537 replies to this topic

[mrkosh1]

I have been doing more research on sulforaphane, and I've learned that it is a potent HDAC inhibitor. Interestingly, HDAC inhibitors boost telomerase in normal cells and inhibit it in cancer cells.

 

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https://www.ncbi.nlm...pubmed/11452025

 

Nucleic Acids Res. 2001 Jul 15;29(14):3006-11.

Telomerase activation by histone deacetylase inhibitor in normal cells.

Takakura M¹, Kyo S, Sowa Y, Wang Z, Yatabe N, Maida Y, Tanaka M, Inoue M.

Author information

Abstract

Although telomerase activity is known to be regulated mainly at the level of transcription of the human telomerase catalytic subunit (hTERT) gene, the molecular mechanism underlying tumor-specific expression of telomerase remains unclear. Emerging evidence suggests that reversible acetylation of nucleosomal histones and the resultant changes in the chromatin structure are important processes in gene transcription. In particular, histone deacetylase (HDAC) inhibitors activate the transcription of certain genes by altering the acetylation status of nucleosomal histones. The present study examines the effects of HDAC inhibitor on hTERT gene transcription. Treatment with tricostatin A (TSA) induced significant activation of hTERT mRNA expression and telomerase activity in normal cells, but not in cancer cells. Transient expression assays revealed that TSA activates the hTERT promoter. Furthermore, the proximal 181 bp core promoter of hTERT, which contains two c-Myc and five Sp1 sites, was determined to be the responsible element. Overexpression of Sp1 enhanced responsiveness to TSA, and mutation of Sp1 sites, but not c-Myc sites, of the core promoter of hTERT abrogated this activation. Introduction of the dominant-negative form of the Sp family inhibited TSA activation. These results indicate that HDAC inhibitor activates the hTERT promoter in normal cells, in which Sp1 plays a key role. This finding suggests one way whereby histone deacetylation may be involved in silencing the hTERT gene in normal cells.

 

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And in this paper sulforaphane is tested and determined to be a potent HDAC inhibitor that is active at FAR lower levels than triichostatin A.

 

https://www.google.c...YVI9emxNKiy8ZtA

 

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And the following paper describes how tricostatin A can induce telomerase in normal human cells.

 

https://www.ncbi.nlm...pubmed/11855854

 

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So what does this all mean? It seems to me that we have more evidence that Sulforaphane is a simply amazing molecule that has a multitude of anti-aging, anti-disease, and anti-cancer mechanisms.

 

Here is a question maybe someone can answer: Has Bill Andrews of Sierra Sciences ever ran a screening on sulforaphane to determine its level of telomerase induction?

 

[mrkosh1]

By the way, I just found this link.

 

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https://www.ncbi.nlm...cles/PMC419886/

 

Activation of the Growth-Differentiation Factor 11 Gene by the Histone Deacetylase (HDAC) Inhibitor Trichostatin A and Repression by HDAC3

Xiaohong Zhang, Walker Wharton, Zhigang Yuan, Shih-Chang Tsai, Nancy Olashaw, and Edward Seto^*

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Abstract

Histone deacetylase (HDAC) inhibitors inhibit the proliferation of transformed cells in vitro, restrain tumor growth in animals, and are currently being actively exploited as potential anticancer agents. To identify gene targets of the HDAC inhibitor trichostatin A (TSA), we compared the gene expression profiles of BALB/c-3T3 cells treated with or without TSA. Our results show that TSA up-regulates the expression of the gene encoding growth-differentiation factor 11 (Gdf11), a transforming growth factor β family member that inhibits cell proliferation. Detailed analyses indicated that TSA activates the gdf11 promoter through a conserved CCAAT box element. A comprehensive survey of human HDACs revealed that HDAC3 is necessary and sufficient for the repression of gdf11 promoter activity. Chromatin immunoprecipitation assays showed that treatment of cells with TSA or silencing of HDAC3 expression by small interfering RNA causes the hyperacetylation of Lys-9 in histone H3 on the gdf11 promoter. Together, our results provide a new model in which HDAC inhibitors reverse abnormal cell growth by inactivation of HDAC3, which in turn leads to the derepression of gdf11 expression.

 

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Since sulforaphane is an HDAC inhibitor, not only may it boost telomerase production but may boost production of GDF11!

