3 replies to this topic

[alc]

https://www.scienced...70328092428.htm

 

http://ir.cardaxphar...ates-anti-aging

[Ruth]

Astaxanthin (C40H52O4, 3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a carotenoid belonging to the
xanthophylls group, which is very attractive for important industrial markets thanks to its
interesting properties, such as food grade, colouring and antioxidant agent. It is used for different
purpose, for example, in aquaculture field as feed additive for salmons, trouts, and crustaceans to
provide the characteristic pink/red colour. Astaxanthin is also appreciated for its antioxidant and
beneficial effects on both reproduction and immune systems of bred species (Amaya et al., 2014;
Lim et al., 2017) and anti-ageing effect in the cosmetic sector (Ambati et al., 2014). However, its ACCEPTED MANUSCRIPT
main use remains the feed additive in the aquaculture for fishes growth and nourishment of
ornamental birds (Irwandi Jaswir et al., 2011). Over its anti-aging effect, several literature studies
showed its anti-inflammatory, cardioprotective, neuroprotective, gastroprotective, nephroprotective,
anti-diabetic, anti-cancer, antiasthmatic and immunoprotective properties. For these reasons,
astaxanthin is also currently used in the prevention and control of many pathological conditions on
low oxidative and inflammatory (Bolhassani, 2015; Chuyen and Eun, 2017; Donà et al., 2013;
Kamath et al., 2008; Liao et al., 2016; Masoudi et al., 2017; Wang et al., 2014).

[orion22]

very important what is the dose they used????????????????????????????????????????????

[Ruth]

1mg-120mg from studies..

The natural carotenoid astaxanthin, a PPAR- agonist and PPAR- antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes Yaoyao Jia1,2, Jin-Young Kim1,2, Hee-Jin Jun1,2, Sun-Joong Kim1, Ji-Hae Lee1,2, Minh Hien Hoang1,2, Kwang-Yeon Hwang1, Soo-Jong Um3, Hyo Ihl Chang1 and Sung-Joon Lee1,2
1Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul, Republic of Korea 2Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea 3Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea
Scope: Anaturalcarotenoidabundantinseafood,astaxanthin(AX),hashypolipidemicactivity, but its underlying mechanisms of action and protein targets are unknown. We investigated themolecularmechanismofactionofAXinhepatichyperlipidemiabymeasuringperoxisome proliferator-activated receptors (PPAR) activity. Methods and results: We examined the binding of AX to PPAR subtypes and its effects on hepatic lipid metabolism. AX binding activated PPAR-, but inhibited PPAR- transactivation activityinreportergeneassayandtime-resolveduorescenceenergytransferanalyses.AXhad noeffectonPPAR/transactivation.AXbounddirectlytoPPAR-andPPAR-withmoderate afnity, as assessed by surface plasmon resonance experiments. The differential effects of AX on PPARs were conrmed by measuring the expression of unique responsive genes for each PPARsubtype.AXsignicantlyreducedcellularlipidaccumulationinlipid-loadedhepatocytes. Transcriptome analysis revealed that the net effects of stimulation with AX (100 M) on lipid metabolic pathways were similar to those elicited by fenobrate and lovastatin (10 M each), with AX rewiring the expression of genes involved in lipid metabolic pathways. Conclusion: AX is a PPAR- agonist and PPAR- antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes

Cannabinoids and PPARα signalling
Y. Sun1, S.P.H. Alexander, D.A. Kendall and A.J. Bennett School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, U.K.
Abstract Cannabinoids have been shown to possess anti-inammatory and neuroprotective properties, which were proposed to occur mainly via activation of the G-protein-coupled receptor CB1 (cannabinoid receptor 1). Recently, certain cannabinoids have been reported to be ligands for members of the nuclear receptor transcription factor superfamily known as PPARs (peroxisome-proliferator-activated receptors). This review summarizes the evidence for cannabinoid activation of PPARs and identies a new intracellular target for cannabinoids as therapeutic agents for neuroprotective treatment.

THC stimulated lipolysis and up-regulated PPARα and CPT-1a implicated in β-oxidation. • …
We demonstrated that THC induced AMPK activation; therefore, this may have contributed
to the upregulation of PPARα in response to THC treatment
"Tetrahydrocurcumin ameliorates free fatty acid-induced hepatic steatosis and improves insulin resistance in HepG2 cells"

http://www.pnas.org/.../31/E7408.short

Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory
Despite its long history, until now, no receptor has been identified for aspirin, one of the most widely used medicines worldwide. Here we report that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor involved in fatty acid metabolism, serves as a receptor of aspirin. Detailed proteomic analyses including cheminformatics, thermal shift assays, and TR-FRET revealed that aspirin, but not other structural homologs, acts as a PPARα ligand through direct binding at the Tyr314 residue of the PPARα ligand-binding domain. On binding to PPARα, aspirin stimulated hippocampal plasticity via transcriptional activation of cAMP response element-binding protein (CREB). Finally, hippocampus-dependent behavioral analyses, calcium influx assays in hippocampal slices and quantification of dendritic spines demonstrated that low-dose aspirin treatment improved hippocampal plasticity and memory in FAD5X mice, but not in FAD5X/Ppara-null mice. These findings highlight a property of aspirin: stimulating hippocampal plasticity via direct interaction with PPARα.


