Migraine, a common neurological disorder, is marked by severe headache with associated symptoms such as light and sound sensitivity, vomiting and cutaneous allodynia. Nitroglycerin (NTG) is widely utilized to induce migraine in rodents due to its ability to replicate central and peripheral sensitization as observed in human migraine patients. The current study investigated the prophylactic and therapeutic effects of geraniin, a polyphenolic ellagitannin, on acute migraine induced with nitroglycerin (NTG) to assess mechanical and thermal hypersensitivities in Sprague Dawley rats. Migraine-like symptoms were induced by NTG (5 mg/kg, i.p.) administration. Behavioural assays including mechanical sensitivity (von Frey), cold hyperalgesia (acetone test) and thermal nociception (hot plate) were conducted. Geraniin was administered in both preventive and therapeutic protocols at 3, 10 and 30 mg/kg. The probable involvement of 5-HT1B/1D receptors in geraniin’s acute anti-migraine action was studied. Geraniin significantly reversed these responses in a dose-dependent manner in both prophylactic and therapeutic settings. Mechanistically, geraniin’s effects were reversed by the 5-HT1B/1D antagonist (GR127935), suggesting its action may be associated with the serotonergic pathway of migraine development. Geraniin demonstrates robust anti-nociceptive effects in an acute NTG-induced migraine model. It can therefore by further studied as a potential therapeutic candidate for migraine management.

Collaborations between neuroscientists and traditional medical practitioners can strengthen the scientific foundations of traditional medicine and enrich neuroscience with culturally grounded insights. Such partnerships, built on mutual learning, can promote more equitable and context-sensitive mental health research.

Neuroscience development in low- and middle-income countries is often constrained by multiple factors, including fragmented training, funding gaps, and limited infrastructure. However, the growth of neuroscience in Ghana has shown that professional coordination, training partnerships, and community-led initiatives can collectively build sustainable neuroscience ecosystems, offering transferable lessons for comparable contexts.

Corosolic acid (CA) is a triterpenoid derivative having pharmaceutical, cosmetic, and nutritional applications. CA’s molecular formula is C30H48O4 and its molecular weight is 472.70. Almost all fruits belonging to Musaceae, Ericaceae, and Myrtaceae families contain CA. This exploratory review delves deeply into the molecular mechanisms, clinical safety and efficacy of CA. Furthermore, its ethnomedicinal, therapeutic, nutraceutical, and cosmeceutical uses are also covered. Since centuries, CA has served as a staple food and in recent years it has emerged as a promising phytoconstituent for treating diabetes, oxidative stress and combating multiple forms of resistant cancer. In addition, its role has also been harnessed in cosmetic preparations. Despite having wonderful nutritional, pharmaceutical and cosmeceutical properties, CA suffers from issues of low permeability and solubility due to having highly hydrophobic nature that does not allow its proper wetting by the gastrointestinal fluids, leading to poor dissolution and absorption. These limitations decrease its oral bioavailability thereby therapeutic efficacy against various diseases. The development of CA as nano pharmaceuticals has received significant attention in recent years. However, nano pharmaceuticals are at their infant stage because their commercialization is fraught with challenges, including those of stability, toxicity, and scaling. As a result, CA is still classified as a drug lead despite the fact that consideration of these challenges during formulation development would undoubtedly give the drug a new appearance. In this review, we have investigated the molecular mechanisms, clinical safety, and efficacy of CA for its therapeutic, nutraceutical, and cosmetic applications.

Traditional healing is a comprehensive healthcare system that includes spiritual practices, divination, and herbal medicine. In many settings, epilepsy and its associated neuropsychiatric conditions are believed to have both natural and supernatural origins. Consequently, many individuals seek care through complementary and alternative medicine (CAM), which can influence adherence to antiepileptic drugs (AEDs). The call to integrate traditional healing into the formal healthcare system is a significant move toward enhancing patient safety and cultural relevance. However, this integration presents several challenges. A major concern is the epistemological gap between traditional and biomedical approaches, which can lead to distrust and miscommunication. Additionally, the lack of standardized training, certification, and regulatory oversight for traditional healers raises questions about safety and quality of care. Another concern involves the potential for adverse interactions between traditional remedies and conventional AEDs, which necessitates rigorous evaluation of natural products before clinical use. Addressing ethical considerations such as intellectual property rights and fair benefit-sharing is also essential to protect traditional knowledge and promote mutual respect. Despite these obstacles, examples of successful collaboration between traditional healers and medical practitioners do exist. In such cases, traditional practitioners have been integrated into healthcare frameworks with positive outcomes, including improved patient trust, increased access to care, and meaningful knowledge exchange.

