PMID: 

Eur J Nutr. 2020 Mar 20. Epub 2020 Mar 20. PMID: 32198672

Abstract Title: 

Dietary intake of choline and phosphatidylcholine and risk of type 2 diabetes in men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

Abstract: 

PURPOSE: To investigate associations of total dietary choline intake and its major dietary form, phosphatidylcholine, with type 2 diabetes risk.METHODS: We included 2332 men aged 42-60 years at baseline in 1984-1989 from the Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Dietary intakes were assessed with 4-d food recording at baseline. Type 2 diabetes diagnosis was based on self-administered questionnaires, fasting and 2-h oral glucose tolerance test bloodglucose measurements, or by record linkage to national health registries. Multivariable-adjusted Cox proportional hazards regression models were used for statistical analysis.RESULTS: During the mean 19.3-year follow-up, 432 men had type 2 diabetes diagnosis. After multivariable adjustments, those in the highest vs. lowest choline intake quartile had 25% (95% CI 2-43%) lower relative risk (P trend across quartiles = 0.02) and those in the highest vs. lowest phosphatidylcholine quartile had 41% (95% CI 22-55%) lower relative risk (P trend 

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PMID: 

J Ethnopharmacol. 2020 Mar 11:112743. Epub 2020 Mar 11. PMID: 32171895

Abstract Title: 

Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: Applicability to Parkinson's disease.

Abstract: 

ETHNOPHARMACOLOGY RELEVANCE: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease.AIM OF THE STUDY: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model.MATERIAL AND METHODS: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Themetabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS.RESULTS: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such asβ-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results.CONCLUSION: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and the possibility to prevent its progression differently from current drugs to treat PD.

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PMID: 

Biol Psychiatry. 2020 Jan 13. Epub 2020 Jan 13. PMID: 32111343

Abstract Title: 

Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity.

Abstract: 

BACKGROUND: The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.METHODS: We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps.RESULTS: Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT(5-hydroxytryptamine 2A) and 5-HT(5-hydroxytryptamine 1A) receptors.CONCLUSIONS: These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.

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PMID: 

Eur Neuropsychopharmacol. 2020 Mar 4. Epub 2020 Mar 4. PMID: 32146028

Abstract Title: 

A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding.

Abstract: 

A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [C]Cimbi-36 positron emission tomography (PET) imaging and on personality and mindfulness. Ten healthy and psychedelic-naïve volunteers underwent PET neuroimaging of 5-HT2AR at baseline (BL) and one week (1W) after a single oral dose of psilocybin (0.2-0.3 mg/kg). Personality (NEO PI-R) and mindfulness (MAAS) questionnaires were completed at BL and at three-months follow-up (3M). Paired t-tests revealed statistically significant increases in personality Openness (p = 0.04, mean change [95%CI]: 4.2[0.4;∞]), which was hypothesized a priori to increase, and mindfulness (p = 0.02, mean change [95%CI]: 0.5 [0.2;0.7]). Although 5-HT2AR binding at 1W versus BL was similar across individuals (p = 0.8, mean change [95%CI]: 0.007 [-0.04;0.06]), a post hoc linear regression analysis showed that change in mindfulness and 5-HT2AR correlated negatively (β [95%CI] = -5.0 [-9.0; -0.9], p= 0.046). In conclusion, we confirm that psilocybin intake is associated with long-term increases in Openness and – as a novel finding – mindfulness, which may be a key element of psilocybin therapy. Cerebral 5-HT2AR binding did not change across individuals but the negative association between changes in 5-HT2AR binding and mindfulness suggests that individual change in 5-HT2AR levels after psilocybin is variable and represents a potential mechanism influencing long-term effects of psilocybin on mindfulness.

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PMID: 

Food Sci Nutr. 2020 Mar ;8(3):1554-1561. Epub 2020 Feb 10. PMID: 32180964

Abstract Title: 

A randomized controlled pilot study of the effectiveness of magnolia tea on alleviating depression in postnatal women.

Abstract: 

The magnolia tea has been used in traditional oriental medicine for multiple purposes including sleep aid. Postpartum depression is a mental illness that adversely affects the health and well-being of many families with newborns. Given the known effectiveness and relative safety, herein we aimed to investigate whether magnolia tea has a palliative effect on postpartum depression. The qualified participants were randomly assigned to the intervention group or the control group. The participants in the intervention group drunk magnolia tea, while the control group received regular postpartum care only. The outcome variables including Postpartum Sleep Quality Scale (PSQS), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Fatigue Scale (PFS) were assessed and compared. In comparison with the control group, the intervention group demonstrated significant difference for physical-symptom-related sleep inefficiency (PSQS Factor 2) at 3 weeks post-test ( = -2.10, = .03). The comparison results also revealed significant differences for PFS at both 3 weeks post-test ( = -2.02, = .04) and 6 weeks post-test ( = -1.99, = .04). Further, magnolia tea intervention significantly alleviated the symptoms of depression, reflected by the EPDS scores at 3 weeks post-test ( = -2.38, = .02) and 6 weeks post-test ( = -2.13, = .02). Our trial results suggested that drinking single-ingredient magnolia tea for a 3-week duration has positive effects on postpartum women. Magnolia tea is recommended as a supplementary approach to ameliorate sleep quality of postpartum women, while alleviating their symptoms of depression.

