5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine.

The purpose of this study was to determine the effects of alstonine, an indole alkaloid with putative antipsychotic effects, on working memory by using the step-down inhibitory avoidance paradigm and MK801-induced working memory deficits in mice. Additionally, the role of serotonin 5-HT2A/C receptors in the effects of alstonine on mouse models associated with positive (MK801-induced hyperlocomotion), negative (MK801-induced social interaction deficit), and cognitive (MK801-induced working memory deficit) schizophrenia symptoms was examined. Treatment with alstonine was able to prevent MK801-induced working memory deficit, indicating its potential benefit for cognitive deficits now seen as a core symptom in the disease. Corroborating previously reported data, alstonine was also effective in counteracting MK801-induced hyperlocomotion and social interaction deficit. Ritanserin, a 5-HT2A/C receptor antagonist, prevented alstonine's effects on these three behavioral parameters. This study presents additional evidence that 5-HT2A/C receptors are central to the antipsychotic-like effects of alstonine, consistently seen in mouse models relevant to the three dimensions of schizophrenia symptoms.

The Amazonian herbal Marapuama attenuates cognitive impairment and neuroglial degeneration in a mouse Alzheimer model.

UNLABELLED: Alzheimer's disease (AD) is expected to affect more than 22 million people worldwide by 2025, causing devastating suffering and enormous costs to families and society. AD is a multifactorial disease, with a complex pathological mosaic. In rodents, AD-like dementia can be induced by cerebral microinjection of Aß peptide, leading to amyloid deposits, amnesia and various features of neurodegeneration. Marapuama (Ptychopetalum olacoides) is regarded as a "brain tonic" in the Amazon region and shows a nootropic profile in rodents. AIM OF THE STUDY: Because a specific extract (POEE) of Marapuama was shown to possess promnesic and anti-amnesic properties, the aim of this study was to verify if POEE is also effective against Aß(1-42)-induced cognitive deficit in mice. Additionally, Aß deposits (Congo red), GFAP immunoreactivity (immunohistochemistry), and neurodegenerative changes in the hippocampal pyramidal layer (Nissl) were examined as measures of Aß(1-42)-induced neurodegeneration. MATERIALS AND METHODS: CF1 mice were subjected to the experimental Alzheimer model with the Aß(1-42) i.c.v. administration. The effects of POEE 800 mg/kg were evaluated over 14 consecutive days of treatment. RESULTS: The data show that 14 days of oral treatment with POEE (800 mg/kg) was effective in preventing Aß-induced cognitive impairment, without altering the levels of BDNF and with parallel reductions in Aß deposits and astrogliosis. CA1 hippocampus loss induced by Aß(1-42) was also diminished in POEE-treated mice. CONCLUSION: This study offers evidence of functional and neuroprotective effects of two weeks treatment with a Ptychopetalum olacoides extract against Aß peptide-induced neurotoxicity in mice. Given the multifactorial nature of neurodegeneration, the considerable potential for an AChE inhibitor displaying associated neuroprotective properties such as here reported warrants further clinic evaluation.

Anti-stress effects of the "tonic"Ptychopetalum olacoides (Marapuama) in mice.

With the recognition that high levels of sustained stress are associated with the natural course of countless illnesses, effective anti-stress agents have gained importance. Improved endurance to particularly stressful periods is one of the medicinal claims for Marapuama (Ptychopetalum olacoides Bentham, PO), a popular Amazonian herbal. The purpose of this study was to evaluate if PO possesses anti-stress properties. To this end, an extract from PO (POEE) was evaluated on anxiety and glucose levels in mice submitted to the unpredictable chronic mild stress (UCMS) paradigm. POEE did not present anxiolytic effects, but was able to prevent (p<0.01) the UCMS-induced anxiety as assessed by the light/dark test (time spent in the lit area, POEE 100 and 300mg/kg 235.9+/-20.6s and 250.4+/-17.4s, respectively, compared to DMSO 104.7+/-24.4s). Likewise, although POEE did not induce noticeable effects on glycemia, it effectively (p<0.01) prevented the UCMS-induced hyperglycemia (POEE 100 and 300mg/kg 106.4+/-6.7mg/dl and 107.3+/-3.3mg/dl, respectively, compared to DMSO 134.6+/-5.9mg/dl). Additionally, POEE (50-200mg/kg i.p. and 800mg/kg p.o.) significantly (p<0.01 and p<0.05, respectively) increased the time to hypoxia-induced convulsion (by 38%, 51%, 59% and 27%, respectively for i.p. and p.o. treatments). The data indicate that POEE counteracts some of the effects brought about by chronic stress. This study combined with the identified antioxidant and neuroprotective properties, as well as the claimed benefits associated with stressful periods suggest that Ptychopetalum olacoides (Marapuama) might possess adaptogen-like properties.

Cofermentation of rutin and hesperidin during two-stage anaerobic pre-treatment of high-loaded brewery wastewater.

In a lab-scale two-stage digester (consisting of an acidification and a methane reactor) operated continuously with high-loaded brewers wastewater (psiCOD 9.000 mg1(-1)) as the primary substrate, the cofermentation of two commonly found flavonoids (rutin and hesperidin) was studied. At overall hydraulic retention times of 48-50 h and organic loading rates in the methane reactor ranging from 8 to 10 g COD 1R(-1) d(-1) the addition of up to (0.71 g 1R(-1) d(-1) of either rutin or hesperidin did not cause adverse effects on the reactor performance, in terms of VFA pattern, COD removal efficiency, and specific biogas production. The added flavonoid glycosides were rapidly converted in the acidification reactor yielding several hydroxyaromatic metabolites. With hesperidin as the cosubstrate, all of the formed metabolites were completely removed during passage through the methane reactor whereas in case of rutin, substantial amounts of m-cresol and 4-hydroxyphenylacetate were built up in the medium and remained in the effluent of the methane reactor.

Degradation of natural polyphenols by methanogenic consortia enriched from digested municipal sludge.

Using digested municipal sludge as the inoculum and either rutin, quercetin or hesperidin as the sole external carbon source. methanogenic consortia were enriched which converted various flavonoids at initial concentration of 0.5 3.0mM during stationary incubation at 37 degrees C in serum bottles with specific rates ranging from 0.025 to 0.073 micromol min(-1) (mg protein)(-1). In the culture fluid, several hydroxyaromatic metabolites as well as VFA (acetate, propionate, n-butyrate) were detected and biogas was formed in the headspace of the test bottles. Most of these metabolites were identified. Based on their sequential appearance/disappearance in the test cultures it was concluded that following initial hydrolysis of the glycosidic bond by cellular enzymes, ring C of the flavane skeleton was hydrolytically cleaved yielding an A- and B-ring fission product. In case of the flavonol quercetin, phloroglucinol (A-ring) and 3,4-dihydroxyphenylacetate (B-ring) were identified as the fission products whereas the flavanone hesperetin was cleaved with formation of phloroglucinol (A-ring) and 3,4-dihydroxyphenylpropionate (B-ring). In pre-adapted subcultures amended with either hesperidin or hesperetin, all of the formed hydroxyaromatic metabolites disappeared within 100 h of incubation whereas in the culture medium of rutin and quercetin degrading consortia m-cresol (3-methylphenol) was formed as the ultimate hydroxyaromatic metabolite being detectable in considerable amounts even after prolonged incubation.

Atrial natriuretic factor and body water distribution.

In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.