Fluoxetine attenuates stress-induced depression-like behavior due to decrease in pro-inflammatory cytokines in male rats.

Background: Pro-inflammatory cytokines are implicated in depression caused by both environmental- and alcohol-induced stress. The purpose of the study was to investigate the cytokine levels in serum and hippocampus following induction of depression-like behaviors (DLB) by either forced swimming test (FST) or ethanol-induced DLB (EID). We also investigated the effect of prior administration of antidepressant drug fluoxetine on cytokines in animals exposed to both models of DLB. Methods: Animals were pretreated with fluoxetine before inducing DLB, while DLB was induced in some animals using FST and ethanol in different groups of rats without fluoxetine pretreatment. The ELISA was used to detect changes in cytokine (IL-1ß, IL-6, and TNF-α) levels in serum and hippocampus. Results: The mean levels of IL-1ß and IL-6 measured in serum and hippocampus were significantly higher in FST and EID models when compared to the control group. The serum concentrations of IL-1ß and IL-6 were significantly reduced in animals pre-treated with 5 mg/kg and 10 mg/kg of fluoxetine in both FST and EID models when compared to the untreated FST and EID groups respectively. Conclusions: In conclusion, both environment and alcohol can induce stress and DLB in rats with similar intensity, and their mechanisms of DLB induction involve activation of pro-inflammatory cytokines. Moreover, fluoxetine can prevent stress-induced inflammation in models of DLB.

Epidemiology of neurodegenerative diseases in the East African region: A meta-analysis.

Introduction: There is a scarcity of epidemiological data on neurodegenerative diseases (NDs) in East Africa. This meta-analysis provides the regional prevalence of NDs, their contributing factors, and evidence of change over time concerning gender per age or year. Methods: Articles were retrieved from electronic databases following the PRISMA standard. Results: Forty-two studies were reviewed, and 25 were meta-analyzed with a random-effects model. The pool estimate proportion of 15.27%, 95% CI (0.09-0.23) (I2 = 98.25%), (Q = 1,369.15, p < 0.0001) among a population of 15,813 male/female and 1,257 with NDs. Epidemiological characteristics associated with NDs include Dyskinesias prevalence 55.4%, 95% CI (13.5; 90.9), I2 (96%) and subsistence farming prevalence 11.3%, 95% CI (5.8; 20.9), I2 (99%). Publication bias by Egger test was (z = 4.1913, p < 0.0001), while rank correlation test using Kendall's model was (tau = 0.1237, p = 0.3873). Heterogeneity (R2 design = 5.23%, p design < 0.0001; R2 size = 52.163%, p size < 0.001; and R2 period = 48.13, p period < 0.0001. Covariates (R2 design + size + period = 48.41%, p < 0.001). Conclusion: There is a high prevalence of NDs in the East African region, which could impact life expectancy, morbidity, and quality of life. Thus, early screening and regular surveillance could assist in management strategies.

Anti-apoptotic effect of Buchholzia coriacea Engl. stem back extracts on AsPC-1 and mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Buchholzia coriacea Engl. is popularly called wonderful cola due to its wide ethnomedicinal use for the treatment of various ailments. We investigated the possible cytotoxic effect of its various fractions on human pancreatic cancer cell (AsPC-1) and also determined its mechanisms of action. MATERIALS AND METHODS: The AsPC-1 cells were cultivated and separately treated with 5-fluorouracil (5-FU) or Buchholzia coriacea Engl. bark (BC) (ethanol, aqueous, chloroform or ethyl acetate extract) for 72 h. Cell viability, caspase 3 and mitochondrial membrane potential (ΔΨm) were determined in vitro after the treatment. Nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals' scavenging property, ferric reducing power and lipid peroxidation assays were also done to examine the antioxidant effect of BC in vitro. RESULTS: Various extracts of BC, especially at 2500 µg/ml and 5000 µg/ml, increased the AsPC-1 viability while 5-FU decreased it. The activity of caspase 3 was increased by 5-FU but reduced by all concentrations of various extracts of BC. Incubation of AsPC-1 with 5-FU showed the majority of cells having the monomeric form of JC-1 dye (bright green fluorescence), which indicated de-energized mitochondria. However, fluorescence photomicrograph of cells incubated with different concentrations (20, 40 and 100 µg/ml) of BC extracts (aqueous, ethanol, chloroform and ethyl acetate) showed strong JC-1 aggregation (yellow), which indicated mitochondria with intact membrane potentials. BC extracts also scavenged NO and DPPH radicals, inhibited lipid peroxidation and increased ferric reduction, though not as much as ascorbic acid. CONCLUSION: This study suggests that BC elicits anti-apoptotic activity in AsPC-1 by increasing cell viability, decreasing caspase 3 activity, stabilizing the ∆Ψm, and scavenging free radicals. Even though BC is used ethnomedicinally as anti-cancer agent, our findings in the present study suggest that it has pro-cancer potential in-vitro, especially on pancreatic cells. Its anti-apoptotic activity in AsPC-1 could be of clinical significance, especially to counteract the effect of apoptotic agents on pancreatic cells.

