LONGECITY

As written in the heading, I wanted to request for any input in those regards.

 

I could only find 2 studies for the GR receptor but only one for the MR receptor.

Any input for up- or down-regulators would be appreciated e.g. even antidepressants.

 

Because I dont know whether the up or down regulation of the receptors do relieves my depression. It seems that by decreasing corticosterone, a decrease appears of my depression.

 

Antidepressant-like effects of Cortex Mori Radicis extract via bidirectional phosphorylation of glucocorticoid receptors in the hippocampus.

http://www.researchg...the_hippocampus

 

Novel Antidepressant-Like Activity of Propolis Extract Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

http://www.hindawi.c...am/2013/217853/

 

A bioactive compound from Polygala tenuifolia regulates efficiency of chronic stress on hypothalamic-pituitary-adrenal axis.

http://www.ncbi.nlm....pubmed/19827305

Not quite what you ask for but could be useful.

Curcumin prevents corticosterone-induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway.


http://www.ncbi.nlm....ubmed/21689105/


Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.

http://www.ncbi.nlm....om=Curcumin HPA

Thank You

11-ketotestosterone interferes with cortisone to cortisol formation. Mifepristone is a GR antagonist.

Danshen extract 15,16-dihydrotanshinone I functions as a potential modulator against metabolic syndrome through multi-target pathways.

http://www.ncbi.nlm....pubmed/20380878

 

Here, we report that the lipophilic component, 15,16-dihydrotanshinone I (DHTH) from danshen potently antagonized both mineralocorticoid and glucocorticoid receptors, and efficiently inhibited the expression of their target genes like Na(+)/K(+) ATPase, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK). In addition, DHTH increased AMPKalpha phosphorylation and regulated its downstream pathways, including increasing acetyl-CoA carboxylase (ACC) phosphorylation, inhibiting transducer of regulated CREB activity 2 (TORC2) translocation and promoting glucose uptake.

 

As usual: Danshen aka Salvia Miltiorrhiza is a potent bloodthinner

 

Effects of tanshinone IIA, a major component of Salvia miltiorrhiza, on platelet aggregation in healthy newborn piglets.

http://www.ncbi.nlm....pubmed/21453766

 

The herb possesses anticoagulation action and probably acts on various coagulation factors

http://eurekamag.com...1/005651213.php

 

And so on.

 

Edited by Flex, 29 September 2014 - 02:09 PM.

11-ketotestosterone interferes with cortisone to cortisol formation. Mifepristone is a GR antagonist.

 

Interresting, I knew only Ursolic acid for this target via inhibitting 11-Beta hydroxysteroid dehydrogenase

http://examine.com/s...cid/#summary8-0

 

Thanks for the contribution.

i think humic/fulvic acid might have some sort of effect...on a side note I love the stuff one of the best substances I've ever used

 

ashwagandha lowers cortisol a lot, couple studies on that. not sure if thats close to what you are looking for

Thanks.

The only what I´ve found is that Shilajit / Fulvic acid has the same effect like Betamethasone

http://www.insidersh..._mountains/2364

 

And I knew this from Ashwa.

I´ve tried it, but somehow was Gotu Kola more effective

Unfortunaetly without any modulating effects.

 

I reconsidered my idea. I need actually something like Mifepristone that somehow enduringly alters the GR or MR activity.

 

I´ve learned that 11β-Hydroxysteroid Dehydrogenase limits the activation of Glucocorticoides on Mineralocorticoid receptors due degradation.

So I´m curious whether my depression was caused by perhaps an epigenetic alteration of 11ß HSD or GR/MR receptors.

 

I´ve found this site with some interresting informations.

11β-Hydroxysteroid Dehydrogenases in the Regulation of Tissue Glucocorticoid Availability

http://www.intechope...id-availability

 

I´m testing right now Salvia miltiorrhiza and it seems to have some enduring effects.

But from my experiences with Chinese skullcap and Sodium Benzoate, which lasted a few days, I cant say it for sure below 1 week .

 

Dont ask me why Sodium benzoate is working

Perhaps this could be the explanation because NaBe alters the glutamate transmission

How physical exercise protects the brain from stress-induced depression

http://ki.se/en/news...uced-depression

 

Btw: Polygala hasnt changed anything

 

I´m also trying to obtain Mifepristone.

If I find something or anything changes, I will update it here.

 

Thanks for Your help again

 

I´m testing right now Salvia miltiorrhiza and it seems to have some enduring effects.

But from my experiences with Chinese skullcap and Sodium Benzoate, which lasted a few days, I cant say it for sure below 1 week .

 

 

How is the salvia miltiorrhiza continuing to work for you. I think you're on to something here. Although mefipristone maybe better, there is some speculation, at least in old M&M threads, that mineralcoid antagonists might offer some benefits and since dan shen is both  a gr/mr antagonist it may work well. I've been trying it for the last 4 days at approx. 1.5 grams BID and I feel really good. Although I've been experimenting with many things lately, I'm really impressed with it for these 4 days anyway.
 

The good and bad thing respectively is that Dan shen acts similair like amphetamine afaik via activating potassium channels,

this in turn releases dopamine.

 

It is good, but this makes it problematic to distinguish between dopamine and GR/MR effects.

So the role of GR/MR for the mood

 

Yes I´ve found interresting informations. 

Here are some findings:

GR do increase themselves, dosedependly, via activating the expression of 11β-Hydroxysteroid Dehydrogenase 1 mrna expression.

this in turn converts more cortisone( the inactive form) into cortisol. So a self reinforcing loop.

But can convert it back(wiki), whereas 11ßHSD2 only converts it to the inactive form.

 

Inhibition of 11ßHSD2 by Liquorice (a nonselective inhibitor of 1&2) leads to an excess of MR.

Aldosterone, a MR, as an example increases anxiety.

 

Btw: THC/Anandamide or perhaps the Sartans( telmisartan) and ACE inhibitors do decrase Aldosterone.

 

The list goes on but I dont want to spam. I want rather to post the reults an the "targets" i.e. epigenetic activation/decativation

and other mechanisms as posted above.

 

If You want to read into, the following links were very interresting for me:

 

http://www.endocrine.../ea0034p243.htm

http://www.intechope...id-availability

 

http://www.plosone.o...al.pone.0074691

http://www.clinicale.../content/4/1/24

 

This thread has some additional informations

http://www.longecity...is-dysfunction/

Edited by Flex, 02 October 2014 - 11:39 PM.

Thanks for the links! I'm definitely very interested in this now.

I just wanted to add an example of a "bad" MR: Aldosterone

http://www.afibbers....aldosterone.pdf

Aldosterone: A forgotten mediator of the relationship between psychological stress and heart disease

http://www.ncbi.nlm....les/PMC3099453/

whatever happened to this ? because its kind of where I reached in my research, plus or minus some stuff