Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice.

Flavonoids are naturally occurring bioactive phytochemical metabolites widely known to prevent and suppress several human diseases, and are important sources of therapeutic compounds from plants. Evidence derived from previous studies suggests that naringin, a neuroactive flavonoid possess functional beneficial neurobehavioral effects including anxiolytic, antidepressant and memory enhancing properties. However, literature search revealed that no studies have been carried out to evaluate the possible biochemical mechanisms involved in the neurobehavioral property of naringin alone following repeated treatment. Hence, this study was designed to evaluate the possible neuro-biochemical mechanisms involved in the neurobehavioral property of naringin following repeated administration in mice. The effects of naringin (2.5, 5 and 10 mg/kg), diazepam (2 mg/kg), imipramine (15 mg/kg) and donepezil (1 mg/kg) or vehicle on neurobehavioral and biochemical effects were evaluated in mice following repeated intraperitoneal injection for 7 consecutive days. Neurobehavioral activities consisting of open-field (locomotor), elevated-plus maze (anxiolytic), forced swim and social interaction (antidepressant and social preference), and Y-maze (memory enhancing) tests were assessed. Thereafter, brains levels of biomarkers of oxidative, nitrosative and cholinergic parameters were determined. Repeated treatment with naringin produced increased locomotor activity, and demonstrated antidepressant-like effects evidenced by decreased immobility time in forced swim test and increased % social preference in the social interaction test relative to controls. Also, naringin induced anxiolytic-like effect and increased cognitive performance in mice. Mechanistically, naringin significantly increased the activities of superoxide dismutase and catalase, and glutathione concentration relative to vehicle-controls. However, naringin significantly decreased malondialdehyde and nitrite contents, and reduced brain acetylcholinesterase activity in mice brains in a significant manner relative to controls. Taken together, these findings suggest that treatment with naringin might be useful to produce functional behavioral effects via mechanisms related to enhancement of cholinergic transmission, antioxidant defense systems, inhibition of lipid peroxidation and nitrosative processes.

Probable mechanisms involved in the antipsychotic-like activity of morin in mice.

Evidence derived from preliminary studies suggests that morin, a neuroactive flavonoid with proven antioxidant and antiinflammatory properties possess antipsychotic-like activity. The present study was designed to evaluate the probable mechanisms involve in the antipsychotic-like activity of morin in ketamine model of schizophrenia. The effects of morin, haloperidol and risperidone on neurobehavioral and anti-schizophrenia-like effects were evaluated in mice (n = 7) following intraperitoneal (i.p.) administration of morin (25-100 mg/kg), haloperidol (1 mg/kg) and risperidone (0.5 mg/kg) alone or in combination with ketamine (20 mg/kg, i.p.) for 10 days. Neurobehavioral and schizophrenia-like activities consisting of open-field (positive symptoms), Y-maze, novel-object recognition (cognitive symptoms), social interaction (negative symptoms) tests were assessed. Also, wood-block catalepsy and rota-rod tests were employed to evaluate extrapyramidal side effects of morin. Thereafter, brain levels of biomarkers of oxidative, nitrergic and acetylcholinesterase alterations as well as histomorphological changes in the striatum and prefrontal-cortex were determined. Administration of morin and risperidone alone but not haloperidol significantly (p > 0.05) prevented ketamine-induced hyperlocomotion, social withdrawal and cognitive impairments relative to controls, and were devoid of extrapyramidal side effects. Morin alone or in combination with ketamine significantly increased glutathione concentration, superoxide dismutase and catalase activities compared with saline- or ketamine-treated mice. Moreover, morin alone or in combination with ketamine also significantly decreased malondialdehyde, nitrite and acetylcholinesterase alterations in mice brains. Furthermore, morin prevented ketamine-induced brain neuronal alterations in the striatum and prefrontal-cortex. Together, our findings suggest that morin may demonstrate antipsychotic-like therapeutic effect via modulation of oxidative/nitrergic, cholinergic actions and neuroprotection.

Protective Effects of Morin Hydrate on Acute Stress-Induced Behavioral and Biochemical Alterations in Mice.