Telfairia occidentalis stimulates hepatic glycolysis and pyruvate production via insulin-dependent and insulin-independent mechanisms.

BACKGROUND: Telfairia occidentalis (TO), a plant consumed for its nutritional and medicinal values, exhibits hypoglycaemic effect. However, the metabolic fate of the glucose following TO-induced insulin secretion and consequent hypoglycaemia is not clear. OBJECTIVE: This study determined the effect of ethyl acetate and n-hexane fractions of TO leaf extracts on some biochemical parameters in the glucose metabolic pathway to explain the possible fate of blood glucose following TO-induced hypoglycaemia. METHODS: Eighteen male Wistar rats (180-200 g) divided into control, n-hexane TO fraction- and ethyl acetate TO fraction-treated groups (n = 6/group) were used. The control animals received normal saline while the treated groups received TO at 100 mg/kg for seven days. After 24 h following the last dose, the animals were anaesthetised using ketamine; blood samples were collected and livers harvested to determine some biochemical parameters. RESULTS: Ethyl acetate TO fraction significantly increased plasma insulin, liver glucokinase activity and plasma pyruvate concentration, but significantly decreased plasma glucose and liver glycogen, without significant changes in plasma lactate, glucose-6-phosphate, liver glucose-6-phosphatase and lactate dehydrogenase activities when compared with control. N-hexane TO fraction significantly reduced liver glucose-6-phosphatase activity and glycogen but significantly increased plasma pyruvate, without significant changes in plasma glucose, insulin, glucose-6-phosphate and lactate concentrations; and liver glucokinase and lactate dehydrogenase activities. CONCLUSION: The present study showed that insulin-mediated TO-induced hypoglycaemia resulted in the stimulation of glycolysis and pyruvate production via insulin-dependent and insulin-independent mechanisms.

Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication.

BACKGROUND: We investigated the mechanism of artesunate's glucose-modulating effect especially with gender implication. METHODS: Twenty-five (25) male and 25 female rats were separately and blindly allocated into five identical groups (n = 5/group). Group I (control) received 0.2 ml/kg distilled water. Groups II and III both received 2.90 mg/kg artesunate on day one, but 1.45 mg/kg from day two till day five and day fifteen respectively. Groups IV and V both received 8.70 mg/kg artesunate on day one, but 4.35 mg/kg artesunate from day two till day five and day fifteen respectively. RESULTS: In male rats, glucose was reduced by both doses of artesunate at 5 days but increased by high dose at 15 days. Artesunate increased glycogen concentration at short duration which normalised at long duration in both genders. Artesunate increased G6P concentration only in male rats at 15 days but reduced G6Pase activity in male and female rats (except in those that received low and high doses of artesunate for 15 days). Artesunate increased insulin only in male rats treated with low dose artesunate for 5 days. Artesunate increased cortisol concentration in male but reduced it in female rats. Artesunate decreased glucagon concentration except in female rats treated with high dose for 5 days. Artesunate increased oestrogen concentration in male rats that received low dose artesunate for 5 days but reduced it in female rats that received high dose for 15 days. CONCLUSIONS: Artesunate reduces plasma glucose by reducing plasma glucagon concentrations and inhibiting liver glycogenolysis via inhibition of G6Pase activity in both sexes. Increase in insulin concentration contributed to the reduction in blood glucose caused by artesunate in male but not female rats; and artesunate-induced increase in G6P, a substrate for G6PD, could enhance NADPH generation and antioxidant enzyme activation in male rats.

Vitamin C ameliorates tetrahydrocannabinol-induced spermatotoxicity in-vitro.