Background:Antidepressant-like effects of the crude extract of Mallotus oppositifolius (MOE) have been previously demonstrated. However, to overcome the limitations of crude extracts as medicines, we produced an immediate-release formulation of MOE (MOE-IR) and tested its efficacy. Methods:Using the wet granulation method, MOE was formulated into immediate-release dosage forms (MOE-IR F1 and F2, 10, 30, 100 mg) and flow properties were assessed with bulk density, tapped density, Carr's index, Hausner's ratio, and the angle of repose. In vitro dissolution and antioxidant studies were conducted. Murine unpredictable chronic mild stress and sucrose preference tests (UCMS-SPTs) assessed the antidepressant-like effect. Except for the vehicle nonstressed (VEH-NS) group, mice were subjected to the UCMS for 7 weeks while receiving normal saline (VEH-S, 10 mL/kg; p.o.), MOE-IR (10, 30, and 100 mg/kg; p.o.), or fluoxetine (FLX 20 mg/kg; p.o.) daily for 5 weeks. The weight of mice and sucrose consumption (test for anhedonia) were monitored, after which forced swim test (FST), tail suspension test (TST), and open field test (OFT) were conducted following treatment termination. Plasma corticosterone concentration was assessed using ELISA, and brains were harvested for Golgi-Cox staining. Results:MOE-IR F1 (10 mg) exhibited the most suitable formulation properties, and the highest release profile in all media, hence, was selected for the proof-of-concept antidepressant study and referred to as MOE-IR. MOE-IR and crude extract demonstrated in vitro antioxidant activity in the DPPH test. MOE-IR just as FLX reversed the stress-induced weight loss, anhedonia as well as decreased immobility time in the FST and TST without affecting locomotor activity. MOE-IR decreased the plasma corticosterone concentration and increased the dentate gyrus (DG) dendritic spine density. Conclusion:Collectively, MOE-IR demonstrated antidepressant-like that may be associated with antioxidant effects, decreased plasma corticosterone levels, and increased DG dendritic spine density.

The traditional use of medicinal plants in Sub-Saharan health management lacks thorough toxicological evaluations, particularly concerning lethal dose levels. This study aims to assess the acute and sub-acute toxicity of Reissantia indica whole-plant extract (RIE) in male Sprague-Dawley rats, with a focal point on delineating its safety profile while exploring potential therapeutic applications.RIE, obtained through precise cold maceration in 70 % ethanol, underwent rigorous analysis, revealing diverse secondary metabolites, including alkaloids, flavonoids, terpenoids, and glycosides. Renowned for antioxidant, anti-inflammatory, and anticancer properties, these compounds enhance RIE's pharmacological potential.In the acute toxicity study, RIE was orally administered at 500 and 5000 mg/kg. Sub-acute toxicity involved oral administration of the extract at various doses (5, 50 and 500 mg/kg) over 28 days, with comprehensive assessments, including hematological, biochemical, and histopathological evaluations.Results from the acute toxicity showed no mortality, suggesting a median lethal dose (LD50) exceeding 5000 mg/kg and indicating a substantial margin of safety. Sub-acute toxicity investigations, spanning 28 days revealed no significant changes in body and organ weights, hematological and biochemical parameters, or histopathological signs compared to the control group. Histological examination of kidney, liver, heart, and lung sections from treated animals showed no signs of degeneration.This study, to our knowledge, pioneers a comprehensive investigation into the toxicity profile of Reissantia indica's whole-plant ethanolic extract, addressing a significant gap in existing literature on medicinal plant safety in the Sub-Saharan region.