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PMID: 

Molecules. 2020 Mar 17 ;25(6). Epub 2020 Mar 17. PMID: 32192065

Abstract Title: 

Insecticidal and Biting Deterrent Activities ofEssential Oils and Selected Pure Compounds against.

Abstract: 

In our natural products screening program for mosquitoes, we tested essential oils extracted from different plant parts ofL. for their insecticidal and biting deterrent activities against. Biting deterrence of seeds essential oil with biting deterrence index value of 0.89 was similar to,-diethyl-3-methylbenzamide (DEET). All the other oils were active above the solvent control but the activity was significantly lower than DEET. Based on GC-MS analysis, three pure compounds that were only present in the essential oil of seed were further investigated to identify the compounds responsible for biting deterrent activity. 1-Decanol with PNB value of 0.8 was similar to DEET (PNB = 0.8), whereas 1-octanol with PNB value of 0.64 showed biting deterrence lower than 1-decanol and DEET. The activity of 1-heptanol with PNB value of 0.36 was similar to the negative control. Since 1-decanol, which was 3.3% of the seed essential oil, showed biting deterrence similar to DEET as a pure compound, this compound might be responsible for the activity of this oil. In in vitro A&K bioassay, 1-decanol with MED value of 6.25 showed higher repellency than DEET (MED = 12.5). Essential oils of immature and mature fruit showed high toxicity whereas leaf, flower, and seeds essential oils gave only 20%, 0%, and 50% mortality, respectively, at the highest dose of 125 ppm. 1-Decanol with LCof 4.8 ppm was the most toxic compound.

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PMID: 

Biomed Pharmacother. 2020 Apr ;124:109886. Epub 2020 Jan 27. PMID: 32000045

Abstract Title: 

Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ.

Abstract: 

This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans. More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effectswere also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.

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PMID: 

Front Immunol. 2020 ;11:77. Epub 2020 Feb 7. PMID: 32117241

Abstract Title: 

Magnolol Attenuates Cisplatin-Induced Muscle Wasting by M2c Macrophage Activation.

Abstract: 

Cancer chemotherapy induces sarcopenia, which is a rapid loss of muscle mass that directly restricts daily activities and leads to poor quality of life and increased mortality. Although hormone-related therapies have been used to improve appetite and nutritional status, current treatments are considered palliative. Thus, the protection of skeletal muscle loss without adverse effects is essential to allow the maintenance of chemotherapy in cancer patients. Magnolol fromhas several pharmacological effects including anti-cancer and anti-inflammatory activities, but the protection from muscle atrophy is not well-understood. In the present study, we investigated the effects of magnolol on muscle wasting and macrophage subtypes in a cisplatin-induced sarcopenia mouse model. We showed that magnolol significantly attenuated the body weight and the muscle loss induced by cisplatin injection. The diameter of the tibialis anterior muscle was markedly increased after magnolol treatment in cisplatin-treated mice. Importantly, magnolol increased macrophage infiltration into skeletal muscle while not affecting proliferation of macrophages. Magnolol attenuated the imbalance of M1/M2c macrophages by increasing CD206CD163M2c tissue reparative macrophages. Further, magnolol increased insulin-like growth factor (IGF)-1 expression. This effect was also observed in bone marrow-derived macrophages upon magnolol treatment. Taken together, magnolol may be a promising chemoprotective agent for the prevention of muscle atrophy through the upregulating M2c macrophages, which are a major source of IGF-1.

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PMID: 

Curr Pharm Des. 2020 03 20. Epub 2020 Mar 20. PMID: 32196444

Abstract Title: 

Magnolia Officinalis Reduces Inflammation And Damage Induced By Recurrent Status Epilepticus In Immature Rats

Abstract: 

BACKGROUND: Neuroinflammation induced in response to damage caused by status epilepticus (SE) activates the interleukin (IL)1-β pathway and proinflammatory proteins that increase vulnerability to the development of spontaneous seizure activity and/or epilepsy.OBJECTIVES: To assess the short-term anti-inflammatory and neuroprotective effects of Magnolia officinalis (MO) on recurrent SE in immature rats.METHODS: Sprague-Dawley rats at PN day 10 were used; n = 60 rats were divided into two control groups, SHAM and KA, and two experimental groups, MO (KA-MO) and Celecoxib (KA-Clbx). The anti-inflammatory effect of a single dose of MO was evaluated at 6 and 24 hr by Western blotting and on day 30 PN via a subchronic administration of MO to assess neuronal preservation and hippocampal gliosis by immunohistochemistry for NeunN and GFAP, respectively.RESULTS: KA-MO caused a decrease in the expression of IL1-β and Cox-2 at 6 and 24 h post treatment, a reduction in iNOS synthase at 6 and 24 hr post treatment and reduced neuronal loss and gliosis at postnatal day 30, similar to Clbx.CONCLUSION: The results indicating that Magnolia officinalis is an alternative preventive treatment for early stages of epileptogenesis are encouraging.

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PMID: 

J Nutr Biochem. 2020 Feb 4 ;79:108352. Epub 2020 Feb 4. PMID: 32145471

Abstract Title: 

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet.

Abstract: 

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteinsinvolved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAThypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.

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