Neuroprotective roles of flavonoid "hispidulin" in the central nervous system: A review.

Interest in naturally occurring phytochemicals has been on the increase, they are believed to reduce the risk of brain disorders. Hispidulin (HN) is a phenolic flavonoid compound with various pharmacological and biological effects on the central nervous system. It belongs to the flavone class of flavonoids. It can be found in different plant materials, especially fruits and vegetables. The literature used in this review was collected from credible scientific databases including ScienceDirect, Scopus, PubMed, Google Scholar, and Hindawi without time restriction, using relevant keywords, such as HN, brain, central nervous system, flavonoids, and flavones. HN was discovered to possess pro-apoptotic properties, act as an antioxidant, inhibit cytokine production and toll-like receptor 4 expression, as well as impede nuclear factor kappa beta and mitogen-activated protein kinase B. HN was also found to inhibit lipid peroxidation in vitro and reduce brain edema in mice. These pharmacological potentials suggest that HN is a promising candidate for neuroprotection in CNS disorders like depression and epilepsy. This review provides an update on the scientific literature concerning how these activities could help provide various forms of neuroprotection in the CNS. Additional experimental data on the effects of HN in models of neurological disorders and neuroprotection should be explored further. Based on the current study, HN is a promising candidate for neuroprotection of the CNS.

Phytochemical and anticonvulsant screening of three medicinal plants used in the treatment of epilepsy in the south-western part of Nigeria

The burden of epilepsy in developing countries made medicinal plants like Xylopia aethiopica fruit; Khaya grandifoliola, Alstonia boonei etc an alternative source in epilepsy management in the south-western part of Nigeria. The aim of the study was to provide pharmacological rationale for the ethnomedicinal use of the plants in epilepsy management. The oral medial lethal dose of methanol stem bark extracts of Alstonia boonei (MEAB) and Khaya grandifoliola (MEKG) and methanol fruit extract of Xylopia aethiopica (MEXAF) were done in accordance with the Organization for Economic Cooperation Development guideline. Quantitative and qualitative phytochemical profiling of the extracts was done. Anticonvulsant screening was carried out on the extracts (doses: 75, 150 and 300 mg/kg) using the pentylenetetrazole (PTZ)-induced seizure and maximum electroshock tests (MEST). Results showed that the MEXAF has the highest amount of phytochemicals except for saponins in MEKG; and MEAB with the least amount (but higher alkaloid) than MEKG. The TLC showed different bands of spots of the extracts. In the PTZ test, MEXAF showed 100 % protection against mortality at 300 mg/kg; MEAB with 66.67 % protection at 75 mg/kg and MEKG 0 % protection. MEAB, MEKG and MEXAF nonsignificantly increased the onset of seizure and latency to death. In the MEST, MEXAF, MEKG and MEAB at 75 mg/kg protected 50, 33.3 and 16.67% of the animals against tonic hind limb extension respectively and nonsignificantly (p˃0.05) decreased the recovery time at a dose of 75 mg/kg. It was concluded that the extracts possess anticonvulsant activities hence, the pharmacological credence for the ethnomedicinal use of these plants in treating epilepsy.

Evaluation of pharmacists' knowledge in emergency preparedness and disaster management.

BACKGROUND: Emergency preparedness and disaster management are global phenomena that have a significant impact on the economy and healthcare system. Pharmacists have assumed additional responsibilities in the wake of emergencies and disasters that are beyond their training curricula. Some research highlighted the need for pharmacists to assume these responsibilities in the cause of emergency and disaster. The objective of this study is to evaluate pharmacists' knowledge in relation to emergency preparedness and disaster management. METHOD: A descriptive cross-sectional survey was carried out from April to August 2020, on selected pharmacists from different areas of practice in Kaduna/Nigeria. Participants were evaluated using a self-reported questionnaire which consisted of 15 knowledge questions that were distributed online using pharmacists' social-media platforms. The questionnaire was adapted from previous studies and was validated by the team of expect using face validation and pre-tested. MAIN OUTCOME: The majority of pharmacists have good knowledge of emergency preparedness and disaster management. RESULTS: The online poll received 102 respondents, and their knowledge was evaluated by rating respondents out of 15 questions. 55%, 40%, and 5% scored good, fair, and poor knowledge respectively. At p<0.05, there was a relationship between knowledge score and years of practice experience, level of education, and area of practice. 44% reported being taught emergency, with the majority at the undergraduate level. 78% of respondents have never participated in drills or workshops. CONCLUSION: Pharmacists demonstrated good knowledge of basic emergency and disaster terms, they do, however, need to be more conversant with other emergency areas, which necessitates more training and drills.

Effects of Mosquito coil Smoke Inhalation on Spatial Memory in Mice.