 

Could aging be mostly -- except for perhaps the accumulation of glucosepane and mitochondrial DNA deletions -- a phenomenon based on too much HDAC activity as we age?

 

[Harkijn]

Interesting finds MRKosh!

This old thread also contains some valuable insights and references:

http://www.longecity...ct-autism-noot/

[mrkosh1]

Here is another paper explaining how Sulforaphane is an HDAC inhibitor. In-vivo, in one cell type, HDAC activity was reduced fifty percent after 68 grams of broccoli sprouts were consumed.

 

https://www.ncbi.nlm...les/PMC2777483/

 

Now, that's a little freaky! 68 grams is a little more than two ounces. That's a little more than half of one four ounce container of broccoli sprouts that are available at supermarkets across the USA. Such a huge decrease has me a little freaked out. Is this much of a decrease a good thing? Well, we know to "normal" cells even high levels of sulforaphane is not very toxic at all, at least in the short term of a week or so. Higher levels (which are unlikely to be achieved in the human body) can be toxic to normal cells.

 

So could there be a sweet spot of sulforaphane consumption that is far below the toxic level that induces NRF2, indirectly boosts the SIRTS, induces hTERT, and induces GDF11?

 

Seriously, this compound seems like a wonder drug.

 

Now I see why the writer on the Self Hacked blog calls it a panacea.

 

I also see why Rhonda Patrick (who is totally awesome and in my opinion needs to be put in charge of the FDA) is so obsessed with it.

 

 

[mrkosh1]

Sulforaphane also blocks myostatin!

 

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http://www.tandfonli....4161/epi.22609

 

Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells

Abstract

Satellite cells function as skeletal muscle stem cells to support postnatal muscle growth and regeneration following injury or disease. There is great promise for the improvement of muscle performance in livestock and for the therapy of muscle pathologies in humans by the targeting of myostatin (MSTN) in this cell population. Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown. Therefore, we aimed to investigate the epigenetic influences of SFN on the MSTN gene in satellite cells. The present work provides the first evidence, which is distinct from the effects of trichostatin A (TSA), that SFN supplementation in vitro not only acts as a HDAC inhibitor but also as a DNA methyltransferase (DNMT) inhibitor in porcine satellite cells. Compared with TSA and 5-aza-2′-deoxycytidine (5-aza-dC), SFN treatment significantly represses MSTN expression, accompanied by strongly attenuated expression of negative feedback inhibitors of the MSTN signaling pathway. miRNAs targeting MSTN are not implicated in posttranscriptional regulation of MSTN. Nevertheless, a weakly enriched myoblast determination (MyoD) protein associated with diminished histone acetylation in the MyoD binding site located in the MSTN promoter region may contribute to the transcriptional repression of MSTN by SFN. These findings reveal a new mode of epigenetic repression of MSTN by the bioactive compound SFN. This novel pharmacological, biological activity of SFN in satellite cells may thus allow for the development of novel approaches to weaken the MSTN signaling pathway, both for therapies of human skeletal muscle disorders and for livestock production improvement

 

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This is getting doubly freaky!

 

[Valijon]

This is getting exciting. Its incredible to discover so many recent substances that can delay or maybe even reverse aging.

[Izan]

Sulforaphane also blocks myostatin!

 

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http://www.tandfonli....4161/epi.22609

 

Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells

Abstract

Satellite cells function as skeletal muscle stem cells to support postnatal muscle growth and regeneration following injury or disease. There is great promise for the improvement of muscle performance in livestock and for the therapy of muscle pathologies in humans by the targeting of myostatin (MSTN) in this cell population. Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown. Therefore, we aimed to investigate the epigenetic influences of SFN on the MSTN gene in satellite cells. The present work provides the first evidence, which is distinct from the effects of trichostatin A (TSA), that SFN supplementation in vitro not only acts as a HDAC inhibitor but also as a DNA methyltransferase (DNMT) inhibitor in porcine satellite cells. Compared with TSA and 5-aza-2′-deoxycytidine (5-aza-dC), SFN treatment significantly represses MSTN expression, accompanied by strongly attenuated expression of negative feedback inhibitors of the MSTN signaling pathway. miRNAs targeting MSTN are not implicated in posttranscriptional regulation of MSTN. Nevertheless, a weakly enriched myoblast determination (MyoD) protein associated with diminished histone acetylation in the MyoD binding site located in the MSTN promoter region may contribute to the transcriptional repression of MSTN by SFN. These findings reveal a new mode of epigenetic repression of MSTN by the bioactive compound SFN. This novel pharmacological, biological activity of SFN in satellite cells may thus allow for the development of novel approaches to weaken the MSTN signaling pathway, both for therapies of human skeletal muscle disorders and for livestock production improvement

 

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This is getting doubly freaky!

