[Lotus]

Yup, I get all that. Coumarins are in a variety of NBE herbs (PM too). What I don't get is saying coumarins cause toxicity but you suggest finding a Purer (higher?) form.


rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone).
Cox D, et al. Hum Toxicol. 1989.
Show full citation
Abstract
1. Two thousand, one hundred and seventy-three patients with cancer or chronic infections were treated with coumarin in a clinical trial. 2. 0.37% of these patients developed elevated liver enzyme levels during therapy with coumarin. 3. This hepatitis was probably a form of idiosyncratic hepatotoxicity and may have been immune in origin.


I suggest reading this study:

Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772644/

[AbiDrew85]

Yup, I get all that. Coumarins are in a variety of NBE herbs (PM too). What I don't get is saying coumarins cause toxicity but you suggest finding a Purer (higher?) form.

Purer as in just coumarin as the only active, no other actives, including coumarin derivatives.

rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone).
Cox D, et al. Hum Toxicol. 1989.
Show full citation
Abstract
1. Two thousand, one hundred and seventy-three patients with cancer or chronic infections were treated with coumarin in a clinical trial. 2. 0.37% of these patients developed elevated liver enzyme levels during therapy with coumarin. 3. This hepatitis was probably a form of idiosyncratic hepatotoxicity and may have been immune in origin.

I would certainly be interested in seeing full text for this research, but it doesn't seem to be available even if you are willing to pay for it, not that I could. EDIT: 0.37% is low enough to be in line with the potential for compromised guts to play a role.

I suggest reading this study:

Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772644/

I have. It says nothing about coumarin itself other than that all these others are derived from it. It does mention the tonka bean as a rich source of "coumarins". But if you do research on the tonka bean you'll find that uncontaminated tonka bean is indeed a rich source of coumarin. ONLY coumarin, no derivatives unless contaminated by bacteria.

[Lotus]

Lol, you want me to provide (and pay) all the research, too funny.


Endogenous estrogens have an important role not only in the hypothalamic-pituitary-gonadal axis, but also in various non-gonadal systems, such as cardiovascular systems, bone, and central nervous systems, and lipid metabolism.
Usui T. Endocr J. 2006.

Coumarin based selective estrogen receptor modulators (SERMs) and coumarin-estrogen conjugates have also been described as potential antibreast cancer agents.

I see coumarins having weak estrogenic potential, (and modulating HPA, SERMS, as stated), I'd like to see you're research on coumarins having anti-androgens properties (I know it does, still, (I'm curios) what you have. There's a lot more to that study then a quick glance of 103 pages. e.g:

For example, coumarin and its active metabolite, 7-hydroxycoumarin, demonstrated growth-inhibitory cytostatic activity in human cancer cell lines, such as A549 (lung), ACHN (renal), H727 (lung), MCF-7 (breast) and HL-60 (leukemia), and have also been reported to demonstrate activity against prostate cancer, malignant melanoma, and metastatic renal cell carcinoma in clinical trials [26–29]

[AbiDrew85]

Lol, you want me to provide (and pay) all the research, too funny.

Nope. Not at all. I was just commenting that that particular synopsis made that research paper sound interesting, and that it was rather unfortunate the rest of it was unavailable, even for money. If you happen to have a link to where the entire paper is available though I wouldn't mind if you provided it. I couldn't find it.

Coumarin based selective estrogen receptor modulators (SERMs) and coumarin-estrogen conjugates have also been described as potential antibreast cancer agents.

This is about derivatives, not coumarin itself.

I see coumarins having weak estrogenic potential, (and modulating HPA, SERMS, as stated)

This is about derivatives, not coumarin itself.

I'd like to see you're research on coumarins having anti-androgens properties (I know it does, still, (I'm curios) what you have.

As I said above, I know I've posted all that I have before, so unless it's been removed like I've noticed some other of my recent posts have been it should be on this forum still somewhere if you search it. Only coumarin has anti-androgenic effects, none of its derivatives do so far as any current research indicates. Except as a side effect from the estrogenic effects of some derivatives.

There's a lot more to that study then a quick glance of 103 pages. e.g:

For example, coumarin and its active metabolite, 7-hydroxycoumarin, demonstrated growth-inhibitory cytostatic activity in human cancer cell lines, such as A549 (lung), ACHN (renal), H727 (lung), MCF-7 (breast) and HL-60 (leukemia), and have also been reported to demonstrate activity against prostate cancer, malignant melanoma, and metastatic renal cell carcinoma in clinical trials [26–29]

Well, yes, coumarin itself is also anti-cancer. There's a lot more research on coumarin and coumarins and cancer than there is on any other properties of coumarin or coumarins. If that was in that paper and I missed it/forgot it, I apologize for that memory lapse. I've never claimed to have a perfect memory.

