ß-Ionone As An DHT-analouge?

LeeLemonoil

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This study:
Activation of an Olfactory Receptor Inhibits Proliferation of Prostate Cancer Cells


identified the common natural terpene Beta-Ionone, which sees wide application as an aromachemical in perfumes and as a flavouring agent, as a major ligand and agonist of an olfactive receptor (OR) in prostrate cancer cells. The natural and physiological occuring ligand/agonist is actually DHT - both substances stop the proliferation of the cancer cells and are therefore anti-cancerous in the prostrate.

The study proclaims that ß-Ionone has a chemical structure that is very similar to that of DHT.

- If ß-Ionone can activate an OR which physiologicaly is only designed to be activated by DHT it may be feasible that ß-Ionone can bind to other types of receptors that DHT binds to as well, probably through molecular conformation. Since ß-Ionone is a terpene which is highly volatile (due to low molecular mass) and fat-soluble, it is easily absorbed through various tissues and will certainly also reach the brain via inhalation alone.
I'm interested if inhalation of the substance will result in some positive mental effects that some ascribe to DHT in the CNS.

It's a very cheap and unrestricted substance which can be obtained here for example:
Beta Ionone

2ml cost 2USD - it should be diluted with alcohol to 10% or even 1% for anyody interested in testing it as an inhalation agent or sublingualy, so 2ml are plenty.


In the above mentioned study, the authors also indictae that the only other ligand to the prostrate specific OR/DHT receptor they identified is
1,4,6-Androstatriene-3,17-dione - Wikipedia

a potent aromatase inhibitor.

And this study found an OR-receptor activated by ß-Ionone in melatocytes in the skin:
Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

Does anybody konow about DHT effects on melanocytes or melanin expression?

So it is certainly an interesting compound, ß-Ionone and used in it's natural and synthetic forms since centuries/decades respectively, meaning it is probably a safe substance, granted for internal use even.
 
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LeeLemonoil

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Well some on this forum observed or claimed that topical Mk-4 or Tetracycline-potions lead to removal of moles. Again, this study
Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

proved the modulating effects of ß-Ionone on melanocytes/melanogenesis - which prompted me to think about if DHT is in any way implicated in melanocyte/melanogenesis. ß-Ionone has a structur that enables it to bind to some Receptors that only DHT would bind to endogenously ...Maybe there is a broader connection between Anrogens and melanogenesis when probably Vitamin K, topical DHEA and so forth lead to similar results.

I apllied some ß-Ionone on a mole of one of my cows ... I don't have any elevated Naevi and wanted to see effects on those .... 5 days of application of pure ß-Ionone on the mole .... the thing shrinks visibly, let's see where it goes.
 
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lol and then people complain about a keto addition... SMH
 

Drareg

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This is a great find,thanks.

Do you have a trail you are following? I'm very interested in this,I was looking more for aroma and effects on DNA methylation etc.
 
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LeeLemonoil

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@Drareg
Aroma? Aromchemicals in scent or food? There is soild evidence that a wide range of aromachemicals of any sort, natural and synthetic, have activity on many different type of receptors in different tissues. I'm not aware of research into DNA methylation, but there are even some aromchemicals that affect nuclear receptors which will absolutely modify DNA.
Most ACs affect G-Protein coupled receptors, but that also can ignite a signal-cascade with effects on DNA.
It's not wel eludicated that field, but research into these fields is progressing and garners more attention recently.

@Such_Saturation
It's only demonstrated so far that ß-Io is an analouge to DHT to one specific type of receptor in the prostate, I'm not saying it is the same substance or has the same effects anywhere in the body except the prostate. I would not draw the conclusion that DHT is as "harmless" as ß-Ionone at all.

What's more, many Peaters don't seem to buy into the receptor-paradigm but in this case it's essential to recognize it if you want argument in favour of DHT based on ß-Ionones activity.
 
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LeeLemonoil

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Is it feasible that ß-Ionone not only binds and activates the same OR as DHT but also the androgen receptor?
This patent-description hints at this possibility without explicitely stating it:

US Patent # 8,470,889. Hybrid-ionone and curcumin molecules as anticancer agents - Patents.com

This pharse got my attention:

It has been recognized that one way to develop novel AR antagonist is to design chemical compound that has a core structure to bind the hormone-binding pocket and an extending bulky arm to displace H12. Such a strategy has been successful in the design of estrogen receptor and several other nuclear receptor antagonists. To date, reports of anti-androgens capable of circumventing multiple mutant ARs are limited. There are two recent reports that disclosed the efforts to develop anti-androgen against resistant mutant ARs: i) McGinley et al (J. Am. Chem. Soc. 2007, 129, 3822-3823) reported identification of bicalutamide derivative such as PLM1 that at a low micromolar concentration shows potent activity in suppressing DHT-induced transcriptional activation of wild-type, W741L and T877A mutant ARs; ii) To develop anti-androgen bearing a bulky chain, Cantin et al. (J Biol Chem 2007, 282, 30910-30919) reported synthesis of a set of DHT-derived molecules bearing various bulky chains, such as EM5744. Unexpectedly, EM-5744 turned out to be a potent agonist of the AR. Crystallographic study indicated the H12 of AR ligand-binding domain is indeed at the agonistic position.