Aim: To identify the challenges that hinder the successful translation of anticonvulsants from plant origins, from preclinical research to clinical application. Design: This review was conducted using the Joanna Briggs Institute (JBI) guidance for a scoping review. Data Sources: The following bibliographic databases were searched between November 11th and 20th, 2023: PubMed, Scopus, Google Scholar and ClinicalTrials.gov. The search in Google Scholar was done via a third-party application called Harzings Publish or Perish, where the search results limit was set at 1000 relevant articles. After full-text review, the reference lists of the included articles were examined to identify additional sources. Review Methods: The Population, Intervention, Comparison, Outcome, Time, Setting (PICOTS) framework was employed in developing the eligibility criteria. The articles were uploaded to Rayyan.ai for title and abstract screening, as well as full-text article review. Data was extracted and synthesised from included studies using a table. Results: Thirty-seven articles met the eligibility criteria. From these articles, six distinct categories of challenges were identified: (1) methodologic issues; (2) insufficient evidence to support the use of herbal drugs in clinical settings; (3) financial disincentives; (4) challenges in obtaining natural products or its active principles; (5) poor pharmacokinetics; (6) clinical trials and regulatory challenges. Conclusion: Understanding and effectively addressing these challenges will ensure that more plant-based anticonvulsants are successfully translated into clinical practice, thereby enhancing the treatment of epilepsy. This review also made recommendations to tackle some of these challenges that plant anticonvulsants face in the drug development process. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols [https://figshare.com/articles/journal\_contribution/Challenges\_Hindering\_the\_Translation\_of\_Plant\_Anticonvulsants\_from\_Bench\_to\_Bedside\_A\_Scoping\_Review_Protocol/27045928?file=49245721][1] ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: https://figshare.com/articles/journal_contribution/Challenges_Hindering_the_Translation_of_Plant_Anticonvulsants_from_Bench_to_Bedside_A_Scoping_Review_Protocol/27045928?file=49245721

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The gut microbiota has been posited as a target for the treatment of major depressive disorder. Herein, we investigated the effect of the hydroethanolic leaf extract of Mallotus oppositifolius (MOE) on the gut microbiota of mice and how this contributes to its known antidepressant-like effect. A 6-week chronic unpredictable mild stress (CUMS) procedure was employed in 7 groups of mice to induce depression. From the third week, oral MOE treatments (10, 30, 100 mg/kg) and two reference drugs, fluoxetine (12 mg/kg) and minocycline (40 mg/kg), known to affect the gut microbiota, were administered. The sixth and seventh groups were the vehicle stressed (VEH-S) and non-stressed groups (VEH-NS). Changes in depressive-like behaviors were assessed using sucrose preference test while the forced swimming test (FST) was used to assess sustained antidepressant-effect after treatment discontinuation. Moreover, changes in prefrontal cortex (PFC) and hippocampal serotonin (5-HT) levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The effect of treatment on the profile of the gut microbiota of the groups was elucidated using 16S rRNA Oxford Nanopore sequencing. MOE and reference drugs reversed the depression-associated reduction in sucrose preference when compared to VEH-S. MOE (with peak effect at 30 mg/kg) reduced immobility while increasing swimming and climbing behaviors. MOE reversed CUMS-induced reduction of 5-HT concentration in PFC and hippocampus. The behavioral effects of MOE were associated with shifts in the gut microbiota of CUMS-exposed mice. The study has provided seminal evidence that MOE ameliorates CUMS-induced depressive symptoms by modulating gut microbiota and increasing brain 5-HT levels.