How much is needed to get powerful strength gaining effects?

[mrkosh1]

 

Sulforaphane also blocks myostatin!

 

--

 

http://www.tandfonli....4161/epi.22609

 

Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells

Abstract

Satellite cells function as skeletal muscle stem cells to support postnatal muscle growth and regeneration following injury or disease. There is great promise for the improvement of muscle performance in livestock and for the therapy of muscle pathologies in humans by the targeting of myostatin (MSTN) in this cell population. Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown. Therefore, we aimed to investigate the epigenetic influences of SFN on the MSTN gene in satellite cells. The present work provides the first evidence, which is distinct from the effects of trichostatin A (TSA), that SFN supplementation in vitro not only acts as a HDAC inhibitor but also as a DNA methyltransferase (DNMT) inhibitor in porcine satellite cells. Compared with TSA and 5-aza-2′-deoxycytidine (5-aza-dC), SFN treatment significantly represses MSTN expression, accompanied by strongly attenuated expression of negative feedback inhibitors of the MSTN signaling pathway. miRNAs targeting MSTN are not implicated in posttranscriptional regulation of MSTN. Nevertheless, a weakly enriched myoblast determination (MyoD) protein associated with diminished histone acetylation in the MyoD binding site located in the MSTN promoter region may contribute to the transcriptional repression of MSTN by SFN. These findings reveal a new mode of epigenetic repression of MSTN by the bioactive compound SFN. This novel pharmacological, biological activity of SFN in satellite cells may thus allow for the development of novel approaches to weaken the MSTN signaling pathway, both for therapies of human skeletal muscle disorders and for livestock production improvement

 

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This is getting doubly freaky!

How much is needed to get powerful strength gaining effects?

 

 

If I remember correctly, myostatin was inhibited strongly at 5 umol, but the inhibition began at 1 umol. To achieve around 2 umol in-vivo in plasma, four or five ounces of sprouts is enough. Probably less would be enough if you heated them to 60C-70C for a couple minutes first to destroy the enzyme that would produce inactive nitrils. I don't think any in-vivo human testing have been done (the above testing was done in pigs), but I think the results would transfer over.

 

The really cool thing about sulforaphane is that you can get very good results with VERY low toxicity in "normal" cells until the 10 umol range. Beyond that, limited toxicity starts to build, but the toxicity is FAR FAR less to human cells than it is to cancer cells. Some cancer cells -- although probably not all -- seem to die very rapidly around 10umol or above. However, the cytotoxic effects on cancer cells begin all the way down at 1 umol.

 

Literally, sulforaphane is turning out to be an almost miraculous substance with MANY different benefits. My hope is that it can be enhanced EVEN MORE by providing optimal levels of nictinamide riboside. In humans, NQO1 controls the ratio of NAD+ to "spent" NAD, because it recycles the used NAD back into NAD+. Sulforaphane activates NQO1 POWERFULLY even at LOW umol levels. So if you are taking NR with sulforaphane, your NAD+ levels should increase dramatically. My hope is that would further boost PCG1a to POWERFULLY stimulate telomerase.

 

I'm dreaming of a sulforaphane, nicotinamide riboside, and high polyphenol extra virgin olive oil serum that I could take every day!

 

My guess is that it would do more for lifespan than C60 and olive oil.

 

 

[BieraK]

Yep Sulforaphane has many positive biological effects, HDAC inhibition, Myostatin inhibition, Nrf2 induction and so on.

The only problem with Nrf2 induction is the inhibition of Melanogenesis, so probably you are at risk of acelerating gray hair

http://journals.plos...al.pone.0096035
https://www.ncbi.nlm...pubmed/20208349

The same happens with other activators of Nrf2, such as Andrographis Paniculata which contains Andrographoline a compound that also activates the Nrf2 in a very powerful way and also possesses potent anti-carcinogenic effects, with good absorption profile, Combining andrographolide and sulforaphane could produce a notorious effect.

