Pes Erase

[elanma]

purtroppo nn sono riuscito a trovare nulla sulla farmacocinetica/farmacodinamica,quindi nn so nemmeno se sia suicida...ho trovato solo l ic50 come paragone...le info sono praticamente nulle

il peso molecolare del dhaa è simile all arimistane(rispettivamente 284,39 e 300,44)quindi l IC50 è relamente migliore,ma senza le altre info è comletamente inutile

[Karmelo90]

Estrogen


Isolation and biological activities of neomyrrhao... [Planta Med. 2009] - PubMed - NCBI

Isolation and biological activities of neomyrrhaol and other terpenes from the resin of Commiphora myrrha.

Su SL, Duan JA, Tang YP, Zhang X, Yu L, Jiang FR, Zhou W, Luo D, Ding AW.
Source

Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, PR China.

Abstract

A new cycloartane-type triterpene named cycloartane-1alpha,2alpha,3beta,25-tetraol (neomyrrhaol) (1), along with four known terpenes, sandaracopimaric acid (2), abietic acid (3), 2-methoxy-5-acetoxyfruranogermacr-1(10)-en-6-one (4), and dehydroabietic acid (5) have been isolated from the resin of COMMIPHORA MYRRHA. Their structures were elucidated by means of 1D, 2 D NMR and HR-mass spectroscopy. Compounds 2-5 are known compounds but not previously isolated from the resin of C. MYRRHA. Compounds 4 and 5 exhibited significant aromatase inhibiting activity with IC50 values at 0.2 microM and 0.3 microM, respectively. As shown in the MTT assay, 2, 3, 4, and 5 had inhibitory effects on HUVEC growth with IC50 values of 0.122 microM (2), 0.125 microM (3), 0.069 microM (5). Compounds 1-5 did not inhibit contraction of the isolated uterine and did not protect HUVEC from damage induced by H2O2 at the tested concentration.





IC50 means the concentration which inhibits half of the aromatase enzyme. So the lower the IC50, the more potent the aromatase inhibition.


The IC50 of dehydroabietic acid is 0.3 mu. M. (mu = micro). This is in comparison to an IC50 of 6.5 mu for 3-OHAT, 0.43 mu for 6-oxo, and 0.6 mu of formestane. The lower the IC50, the more potent the compound is at inhibiting aromatase. The previous rendition of Erase used a compound with a slightly lower IC50 value, but it was very close, making this a moot point. Why? Because one can simply use a higher dose of DHAA (>75 mg per day) to compensate and exceed the differences in potency. DHAA also comes with several additional effects (read below).





Remember, lower IC50 = more potent.






In vivo: In fish, DHAA has an anti-estrogenic effect that is actually unfavorable because this obviously disrupts female reproduction in fish, which means less offspring, which means less fish in the food supply. This occurs at the level of the estrogen receptor, adding a second layer to the previously mentioned MOA of aromatase inhibition. Whether or not this carries over to healthy human male, non-carcinoma cells is unknown.


Fat Loss, Blood Glucose, and Triglycerides


Dehydroabietic acid, a diterpene, improve... [Biofactors. 2009 Sep-Oct] - PubMed - NCBI


Dehydroabietic acid, a diterpene, improves diabetes and hyperlipidemia in obese diabetic KK-Ay mice.


Kang MS, Hirai S, Goto T, Kuroyanagi K, Kim YI, Ohyama K, Uemura T, Lee JY, Sakamoto T, Ezaki Y, Yu R, Takahashi N, Kawada T.


Source


Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
Erratum in
Biofactors. 2010 May-Jun;36(3):240.


Abstract


Terpenoids, which are contained in a large number of dietary and herbal plants, have many biological effects. In this study, the effects of dehydroabietic acid (DAA), a diterpene, on glucose and lipid metabolism were examined using obese diabetic KK-Ay mice. We showed here that DAA treatment decreased not only plasma glucose and insulin levels but also plasma triglyceride (TG) and hepatic TG levels. To examine the mechanism underlying the effects of DAA, the production of inflammatory cytokines was measured. It was shown that the DAA treatment suppressed the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFalpha) (proinflammatory cytokines) and increased that of adiponectin (an anti-inflammatory cytokine). As a result of the changes in the production of inflammatory cytokines caused by the DAA treatment, the accumulation of macrophages in adipose tissues was reduced. These results indicate that treatment with DAA improves the levels of plasma glucose, plasma insulin, plasma TG, and hepatic TG through the decrease in the macrophage infiltration into adipose tissues, suggesting that DAA is a useful food-derived compound for treating obesity-related diseases.








Summary:


1. In the above figures, "beza" is a pharmaceutical used to lower triglycerides and "pio" is a pharmaceutical used to lower glucose/insulin.


2. Dehydroabietic acid was roughly as effective as the clinical drug "pio" in reducing blood glucose.


3. Dehydroabietic acid was roughly as effective as the clinical drug "beza" for lowering triglycerides.


4. Dehydroabietic acid is orally bioavailable in mammals.


5. Dehydroabietic acid reduces various inflammatory markers like MCP-1 and TNF-alpha, which are associated with, among other things, obesity and joint disorders/pain.


