Anticonvulsant activity of Nymphaea lotus Linn. extract in mice: The role of GABAergic-glutamatergic neurotransmission and antioxidant defence mechanisms.

Epilepsy remains an unmet medical need affecting more than 50 million people worldwide with about 125,000 mortality annually and more prevalent in low- and middle-income countries. Nymphaea lotus (also known as water lilly) is an aquatic plant used traditionally to treat convulsive episodes in Southwestern Nigeria. This study was undertaken to evaluate anticonvulsant activity of aqueous Nymphaea lotus extract (ANL) and ethanol Nymphaea lotus extract (ENL) on chemical-induced seizures in mice as well as possible mechanisms of action. Vehicle (10 mL/kg, p.o.), ANL (50-200 mg/kg, p.o.), ENL (50-200 mg/kg) or diazepam (5 mg/kg, p.o.) was administered 1 h prior to chemo-convulsant (picrotoxin (PCT), pentylenetetrazol (PTZ), strychnine or N-methyl-D-aspartate (NMDA)) administration. Most effective doses of the extracts were administered to mice after the establishment of temporal lobe epilepsy (TLE) induced by kainic acid. Thereafter, memory assessment in Y-maze, depressive-like behaviour in tail suspension test (TST) and anxiety model in elevated plus maze test (EPM). The prefrontal cortex and hippocampus were assayed for oxidative stress parameters. The pretreatment of mice with ANL or ENL significantly prolonged onset of seizures and reduced the duration of picrotoxin-, pentylenetetrazol-, and strychnine-induced seizures or NMDA-induced turning behaviour. Kainic acid induced spontaneous recurrent seizures and oxidative stress were ameliorated by N. lotus extracts. Moreover, N. lotus-induced anticonvulsant action was reversed by the pretreatment of mice with flumazenil (benzodiazepine receptor antagonist) or L-arginine (nitric oxide precursor). In addition, kainic acid induced neurodegeneration was reduced by N. lotus extract. Findings from this study showed anticonvulsant activity of Nymphaea lotus in neurotoxins-induced seizures through enhancement of inhibitory GABAergic/ antioxidant signalling and inhibition of glutamatergic neurotransmission.

COVID-19 Pandemic: A Case for Phytomedicines.

Coronavirus disease 2019 (COVID-19) is an infection caused by a newly discovered coronavirus which was identified in Wuhan, China. The race is on globally to repurpose drugs for COVID-19 and develop a safe and effective vaccine against the disease. There is an urgent need to search for effective remedies against COVID-19 from the rich and extensive flora of Africa and the world. A literature search was conducted to obtain information on drugs with the potential for effectiveness in the treatment of COVID-19 based mostly on outcomes of preclinical studies and a few clinical investigations. This was considered important to this perspective as some of the identified mechanisms of action may be related to potential anti-COVID-19 actions of phytomedicines. The findings from the literature search were also used to establish the need for exploration of phytomedicines in the fight against COVID-19. This perspective identifies the need to preserve the rich tradition of herbal medicine in Africa, repositioning it by inculcating all aspects of discovery, development, and chemical evaluation of pharmaceuticals from medicinal plants for effective management of prevalent diseases. The identified mechanisms of action of current drugs under consideration for the treatment of COVID-19 include preventing fusion of SARS-CoV-2 with human cells; decrease acidity in endosomes, cell membrane-derived vesicles for transportation of the virus within the host cell and within which the virus can replicate; and blockade of the production of proinflammatory cytokines. Phytomedicines may possibly elicit either one or a combination of these effects. The case for the exploration of phytomedicines against COVID-19 is strengthened by the emergence of a number of conventional drugs from medicinal plants and the emergence of botanicals with proven efficacy for some medical conditions. Caution against indiscriminate use of medicinal plants in the guise of treating COVID-19 has been highlighted and the need for reliable preclinical and clinical studies.

Roles of monoaminergic, antioxidant defense and neuroendocrine systems in antidepressant-like effect of Cnestis ferruginea Vahl ex DC (Connaraceae) in rats.

We have earlier reported antidepressant-like effect of Cnestis ferruginea and its bioflavonoid constituent, amentoflavone in behavioural paradigms but its effects on neurochemical and neuroendocrine systems are yet to be elucidated. This study sought to investigate the effect of subchronic treatment of C. ferruginea (CF) on monoamines system, hypothalamo-pituitary adrenal axis and nitrosative/oxidative stresses. Male albino rats (150-200g) randomly divided into seven groups; Group I: vehicle treated (0.2%v/v Tween 80 in normal saline (10ml/kg; p.o.; unstressed), Group II: vehicle treated+restraint stress, Group III: imipramine (20mg/kg; p.o.), Group IV-VI: CF (12.5, 50, or 100mg/kg; p.o., respectively), Group VII: CF 6.25+imipramine 5mg/kg. One hour post-treatment, animals were subjected to 20min restraint stress and 6min, forced swim test (FST) for a period of 14 days. CF (12.5, 50 and 100mg/kg) produced significant reduction in immobility time and an increase in climbing behaviour. CF attenuated repeated restraint stress×FST-induced serum corticosterone [F(6,28)=5.45,P<0.01]. Exposure of rats to FST+restraint stress paradigms produced significant (P<0.05) increase in malondialdehyde and nitrite level, also reduced the glutathione level and superoxide dismutase activity which was reversed by subchronic treatment of rats with CF. Restraint stress×FST significantly decreased NA, DA and 5-HT concentrations, with increased DA and 5-HT turnover ratios in discrete brain regions which was ameliorated by CF or imipramine subchronic treatment. These results suggest that the antidepressant-like effect of C. ferruginea involved enhancement of monoamines and antioxidant as well as normalization of neuroendocrine systems.

Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: involvement of monoaminergic system.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST. MATERIALS AND METHODS: HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST. RESULTS: HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST. CONCLUSION: The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.