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Nomilin

mr.cooper69

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Nomilin

What is TGR5?

There will be a series of articles on the topic in the near future, but for now, here is the scientifically established role of this completely unique fat loss pathway that has only recently come under the pharmacological spotlight:

1. Fat loss – via the complex BAs/TGR5/cyclic AMP/D2/T3/UCP pathway
2. Enhanced Glucose Metabolism
3. Vasodilation
4. Bile homeostasis/liver health
5. Improving Immune Function
6. Protection Against Atherosclerosis

What is Nomilin?

Simply put, Nomilin is among the strongest naturally occurring TGR5 agonists on the planet. Agonism = activation, so nomilin activates the TGR5 pathway and should cause the above 6 effects, among others.

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Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet.
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Abstract
TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids (BAs). TGR5 is thought to be a promising drug target for metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet (HFD). In the present study, we identified a naturally occurring limonoid, nomilin, as an activator of TGR5. Unlike BAs, nomilin did not exhibit the farnesoid X receptor ligand activity. Although the nomilin derivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a HFD for 9 weeks were further fed a HFD either alone or supplemented with 0.2%w/w nomilin for 77 days,nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance. Our results suggest a novel biological function of nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5.

Summary:

In vivo, nomilin activates TGR5 and reduces fat, blood glucose, and insulin. These are simultaneous fat loss + GDA properties. The data is below. Note that mice fed a high fat diet PLUS nomilin actually LOST bodyweight from when they first started despite the excessively high-calorie diet.


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Ono, Eri, Jun Inoue, Tsutomu Hashidume, Makoto Shimizu, and Ryuichiro Sato. "Anti-obesity and Anti-hyperglycemic Effects of the Dietary Citrus Limonoid Nomilin in Mice Fed a High-fat Diet." Biochemical and Biophysical Research Communications 410.3 (2011): 677-81. Print.


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Nomilin as an anti-obesity and anti-hyperglycemic agent.
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Abstract
Recent scientific findings support the notion that bile acids, which are cholesterol catabolites, are bioactive signaling molecules that function as ligands for the farnesoid X receptor or a G-protein-coupled receptor, TGR5. Through these receptors, bile acids can maintain not only bile acid homeostasis but also lipid and carbohydrate homeostasis. An intriguing finding regarding the role of TGR5 in energy metabolism and glucose homeostasis suggests a potential approach to combat obesity and insulin resistance by targeting this receptor to increase thermogenesis and incretin secretion. In this review, I have summarized the latest findings related to TGR5 agonists, in particular, a citrus limonoid, nomilin, and the roles of these agonists in energy metabolism and glucose homeostasis.

The author deems nomilin one of the few future natural products to pursue for combating the obesity epidemic:


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Sato, R. "Nomilin as an Anti-obesity and Anti-hyperglycemic Agent." Vitam. Horm. 91 (2013): 425-39. Web.

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Studies on the constituents of edible and medicinal plants. III. Effects of seven limonoids on the sleeping time induced in mice by anesthetics.
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Abstract
Effects of seven limonoids, obakunone (1), 7 alpha-obakunol (2), 7 beta-obakunol (3), limonin (4), 7 alpha-limonol (5), 7 beta-limonol (6) and nomilin(7), on the sleeping time induced in mice by anesthetics were assayed. All the limonoids, except for 2, shortened the sleeping time induced by alpha-chloralose and urethane. 7 gave the highest reduction rate of sleeping time, and the order of the reduction rate of sleeping time was as follows; 7 > 1 and 3 > 4, 5 and 6. As the chemical structures of these compounds are similar to each other, the relationship between the structure and the effects of limonoids on sleeping time was discussed.

Summary:

Nomilin (7) was the strongest “stimulant” out of all tested limonoids, capable to reducing sleep-time induced by tranquilizers/sedatives by the largest margin.

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Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system.
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Abstract
The effect of naturally occurring triterpenoid compounds such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin on the immune system was studied using Balb/c mice. Intraperitoneal treatments with 5 doses of these terpenoid compounds were found to enhance the total white blood cells (WBC) count. In ursolic acid, oleanolic acid and nomilin treated animals the maximum total WBC count was observed on the 6th day, while in glycyrrhizic acid treated animals it was observed only on the 9th day after the drug treatment. In ursolic acid, oleanolic acid and nomilin treated animals the percentage of increase in the total WBC count was to 91.48 +/- 4.6%, 135.75 +/- 6.4% and 117.33 +/- 17.9% respectively. In the glycyrrhizic acid treated animals the total WBC count was increased to 114.9 +/- 18%. Bone marrow cellularity and alpha-esterase positive cells were also enhanced by the treatment with these terpenoids. Treatment with various triterpenoids along with antigen produced an enhancement in the specific antibody titre and the number of plaque forming cells (PFC) in the spleen. Triterpenoids remarkably inhibited delayed type hypersensitivity reaction (DTH). These results indicate the immunomodulatory activity of naturally occurring triterpenoids such as glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin.

Summary: Nomilin over DOUBLED the amount of WBCs as part of the immune response. This indicates strong immune system stimulation.
 
Great information, as always. :)
 
Cy always drops all the goodies while I'm asleep, gives me a good start to my day to read up and get excited
 
This is the ingredient that really makes me want Norco, I was even tempted to just buy some GSE and try that out for a while.

Great write ups Coop, can't wait for the insider.
 
This is the ingredient that really makes me want Norco, I was even tempted to just buy some GSE and try that out for a while.

Great write ups Coop, can't wait for the insider.

I'm not sure thats a great short hand for the product lol at first I was like what??

Interesting information to say the least.
Some good preliminary studies.
 
PES has been coming hard with the innovation lately. Very interesting reads.
 
I'm not sure thats a great short hand for the product lol at first I was like what??

Interesting information to say the least.
Some good preliminary studies.

Haha didn't even catch that at first, just thought it sounded better than 'dren.
 
Did a quick google search and if what I'm reading is correct nomilin has an effect on cyp3a. Will the nomilin in norcodrene significantly effect drug metabolism?
 
Most grapefruit constituents do to some degree. Always consult a doctor if you're on a medication

A lot of herbs inhibit a few cyp's

Compile a list of your supplements and the respective enzymes they play with and get a hold of a pharmacist/doctor and discuss any interaction
 
mr.cooper69 - I know I'm late to be asking questions on this :) I love Norcodrene and I find it to be both innovative and mainstream, which is a compliment. It's hard to fill those two categories with something that is novel but safe enough for wide distribution.

I've been reading up on the TGR5 pathway, and the more I learn, the more promising this looks - especially if it were to be coupled with some of the other products that are out there targeting BAT activation (Brite, Lipomorph, etc.).

One thing I'm not quite understanding is the effect of TGR5 activation on gallstones. It appears that TGR5 activation causes the gall bladder to fill, but does this increase or decrease the formation of gallstones? I can't seem to put it all together in my brain, it seems like it could go either way.
 
Strong year old bump to member not on board anymore ��

He's around, just not as frequently and not as a PES rep anymore. He was around a couple weeks ago. I figured it was better than starting a new thread....the Coop's corner threads are all so valuable.
 
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