INTRODUCTION: As stress affects the brain both physiologically and chemically, researchers try to find novel anti-stress compounds with beneficial therapeutic effects. In this regard, the effect of stress and its modulation by Morin hydrate was studied using different acute models in mice. METHODS: The models employed were anoxic tolerance, swimming endurance, and acute restraint test. Morin hydrate or the vehicle was administered 30 minutes prior to each stress exposure while in the acute restraint test; the animals were pretreated for 7 days with Morin hydrate, vehicle, imipramine, or diazepam before stress exposure. The measured parameters were the onset of convulsion and immobility time in the anoxic tolerance and swimming endurance test, respectively, while in the acute restraint test, the animals were assessed for stress-induced anxiety using the elevated plus maze and depression using the forced swim test. Thereafter blood was withdrawn from the retro-orbital plexus and plasma separated, the brain was also isolated, homogenized, centrifuged, and the supernatant was obtained for biochemical estimation. RESULTS: Morin hydrate (5, 10, 20 mg/kg) produced a significant reduction in immobility time in the swimming endurance test, while significantly increased the anoxic stress tolerance time. Acute restraint stress caused a significant decrease in reduced glutathione levels (which was reversed by Morin hydrate) and increased the level of malondialdehyde, a thiobarbituric acid reactive substance which is an index of oxidative stress and nitrite. These effects were attenuated by Morin hydrate. Also, pretreatment with Morin hydrate attenuates acute restraint stress-associated anxiety and depression, reversed the hyperglycemia evoked by the stressful exposure and normalized serum cholesterol levels. CONCLUSION: These findings suggest that Morin hydrate exhibits anti-stress effects and may be useful in the relief of stress.

Anti-nociceptive activity of the crude extract of Myrianthus arboreus P. Beauv (Cecropiaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrianthus arboreus P. Beauv (Cecropiaceae) is a shrub or a tree plant widely distributed in Tropical Africa. In the South Eastern part of Nigeria, the leaves are used in traditional medicine as an analgesic for muscular pains, and also as an enema to relieve pain in the back and loins. Although no scientific study has been performed to validate its traditional use in pain management, this study therefore aims at investigating the anti-nociceptive activity of M. arboreus leaves extract in mice. MATERIALS AND METHODS: Anti-nociceptive activity of M. arboreus was investigated using acetic acid induced writhing, formalin induced paw licks, hot plate, and tail flick tests. Acute toxicity was determined using a slightly modified Lorkes method. RESULTS: The extract of M. arboreus produced a significant dose-dependent [F (4, 20)=13.48 p<0.001] inhibition of abdominal writhings induced by acetic acid. In the formalin paw licking test, it produced a significant dose-dependent inhibition of neurogenic and inflammatory pain [F (4, 17.5)=60.13 p<0.001]. It also produced a significant dose dependent [F (4, 20)=30.5 p<0.001; F (4, 20)=0.321 p<0.0001] prolongation of the latency and reaction time in the hot plate and tail immersion tests. Peak effect was observed at the highest dose (40 mg/kg). LD50 of the plant was found to be 894 mg/kg. CONCLUSION: M. arboreus possesses potent antinociceptive activity mediated centrally and peripherally, an effect which may justify its traditional use in the management of pain.

Antinociceptive property of Olax subscorpioidea Oliv (Olacaceae) extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax subscorpioidea is a shrub or tree found in Nigeria, and other parts of Africa. It is used in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer. However, there is dearth of information on scientific basis for its folkloric use in the management of pain. Therefore, the study was designed to investigate the antinociceptive property of the extract of Olax subscorpioidea (EOS) leaves in mice. MATERIALS AND METHODS: Antinociceptive activity of EOS (12.5-50 mg/kg, i.p.) was investigated using acetic acid induced abdominal writhing, tail immersion, hot plate and formalin tests. RESULTS: Extract of Olax subscorpioidea produced significant dose dependent inhibition of writhing frequency [F(4,20)=155.9, p<0.0001] and significant dose dependent inhibition of neurogenic and inflammatory pains [F(4,20)=116.7, p<0.0001; F(4,20)=40.05, p<0.0001]. It also produced a significant dose dependent prolongation of the latent period and reaction times in tail immersion and hot plate tests in mice [F(4,20)=19.49, p<0.0001; F(4,20)=97.95, p<0.0001]. CONCLUSION: Olax subscorpioidea possessed potent analgesic action, mediated centrally and peripherally, thus justifying its use in the management of pain.