Voacanga africana, is a medicinal plant widely used in many African countries. Various parts of this plant are used, but more especially the seeds are held in high esteem for it’s their additional economic value due to the presence of the alkaloids ibogaine, tabersonine, and voacangine. These alkaloids have peculiar medicinal uses in the treatment of psychotic ailments, drug addiction, and also serve as precursors for drug synthesis. V. africana is traditionally used to treat a myriad of diseases including malaria, worm infestation, amoebiasis, ulcers, pain, cardiovascular conditions, depression, fatigue, shortness of breath, diarrhoea, gynaecological conditions, delayed labour, kidney conditions, malaria, asthma and convulsions, however not all these have been investigated. Studies have demonstrate possible efficacy in the treatment of worm infestation, amoebiasis, ulcer, pain and inflammation, cardiovascular condition, depression, diarrhoea, onchocerciasis, mental disorder, and microbial infections. The plant also has CNS, neuro-protective, sedative, anti-microbial, anti-tumor and anti-oxidant activities. Further studies is however needed to verify its activity in the treatment of malaria, fatigue, gynaecological and, labour conditions, respiratory conditions and carious teeth. With respect to safety, the ethanolic leaf extract is reported to be relatively non-toxic with an estimated LD 50 of ≥ 5000 mg while the aqueous leaf extract had no significant alteration on the blood biochemistry or histopathology of essential organs in murine models. Some isolated alkaloids from this plant: vobtusine, voacangine and voacamine are however known to exhibit toxicity in the form of cardiac depressor activity, asphyxia and convulsions, hypertension and CNS depressant activities. In addition to alkaloids, the plant is also rich in saponins, tannins, terpenes, steroids, flavonoids, phenols, anthranoids, glycosides, and oils. This review therefore suggests the need for further robust and detailed investigations on the activity of the extracts and compounds of this plant and their potential toxicities.

Background: Bendroflumethiazide is often prescribed with fluoxetine or imipramine for patients with both depression and hypertension. However, there is little data on the potential interactions between these drugs. Objective: The objective of this study was to investigate the potential antidepressant effects of bendroflumethiazide, as well as sub-effective dose combinations of bendroflumethiazide with fluoxetine or imipramine. Methods: Forced swimming and tail suspension tests were used to investigate the behavioural effects of bendroflumethiazide [5-20 mg/kg; per os (p.o],imipramine (3-30 mg/kg; p.o) and fluoxetine (3-30 mg/kg; p.o). Mean immobility, swimming, climbing, curling,and swinging scores were measured. Median effective dose (ED50) values were calculated from the immobility scores. The antidepressant effect of the combination of bendroflumethiazide with imipramine or fluoxetine at sub-effective doses was then investigated. Isobolographic analyses were performed on these combinations to investigate possible synergism, additivity or antagonism. Results: Bendroflumethiazide produced a significant diminution in mean immobility scores, suggestive of an antidepressant-like effect, while increasing swimming, climbing and swinging scores. Imipramine and fluoxetine also exhibited antidepressant-like effects. A combination of bendroflumethiazide and imipramine at sub-effective doses showed a synergistic antidepressant-like effect with an interaction index of 0.31 as did the bendroflumethiazide-fluoxetine combination (interaction index:0.41). Conclusion: This study demonstrated the acute antidepressant-like effect of bendroflumethiazide. Moreover, bendroflumethiazide-imipramine combinations offer greater synergy when compared to bendroflumethiazide-fluoxetine combinations.

One-third of people will be diagnosed with cancer at some point in their lives, making it the second leading cause of death globally each year after cardiovascular disease. The complex anticancer molecular mechanisms have been understood clearly with the advent of improved genomic, proteomic, and bioinformatics. Our understanding of the complex interplay between numerous genes and regulatory genetic components within cells explaining how this might lead to malignant phenotypes has greatly expanded. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. It was discovered that epigenetic resistance and a lack of multitargeting drugs were highlighted as major barriers to cancer treatment, spurring the search for innovative anticancer treatments. Many popular anticancer drugs, including irinotecan, vincristine, etoposide, and paclitaxel, have botanical origins. Actinomycin D and mitomycin C come from bacteria, while bleomycin and curacin come from marine creatures. However, there is a lack of research evaluating the potential of algae-based anticancer treatments, especially in terms of their molecular mechanisms. Despite increasing interest in the former, and the promise of the compounds to treat tumours that have been resistant to existing treatment, pharmaceutical development of these compounds has lagged. Thus, the current review focuses on the key algal sources that have been exploited as anticancer therapeutic leads, including their biological origins, phytochemistry, and the challenges involved in converting such leads into effective anticancer drugs.