So they took ß-Ionone and Curcumin as base-structures because they bind to the AR and changed the structure to achieve an antagonistic ligand?
So if ß-Ionone binds the same OR as DHT as mentioned in the prvious posts in this threads and also activates it in the same way, then maybe the same is true for the AR?
ß-Ionone and Curcumin as androgens?
 
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LeeLemonoil

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So Chalconoids, of which ß-Ionone is one, are aromatase-inhibitors as well:
Chalconoid - Wikipedia

Also:
Chalcones and their derivatives demonstrate wide range of biological activities such as anti-diabetic, anti-neoplastic, anti-hypertensive, anti-retroviral, anti-inflammatory, anti-parasitic, anti-histaminic, anti-malarial, anti-oxidant, anti-fungal, anti-obesity, anti-platelet, anti-tubercular, immunosuppressant, anti-arrhythmic, hypnotic, anti-gout, anxiolytic, anti-spasmodic, anti-nociceptive, hypolipidemic, anti-filarial, anti-angiogenic, anti-protozoal, anti-bacterial, anti-steroidal, cardioprotective, etc

I've outlined in this thread that ß-Ionone show some similar properties as DHT in some specific tissues.
We here are convinced of many positive healt-effects of DHT and androgens, ß-Ionone/Chalcones might act in some way as exogenous analouges to androgens.
They might be promising agent for topical applications as well, especially ß-Ionone, given that it is penetrative and fat-slouble by itself (Hairloss-tratment?)

Some more anti-cancer action studies additionaly to the one's above:

http://www.sciencedirect.com/science/article/pii/S0223523416305980
β-Ionone and its analogs as promising anticancer agents

http://www.sciencedirect.com/science/article/pii/S0223523415300350
Anti-cancer chalcones: Structural and molecular target perspectives

Curiously, the picture does not seem so bright as a whole. Here is a study that claims meatstasis inducing effects of Ionones n prostate cancer:
Structurally related odorant ligands of the olfactory receptor OR51E2 differentially promote metastasis emergence and tumor growth. - PubMed - NCBI






 
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LeeLemonoil

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Here ß-Ionone is featued as a main ingredient in a scar and keloid reducing cream:
http://www.keloidcare.com/

It's formulated especially for people with darker skin complexion - interesting, given that ß-Ionone acts on melanocytes ... seems this doc knew something before it was published
 
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LeeLemonoil

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Odorants could elicit repair processes in melanized neuronal and skin cells


This paper indicates that ß-Ionone is a ligand on above discussed OR, and that propertie is due to a certain pattern in its molecular structure, a structure it shares with steroids α-4,6-androstadiene-17-ol-3-one, 6-dehydrotestosterone or 1,4,6-androstadiene-3-17-dione among others.

In addition, the isoprenoid β-ionone, a violet-like scent, has been demonstrated to activate the olfactory receptor OR51E2 expressed in pigment-producing melanocytes of the human skin (Gelis et al., 2016). OR51E2 is also known as prostate-specific G-protein-coupled receptor (PSGR) and acts as a cell surface steroid receptor that mediates rapid, nongenomic, steroidal signaling in prostate cancer cells (Neuhaus et al., 2009). OR51E2 appears activated by compounds characterized, as β-ionone, by the presence in their molecular structure of a carbonyl group conjugated to a butadiene system, such as α-4,6-androstadiene-17-ol-3-one, 6-dehydrotestosterone or 1,4,6-androstadiene-3-17-dione (Pavan et al., 2017) (Figure 1). Therefore, OR51E2 activating steroids or terpenoids might provide novel compounds for the treatment of pigmentation disorders and proliferative pigment cell disorders such as melanoma. In addition, taking into account that a carbonyl group conjugated to a butadiene system belongs also to cinnamaldehyde (Figure 1), this compound or its derivatives may be OR51E2 promising ligands

Cinnamaldehyde, as theorized by the author above, is close to the aromachemcial Helional, which seems to have potent anti-cancer properties:

Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line - ScienceDirect
 

KyleKingsly

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Wow, this sounds incredibly exciting for androgenic purposes! Did anyone ever get to try this stuff? All this skin-healing stuff is great but I'm trying to be and feel more manly :D
 
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LeeLemonoil

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how does it feel?
have you used dht?
No.
Mind that the studies indicate that BI binds the same OR like DHT, that’s no proof it acts androgenic in any way.
But used as a diluted perfume-like „inhalation“ agent, it seems to have grounding, steadying mental effects, not unlike androgenic molecules. It‘s very likely also an aromatase Inhibitor in the CNS
 

Ras

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