Influence of Melatonin on Behavioral and Neurological Function of Rats with Focal Cerebral Ischemia-Reperfusion Injury via the JNK/FoxO3a/Bim Pathway.

OBJECTIVE: To investigate the influence of melatonin on behavioral and neurological function of rats with focal cerebral ischemia-reperfusion injury via the JNK/FoxO3a/Bim pathway. METHODS: One hundred and twenty healthy male SD rats were randomized into the model group (Model: the middle cerebral artery occlusion (MCAO) model was constructed and received an equal volume of normal saline containing 5% DMSO), sham operation group (Sham: received no treatment except normal feeding), and low, medium, and high dose of melatonin group (L-MT, M-MT, and H-MT intraperitoneally injected 10, 20, and 40 mg/kg melatonin 30 min after IR, respectively), with 24 rats in each group. Following 24 h of reperfusion, the rats in each of the above groups were tested for neurological deficit symptoms and behavioral changes to screen the rats included in the study. HE and TUNEL stainings were performed to observe pathological changes. Levels of oxidative stress-related indexes, inflammatory factor-related indexes, nuclear factor-κB p65 (NF-κB p65), and interferon-γ (IFN-γ) in the rat brain were measured by ELISA. The JNK/FoxO3a/Bim pathway-related proteins as well as Bcl-2, Caspase-3, and Bax were examined using Western blot. RESULTS: Detection of behavioral indicators showed that the MACO model was successfully constructed in rats. L-MT, M-MT, and L-MT groups presented reduced malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-1ß, IFN-γ, NF-κB p65, and apoptosis compared with the Model group (P < 0.05), and the improvement degree was better in the M-MT group versus the L-HT group. Bcl-2 protein expression in the brain tissue of L-MT, M-MT, and H-MT groups increased significantly, while Bax, Caspase-3, p-JNK, p-FoxO3a, and Bim protein expression declined markedly, versus the Model group (P < 0.05). The changes of indexes were greater in the M-MT group compared with that in the L-MT group. No significant difference was observed in all the above indexes between the M-MT group and the H-MT group (P > 0.05). CONCLUSIONS: In the MACO rat model, melatonin can effectively reduce Bax and Caspase-3 levels by modulating the JNK/FoxO3a/Bim pathway, inhibit neuronal apoptosis, and alleviate neurological deficits by reducing the release of proinflammatory mediators, with anti-inflammatory and antioxidant effects. In addition, 20 mg/kg is the optimal melatonin concentration.

Usefulness of pumpkin seeds combined with areca nut extract in community-based treatment of human taeniasis in northwest Sichuan Province, China.

Taeniasis refers to the infection with adult tapeworms of Taenia spp. in the upper small intestine of humans, which is also a cause of cysticercosis infection in either both humans and/or animals. Currently the most commonly applied anthelminthics for treatment of taeniasis are praziquantel and niclosamide. Praziquantel is very effective, but has the risk of induction of epileptic seizures or convulsions in carriers with asymptomatic concurrent neurocysticercosis. In contrast, niclosamide is safe and effective, but is not readily available in many endemic countries including China. In the current community-based study, we assessed the curative effect of either pumpkin seeds or areca nut extract alone in taeniasis, and also looked at synergistic effects of these two herb drugs on tapeworms. In the study group with the pumpkin seed/areca nut extract treatment, 91 (79.1%) of 115 suspected taeniasis cases (with a history of expulsion of proglottids within the previous one year) released whole tapeworms, four (3.5%) expelled incomplete strobila, and no tapeworms or proglottids were recovered in the remaining 20 cases. In these 115 persons, 45 were confirmed as taeniasis before treatment by microscopy and/or coproPCR. Forty (88.9%) of 45 confirmed cases eliminated intact worms following treatment. The mean time period for complete elimination of tapeworms in 91 taeniasis cases was 2 h (range 20 min to 8 h 30 min), and 89.0% (81) of 91 patients discharged intact worms within 3h after drug administration. In Control Group A with treatment of pumpkin seeds alone, 75.0% (9/12) of confirmed taeniasis cases expelled whole tapeworms, but the mean time period for complete elimination was about 14 h 10 min (range 3 h 20 min to 21 h 20 min), which was much longer than that (2 h) for the study group, whereas in Control Group B treated with areca nut extract alone, only 63.6% (7/11) of taeniasis cases discharged whole tapeworms, and the mean time period was 6 h 27 min (range 1-22 h). Mild side effects included nausea and dizziness in about 46.3% of patients with the pumpkin seeds/areca nut extract treatment, but all discomforts were transient and well tolerated. In conclusion, a synergistic effect of pumpkin seed and areca nut extract on Taenia spp. tapeworms was confirmed in the current study, primarily in producing an increased rate of effect on tapeworm expulsion (average time 2 h for combination vs 6-21 h for individual extracts). The pumpkin seed/areca combined treatment was indicated to be safe and highly effective (89%) for human taeniasis.