 

I have not seen all the videos that have posted, but looking on the internet I wonder why not buy extracts of broccoli that have glucoraphanin and then consume them with mustard seeds in powder like the following video says?
http://nutritionfact...oking-broccoli/

Edited by BieraK, 17 January 2017 - 12:52 AM.

[mrkosh1]

I am not too concerned about normal doses of sulforaphane inducing hair graying. That wasn't a reported side effect in the sulforadex trials so far. Also, Rhonda Patrick has absolutely wonderful hair, and in the videos I cannot see any gray strands. She consumes a ton of sulforaphane every day (probably as much as someone that is on sulforadex) and has been doing so for many months or longer. It is possible that it could take place, but I don't think it is likely.

 

Sulforaphane does seem like it can help with many issues of aging. The following areas concern me a little.

 

1) Telomerase Induction: There are multiple mechanisms by which sulforaphane should activate telomerase. For example, the endogenous anti-oxidants will help spare telomerase and prevent shorting of telomeres by free radicals. Secondly, there are studies that show sulforaphane (perhaps not directly) activates PGC1a which activates telomerase. Third, sulforaphane is an HDAC inhibitor that can activate telomerase. There are a very few studies that do show that it can produce telomerase in some non-cancerous "normal" cell types. In one study, sulforaphane allowed cells to bypass, by a few doublings, the Hayflick limit. However, the effect of inhibiting telomerase in cancer cells seems much stronger than inducing telomerase in normal cells. If sulforaphane is not a strong inducer, then we may need to find another substance that could help in this area.

 

2) Glucosepane Breaking/Removal: I have seen nothing that indicates that sulforaphane would have any effect on glucosepane.In my guess, these almost impossible to remove (by ordinary biology) compounds might be part of what would stop substances like sulforaphane from extending maximum lifespan significantly.

 

3) Mitochondrial DNA Repair: I'd like to see how effective sulforaphane is in this regard. The good thing is that it does stimulate genes that are involved with mitochondrial protection and biogenesis.

 

 

[mrkosh1]

To answer your question about broccoli powder, the production of sulforaphane is less efficient inside of the gut than if you produce the sulforaphane before hand and consume it. If I remember correctly, the efficiency of sulforaphane production from the precursor is around 10% average (with wide swings from person to person) if you just consume the powder with no active myrosinase, 30% if you consume powder with myrosinase, and around 70% or higher if you consume the sulforaphane (for example blending the sprouts before hand).

 

 

[Valijon]

Someone was asking about myostatin. I was extremely interested in myostatin inhibitors many years ago. Iirc there were two main problems with them at the time. One was nose bleeds and the other was heart enlargement. Its be great if broccoli sprouts had similar effects without the horrific sides.

[mrkosh1]

Valijon,

 

Interestingly, sulforaphane seems to inhibit myrostatin while inducing GDF-11. In the lab, GDF-11 reduced the size of enlarged hearts in animals. In addition, sulforaphane can increase and modulate (not fully understood yet) mitochondrial biogenesis by inducing PGC1a among other proteins. Sulforaphane has also proven to protect heart cells in-vitro (maybe in-vivo too but I can't remember) as long as the concentration of sulforaphane was not too high. Above 10 umol, there is some toxicity towards just about any cell type, even "normal" cells. Of course it is MUCH less toxicity than towards cancer cells. What's exciting to me is that positive effects seem to take place at levels as low as 1 umol to 5 umol, which are realistically attainable by four ounces of broccoli sprouts heated to 60C for a few minutes, blended, allowed to sit (to facilitate the conversion process to take place), and consumed.

 

I think we've only seen the tip of the iceburg when it comes to the huge amount of research on sulforaphane that will be appearing in the next few years. I'm EXTREMELY curious about how it would interact with Nicotinamide Riboside to boost NAD+ levels, since sulforaphane induces NQO1 which recycles spent NAD into NAD+.

 

We also need to know if sulforaphane has any long term negative side effects at lower doses. Most likely, if there are any, they are weak because a diet of carniferous vegetables is related to longevity.

[Valijon]

Mrkosh,

This just gets better and better. It sounds like we at longecity are way ahead of the curve. Sulphoraphane sounds like the direction the big pharmacutical companies should have been going this whole time.

