Protective role of Spondias mombin leaf and Cola acuminata seed extracts against scopolamineinduced cognitive dysfunction

The leaves of Spondias mombin L. (Anacardiaceae) when chewed with Cola acuminata (P. Beauv.) Schott & Endl. (Sterculiaceae) seeds have memory enhancing and anti-ageing properties. This study sought to investigate the protective effect of hydroethanolic leaf extract of Spondias mombin (SM) and Cola acuminata seed extract (CA) against scopolamine-induced cognitive dysfunction. SM or CA (50, 100 or 200 mg/kg, p.o.) or SM +CA (50 mg/kg, p.o.) was administered to rats for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg i.p) was administered and 5 min later, the Y-maze test or Morris water maze test (MWM; days 3–7) was conducted. The rat’s brains were isolated for the estimation of oxidative-nitritive stress status following the MWM task. The antioxidant capacity of SM and CA was also evaluated in vitro using the 1,1- diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Pretreatment of rats with SM, CA or SM + CA significantly ameliorated the learning and memory impairment induced with scopolamine as evidenced in Y-maze and MWM paradigms. Moreover, SM, CA or SM + CA significantly attenuated the oxidative-nitritive stress induced by scopolamine, evidenced in the decrease in malondialdehyde and nitrite levels and restoration of glutathione, catalase and superoxide dismutase levels. Furthermore, SM and CA showed promising free radical scavenging effect against DPPH and moderate antioxidant activity in NO and FRAP tests. This study showed that Spondias mombin and Cola acuminata have significant protective effect against scopolamine-induced memory deficit that could be attributed to their antioxidant properties.Keywords: Dementia; Lipid peroxidation; Nitrite; Morris water maze; Y-maz

Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) in Rodents: possible mechanism of actions

Summary: The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for the treatment of various ailments including arthritis. The present study sought to investigate the antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA). HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar injection of formalin 1%v/v in saline to evaluate antinociceptive effect. Moreover, its possible mechanism of antinociceptive action was investigated through pretreatment of mice with antagonists of receptors implicated in nociception. Anti¬inflammatory effect of the extract was investigated using the carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the duration of paw licking/biting during both in the early (42.12%) and late (75.79%) phases of formalin-induced nociception. However, the antinociceptive effect elicited by HeCA was reverse by pretreatment of mice with naloxone, prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA). HeCA produced dose-dependent and time course decrease in carrageenan-induced paw oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced arthritis evidenced in the significant decrease in arthritic index comparatively similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress were attenuated by subchronic treatment with HeCA. Findings from this study shows that C. anisata possesses antinociceptive activity through possible interaction with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic pathways as well as anti-arthritic property which could be attributed to its ability to prevent the release of inflammatory mediators and oxidative stress.Keywords: Complete Freund's adjuvant; L-arginine-nitric oxide; nociception; antioxidant; rheumatoid arthritis; serotonergic

Protective role of Spondias mombin leaf and Cola acuminata seed extracts against scopolamine-induced cognitive dysfunction

The leaves of Spondias mombin L. (Anacardiaceae) when chewed with Cola acuminata (P. Beauv.) Schott & Endl. (Sterculiaceae) seeds have memory enhancing and anti-ageing properties. This study sought to investigate the protective effect of hydroethanolic leaf extract of Spondias mombin (SM) and Cola acuminata seed extract (CA) against scopolamine-induced cognitive dysfunction. SM or CA (50, 100 or 200 mg/kg, p.o.) or SM + CA (50 mg/kg, p.o.) was administered to rats for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg i.p) was administered and 5 min later, the Y-maze test or Morris water maze test (MWM; days 3–7) was conducted. The rat’s brains were isolated for the estimation of oxidative-nitritive stress status following the MWM task. The antioxidant capacity of SM and CA was also evaluated in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Pretreatment of rats with SM, CA or SM + CA significantly ameliorated the learning and memory impairment induced with scopolamine as evidenced in Y-maze and MWM paradigms. Moreover, SM, CA or SM + CA significantly attenuated the oxidative-nitritive stress induced by scopolamine, evidenced in the decrease in malondialdehyde and nitrite levels and restoration of glutathione, catalase and superoxide dismutase levels. Furthermore, SM and CA showed promising free radical scavenging effect against DPPH and moderate antioxidant activity in NO and FRAP tests. This study showed that Spondias mombin and Cola acuminata have significant protective effect against scopolamine-induced memory deficit that could be attributed to their antioxidant properties