Pre-eclampsia is an obstetric disorder that affects the prognosis of pregnancy, resulting in complications or mortalities.It is typically associated with hypertension which should be managed pharmacologically to protect the health of the mother and the fetus.Yet, not much is known about pharmacists' roles and commitment to pre-eclampsia management.In this review, we update pharmacists on antihypertensives indicated in pre-eclampsia as well as parameters they have to monitor during pharmacotherapy in line with their duty of care to women with pre-eclampsia.Using recent evidence from 16 national/international guidelines (2014-2022), we compared antihypertensives approved for use in pregnancy and highlighted major drug information that pharmacists require to optimize the use of these medications in pre-eclampsia.Intravenous labetalol, hydralazine or oral nifedipine agents are mostly indicated in pre-eclampsia with severe hypertension.In mild-moderate hypertension, oral agents such as methyldopa, labetalol, sustained released nifedipine and hydralazine are the commonest recommendations.While monitoring for maternal bronchoconstriction, neonatal bradycardia or hypoglycemia is required with the administration of intravenous labetalol; intravenous hydralazine is observed for maternal shock; nifedipine for tachycardia, headache, ankle edema and methyldopa for depression if use is extended to the postpartum period.Controlled hypertension in pre-eclampsia mitigates maternal vascular complications.Apart from early referral and counselling of pregnant women at risk, pharmacists with sound knowledge of the pharmacotherapy of pre-eclampsia could advise on appropriate antihypertensive therapy and follow on to ensure that these medicines are responsibly used for optimal outcomes.These roles by pharmacists, may reduce adverse maternal outcomes associated with pre-eclampsia.

Background: Natural remedies with neuroprotective effect are useful in neuroinflammation-associated depression. Although Mallotus oppositifolius extract (MOE) has previously demonstrated antidepressant and anti-inflammatory properties, its neuroprotective effect remains unknown. Thus, the study evaluated the effect of MOE on lipopolysaccharide (LPS)-induced neuroinflammation-associated depression in mice. Methods: Antidepressant-like effect of MOE (10 - 100 mg/kg), fluoxetine (20 mg/kg) and minocycline (50 mg/kg) was established in naïve Institute of Cancer Research (ICR) mice using the forced swim (FST), tail suspension (TST) and open-space swim (OSST) tests. In a separate experiment, FST and TST were used to assess the effect of an 11-day pre-treatment with MOE (10 - 100 mg/kg) or minocycline (50 mg/kg) on LPS (1 mg/kg) neuroinflammation at 6 and 24 hours post LPS. Following these tests, mice were sacrificed and their hippocampi isolated to evaluate their resting and activated microglial cells using Golgi-Cox staining technique. Open-field test was used to assess locomotor activity. Results: MOE, fluoxetine and minocycline significantly reduced immobility in FST, TST and OSST compared to vehicle (p < 0.05), confirming their antidepressant-like effect. Interestingly, MOE’s antidepressant-like effect was faster than fluoxetine and minocycline. Conversely, LPS treatment increased immobility behavior at 6 and 24 hours, suggestive of neuroinflammation-induced depression. Compared to vehicle group, pre-treatment with MOE and minocycline ameliorated LPS-induced hippocampal microglial activation and reversed increased immobility behavior without affecting locomotor activity (p < 0.05). Resting microglial cell count was significantly increased by MOE pre-treatment in the OSST-challenged mice compared to vehicle group (p < 0.01). Similarly, MOE pre-treatment reversed LPS-induced reduction in resting microglial count, and restored resting microglial count to normal levels compared to LPS naive vehicle group. Conclusions: Collectively, the results suggest that MOE exerts neuroprotective effect against LPS-induced neuroinflammation by decreasing the activation of microglia and increasing resting microglial count. This contributes to its antidepressant-like effect.