[mrkosh1]

Valijon,

 

We are very ahead of the curve. The problem is taking this information and having some relatively simple experiments confirmed to validate the conjectures that emerge. For example, we know NR boosts NAD+ in human beings in-vivo. However, as far as I know, there has never been a test -- even in lab animals -- of a combination of NR and sulforaphane OR a combination of NR and R-Alpha Lipoic Acid (another molecule that boosts NRF2 and NQO1). The problem is that probably very few people on this board (if any) have the means to perform the testing themselves OR the funds to have someone else perform it. These are relatively SIMPLE tests that could tell us a LOT. But the lack of hardly *any* resources gets in the way.

 

This is the same problem I've ran into with other areas I'm interested in. There are people "ahead of the curve" and could produce amazing results with a tiny miniscule fraction of the money big companies have at their disposal, but they find it very difficult to aquire any funding at all! Then there are another minority of people who DO have the money, skill, and equipment but DO NOT HAVE THE TIME!

 

To be blunt, although I'm VERY excited about the breakthroughs that are coming out, I'm equally as discouraged by the lack of ability to perform some relatively simple tests. For example, I know an individual who is close to a breakthrough in a totally different field. He has his own lab, equipment, skill, and experience. But for the last few months he's had one family tragedy after another in addition to semi-serious health problems. Since he has almost no help whatsoever (except for the occasional visitor to stops by for a few hours and doesn't come back for weeks) some very simple tests are not being performed.

 

I don't know what the solution is to this problem.

[Valijon]

As we know, nothing gets done without a big monetary incentive. Last thing I read was $1 billion and ten years to bring any new drug to market. Supplementation would be faster, we just need someone who could make a decent profit to put some money into r and d.

The problem I have with the supplement market is insufficient research. They often take one small bit of information and run wild with it. Hocking products that might actually do little to nothing in the human body.

Perhaps some research grants at bigger universities would help? We could also try crowdfunding. We run into the problem of not being able to offer a product to the people who would be interested in donating. We need to convince people that aging can be slowed down and we aren't trying to con anyone.

[mrkosh1]

As we know, nothing gets done without a big monetary incentive. Last thing I read was $1 billion and ten years to bring any new drug to market. Supplementation would be faster, we just need someone who could make a decent profit to put some money into r and d.

The problem I have with the supplement market is insufficient research. They often take one small bit of information and run wild with it. Hocking products that might actually do little to nothing in the human body.

Perhaps some research grants at bigger universities would help? We could also try crowdfunding. We run into the problem of not being able to offer a product to the people who would be interested in donating. We need to convince people that aging can be slowed down and we aren't trying to con anyone.

 

Valijon,

 

Or we need a way to do testing and experimentation even more cost effectively. For example, is there a lab anywhere that can you can send blood samples too that can measure NAD+ levels? If so, volunteers could submit blood samples after supplementing with various supplements and combinations of supplements. If we were to find a big spike in NAD+ or expression of various proteins, then we would have a target to focus on.

[Valijon]

I know next to nothing about sending in home based blood samples to any labs. This is a very good idea though. We would need a decent sample size. Of all the ideas presented, this would be the fastest. Any idea who we would contact to get this started? I'm not adverse to having my blood drawn. You want a trained phlebotomist to do it. Its a shame we can't do swabs. Get a lot more volunteers that way.

[mrkosh1]

Valijon,

 

We would need a group of people all willing to take the same supplement(s) at the same dosage after a period of fasting. Also, we need to know how much blood would be required. If it is only a small amount, then I wonder if someone could prick their fingers (like someone with diabetes does) and let the blood drip into a tiny vial (before and after taking the supplements). Then I expect they'd have to package the blood in dry ice for shipment. Then, as you said, we would need a lab that could run the tests at a reasonable cost. If it would require a phlebotomist, that could be a major problem.  I don't know if a swab would work for testing NAD+ content, gene expression (such as PGC1a or NRF2 or the SIRTs), etc.

 

Alternatively, it would be interesting to figure out the minimal amount of equipment required to perform these tests. If it was portable, a single person could travel around to the volunteers OR the equipment could be shipped from person to person -- if they would be qualified to perform the testing themselves.

 

If this is a concept that could work, I think it would be very interesting to put a group together of volunteers who'd cooperate to get something like this started. Right now, just blindly taking supplements, we are shooting in the dark. But this way we could perhaps find combinations that are highly synergistic.

[mrkosh1]

I just found another interesting benefit of sulforaphane!

 

Here is an article about how the protein VCAM1 is a cause of brain aging.