Protective effect of Tetrapleura tetraptera (Schum. & Thonn.) fruit extract against haloperidol-induced catalepsy and scopolamine-induced memory impairment: Involvement of antioxidant system

Tetrapleura tetraptera fruit infusion is taken as a recuperative tonic and memory enhancer in the traditional African medicine. This study investigates the  neuroprotective and memory enhancing effects of T. tetraptera. The ethanolic fruit extract of Tetrapleura tetraptera (HeTA) (25-100 mg/kg, p.o) was administered for 3 consecutive days, scopolamine (3 mg/kg, i.p.) or haloperidol (1 mg/kg, i.p.) given 1 h post-treatment on day 3. The bar test, elevated plus maze test (EPM) and Morris water maze paradigm (MWM) were used to evaluate the effect of the extract on cataleptic behaviour and memory function, respectively. Biochemical markers of oxidative and nitrosative stress were estimated in rats’ brains after the completion of the MWM task. Haloperidol injection induced time course cataleptic behaviour which was reversed by HeTA (25-100 mg/ kg) treatment in bar test. Scopolamine injection impaired memory function in the EPM and MWM tasks. However, HeTA (25-100 mg/kg) administration significantly (P<0.001) reduced the transfer latency in the EPM as well as session dependent decrease (P<0.001) in escape latency in MWM. Also, HeTA and tacrine improved spatial learning evidenced in the increase (P<0.01) time spent in the target quadrant in the MWM. Moreover, scopolamine increased (P<0.05-0.001) the levels of lipid peroxidation and nitrite generation with concomitant decrease (P<0.05-0.001) in antioxidant enzymes activities in the prefrontal cortex, striatum and hippocampus which were ameliorated with the pretreatment of rats with HeTA or tacrine. Findings from this study indicate anticataleptic and memory enhancing effects of T. tetraptera fruit extract through enhancement of antioxidant defense systems.Keywords: Dementia; elevated plus maze; Morris water maze; scopolamine; malondialdehyde; 1,1-Diphenyl- 2-picrylhydrazyl (DPPH

Analgesic and anti-inflammatory actions of Alafia barteri: Involvement of monoaminergic, nitrergic and opioidergic pathway.

Background: We have earlier reported the antinociceptive and anti-inflammatory effects of Alafia barteri Oliver (Apocynaceae) in rodents but its mechanism of actionsare yet to be elucidated.Objective: This study sought toinvestigate the involvement of monoaminergic, nitric oxide-cyclic GMP-K+ channel and opioidergic pathways in its mechanism of actions.Methods: methanol root extract of Alafia barteri (ALA) (100-400 mg/kg, p.o.) was given 1 h before administration of chemical or thermal - induced nocicept ion andhistamine/serotonin-induced inflammation. Themechanism of the antinociceptive effect was investigated through intraperitoneal injection of prazosin (62.5 μg/kg; á adrenoceptor antagonist), yohimbine (1 1- mg/kg; á adrenoceptor antagonist) NG-nitro-L-arginine (L- 2 , NNA) (20 mg/kg; nitric-oxide-synthase inhibitor), cyproheptadine(10mg/kg;5-HTR2antagonist),glibenclamide (10 mg/kg; ATP-sensitive K+- channel inhibitor), or naloxone (5 mg/kg; opioid-receptor antagonist) before the nociceptive models.Results: ALA(100-400 mg/kg)treatment produced dose and time dependent (P<0.001; 87.11%)increase in pain threshold in acetic acid-induced-writhing, inhibition ofneurogenic (50.96%), and inflammatory (70.02%) phases of formalin test, and 41.75% maximum possible effect (MPE) in tail immersion testat 400 mg/kg in comparison with vehicle-treated control. The antinociceptive-effect was blocked by pretreatmentof mice withprazosin, yohimbine or L-NNA, (P<0.001) in writhingassay. Similarly, naloxone pretreatment blocked the inhibition of neurogenic- and inflammatory-pain induced by ALA in formalin test. Interestingly, ALA produced dose related time course inhibition (P<0.05) of histamine and serotonin-induced paw inflammation with peak effects (57.89, and 81.82%), respectively, at 400 mg/kg.Conclusion: Findings from these studies suggest central and peripheral analgesic effect of A. barteri through interaction with L-arginine-nitric-oxide pathway, á - 1/2 adrenoceptors, and/or, opioidergic pathway, while, the antiinflammatoryeffect involves marked inhibition of histamine and serotonin release.Keywords: á-adrenoceptor; ATP-sensitive potassium channel; histamine; opioidergic ;pathway; serotonin; formalin-induced nociception

