hijo expuestas a VIP y un grupo de control de 25 díadas madre-hijo. Todas las madres completaron cuestionarios, incluida la Escala de Tácticas de Conflicto revisada para evaluar la VIP, la Escala de Sentido de Coherencia y la Escala de Autoestima, para evaluar sus recursos psicológicos. Se pidió a las madres que recogieran 3 muestras de saliva de ellas mismas y 3 de sus hijos en un solo día de la semana: inmediatamente después de despertarse, 30 minutos después de despertarse y 45 minutos después de despertarse. La secreción total de cortisol durante la primera hora después del despertar se determinó calculando el área bajo la curva con respecto a la base (AUCg).Resultados: Las madres expuestas a VIP exhibieron concentraciones de cortisol total, después del despertar, más altas en comparación con las del grupo de control. Sin embargo, no se encontraron diferencias significativas entre niños expuestos y no expuestos. Además, una mayor VIP, específicamente las lesiones, se asociaron significativa y positivamente con un mayor AUCg entre las madres que mostraban una menor autoestima. Sin embargo, cuando la autoestima era alta, no se observaron efectos significativos de la VIP sobre el AUCg.Conclusiones: Que la autoestima pueda modular los niveles de estrés de las mujeres expuestas a VIP es de particular importancia clínica, una valiosa información sobre el desarrollo de intervenciones psicosociales efectivas para apoyar a las víctimas de VIP en África subsahariana.

Memory and exploratory behavior impairment in ovariectomized Wistar rats.

BACKGROUND: Estrogen deficiency is linked to changes in several physiological processes, but the extent to which it associates with cognitive changes in menopause context is controversial. RATIONALE: We evaluated the impact of ovariectomy on memory processes and normal exploratory behavior in Wistar rats. METHODS: Young adult rats (4-6 months) were either ovariectomized (OVX group) (N = 10), sham operated (N = 10), or untouched (naïve controls) (N = 8). Afterwards, they were monitored for 12 weeks during which their cognitive functions were evaluated at first week (S1), second (S2), every 3 weeks (S5, S8) and then at week 12 (S12) using: (i) object recognition test to evaluate the short-term and long-term non-spatial memory; (ii) the object placement test to assess the spatial memory; and (iii) normal exploratory behavior components like locomotor and vertical activities in an open field arena. RESULTS: Marked changes in ovariectomized rats were observed in long-term non-spatial memory (~ 40% change vs. naïve and sham, P < 0.001) and spatial memory (~ 30% change, P < 0.05) from S2. Instead, from S5 the exploratory behavior was affected, with decreases in line crossing and rearing episode numbers (~ 40% change, P < 0.01), and in the time spent in the center of open field arena (~ 60% change, P < 0.01). CONCLUSIONS: Our findings support the involvement of sex hormones in cognitive functions in female rats and suggest that controversy on the importance of cognitive affections in menopause context may emerge from differences between short-term and long-term memory processes.

Anxiolytic and sedative activities of aqueous leaf extract of Dichrocephala integrifolia (Asteraceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dichrocephala integrifolia (Asteraceae) is commonly used in the folk medicine in Cameroon to treat various ailments including headaches, jaundice, filariasis, neuritis and children's night agitation. It is also known to have anxiolytic properties. Since there were no scientific data supporting the above claims, we therefore aimed to evaluate the anxiolytic and sedative effects of the aqueous leaf extract of D. integrifolia. MATERIALS AND METHODS: The extract used was obtained after maceration of leaves of D. integrifolia in water at room temperature. The anxiolytic effect was tested by the elevated plus-maze (EPM) and Open Field tests while the sedative effect was evaluated by the diazepam-induced sleep test. RESULTS: D. integrifolia significantly induced an increase in the percentage of entries into open arms and a decrease in percentage of entries into closed arms at the dose of 22 mg/kg BW. The extract also induced a decrease of rearing and head dipping at the doses of 22 and 40 mg/kg BW during the EPM test. In addition, D. integrifolia extract induced a significant increase of crossing and time spent at the center of the experimental set at the dose of 40 mg/kg BW during the open field test. Lastly, D. integrifolia caused a significant reduction of the latency to sleep and an increase of total sleep time at the doses of 22 and 40 mg/kg BW in the diazepam-induced sleep test. CONCLUSION: The results obtained in this study suggest that the aqueous leaf extract of D. integrifolia is endowed with anxiolytic and sedative properties, which justify its traditional use.

Botanicals for mood disorders with a focus on epilepsy.