BACKGROUND: We investigated the in-vitro effects of vitamin C on delta-9-tetrahydrocannabinol (THC) -induced reduction in spermatozoa motility and kinematics. METHODS: Six rats were used for the study. Semen from each of the 6 rats was randomly divided into 6 groups such that each rat's semen was in all of the groups. Groups I-III received placebo, THC (1 mM), and vitamin C (5 mM) respectively. Group IV was pre-treated with cannabinoid receptors' blockers (CBs-) 1 and 2, followed by THC. Groups V and VI received THC and vitamin C, but group VI was additionally pre-treated with CBs-. RESULTS: The spermatozoa progressive motility, average path velocity (VAP), curvilinear velocity (VCL), straight-line velocity (VSL), amplitude of lateral head (ALH) and beat cross frequency (BCF) were reduced by THC (6.08 ± 1.16%; 5.64 ± 0.82 µm/s; 6.96 ± 0.74 µm/s; 2.75 ± 0.23 µm/s; 0.31 ± 0.02 µm; and 0.78 ± 0.08 Hz respectively) but increased by vitamin C (51.20 ± 1.32%; 17.90 ± 0.21 µm/s; 25.11 ± 0.96 µm/s; 8.80 ± 0.27 µm/s; 0.75 ± 0.01 µm; and 3.15 ± 0.03 Hz respectively) when compared to control (39.72 ± 0.38%; 13.70 ± 0.29 µm/s; 18.04 ± 0.58 µm/s; 7.54 ± 0.34 µm/s; 0.65 ± 0.02 µm; and 2.79 ± 0.01 Hz respectively). Vitamin C inhibited the THC-induced reduction in these parameters (37.36 ± 0.73%; 10.98 ± 0.45 µm/s; 13.58 ± 0.30 µm/s; 7.11 ± 0.22 µm/s; 0.58 ± 0.01 µm; and 2.60 ± 0.01 Hz respectively) in the absence of CBs- 1 and 2, and even caused additional increases in progressive motility (49.54 ± 1.01%), VAP (15.70 ± 0.38 µm/s) and VCL (22.53 ± 0.29 µm/s) above the control levels with CBs-. CONCLUSION: Vitamin C ameliorates the THC-induced reduction in spermatozoa motility in-vitro by modulation of their kinematics.

Cannabinoid-deficient Benin republic hemp (Cannabis sativa L.) improves semen parameters by reducing prolactin and enhancing anti-oxidant status.

BACKGROUND: Nigerian Cannabis sativa (hemp) causes male gonadotoxicity by inducing hyperprolactinemia, down-regulation of hypothalamic-pituitary-testicular axis, and oxidative stress. Benin republic hemp has been preferred by illicit users in Nigeria but its effect on male fertility is not understood. This study determined and compared the compositions of Benin republic hemp ethanol extract (BHE) and Nigerian hemp. The effects of BHE on semen parameters, reproductive hormones, and anti-oxidant status, and the possibility of bromocriptine (prolactin inhibitor) to abolish hemp-induced toxicities in rats were also investigated. METHODS: Thirty-six male Wistar rats were blindly randomized into 6 oral treatment groups (n = 6 each). Groups I (control) and II received normal saline and bromocriptine (3 mg/kg) respectively. Groups III and IV received 2 mg/kg of BHE alone and in combination with bromocriptine respectively, while groups V and VI received 10 mg/kg BHE alone and in combination with bromocriptine respectively. Comparisons among the groups were done by one-way analysis of variance, followed by post-hoc Tukey multiple comparison test. Statistical significance was considered at p < 0.05. RESULTS: The BHE has no cannabichromene and tetrahydrocannabinol but a very small quantity of cannabinol and higher quantity of fatty acids when compared to Nigerian hemp. Both doses of BHE increased sperm count, morphology and viability but not motility. Co-administration of BHE with bromocriptine lowered sperm count but increased sperm morphology and viability. Bromocriptine and/or BHE caused reduction in the plasma prolactin level, increase in the plasma superoxide dismutase activity, but no significant change in the plasma gonadotropin releasing hormone, follicle stimulating hormone (except for the increase in rats that received bromocriptine+ 10 mg/kg BHE), luteinizing hormone, estradiol, malondialdehyde and glutathione peroxidase. The 10 mg/kg BHE or bromocriptine+BHE (both doses) increased total anti-oxidant capacity and catalase. CONCLUSIONS: The BHE improves semen parameters by reducing plasma prolactin and enhancing plasma anti-oxidant status. Its pro-fertility potential might be associated with its deficiency in the widely known gonadotoxic phytocannabinoids.

High-fat diet reduces weight gain but increases other cardio-metabolic indices in offspring of normotensive and hypertensive rats.

This study investigated the effect of post-natal consumption of high-fat diet (HFD) on cardio-metabolic indices in male offspring of hypertensive female rats. There were neither significant differences in body weight gain either in pups from normotensive or hypertensive dams that received normal diet during the post-weaning periods (except at 7th and 9th weeks), nor in both pup groups that received HFD. However, both pup groups that received HFD had reduced body weight gain when compared to their counterparts that received normal diet. Post-weaning administration of HFD to pups of hypertensive and normotensive dams significantly increased their blood glucose, pressure and lipid profiles when compared to those weaned to normal diet. It was concluded that male offspring consumption of HFD diet elicits cardio-metabolic disturbance that slightly depended of maternal cardiovascular status but majorly depended on post-weaning weight gain, while that elicited by maternal hypertension is not related to post-weaning weight gain.