A large number of people annually lose their lives to tuberculosis (TB), which is an age-old disease caused by the Mycobacterium tuberculosis. The global spread of TB is a concern for all regions. The south-east Asian region recorded 46% of all new TB cases in 2021, followed by the African and western Pacific regions with 23% and 18%, respectively. Researchers are always searching at natural substances for potential alternative therapeutics to tackle the worrisome growth in multi-drug-resistant (MDR) tuberculosis due to the high costs associated with developing new treatments and unfavourable side effects of currently used synthetic pharmaceuticals. Phytochemicals show promising results as a future health aid due to their multi-targeting ability on pathogen cells. In the search for new drug leads, the Ayurvedic and Siddha medical systems have made an extensive use of ethnomedicinal tools, including the use of plants like Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), turmeric (Curcuma longa Mal.) and Green tea (Camellia sinensis Linn.). These sources are high in flavonoids, polyphenols, tannins and catechins, has been shown to reduce the risk of TB. In this overview, we look at how natural sources like plants, algae and mushrooms have helped researchers to find new drug leads, and how to back these natural sources through mapping the molecular approaches and other approaches has helped them to defeat MDR.

supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. Mice (n = 8) received iron (0.8-7.2 mg/kg), citalopram (3-30 mg/kg), imipramine (3-30 mg/kg), desferrioxamine (50 mg/kg) or saline in the single treatment phase of each model and subsequently a sub-therapeutic dose of iron co-administered with citalopram or imipramine. Assessment of serum brain derived neurotrophic factor (BDNF) and dendritic spine density was done using ELISA and Golgi staining techniques respectively. Iron, citalopram and imipramine, unlike desferrioxamine, reduced immobility score in the TST, FST and OSST without affecting locomotor activity, suggesting antidepressant-like effect. Sub-therapeutic dose of iron in combination with citalopram or imipramine further enhanced the antidepressant-like effect, producing a more rapid effect when compared to the iron, citalopram or imipramine alone. Iron, citalopram and imipramine or their combinations increased serum BDNF concentration, hippocampal neuronal count and dendritic spine densities. Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.(c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Background: Postpartum depression is a mood disorder that affects about 9-20% of women after child birth. Reports suggest that gestational iron deficiency can cause a deficit in behavioral, cognitive and affective functions and can precipitate depressive symptoms in mothers during the postpartum period. The present study examined the effect of iron supplementation on depressive behavior during postpartum period in a rat model. Method: Female Sprague-Dawley rats were crossed. Pregnant rats received iron, fluoxetine, desferrioxamine or vehicle throughout the period of gestation. During the postpartum period, mothers from all groups were taken through the open field test (OFT), forced swim test (FST), novelty-induced hypophagia (NIH) and sacrificed for histological examination of the brains. Results: Results showed that rats treated with iron-chelating agent, desferrioxamine, and vehicle during gestation exhibited increased immobility scores in the FST, increased latency to feed and reduced feeding in the NIH with corresponding decreased number of neurons and dendritic branches in the cortex of the brain. These depressionrelated effects were attenuated by perinatal iron supplementation which showed decreased immobility scores in the FST comparable to rats treated with fluoxetine, a clinically effective antidepressant. Iron treatment also decreased latency to feeding while increasing feeding behavior in the NIH. Iron-treated dams had a higher number of neurons with dendritic connections in the frontal cortex compared to vehicle- and desferrioxaminetreated groups. Conclusion: The results suggest that, iron supplementation during gestation exerts an antidepressant-like effect in postpartum Sprague-Dawley rats, attenuates neuronal loss associated with depression and increases dendritic spine density.