[Lotus]

I grew 2-3 cups using Reishi (w/no unfair advantages) 4+ cups overall with NBE. BO did not agree with me. Reishi coumarins ARE NOT the main bioactives that inhibit 5 AR..........it's polysaccharides, triterpines, and other lipids are the main bioactives that does the inhibiting in the Prostate. Reishi has a 2,000 year track record. Information supplied here @ BN is complete w/attached studies. I'll attach more related papers, (located in my project x thread). Btw Abi, none of your files are deleted, just moved here, so you and i dont hijack another thread, apologies for any inconvenience.

In many cases no lab research is related to NBE, or how it effects male breast growth. We are, in fact the lab test subjects to carry out the business of real world result (or not). FWIW.


Reishi has 5a-reductase inhibitory activity of more than 90% at 200 m g/ml.

5α-Reductase inhibitory activity-guided fractionation of the EtOH extract of the fruiting body of Ganoderma lucidum (LEYSS.:FR.) KARST. (Ganodermataceae), which is called Reishi, or Mannentake in Japan and Lingzhi in China, led to the isolation of two active compounds which were ganoderic acid DM and 5α-lanosta-7,9(11),24-triene-15α,26-dihydroxy-3-one with an IC50 of 10.6 μM and 41.9 μM respectively. A carboxyl group of side chain of ganoderic acid DM is essential to elicit the inhibitory activity because of much less activity of its methyl ester.
http://www.ncbi.nlm.nih.gov/pubmed/16462054


For those who need more science lol, here's a sampling:

i've been reading different things on this website, and i'd appreciate one more from this thread please =]]

is Green Tea (preferably green tea capsules - 500mg) an anti-androgen? or does it block DHT???

thanks in advance xoxoxo

Sorry 45 for the DHT frustration, green tea is not so cut and dry in terms of an effective DHT blocker, it depends on what research you find, meaning it's pretty confusing. If you want the short answer (which I assume is yes), I'd choose something else (e.g. reishi). According to this report its effective as a 5 ar inhibitor (blocks the conversion path to DHT). Human studies are lacking though.


Department of Biochemistry and Molecular Biology, The Ben May Institute for Cancer Research, and The Tang Center for Herbal Medicine Research MC6027, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA.

The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.

Sorry people, I have to share this rather unique way to box out DHT, I stumbled across it when I was collecting some research, please follow along (my apologies for the technical crap explanation) I'll try to keep it in the ball park.

The problem with DHT is when it enters into receptors it locks it up, and thereby making Aromatase an after thought, Aromatase is enzyme that converts free T to estrogen. (Aka boob growth), here I suggest a novel (well, at least for BN) called "Androgen Decoy's".


http://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=3132148_nihms255516f1.jpg





A transcriptional factor decoy strategy is the use of short double-stranded oligodeoxynucleotides containing a high-affinity binding site for specific transcription factors as a decoy DNA to be transfected into target cells [12–16]. Inside the cells, the decoy DNA competes with the endogenous high-affinity binding site of the target genes for binding to specific transcription factors, and consequently inhibits activated AR function [16]. Decoy DNA has potential for treatment of cardiovascular disease [12]. It also induces apoptosis in certain cell lines [13].

Androgen receptor decoy molecules block the growth of prostate cancer
http://www.pnas.org/content/104/4/1331.abstract


Androgen receptor: structure, role in prostate cancer and drug discovery
Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herei
http://www.nature.com/aps/journal/vaop/n....html#fig1

The mechanism of action of testosterone.
Testosterone enters the cell by passive diffusion and is converted to DHT and estradiol. Testosterone and DHT bind to the androgen receptor located in the cytoplasm attached to heat-shock proteins (not shown). Upon binding of testosterone and DHT to androgen receptor, heat-shock protein is released and the receptor dimerizes. Estradiol binds to the estrogen receptors ERα, ERβ

Androgen and AR action. Genome organization of the human androgen receptor gene and the functional domain structure of the androgen receptor protein. (A) Androgen and AR signaling in prostate cells. After testicular synthesis, testosterone is transported to target tissues such as the prostate and becomes converted to dihydrotestosterone (DHT) by 5-α-reductase. DHT binds to the ligand-binding pocket and promotes the dissociation of heat-shock proteins (HSPs) from the AR. The AR then translocates into the nucleus, dimerizes and binds to the androgen response element (ARE) in the promoter region of target genes such as prostate-specific antigen (PSA) and TMPRSS2. At the promoter, the AR is able to recruit members of the basal transcription machinery [such as TATA-box-binding protein (TBP) and transcription factor IIF (TFIIF)] in addition to other coregulators such as members of the p160 family of coactivators and cAMP-response element-binding protein (CREB)-binding protein (CBP). SHBG: serum sex hormone-binding globulin. (B) The androgen receptor gene has been mapped to the long arm of the X-chromosome (locus: Xq11-q12). It contains eight exons interrupted by introns of varying lengths (0.7–2.6 kb) and codes for a protein of 919 amino acids consisting of several functional domains (N-terminal domain (NTD), DNA binding domain (DBD) and ligand binding domain (LBD); amino acid residue numbers are indicated above the AR protein domain map). Exon 1 codes for the NTD, exons 2 and 3 encode the DBD, and exons 4 to 8 encode both the hinge and LBD.






Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.

Abstract
Androgens exert their effects by binding to the highly specific androgen receptor (AR). In addition to natural potent androgens, AR binds a variety of synthetic agonist or antagonist molecules with different affinities. To identify molecular determinants responsible for this selectivity, we have determined the crystal structure of the human androgen receptor ligand-binding domain (hARLBD) in complex with two natural androgens, testosterone (Testo) and dihydrotestosterone (DHT), and with an androgenic steroid used in sport doping, tetrahydrogestrinone (THG), at 1.64, 1.90, and 1.75 A resolution, respectively. Comparison of these structures first highlights the flexibility of several residues buried in the ligand-binding pocket that can accommodate a variety of ligand structures. As expected, the ligand structure itself (dimension, presence, and position of unsaturated bonds that influence the geometry of the steroidal nucleus or the electronic properties of the neighboring atoms, etc.) determines the number of interactions it can make with the hARLBD. Indeed, THG--which possesses the highest affinity--establishes more van der Waals contacts with the receptor than the other steroids, whereas the geometry of the atoms forming electrostatic interactions at both extremities of the steroid nucleus seems mainly responsible for the higher affinity measured experimentally for DHT over Testo. Moreover, estimation of the ligand-receptor interaction energy through modeling confirms that even minor modifications in ligand structure have a great impact on the strength of these interactions. Our crystallographic data combined with those obtained by modeling will be helpful in the design of novel molecules with stronger affinity for the AR.

http://www.ncbi.nlm.nih.gov/pubmed/16641486?dopt=Abstract&holding=npg

[/quote]

[Lotus]

Reishi has 5a-reductase inhibitory activity of more than 90% at 200 ug/ml.

5α-Reductase inhibitory activity-guided fractionation of the EtOH extract of the fruiting body of Ganoderma lucidum (LEYSS.:FR.) KARST. (Ganodermataceae), which is called Reishi, or Mannentake in Japan and Lingzhi in China, led to the isolation of two active compounds which were ganoderic acid DM and 5α-lanosta-7,9(11),24-triene-15α,26-dihydroxy-3-one with an IC50 of 10.6 μM and 41.9 μM respectively. A carboxyl group of side chain of ganoderic acid DM is essential to elicit the inhibitory activity because of much less activity of its methyl ester.
http://www.ncbi.nlm.nih.gov/pubmed/16462054

Here's the attached pdf:

https://www.jstage.jst.go.jp/article/bpb...2_392/_pdf

[AbiDrew85]

That's interesting. So two other compounds have been isolated in reishi that have a strong 5ar-inhibitory activity. So it'd combine well with a more competitive estrogen that is also stronger than the estrogenic compound in reishi and with something with a stronger source of coumarin to help block the total testosterone as well for someone with REALLY high testosterone of both types (like me) and EGCg to help convert whatever's left to E.

Unless someone actually manages to combine reishi and BO and the estrogenic compound in reishi does not interfere with the BO, then I'm still going to have to hold that it is unlikely to combine well with BO, however. Which has been a frequent question of late. With PM, clearly it works out without the reishi compromising the (deoxy)miroestrol.

I'll give it a try adding it to my GTE routine next month as it is fairly inexpensive and if it works it should raise effectiveness of GTE towards NBE, though I'll probably still need to add tonka bean eventually to really block my testosterone sufficiently as well as a replacement estrogen.

And no, coumarin is not a 5AR inhibitor, it's a 17,20 lyase inhibitor IIRC, I do remember it's higher up the chain at least, but I could be confusing exactly where without looking it up again. It inhibits TESTOSTERONE production, not the reduction of testosterone to DHT. It has similar efficacy though, but on total T, not DHT.

[Lotus]

Thanks for the follow up Abi, good luck, I hope it works.

[AbiDrew85]

How much were you using exactly in milligrams? You mentioned a capsule count, not a mg dose. Bassett's has literally dozens of reishi products in it's inventory list, and that's the place I can send the BF to.

[Lotus]

How much were you using exactly in milligrams? You mentioned a capsule count, not a mg dose. Bassett's has literally dozens of reishi products in it's inventory list, and that's the place I can send the BF to.

I started with capsules (swansons, 400-500 mg) I went up in potencies till I switched to extracts, which I felt the extracts work better (for me). 4x a day I think lines up with hormone release and half-life pharmacokinetics, as you most likely already know.

Reishi
http://www.swansonvitamins.com/reishi