AQUEOUS LEAF EXTRACT OF CARICA PAPAYA (CARICACEAE) LINN. CAUSES LIVER INJURY AND REDUCED FERTILITY IN RATS

Objective: Dried Carica papaya (Caricaceae) leaves have been used in traditional medicine as a contraceptive. The objective of the present study was to evaluate the safety of the aqueous leaf extract of Carica papaya and study its effects on fertility in rats.Methods: The aqueous extract of Carica papaya was administered as single doses to Sprague Dawley rats in an acute study. Animals were observed over a 24 h period for various signs of toxicity. In a separate experiment, the extract was administered to different groups of rats daily for 14 d in a sub-acute study. Animals were observed each day and sacrificed on the 15th day. Organs were then harvested for histopathology. Reproductive studies were also carried out in both male and female rats by administration of the extract at different doses. Markers for fertility were assessed in the rats by determination of fertility indices in the female and sperm analysis in the males. Hormonal assays were also performed.Results: In the acute toxicity study, the LD50 (lethal dose) of the aqueous extract was above 5000 mg/kg with no signs of autonomic or other symptoms of toxicity. In the sub-acute study, treatment of rats with extract (10-500 mg/kg; p. o) for 14 d had no effect on the formed elements of blood or haemoglobin. However, the levels of alkaline phosphatase (AP), gamma glutamyl transferase (GGT) and bilirubin (BIL) increased dose-dependently, suggesting a possible damage to the hepato-billiary system. In the reproductive studies in adult male and female rats, administration of the aqueous leaf extract (10-500 mg/kg; p. o) for 14 d to male rats resulted in significant reduction in sperm count, sperm motility, sperm viability and testosterone. Transverse sections of testes exhibited mild to moderate atrophy. Treatment of female rats with the extract also showed reduction in fertility and increases in maternal mortality and embryolethality.Conclusion: The study shows that the aqueous extract of Carica papaya has the potential to cause liver injury and adversely affect reproduction in rats. Keywords; Carica papaya, Fertility, Toxicity, Sperm count, Testosteron

Preclinical evidence of a rapid-onset antidepressant-like effect of Pseudospondias microcarpa hydroethanolic leaf extract in a chronic depression model

Background: Depression is a widespread, devastating mental illness and currently available treatments have significant limitations including low response rates and delayed onset of action. N-methyl-D-aspartate (NMDA) receptor antagonists exert fast-acting antidepressant effects. Pseudospondias microcarpa produces an antidepressant-like effect via inhibition of the glycine/NMDA receptor complex, and could therefore possess a rapid onset of action. Therefore, the present study investigated the possible rapid-onset antidepressant action of P. microcarpa in mice.Methods: In this study, rapid-onset and sustained antidepressant effects of the hydroethanolic leaf extract of P. microcarpa (PME) was investigated in the open-space swim test, a chronic model of depression. Antidepressant effect was further assessed in the tail suspension test (TST). In addition, the effect of the extract on cognitive function in the Morris water maze (MWM) test was investigated.Results: Depressed mice showed a significant increase in immobility and decrease in distance swum. However, treatment with PME and the classical antidepressants significantly decreased immobility time and increased distance swum. Furthermore, unlike the classical antidepressants which required 10-14 days to significantly improve mobility behaviour, PME treatment significantly decreased immobility time (P<0.001) on the first day of treatment (day 5 of stress procedure). This effect was also sustained for the remainder of the experiment. The extract also significantly decreased immobility time in the TST (F3,16=4.881, P=0.0135) and decreased escape latency (F4,24=12.07, P<0.0001) in the MWM procedure.Conclusions: The leaves of P. microcarpa exhibits rapid and sustained antidepressant effects and improve cognitive function in depressed mice

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Background: Depression is a global burden whose therapy is plagued with inconsistent efficacy. Hence, the need for the discovery of newer therapies.Methods: In this study, Antiaris toxicaria extract (200, 400 and 800 mg/kg, p.o.), was evaluated for antidepressant activity using behavioral tests battery particularly the forced swim test (FST) and tail suspension test (TST). In order to investigate its mechanism of action, animals groups were pretreated with α-methyldopa (α-MD), para-chlorophenylalanine (PCPA), reserpine, D-serine and 5-hydroxytryptophan.Results: It increased the mobility periods and decreased immobility periods significantly in both the FST and the TST when compared to the control group. But the TST showed more promising effect than the FST. Pre-treatment with α-MD reversed the antidepressant property of A. toxicaria aqueous extract as did PCPA, reserpine and reserpine combined with α-MD. The extract increased the number of head twitches produced by 5-hydroxytryptophan confirming the involvement of serotonin in the antidepressant property and inhibited carbachol-induced contractions on the isolated rat uterus, which was non-competitively antagonized by propranolol.Treatment with D-serine produced no significant increase in the immobility time produced by the extract at the doses studied. This excludes the involvement of N-methyl-d-aspartate in the possible mechanisms of action.Conclusion: A. toxicaria possesses antidepressant-like action in rodents

SARS-CoV-2 viral shedding and transmission dynamics : implications of WHO COVID-19 discharge guidelines

This work was supported through the Alliance for Accelerating Excellence in Science in Africa (AESA), a funding, agenda-setting, programme management initiative of the African Academy of Sciences (AAS), the African- Union Development Agency (AUDA-NEPAD), founding and funding global partners and through a resolution of the summit of African Union Heads of Governments.The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria.Publisher PDFPeer reviewe