6. Dehydroabietic acid elevates adiponectin, a hormone produced by lean, low bodyfat humans primarily that keeps insulin sensitivity high.








Dehydroabietic acid activates peroxisome ... [Biofactors. 2011 Jul-Aug] - PubMed - NCBI


Dehydroabietic acid activates peroxisome proliferator-activated receptor-γ and stimulates insulin-dependent glucose uptake into 3T3-L1 adipocytes.


Takahashi N, Yao R, Kang MS, Senda M, Ando C, Nishimura K, Goto T, Hirai S, Ezaki Y, Kawada T.


Source


Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.


Abstract


Dehydroabietic acid (DAA) is a food-derived terpenoid with various bioactivities. Our previous study has revealed that DAA activates peroxisome proliferator-activated receptor-γ (PPARγ) in luciferase assay and suppresses chronic inflammation in obese adipose tissues. In this study, we examined the effects of DAA on adipocyte differentiation. DAA treatment stimulated the adipocyte differentiation of 3T3-L1 preadipocytes. The DAA treatment increased the mRNA expression levels of adipocyte differentiation marker genes such as aP2, lipoprotein lipase (LPL), and PPARγ. In particular, the expression level of adiponectin, which is an adipocytokine with stimulatory effects on insulin sensitivity, was increased at both the mRNA and protein levels by the DAA treatment. Moreover, the DAA treatment stimulated insulin-dependent glucose uptake into differentiated 3T3-L1 adipocytes. These findings indicate that DAA stimulates adipocyte differentiation and insulin sensitivity in 3T3-L1 cells, suggesting that DAA is a valuable food-derived compound for the management of metabolic syndrome.









Summary:


1. Of all the tested compounds, dehydroabietic acid had the highest affinity for all three PPARs. Few compounds, both in nature and in pharmaceuticals, are known to stimulate all three PPAR receptors.


For those who don't know what the PPARs do, here is a summary from wikipedia:


"PPARα and PPARγ are the molecular targets of a number of marketed drugs. For instance the hypolipidemic fibrates activate PPARα, and the anti diabetic thiazolidinediones activate PPARγ. The synthetic chemical perfluorooctanoic acid activates PPARα while the synthetic perfluorononanoic acid activates both PPARα and PPARγ. Berberine activates PPARγ."


Examples of other PPAR agonists: TTA, berberine, etc.












Dehydroabietic acid, a phytochemi... [Biochem Biophys Res Commun. 2008] - PubMed - NCBI


Dehydroabietic acid, a phytochemical, acts as ligand for PPARs in macrophages and adipocytes to regulate inflammation.


Kang MS, Hirai S, Goto T, Kuroyanagi K, Lee JY, Uemura T, Ezaki Y, Takahashi N, Kawada T.


Source


Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.


Abstract


Obesity is characterized by an enhanced infiltration of macrophages to adipose tissues, which is closely associated with the low-grade inflammatory state and obesity-related pathologies such as type 2 diabetes and cardiovascular diseases. We showed here that dehydroabietic acid (DAA) is a potent PPARalpha/gamma dual activator. Furthermore, we examined the anti-inflammatory effects of DAA in stimulated macrophages and in the coculture of macrophages and adipocytes. DAA significantly suppressed the production of proinflammatory mediators such as MCP-1, TNF-alpha, and NO in stimulated RAW 264 macrophages and in the coculture of RAW 264 macrophages and 3T3-L1 adipocytes. These results suggest that DAA is a valuable medicinal and food component for improving inflammatory changes associated with obesity-related diabetes.


Summary:


1. Further confirmation that dehydroabietic acid modulates multiple PPARs.


2. It has the ability to reduce inflammation associated with obesity, which recent research shows is a significant factor in potentiating metabolic syndrome and other fat-related, unhealthy conditions.




Kang, Min-Sook, Shizuka Hirai, Tsuyoshi Goto, Kayo Kuroyanagi, Joo-Young Lee, Taku Uemura, Yoichiro Ezaki, Nobuyuki Takahashi, and Teruo Kawada. "Dehydroabietic Acid, a Phytochemical, Acts as Ligand for PPARs in Macrophages and Adipocytes to Regulate Inflammation." Biochemical and Biophysical Research Communications369.2 (2008): 333-38. Web.


Kang, Min-Sook, Shizuka Hirai, Tsuyoshi Goto, Kayo Kuroyanagi, Young-II Kim, Kana Ohyama, Taku Uemura, Joo-Young Lee, Tomoya Sakamoto, Yoichiro Ezaki, Rina Yu, Nobuyuki Takahashi, and Teruo Kawada. "Dehydroabietic Acid, a Diterpene, Improves Diabetes and Hyperlipidemia in Obese Diabetic KK-Ay Mice." BioFactors35.5 (2009): 442-48. Web.

[Street]

Ok,ma questa roba in inglese la postò un rappresentante PES su anabolic minds...ergo

[Karmelo90]

yeser!!!!