Mood disorders are among the major health problems that exist worldwide. They are highly prevalent in the general population and cause significant disturbance of life quality and social functioning of the affected persons. The two major classes of mood disorders are bipolar disorders and depression. The latter is assumed to be the most frequent psychiatric comorbidity in epilepsy. Studies published during the second half of the 20th century recognized that certain patients with epilepsy present a depressed mood. Synthesized pharmaceuticals have been in use for decades to treat both mood disorders and epilepsy, but despite their efficiency, their use is limited by numerous side effects. On the other hand, animal models have been developed to deeply study potential botanicals which have an effect on mood disorders. Studies to investigate the potential effects of medicinal plants acting on the nervous system and used to treat seizures and anxiety are increasingly growing. However, these studies discuss the two conditions separately without association. In this review, we present animal models of depression and investigative models (methods of assessing depression) of depression and anxiety in animals. Other classical test models for prediction of clinical antidepressant activity are presented. Finally, this review also highlights antidepressant activities of herbals focusing specially on depression-like behaviors associated with epilepsy. The pharmacological properties and active principles of cited medicinal plants are emphasized. This review, therefore, provides an overview of the work done on botanicals for mood disorders, potential mechanisms of action of botanicals, and the major compounds. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

Newtonoate as an active principle of Newtonia griffoniana for anxiolytic activity in Swiss mice.

BACKGROUND: Newtonia griffoniana (Mimosaceae) is a Central African rain forest tree, whose bark extracts are used in Cameroonian folk medicine for the treatment of anxiety and sleep disorders. METHODS: We evaluated the anxiolytic effects of N. griffoniana stem bark methanol extract and its major isolated constituent 2,3,4-trihydroxybutylpentatriacontanoate (newtonoate) on the elevated plus maze. RESULTS: Significant increases in the percentage of entries into open arms were induced by both N. griffoniana extract (100 and 150 mg/kg BW; p<0.01) and newtonoate (doses of 3 and 15 mg/kg BW; p<0.05). Conversely, decreases in the percentage of entries into closed arms were observed at the same doses. In addition, N. griffoniana methanol extract (100 mg/kg) and the isolated newtonoate (30 mg/kg) induced significant (p<0.01 and p<0.05, respectively) increases in the time spent in the open arms, while inducing a decrease in the time spent in the closed arms. Newtonoate treatment also decreased head dipping number at doses of 3 and 15 mg/kg, while N. griffoniana methanol extract induced the same effect at 200 mg/kg. CONCLUSIONS: These results suggest that N. griffoniana bark extract has anxiolytic properties, which justify its use in folk medicine. Such effects are at least partly mediated by newtonoate.

Phytotherapy and women's reproductive health: the Cameroonian perspective.

Approximately 80 % of the population in Africa use traditional medicinal plants to improve their state of health. The reason of such a wide use of medicinal plants has been mainly attributed to their accessibility and affordability. Expectation of little if any side effects, of a "natural" and therefore safe treatment regimen, as well as traditional beliefs additionally contribute to their popularity. Several of these plants are used by women to relieve problems related to their reproductive health, during or after their reproductive life, during pregnancy, or following parturition. The African pharmacopoeia thus provides plants used for preventing and/or treating gynecological infections, dysmenorrhea, irregular menstruations, oligomenorrhea or protracted menstruation, and infertility. Such plants may then be used as antimicrobians, emmenagogues, or as suppressors of uterine flow. African medicinal plants are also used during pregnancy for prenatal care, against fetal malposition or malpresentation, retained dead fetus, and against threatened abortion. Some others are used as anti-fertilizing drugs for birth control. Such plants may exert various activities, namely, anti-implantation or early abortifacient, anti-zygotic, blastocytotoxic, and anti-ovulatory effects. Some herbs could also act as sexual drive suppressors or as a post-coital contraceptive by reducing the fertility index. A number of these plants have already been subject to scientific investigations and many of their properties have been assessed as estrogenic, oxytocic, or anti-implantation. Taking into account the diversity of the African pharmacopoeia, we are still at an early stage in the phytochemical and pharmacological characterization of these medicinal plants that affect the female reproductive system, in order to determine, through in vitro and in vivo studies, their pharmacological properties and their active principles.

Modulation of some estrogen-responsive genes in the vena cava of ovariectomised Wistar rats by griffonianone C, an isoflavone derived from Millettia griffoniana Baill. (Fabaceae).

In the present study, we investigated whether griffonianone C (Griff C), extracted from root bark of Millettia griffoniana, changes the expression of several estrogen-responsive genes in the vena cava of ovariectomised rats. For this purpose, we subcutaneously administered Griff C (2, 10, or 20mg/kg/d BW), 17ß-estradiol (E2: 10µg/kg/d BW) as positive control, and a vehicle control respectively for three days. Relative expression levels of estrogen receptor α (ERα), progesterone receptor (PR), cyclooxygenase2 (Cox-2), vascular endothelial growth factor (VEGF), VEGF-receptor 2, angiotensin converting enzyme (ACE), endothelial NO synthase (eNOS), proliferating cell nuclear antigen (PCNA) and Ki67 mRNA extracted from the vena cava of these rats were quantified by real-time PCR. Results showed that Griff C up-regulated the expression of PR, ACE, ERα, VEGF, VEGFR2 and Ki67. However, the results of Cox-2, PCNA, and eNOS expression did not reach significance in the E2 and Griff C treated samples. These results show that griffonianone C regulated a few of the analysed genes in a similar fashion than estradiol; however, others showed a different pattern. This suggests that some of the biological effects attributed to M. griffoniana are mediated via ER pathway others may be mediated via other pathways.