SARS-CoV-2 Viral Shedding and Transmission Dynamics: Implications of WHO COVID-19 Discharge Guidelines

The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria

The possible mode of antitussive and expectorant activity of the ethanol seed extracts of Picralima nitida ((Stapf) Th. & H. Durand)

It has been established that Picralima nitida has antitussive effect. This study therefore aimed at determining the possible mode of antitussive and expectorant activity of an ethanolic seed extract of P. nitida (PNE). The muco-suppressant, mast cell stabilization, and the anxiolytic effects of PNE were ascertained using ammonium chloride-induced phenol red secretion in BALB/c mice; compound 48/80-induced mesenteric mast cell degranulation assay; and the open field and the elevated plus maze models respectively. Antibacterial potential was ascertained by the agar plate diffusion method and its antioxidant potential by the 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) free radical scavenging, linoleic acid lipid peroxidation, reducing power, and total antioxidant assays. Data obtained was analyzed using One-way analysis of variance (ANOVA) with Dunnett's Multiple Comparison post hoc test. PNE (100–500 mg/kg) reduced (P ≤ 0.05–0.001) tracheal phenol red secretion. The extract (100–500 μg/ml) also dose-dependently (P ≤ 0.05–0.0001) stabilized mast cells. PNE (100–500 mg/kg) increased open arm activities in the elevated plus maze (P ≤ 0.05) as well as central zone exploration (P ≤ 0.05) in the open field test. PNE (10–50 mg/ml) showed activity against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, Klebsiella pneumonia, and Salmonella typhi. By the assays, PNE showed significant antioxidant effect. The ethanolic seed extract of P. nitida has demonstrated very significant mast cell stabilizing, mucus suppressant, and antioxidant activity as well as substantial antibacterial and anxiolytic properties; all of which could contribute to its antitussive and expectorant property

Gut-Brain-axis: effect of basil oil on the gut microbiota and its contribution to the anticonvulsant properties

Abstract Background Epilepsy is a chronic neurological condition that disrupts the normal functioning of the brain and it is characterized by seizures. Research suggests the involvement of the Gut-Brain axis in epilepsy. This study seeks to determine the role of the gut microbiota in the anticonvulsant effect of basil oil (BO) using antibiotic-depleted and altered germ-free mice against naïve mice in Pentylenetetrazole (PTZ) induced seizure model. There is an ever growing interest in improvement of treatment outcomes in epilepsy and also in the development of newer therapeutic options, especially in the population of patients that do not attain seizure relief from available antiseizure medications (ASMs). According to research, gut microbiota can alter brain function and development. Increasing evidence suggests disrupting the delicate symbiotic balance existing between the gut and brain results in disease conditions. Also, the oil from Ocimum basilicum L., (BO) has been proven scientifically to significantly block clonic seizures induced by PTZ and picrotoxin in seizure models. Methods The microbiota of mice were depleted or altered by administering cocktail antibiotics and individual antibiotics respectively. DNA was isolated from mouse stool, and then the 16S ribosomal ribonucleic acid (16S rRNA) gene was quantitatively amplified using reverse transcription-polymerase chain reaction (RT-PCR). Amplicons were sequenced to determine the phylogenetic make-up of the bacteria involved. Metabolic profiles of the serum and stool of mice were determined using Proton (1H) Nuclear Magnetic Resonance (NMR) spectroscopy. Results Cocktail antibiotic pre-treatment significantly reversed the anticonvulsant effect of BO by increasing frequency and duration of seizures but did not affect latency to seizure. In mice pre-treated with single antibiotics, the anticonvulsant effect of BO was lost as latency to seizures, frequency and duration of seizures increased compared to mice that received only BO. Assessment of the phylogenetic make-up of the microbiota in antibiotic pre-treated mice showed a distorted composition of the microbiota compared to the control group. Conclusion Depletion of the microbiota significantly reversed the anticonvulsant actions of BO. The concentrations of short chain fatty acids (SCFAs) was higher in stool than in the serum of the mice. Administration of BO probably does not influence the microbial composition within the mouse microbiota. The elevated ratio of Firmicutes to Bacteroidetes in microbiota-depleted groups might have contributed to the reversal of anticonvulsant actions of BO

Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model.A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 ​mg/kg), SLN-CRYP (5 ​mg/kg), ABZ (50 ​mg/kg) DXM (0.5 ​mg/kg), and PHE (30 ​mg/kg).were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains.All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p ​< ​0.0001); as were frequency (p ​< ​0.0001) and duration (p ​< ​0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p ​= ​0.0016) and IFN-γ (p ​< ​0.0001).Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model

Enhancement of inhibitory neurotransmission and inhibition of excitatory mechanisms underlie the anticonvulsant effects of Mallotus oppositifolius

Context: Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated. Aims: This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius.Materials and Methods: Inprinting control region (ICR) mice (25–30 g) were pretreated with the M. oppositifolius leaf extract (10–100 mg/kg) before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine). The effect of the extract in maximal electroshock seizure (MES) model was investigated also. Statistical Analysis: Data were presented as mean ± standard error of the mean and were analyzed with one-way analysis of variance (ANOVA) or two-way ANOVA where appropriate with Newman–Keuls or Bonferroni post hoc test respectively. P< 0.05 was considered significant. Results: In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4-AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA) receptor antagonist. Conclusion: These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic receptor activation and N-Methyl-D-aspartate receptor activation