Cyclooxygenase inhibitory compounds from Gymnosporia heterophylla aerial parts

http://dx.doi.org/10.1016/j.fitote.2017.04.015Gymnosporia heterophylla (Celastraceae) is an African medicinal plants used to treat painful and inflammatory diseases with partial scientific validation. Solvent extractions followed by repeated chromatographic purification of the G. heterophylla aerial parts led to the isolation of one new β-dihydroagarofuran sesquiterpene alkaloid (1), and two triterpenes (2–3). In addition, eight known compounds including one β-dihydroagarofuran sesquiterpene alkaloid (4), and six triterpenes (5–10) were isolated. All structures were determined through extensive analysis of the NMR an MS data as well as by comparison with literature data. These compounds were evaluated for the anti-inflammatory activities against COX-1 and -2 inhibitory potentials. Most of the compound isolated showed non selective COX inhibitions except for 3-Acetoxy-1β-hydroxyLupe-20(29)-ene (5), Lup-20(29)-ene- 1β,3β-diol (6) which showed COX-2 selective inhibition at 0.54 (1.85), and 0.45 (2.22) IC50, in mM (Selective Index), respectively. The results confirmed the presence of anti-inflammatory compounds in G. heterophylla which are important indicators for development of complementary medicine for inflammatory reactions; however, few could be useful as selective COX-2 inhibitor