BACKGROUND: Mosquito coil (MC) is widely used to repel mosquitoes in order to prevent malaria in many malaria-endemic countries. Although we are fully aware and concerned about carbon monoxide (CO) and its toxicity, exposure to CO from common, though occult sources like MC smoke is often overlooked. Equally, the adverse health effects, especially to the brain, are usually underestimated. OBJECTIVE: To assess the effects of exposure to CO from MC smoke inhalation on spatial memory in mice. METHODS: Sixteen, adult, male, mice, were randomly assigned to either the experimental or the control group; each having 8 mice. The experimental group was exposed to the MC smoke (Wavetide, China) that was allowed to burn inside the gas chamber (75 cm x 50 cm x 50 cm) for 15 minutes, daily, for 14 days. Digital CO meter (PCMM05 Pyle) was used to measure the amount of CO and Barnes maze protocol to assess the spatial memory. RESULTS: Our results indicate that burning MC for 15 minutes produced up to 312 parts per million (ppm) of CO and raised the blood carboxy-hemoglobin (COHb) level by 15.8%. This is higher than the WHO recommended limit (<100 mg/m3 or 87 ppm for 15 min.) of CO exposure and the %COHb level of <2%. Mosquito coil smoke was also associated with impaired spatial memory. However, the dose and duration of exposure did not significantly affect weight gain in the mice. CONCLUSION: Although widely used to prevent malaria, MC could serve as a potential source of CO and other neurotoxins that could be harmful to the brain; the use and toxicity of which is mostly overlooked even by the public health professionals.

Ameliorative effect of methanol stem extract of Parquetina nigrescens (Afzel) bullock on scopolamine-induced sub-chronic cognitive deficit in mice.

Background Parquetina nigrescens (Afzel) Bullock is a commonly used medicinal plant in African traditional medicine. The powdered roots and stems of the plant are taken with pap as a memory enhancer among the Yorubas of southwestern Nigeria. The mechanism by which scopolamine induces cognitive deficit mimics the pathogenesis of neurodegeneration in cognitive impairment. This study therefore, aimed at investigating the effect of the methanol stem extract of P. nigrescens on sub-chronically scopolamine-induced cognitive deficit in mice. Method Phytochemical screening was carried out on the extract using standard protocols. The oral median lethal dose (LD50) was estimated according to the Organisation for Economic Cooperation and Development (OECD) 425 limit test guideline. Doses of 250, 500, and 1000 mg/kg of the extract were used for the study. The elevated plus maze (EPM) and novel object recognition tests (NORT) were used to assess cognitive function. The brain tissue was assayed for the level of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activity. Results The plant extract contains phenolics, carbohydrates, tannins, saponins, and unsaturated sterols.The extract decreased the transfer latencies on days 7 and 8 against the scopolamine group in EPM and increased the discrimination index decreased by scopolamine in NORT. The methanol stem extract of P. nigrescens significantly (p ≤ 0.01) reduced MDA level;  significantly  (p ≤ 0.01) increased SOD activity;  non-significantly increased GSH activity and the activity of AChE apeared not altered. Conclusion The methanol stem extract of P. nigrescens ameliorated sub-chronically scopolamine-induced cognitive deficit via antioxidant mechanism.

IL35 modulation altered survival, cytokine environment and histopathological consequences during malaria infection in mice.

BACKGROUND: The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated. RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice. CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.

Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways.

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.

Effect of resveratrol and environmental enrichment on biomarkers of oxidative stress in young healthy mice.

Resveratrol (RESV) and Environmental Enrichment (EE) have been separately reported to protect organisms against various diseases. This study investigated the potential benefit of the combination of RESV and EE on biomarkers of oxidative stress in young healthy mice. Fifty mice of both sexes were randomly divided into five groups of 10 animals each: group I served as control, group II were maintained on alternate day feeding, group III received RESV 50 mg/kg, suspended in caboxymethylcellulose orally per kg/day. Group IV received CMC and kept in an Enriched Environment, group V received RESV + EE. The treatment lasted for 28 days. The animals were sacrificed 24 h after the last treatment and brain samples were collected for biochemical evaluation. The results obtained showed a significant decrease (P < 0.05) in malondialdehyde concentration in EE group and RESV treated group kept EE when compared to the control. A significant decrease was also observed in glutathione peroxidase activity in all the treatment groups when compared to the control. A significant decrease in GPx activities in RESV, EE and RESV + EE treated groups in male and female mice when compared to the control groups respectively. However, a significant increase in GPx activities was observed in EE group in male mice and EODF, RESV groups in female mice when compared to RESV + EE groups respectively. In conclusion, the result of our study indicates that EE possesses antioxidant properties by decreasing MDA concentration and attenuating lipid peroxidation in the brain of young Swiss albino mice.

Neurobehavioural evaluation of resveratrol in murine models of anxiety and schizophrenia.