Background/Aim: Depression-related aggression is linked to serotonin (5-HT) and dendritic spine alterations. Although Mallotus oppositifolius extract (MOE) has potential for reducing this effect, its specific role remains uncertain. Herein, we evaluated this potential and associated alterations in the brain. Methods: A standard resident-intruder model of para-chlorophenylalanine (pCPA)-induced depression-associated aggression in male ICR mice was used. The resident mice received pCPA (300 mg/kg, i. p.) for 3 consecutive days while saline-treated mice served as negative control. The pCPA aggressive mice were subsequently treated orally with either MOE (30, 100, 300 mg/kg), fluoxetine (20 mg/kg), tryptophan (20 mg/kg) or saline (untreated pCPA group) for 28 days. Locomotor activity was assessed using open field test. Serotonin (5-HT) levels in mice brain and phytochemical fingerprint of MOE were determined by high performance liquid chromatography (HPLC) while gas chromatography-mass spectrometry (GC-MS) was used to identify constituents of MOE. Dendritic spine density and morphology were evaluated using Golgi-Cox staining technique and analyzed with ImageJ and Reconstruct software. Results: Administration of pCPA induced aggressive behavior in mice, evidenced by increased attack behaviors (increased number and duration of attacks), which positively correlated with squeaking and tail rattling. MOE treatment significantly reduced these characteristics of aggression in comparison with vehicle (non-aggressive) and untreated pCPA groups (p < 0.001), and also reduced social exploration behavior. Although the behavioral effects of MOE were comparable to those of fluoxetine and tryptophan, these effects were quicker compared to fluoxetine and tryptophan. Additionally, MOE also markedly increased 5-HT concentration and dendritic spine density in the prefrontal cortex relative to vehicle and untreated pCPA groups (p < 0.05). Interestingly, these behavioral effects were produced without compromising locomotor activity. GC-MS analysis of the MOE identified 17 known compounds from different chemical classes with anti-inflammatory, antioxidant, neuroprotective and antidepressant activities, which may have contributed to its anti-aggressive effect. Conclusion: MOE decreased depression-associated aggressive behavior in mice via increased 5-HT concentration and dendritic spine density in the prefrontal cortex. The MOE-mediated effects were faster than those of fluoxetine and tryptophan. Our finding suggests that MOE may have clinical promise in decreasing aggressive and depressive behaviors.

Background: Cognitive dysfunction, presenting as learning and memory impairment, is a common manifestation in many chronic diseases of the nervous system. Some of these diseases include depression, epilepsy, and Alzheimer's disease. To date, few drugs or medicinal products have shown ability to improve learning and memory deficits. Neuroprotection is one of the mechanisms by which memory could be improved. The extract of Xylopia aethiopica and its kaurene derivative, xylopic acid, have previously demonstrated neuroprotective effects in animal models. The aim of the present study was to investigate the effect of an extract of Xylopia aethiopica fruit and xylopic acid, on learning and memory using murine models. Materials and methods: Unripe Xylopia aethiopica fruits were collected, dried, and extracted using 70% v/v ethanol. Xylopic acid was isolated from the fruits using petroleum ether, concentrated with ethyl acetate and then recrystallized with petroleum ether before purifying with ethanol (96%v/v). Institute of Cancer Research (ICR) mice received oral doses of the extract of Xylopia aethiopica (XAE; 30, 100 and 300 mg/kg), xylopic acid (XA; 30, 100 and mg/kg), citicoline (300 mg/kg), piracetam (300 mg/kg) or ketamine (30 mg/kg) and saline (vehicle). The animals were then taken through the Morris water maze test (MWM), spontaneous alternation Ymaze test (Y-maze), and novel object recognition test (NOR), to assess learning and memory. Results: In the NOR test, XAE (30, 100 and 300 mg/kg) and XA (30, 100 and 300 mg/kg) increased the percentage exploration and recognition index (p = 0.0005 and p < 0.0001, respectively) when compared to both vehicle and ketamine groups. Similarly, doses of XAE and XA as used in the NOR test increased the percentage alternation in the Y-maze test. Although XAE and XA treatments decreased the latencies to find hidden platform in the MWM test, it was not significantly different from the vehicle group. However, this decrease in latency differed significantly when compared to the ketamine group. Interestingly, both XAE and XA treatments increased the percentage frequency to the target quadrant in the probe trial of the MWM. It is noteworthy that in all the three models used, both the extract and xylopic acid performed better than piracetam and citicoline, the reference drugs. Conclusion: The ethanolic extract of Xylopia aethiopica fruit and xylopic acid improved exploratory learning and recognition memory, spatial working, recognition, and reference memories in the behavioral tests.