Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats.

Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical profiles, and behavioural outcomes in Long-Evans rats were evaluated. The combination of chronic sleep deprivation and high-dose caffeine treatment produced varying degrees of behavioural impairments, depletion of antioxidants, serotonin, and an upregulation of acetylcholinesterase (AChE) activity in the prefrontal cortex. An immunohistochemical assessment revealed a reduction in synaptophysin protein expression in the prefrontal cortex following exposure to high-dose caffeine and chronic sleep deprivation. Overall, our findings support the advocacy for adequate sleep for optimal mental performance as a high intake of caffeine to attenuate the effects of sleep deprivation that may alter the neurochemical profile and synaptic plasticity in the prefrontal cortex, significantly increasing the risk of neuropsychiatric/degenerative disorders.

Cyperus esculentus L. and Tetracarpidium conophorum Müll. Arg. Supplemented Diet Improved Testosterone Levels, Modulated Ectonucleotidases and Adenosine Deaminase Activities in Platelets from L-NAME-Stressed Rats.

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250-300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control.

Quercetin enhances sexual behavior and improves ectonucleotidases activity in the hypothalamus of rats treated with cyclosporine.

In order to confirm the erectile potential of Quercetin (Q) in cyclosporine-induced hypertensive rats, this research assesses the influence of Q on the ectonucleotidases and adenosine deaminase (ADA) in the brains of rats. Male Wistar rats (200 g-250 g) were divided into five groups at random: Normal control (CTRL), cyclosporine-induced hypertensive rats (25 mg kg day-1 ) (HT) group, positive control (Sildenafil [SIL], 5 mg kg day-1 ), Quercetin 25 mg kg day-1 (25 Q), and Quercetin 50 mg kg day-1 (50 Q). Aside from standard diet-fed male rats; cyclosporine was given i.p for the period of 30 days as well as Q orally while the female rats were only given a standard diet. The animals were subjected to sexual activity (copulation) after which the male rat hypothalamus was dissected for biochemical examination (E-NTPDase activities, ecto-5'-nucleotidase as well as ADA and also levels of nitric oxide [NO]). We observed that Q enhanced copulatory behavior as evident in mounting, intromission, ejaculation numbers, and latencies. A substantial (p < .05) increase in the activity of E-NTPDase (ATP and ADP as substrate) without any notable difference in the action of ecto-5' nucleotidase was facilitated by cyclosporine-induction when compared to the CTRL. The 50 mg/kg, however, had the highest reversal effect in accordance with dose manner. Also, cyclosporine increased ADA activity with a concomitant reduction of NO level while both doses of Q down-regulated ADA activity and, increased NO levels. Enhanced sexual behavior, modulation of ectonucleotidases as well as ADA activity and increased NO levels suggest that Q-rich plant foods may be promising sources of dietary phytonutrients for erectile dysfunction (ED) management. PRACTICAL APPLICATIONS: Behavioral and biochemical assays evaluated showed that Q significantly enhanced sexual behavior as well as improved ATP bioavailability in cyclosporine-induced erectile dysfunctional rats. The modulatory effects of Q on ectonucleotidases, along with its ability to minimize adenosine deaminase activity and increase nitric oxide levels, indicate that Q-rich plants and/or plant foods may be promising sources of dietary phytonutrients for erectile dysfunction management.

Assessment of sexual behavior and neuromodulation of Cyperus esculentus L. and Tetracarpidium conophorum Müll. Arg dietary supplementation regulating the purinergic system in the cerebral cortex of L-NAME-challenged rats.

This study examined the behavioral responses, purinergic receptor densities, ectonucleotidases (E-NTPDase), adenosine deaminase (ADA) activity, and nitric oxide (NO) levels along with the parameters of oxidative stress-related to erectile function in the cerebral cortex (CC) of L-NAME-challenged rats pretreated with tigernut (TN) and walnut (WN) dietary supplementation. Wistar rats (male) of 70 total animals (250-300 g) were used in this research and hence separated into seven groups (n = 10): Group I: normal control-fed basal diet; Group II: positive control-fed basal diet/L-NAME/Sildenafil citrate (5 mg kg-1  day-1 ); Group III: ED-induced (placed on a basal diet/L-NAME); Group IV: diet supplemented with processed TN (20%)/L-NAME; Group V: diet supplemented with raw TN (20%)/L-NAME; Group VI: diet supplemented with processed WN (20%)/L-NAME; and Group VII placed on a diet supplemented with raw WN (20%)/L-NAME. The rats were pretreated for 2 weeks before the L-NAME (40 mg kg-1  day-1 ) challenge on their respective diet. L-NAME brought about a decrease in the sexual behaviors evaluated while the effect was significantly reversed by supplemented diets containing TN and WN. L-NAME increased the levels of reactive oxygen species and malondialdehyde, E-NTPDase as well as ADA activities, and caused the level of NO in the CC as well as the purinoreceptor densities to be downregulated. Treatments with enriched diets, however, greatly reverse these effects. The behavioral responses and neuromodulatory capacity of the nuts displayed on the CC can, therefore, further support their aphrodisiac property. PRACTICAL APPLICATIONS: The results revealed the ability of tigernut (TN; Cyperus esculentus L.) and walnut (WN; Tetracarpidium conophorum Müll. Arg.) to enhance behavioral responses; modulate purinergic receptor densities, E-NTPDase, and ADA activities; increase NO levels; and prevent oxidative stress related to erectile function in the CC of L-NAME-challenged Wistar rats. The results show that these nuts are useful feeds for both animal and human nutrition.

Lactobacillus plantarum mitigates sexual-reproductive deficits by modulating insulin receptor expression in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice.