Resveratrol, a caloric restriction mimetic, is a naturally occurring polyphenolic compound with antioxidant and anti-inflammatory properties. Oxidative stress has been implicated in the etiology of a number of neuropsychiatric disorders including generalized anxiety and schizophrenia. This study investigated the anxiolytic and antipsychotic potentials of resveratrol in murine models of anxiety and schizophrenia. Mice were pretreated with resveratrol (200 and 400 mg/kg) in 1% carboxymethyl cellulose for 14 days and subjected to behavioural tests on the 15th day. Anxiolytic activity of resveratrol was determined using the hole board and staircase tests while its anti-psychotic property was evaluated via apormorphine induced stereotypy and swim-induced grooming tests. Although resveratrol did not significantly reduce the mean number of head dips at doses used in the hole board test, it significantly (p < 0.01) decreased the mean episodes of rearing without significantly altering the total number of upward steps climbed in the staircase test. Resveratrol significantly (p < 0.05) reduced the mean climbing scores in the first ten minutes of the apormorphine induced stereotypic climbing and significantly decreased (p < 0.01) episodes and total duration of swim induced grooming in mice. Administration of resveratrol at doses used in this study produced anxiolysis and anti-psychotic effects in mice.

Isolation of bergenin from the root bark of Securinega virosa and evaluation of its potential sleep promoting effect.

OBJECTIVES: Securinega virosa Roxb (Ex Willd) Baill (Euphorbaiceae) root bark has been reportedly used in African traditional medicine in the management of mental illnesses. Previously, the sleep-inducing potential of the crude methanol root bark of Securinega virosa extract and its butanol fraction have been reported. The study aimed to isolate and characterize the bioactive constituent that may be responsible for the sleep inducing property of the root of the plant. MATERIALS AND METHODS: The phytochemical investigation of the S. virosa root bark was carried out leading to the isolation of a compound from the butanol-soluble fraction of the methanol extract. The structure of the compound was elucidated on the basis of its spectral data, including IR, 1D and 2D NMR, mass spectrometry as well as X-ray diffraction analysis. The compound was investigated for sleep-inducing potential using diazepam-induced sleeping time test and beam walking assay in mice. RESULTS: This is the first report on the isolation of bergenin from the root of the plant. It significantly decreased the mean onset of sleep [F (2, 15) =7.167; p< 0.01] at the dose of 10 mg/kg, without significantly affecting the total sleep duration [F (2, 15) = 0.090, p=0.914]. Conversely, it did not significantly affect the number of foot slips at the doses of 5 and 10 mg/kg tested. CONCLUSION: Bergenin isolated from the root bark of S. virosa possesses sleep-inducing property and could be partly responsible for the sedative potential of the root of S. virosa.

Central depressant activity of butanol fraction of Securinega virosa root bark in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Securinega virosa is a commonly used medicinal plant in African traditional medicine in the management of epilepsy and mental illness. Previous studies in our laboratory showed that the crude methanol root bark extract of the plant possesses significant behavioral effect in laboratory animals. In an attempt to isolate and characterize the biological principles responsible for the observed activity, this study is aimed at evaluating the central depressant activity of the butanol fraction of the methanol root bark extract of Securinega virosa. MATERIALS AND METHODS: The medial lethal dose of the butanol fraction was estimated using the method of Lorke. Preliminary phytochemical screening was conducted on the butanol fraction using standard protocol. The behavioral effect of the butanol fraction (75, 150 and 300mg/kg) was evaluated using diazepam induced sleep test, hole-board test, beam walking assay, staircase test, open field test and elevated plus maze assay, all in mice. RESULTS: The median lethal dose of the butanol fraction was estimated to be 1256.9mg/kg. The preliminary phytochemical screening revealed the presence of tannins, saponins, alkaloids, flavonoids, cardiac glycosides, similar to those found in the crude methanol extract. The butanol fraction significantly (P<0.001) reduced the mean onset of sleep in mice and doubled the mean duration of sleep in mice at the dose of 75mg/kg. The butanol fraction and diazepam (0.5mg/kg) significantly (P<0.01-0.001) reduced the number of head dips in the hole-board test suggesting sedative effect. The sedative effect of the butanol fraction was further corroborated by its significant (P<0.01-0.001) reduction of the number of step climbed and rearing in the staircase test. The butanol fraction did not significantly increase the time taken to complete the task and number of foot slips in the beam walking assay, suggesting that it does not induce significant motor coordination deficit. Diazepam (2mg/kg), the standard agent used significantly (P<0.01) increased the number of foot slips. In the open field test, the butanol fraction significantly reduced the number of square crossed as well as the number of rearing. However, the butanol fraction did not significantly alter the behavior of mice in the elevated plus maze assay, while diazepam (0.5mg/kg) significantly (P<0.05) increased the time spent in the open arm and reduced the number of closed arm entry. CONCLUSION: The findings of this study suggest that the butanol fraction of Securinega virosa root bark contains some bioactive principles that are sedative in nature.