CREB: The Transcription Factor That Thirsts After Your Soul! (Propped Up by the Pillars of Illness) | |
deluded_dawn_drizzle
(OP) User ID: 67667907 United States 02/12/2015 08:39 PM Report Abusive Post Report Copyright Violation | Re: CREB: The Transcription Factor That Thirsts After Your Soul! (Propped Up by the Pillars of Illness) Emodin (from Cascara sagrada) is antiproliferative [link to www.pubfacts.com] [link to www.pubfacts.com] - a property dependent on its ability to inhibit the signaling of a group of CREB-supporting kinases (MAPK) that play a part in typical diabetic issues. At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in retinal superoxide, nitric oxide (NO), cyclooxygenase (COX)-2, and leukostasis within retinal microvessels. All these abnormalities were significantly inhibited by the p38 MAPK inhibitor (25 mg/kgBW/d). At 10 months of diabetes, significant increases in the number of degenerate (acellular) capillaries and pericyte ghosts were measured in control diabetic rats versus those in nondiabetic control animals, and pharmacologic inhibition of p38 MAPK significantly inhibited all these abnormalities (all P < 0.05). This therapy also had beneficial effects outside the eye in diabetes, as evidenced by the inhibition of a diabetes-induced hypersensitivity of peripheral nerves to light touch (tactile allodynia). Quoting: [link to www.ncbi.nlm.nih.gov] Apparently emodin is able to achieve this by increasing expression of the PPARG gene. [link to www.pubfacts.com] Emodin also antagonizes the P2X7 (a purinergic) receptor. [link to www.ncbi.nlm.nih.gov] This antipurinergic property is shared by sumarin, a drug hinted at in the OP that could benefit ASD by restabilizing metabolic function. Berberine (from the bark of phellodendron) also ameliorates overactivation of the p38 MAPK pathway (thus reducing phospho-CREB) [link to www.pubfacts.com] and is antidiabetic/prometabolic. RESULTS: After berberine administration, patients had a remission of 36% (P=0.037) in the presence of metabolic syndrome and a significant decrease in waist circumference in females (106±4 vs. 103±3 cm, P<0.05), systolic blood pressure (SBP) (123±7 vs. 115±9 mmHg, P<0.01), triglycerides (2.4±0.7 vs. 1.4±0.5 mmol/L, P<0.01), area under the curve (AUC) of glucose (1182.1±253.6 vs. 1069.5±172.4 mmol/l, P<0.05), AUC of insulin (92,056±72,148 vs. 67,407±46,441 pmol/L, P<0.01), and insulinogenic index (0.78±0.69 vs. 0.62±0.46, P<0.05), as well as an increase in the Matsuda index (2.1±1.0 vs. 3.1±1.6, P<0.01). Quoting: [link to www.ncbi.nlm.nih.gov] CONCLUSIONS: Administration of berberine leads to remission of metabolic syndrome and decreases in waist circumference, SBP, triglycerides, and total insulin secretion, with an increase in insulin sensitivity. To suppress NO formation & CREB activation, the mitigation of oxidative stress is crucial. Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway. [link to www.pubfacts.com] Retinoic acid (metabolite of vitamin A) also has this ability [link to www.pubfacts.com] and is crucial for D2R mRNA expression. [link to www.ncbi.nlm.nih.gov] More on AGEs: [link to blog.cholesterol-and-health.com] The dysregulation of blood glucose has a key role in sustaining these vicious circles by relentlessly keeping CREB activated, perpetuating the numbness that would seek remediation through overeating & the like. Suppressing CREB is of obvious desirability. A thirst to allay thirst. Without energy life would be extinguished instantaneously, and the cellular fabric would collapse. - Albert Szent-Györgyi What the midnight creep said to the fine black sheep: Help me stir her stolen blood with the jealousy of death above... [link to musescore.com (secure)] |
deluded_dawn_drizzle
(OP) User ID: 67667907 United States 02/14/2015 09:25 PM Report Abusive Post Report Copyright Violation | Re: CREB: The Transcription Factor That Thirsts After Your Soul! (Propped Up by the Pillars of Illness) And so it comes together. Licorice root can gradually lay an anhedonic framework (as in my case) by temporarily inhibiting CREB phosphorylation through its phytoestrogenic activity. Predictably, phytoestrogens are generally calcium antagonistic. [link to content.onlinejacc.org] Cocaine, as an indirect dopamine agonist, induces selective behavioral and physiological events such as hyperlocomotion and dopamine release. These changes are considered as consequences of cocaine-induced molecular adaptation such as CREB and c-Fos. Recently, methanolic extracts from licorice was reported to decrease cocaine-induced dopamine release and c-Fos expression in the nucleus accumbens. In the present study, we investigated the effects of liquiritigenin (LQ), a main compound of licorice, on acute cocaine-induced behavioral and molecular changes in rats. LQ attenuated acute cocaine-induced hyperlocomotion in dose-dependent manner. In addition, LQ inhibited CREB phosphorylation and c-Fos expression in the striatum and the nucleus accumbens induced by acute cocaine. Results provide strong evidence that LQ effectively attenuates the acute behavioral effects of cocaine exposure and prevents the induction of selective neuroadaptive changes in dopaminergic signaling pathways. Further investigation of LQ from licorice extract might provide a novel therapeutic strategy for the treatment of cocaine addiction. Quoting: [link to citeseerx.ist.psu.edu] This study shows the same phytoestrogen inhibiting COX-2 expression [link to www.ncbi.nlm.nih.gov] by "modulating" ERK1/2 signaling, which activates CREB (which is how cortisol upregulates COX-2). [link to www.ncbi.nlm.nih.gov] Isoliquiritigenin is also an NMDAR antagonist [link to www.researchgate.net] - a property which would potentiate its ability to inhibit calcium influx. Phytoestrogens Inhibit Growth and MAP Kinase Activity in Human Aortic Smooth Muscle Cells [link to hyper.ahajournals.org] All of this sounds nice, but the price is inevitably enhanced signaling of these CREB-supporting pathways (as I've felt first hand). CREB activation/calcium influx increases nitric oxide production. [link to www.pnas.org] Not only does the phytoestrogen genistein directly activate cAMP signaling, the role of the cAMP messenger system in estrogen's facilitation of calcium influx activating CREB suggests that this is not the only mechanism by which it upregulates NO production [link to jn.nutrition.org] (i.e. estrogen receptor upregulation). Other xenoestrogens though, like BPA, appear to be outright estrogenic and thus provide some blatantly undesirable effects. Xenoestrogens are potent activators of nongenomic estrogenic responses [link to www.ncbi.nlm.nih.gov] Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells. [link to www.ncbi.nlm.nih.gov] Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway. [link to www.ncbi.nlm.nih.gov] MAPK and NF-KB Pathways Are Involved in Bisphenol A-Induced TNF-a and IL-6 Production in BV2 Microglial Cells. [link to www.researchgate.net] Moral of the story? Certain xenoestrogens are unapologetic haymakers, and phytoestrogens are insidious little devils to avoid resolutely if you value your health & hedonic resonance. Without energy life would be extinguished instantaneously, and the cellular fabric would collapse. - Albert Szent-Györgyi What the midnight creep said to the fine black sheep: Help me stir her stolen blood with the jealousy of death above... [link to musescore.com (secure)] |