https://www.scienced...028390807001967
CB1 receptor agonists increase the state of phosphorylation of the dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at the cAMP-dependent protein kinase site, Thr34. This effect, which occurs in the medium spiny neurons of the striatum, has been proposed to mediate the motor depressant action of cannabinoids. In this study, we have examined the effect produced by systemic administration of Δ9-tetrahydrocannabinol (THC), the major component of marihuana and hashish, on DARPP-32. We show that THC increases DARPP-32 phosphorylation at Thr34 both in dorsal striatum and nucleus accumbens. Time-course and dose-response experiments indicate that DARPP-32 phosphorylation is maximal 30 min following administration of 10 mg/kg of THC. The THC-mediated increase in DARPP-32 phosphorylation is reduced by administration of the CB1 receptor antagonist, SR141716A (3 mg/kg). A similar attenuation of the effect of THC is also exerted by suppression of cAMP signaling achieved using the dopamine D1 receptor antagonist, SCH23390 (0.125 mg/kg), or the adenosine A2A receptor antagonist, KW6002 (3 mg/kg). These results indicate that, in the striatum, THC promotes PKA-dependent phosphorylation of DARPP-32 in striatal medium spiny neurons expressing dopamine D1 and adenosine A2A receptors.
https://link.springe...1481-018-9808-3 Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson’s Disease
Increasing the function of residual dopaminergic neurons in the nigra of PD patients is an important area of research as it may eventually compensate the loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to upregulate TH and increase the production of DA in nigral dopaminergic neurons. This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in the promoter of TH gene and the rapid induction of cAMP response element binding (CREB) activation by aspirin in dopaminergic neuronal cells. Aspirin treatment also increased the level of phospho-CREB in the nigra of C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin suggest that aspirin stimulates the transcription of TH in dopaminergic neurons via CREB. These results highlight a new property of aspirin in stimulating the TH-DA pathway, which may be beneficial in PD patients.
https://onlinelibrar...68.2004.03230.x Repeated acetyl‐l‐carnitine administration increases phospho‐Thr34 DARPP‐32 levels and antagonizes cocaine‐induced increase in Cdk5 and phospho‐Thr75 DARPP‐32 levels in rat striatum
Acute cocaine administration increases phosphorylation of dopamine and cAMP‐regulated phosphoprotein (Mr 32 kDa) (DARPP‐32) at threonine (Thr)‐34, whereas repeated cocaine administration increases DARPP‐32 phosphorylation at Thr‐75 in Sprague–Dawley rat striatum. Repeated acetyl‐l‐carnitine (ALCAR) administration persistently increases dopamine outflow in the nucleus accumbens. The present study examined the effect of repeated ALCAR administration on the DARPP‐32 phosphorylation pattern in the nucleus accumbens and caudate‐putamen. ALCAR increased phosphoThr‐34 DARPP‐32 levels and decreased phosphoThr‐75 DARPP‐32 levels, after 1 and 10 days of washout. We compared the effects of repeated cocaine and repeated ALCAR administrations on the behavioural response to cocaine challenge and on the DARPP‐32 phosphorylation pattern and cyclin‐dependent kinase 5 (Cdk5) levels in the striatum. We also studied whether ALCAR administered daily during or after cocaine sensitization procedure would interfere with the effects of cocaine. When the response to the cocaine challenge was assessed, cocaine‐ and ALCAR‐treated rats showed a similar sensitized behavioural response, and rats receiving combined cocaine and ALCAR treatments, irrespective of treatment order, also showed a sensitized response. A week after the cocaine challenge, the two drugs had induced opposite modifications in DARPP‐32 phosphorylation, as cocaine increased phosphorylation at Thr‐75, while ALCAR increased phosphorylation at Thr‐34. In cocaine plus ALCAR treated rats, irrespective of treatment order, ALCAR administration antagonized cocaine effects on DARPP‐32 phosphorylation. Moreover, cocaine, but not ALCAR, increased ΔFosB and Cdk5 expression, and the increase in Cdk5 was antagonized by ALCAR administration in rats receiving combined treatments. These effects were relatively persistent, as they were still present 7 days after the last treatment

Edited by Ruth, 07 October 2018 - 08:09 PM.