Roles of insulin in olanzapine-induced blood glucose dysregulation in rodents

Olanzapine is an effective pharmacologic treatment of psychosis. However, its use is commonly associated with metabolic side effects. This study was designed to investigate the possible mechanisms of olanzapine-induced blood glucose dysregulation in rats. Olanzapine (10 mg/kg, i.p.), or co-administration of olanzapine (10 mg/kg) and metformin (500 mg/kg), respectively, to rats, acutely or chronic for 28 consecutive days. Fasting glucose and insulin levels, were measured, followed by a 2h glucose tolerance test. Then, blood samples were collected for estimation of biochemical and haematological parameters. The liver, kidney and brain were harvested to estimate the level of oxidative/nitrosative stress status. Subacute administration of olanzapine did not affect body weight but decreased insulin secretion (P<0.05), induced glucose intolerance in OGTT test and enhanced insulin-blood glucose reduction in insulin tolerance test (P<0.001). Both acute treatments with olanzapine and metformin increased insulin secretion but no significant change were seen in subacute study. Conversely, acute injection of olanzapine induced hypoglycemia with concomitant increase in insulin secretion by 1.9 fold (P<0.01) with no significant change in body weight. Sub-chronic olanzapine induced 1.2 fold increase in ALT (P<0.01), 2.1 fold increase in ALP(P<0.01) and 1.8 fold increase in bilirubin (P<0.01) concentration, while decreasing creatinine and urea levels by 1.1 fold (P<0.05) compared with vehicle-treated control. Olanzapine injection decreased anti-oxidant activity (GSH, P<0.05) in the brain by 1.9 fold and in the liver by 17.6 fold (GSH, P<0.0001) with increase in lipid peroxidation by 1.6 fold (P<0.05) and increased nitrosative stress (P<0.05). In contrast, there was an increase in kidney antioxidant level (GSH, P<0.05) by 2.4 fold and increase in lipid peroxidation by 2.5 folds (MDA, P<0.05). Sub-chronic administration of olanzapine induced metabolic syndrome (glucose intolerance, increased TG, reduced HDL), hepatotoxicity, and anemia through induction of oxidative stress. ABSTRAITL'olanzapine est un traitement pharmacologique efficace de la psychose. Cependant, son utilisation est généralement associée à des effets secondaires métaboliques. Cette étude a été conçue pour étudier les mécanismes possibles de la dérégulation de la glycémie induite par l'olanzapine chez le rat. L'olanzapine (10 mg / kg, ip), la metformine (500 mg / kg) ou la coadministration d'olanzapine (10 mg / kg) et de metformine (500 mg / kg), respectivement, ont été administrés à des rats, de manière aiguë ou pendant 28 jours consécutifs. traitements de jours. Les taux d'insuline et de glucose à jeun ont été mesurés, suivis d'un test de tolérance au glucose de 2h. Ensuite, des échantillons de sang ont été recueillis pour l'estimation des paramètres biochimiques et hématologiques. Le foie, les reins et le cerveau ont été récoltés pour estimer le niveau de stress oxydant / nitrosatif. L'administration subchronique d'olanzapine n'a pas eu d'incidence sur le poids corporel, mais a diminué la sécrétion d'insuline (p <0,05), induit une intolérance au glucose dans le test OGTTet une réduction accrue de la glycémie dans le test de tolérance à l'insuline (p <0,001). Les deux traitements aigus avec l'olanzapine et la metformine ont augmenté la sécrétion d'insuline, mais aucun changement significatif n'a été observé dans l'étude subchroniqueune réduction du nombre d'hémoglobine et de globules rouges (P <0,05). Inversement, une injection aiguë d'olanzapine a provoqué une hypoglycémie avec une augmentation concomitante de la sécrétion d'insuline de 1,9 fois (P <0,01) sans modification significative du poids corporel. L'olanzapine subchronique a induit une augmentation de 1,2 fois de l'ALT (P <0,01), de 2,1 fois de la PAL(P <0,01) et de 1,8 fois de la concentration en bilirubine (P <0,01), tout en diminuant les taux de créatinine et d'urée de 1,1 fois (P <0,05) par rapport au témoin traité avec le véhicule. L'injection d'olanzapine a diminué l'activité anti-oxydante (GSH, p <0,05) dans le cerveau de 1,9 fois et dans le foie de 17,6 fois (GSH, p <0,0001) avec une augmentation de la peroxydation lipidique de 1,6 fois (p <0,05) et une augmentation de la nitrosation stress (P <0,05). en revanche, le niveau d'antioxydant dans les reins (GSH, p <0,05) a augmenté de 2,4 fois et celui de la peroxydation lipidique de 2,5 fois (MDA, p <0,05). Administration subchronique du syndrome métabolique induit par l'olanzapine (intolérance au glucose, TG accrue, HDLréduit), une hépatotoxicité et une anémie, probablement à cause de l'induction d'un stress oxydatif

Ameliorative effect of the hydroethanolic whole plant extract of Digitaria horizontalis (Poaceae) against haloperidol-induced catalepsy in mice

Background: Digitaria horizontalis is used in Traditional African Medicine in the management of nervous disorders.Objective: This study was carried out to investigate the protective effect of hydroethanolic whole plant extract of D. horizontalis 1 against haloperidol-induced catalepsy in mice.Methods: Male albino mice (17-21 g) randomly divided into six groups (n=6); (1) normal saline, vehicle control (10 ml/kg), (2) vehicle positive control, (3) trihexylphenidyl (0.5 mg/kg, i.p.), (4-6) DH (12.5, 50 or 100 mg/kg), 1 h posttreatment haloperidol (1 mg/kg, i.p.) for 14 consecutive days. The neurobehavioral effect of the extract was evaluated using the bar, open field, elevated plus maze, forced swim and climbing tests. At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined.Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), depressive-like behavior and motor coordination deficits (forced swim and climbing tests, respectively) compared to vehicle-treated control. Haloperidol injection increased level of lipid peroxidation and deficits in the level of antioxidant enzymes which was attenuated by pretreatment of mice with DH. To corroborate these findings, DH scavenged 1-1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide and ferric ion induced free radicals in vitro.Conclusion: Findings from this study suggests that the hydroethanolic whole plant extract of D. horizontalis possesses antioxidant, neuroprotective, nootropic andantidepressant-like properties. Thus, could be a potential phytotherapeutic in the management of drug-induced Parkinsonism.Keywords: Digitaria horizontalis; neuroprotective; haloperidol; nootropic; catalepsy; antioxidant