OBJECTIVES: Hyperinsulinemia increases the risk factor of diabetes and infertility at a manifold. Lactobacillus plantarum has several medical significances with limited reports. Hence, this study assessed the effect of L. plantarum on sexual-reproductive functions and distribution of insulin receptors in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. METHODS: Forty male adult mice were divided into five groups as follows: control, high-fat diet (HFD) + streptozotocin (STZ), therapeutic, co-administration group type 1 (CO-AD) and probiotics. They were either simultaneously exposed to an HFD and L. plantarum treatment for 28 days with a dose of STZ injection to induce hyperinsulinemia on day 28 or treated with L. plantarum for 14 days, and following induction of hyperinsulinemia. Mice were subjected to a sexual behavioural test and thereafter sacrificed under euthanasia condition. Blood, brain and testes were collected for biochemical and immunohistochemical assays. RESULTS: Treatment with L. plantarum ameliorated reproductive hormones activity disruption, sexual behavioural defects, antioxidant imbalance, insulin dysregulation and lipid metabolism dysfunction following exposure to HFD + STZ when compared to the hyperinsulinemic untreated mice. CONCLUSIONS: Taken together, data from this study reveal that L. plantarum abrogated hyperinsulinemia-induced male sexual and reproductive deficits by modulating antioxidant status, lipid metabolism and insulin signalling in the hypothalamic-pituitary-testicular axis of mice.

Tetracarpidium conophorum Müll. Arg modulates sexual behaviour and biochemical parameters relevant to sexual function in male Wistar rats.

Walnut (Tetracarpidium conophorum Müll. Arg) has been reported to be an essential ingredient in folklore medicine for sexual enhancement with little scientific validation. Hence, this study investigated the effects of walnut supplemented diet on sexual behaviour and biochemical parameters relevant to erection in male Wistar rats. Forty animals used in this study were divided into five groups (n = 8); Group 1 - normal control rats fed with basal diet, Group II - rats fed diet supplemented with 10% processed walnut, Group III - rats fed diet supplemented with 10% raw walnut, Group IV - rats fed diet supplemented with 20% processed walnut and Group V - rats fed diet supplemented with 20% raw walnut. Behavioural studies (copulation tendency and anxiety) associated with sexual function, measurement of nitric oxide (NO) levels, adenosine deaminase (ADA), arginase and acetylcholinesterase (AChE) activities in the Corpus cavernosum as well as characterization of bioactive components of the nut were evaluated. Marked reductions in ADA and arginase activities and a concomitant increase (% inclusion dependent) in the level of NO as well as enhanced sexual behaviours were observed in rat fed supplemented walnut when compared to the control. Furthermore, analysis of the walnut using high performance liquid chromatography indicated the presence of some polyphenols. From our findings, it showed that walnut improves sexual behaviour and modulates activities of key enzymes relevant to erection in male rats which may justify its used in traditional medicine.

Coffee, caffeine, chlorogenic acid, and the purinergic system.

Coffee is a drink prepared from roasted coffee beans and is lauded for its aroma and flavour. It is the third most popular beverage in the world. This beverage is known by its stimulant effect associated with the presence of methylxanthines. Caffeine, a purine-like molecule (1,3,7 trymetylxantine), is the most important bioactive compound in coffee, among others such as chlorogenic acid (CGA), diterpenes, and trigonelline. CGA is a phenolic acid with biological properties as antioxidant, anti-inflammatory, neuroprotector, hypolipidemic, and hypoglicemic. Purinergic system plays a key role inneuromodulation and homeostasis. Extracellular ATP, other nucleotides and adenosine are signalling molecules that act through their specific receptors, namely purinoceptors, P1 for nucleosides and P2 for nucleotides. They regulate many pathological processes, since adenosine, for instance, can limit the damage caused by ATP in the excitotoxicity from the neuronal cells. The primary purpose of this review is to discuss the effects of coffee, caffeine, and CGA on the purinergic system. This review focuses on the relationship/interplay between coffee, caffeine, CGA, and adenosine, and their effects on ectonucleotidases activities as well as on the modulation of P1 and P2 receptors from central nervous system and also in peripheral tissue.

Hesperidin attenuates inflammation and oxidative damage in pleural exudates and liver of rat model of pleurisy.

OBJECTIVES: This study investigated the potential anti-inflammatory effect of hesperidin against carrageenan induced pleurisy in rat model. METHODS: Twenty-four adult female Wistar rats (350 - 450g) were grouped as follows: Group I: rats were administered saline solution only (Normal control group); Group II: rats were administered saline solution (NaCl 0.9%) orally and injected with carrageenan (Inflammation control group); Group III: rats were administered hesperidin only (Hesperidin group); Group IV: rats were administered hesperidin orally and intrapleurally injected with 2% carrageenan (Inflammation treated with hesperidin group). The exudate volume, total leukocyte count, reactive oxygen species (ROS), myeloperoxidase (MPO),δ-aminolevulinate dehydratase (δ-ALA-D), catalase (CAT), superoxide dismutase (SOD), activities as well as non-protein thiol group (NPSH) and thiobarbituric acid reactive substances (TBARS) levels were determined. RESULTS: Pretreatment with hesperidin at a dose of 80 mg/kg orally per day for 21 days, minimized the increase in pleural exudate volume and leucocyte count and modulated the activities of MPO, SOD and CAT, as well as the levels of ROS, NPSH and TBARS in carrageenan-induced rats. CONCLUSION: Our results suggest that hesperidin can elicit its anti-inflammatory action by blocking exudate and leukocyte influx into pleural cavity, inhibiting MPO activity and preventing oxidative damage.