 

https://www.fightagi...l-in-old-blood/

 

Guess what inhibits VCAM1?

 

Sulforaphane!

 

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http://www.fasebj.or...nt/656.16.short

The inhibitory effect of sulforaphane on the expression of VCAM-1 in vascular smooth muscle cells

1. JI YUN KIM,
2. Dong-Kwon Rhee and
3. Suhkneung Pyo

+ Author Affiliations

1. Sungkyunkwan Univ., Suwon, Korea, Republic o

Abstract

Atherosclerosis is a chronic inflammatory disease of the large arteries. Since inflammation involves an upregulation of various adhesion molecules, inhibiting the expression of adhesion molecules can be a critical therapeutic target of inflammatory disease. Sulforaphane has been demonstrated to have a variety of biological effects including anti-inflammatory activity; however, its molecular mechanisms are poorly understood. Here we investigate the effect of sulforaphane on the expression of the vascular cell adhesion molecule(VCAM-1) induced by TNF-α in cultured vascular smooth muscle cells. Cell adhesion assay and western blot analysis revealed that preincubation of VSMCs for 2 h with sulforaphane (1–5μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of vascular cell adhesion molecule-1 (VCAM-1). In addition, flow cytometry analysis showed that sulforaphane attenuated TNF-α induced production of intracellular reactive oxygen species (ROS). The present data also demonstrated that sulforaphane inhibited the phosphorylation of p38, ERK, JNK and the activation of NF-κB and AP-1 induced by TNF-α. Overall, our results suggest that sulforaphane inhibits the adhesive capacity of VSMCs and downregulates the TNF-α-mediated induction of VCAM-1 in VSMCs by inhibiting the MAPK/NF-κB/AP-1 signaling pathway and ROS production.

 

http://www.fasebj.or...nt/656.16.short

 

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https://www.ncbi.nlm...icles/27681094/

 

Inhibition of STAT3 Phosphorylation by Sulforaphane Reduces Adhesion Molecule Expression in Vascular Endothelial Cell

YS Cho et al. Can J Physiol Pharmacol 1-7. 2015 Nov 18. more

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Abstract

Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.

 

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https://www.ncbi.nlm...pubmed/22155163

 

Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells: involvement of the MAPK, NF-κB and AP-1 signaling pathways.

Kim JY¹, Park HJ, Um SH, Sohn EH, Kim BO, Moon EY, Rhee DK, Pyo S.

Author information

Erratum in

• Vascul Pharmacol. 2013 Jan-Feb;58(1-2):157.

Abstract

Atherosclerosis is a long-term inflammatory disease of the arterial wall. Increased expression of the cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is associated with increased proliferation of vascular smooth muscle cells (VSMCs), leading to increased neointima or atherosclerotic lesion formation. Therefore, the functional inhibition of adhesion molecules could be a critical therapeutic target of inflammatory disease. In the present study, we investigate the effect of sulforaphane on the expression of VCAM-1 induced by TNF-α in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2h with sulforaphane (1-5μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-α-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-κB and AP-1 activation induced by TNF-α. Sulforaphane inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα and nuclear translocation of p65 NF-κB and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-κB and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion.

 

[Valijon]

Thanks for the new information in the links above. I just can't see people doing this at home, too much trouble. Your need a clinical trial to get this going more.

[mrkosh1]

Here is another article about Sulforaphane. In this article, it discusses how sulofraphane can improve muscle mass, muscle strength, and reduce hypertrophy in heart size in mice with muscular dystrophy.

 

Maybe I'm wrong, but it seems to me that sulforaphane is performing in a similar manner to Heterochronic parabiosis.

 

Perhaps instead of getting expensive blood transfusions, people could just grow a few ounces of sprouts and consume them each day?

 

Also, I'd like to see how having more NAD+ from NR would increase these benefits.

 

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http://jap.physiolog...ntent/118/2/224

 

Sulforaphane alleviates muscular dystrophy in mdx mice by activation of Nrf2

Chengcao Sun, Cuili Yang, Ruilin Xue, Shujun Li, Ting Zhang, Lei Pan, Xuejiao Ma, Liang Wang, Dejia Li

Journal of Applied Physiology Published 15 January 2015 Vol. 118 no. 2, 224-237 DOI: 10.1152/japplphysiol.00744.2014

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Abstract

Sulforaphane (SFN), one of the most important isothiocyanates in the human diet, is known to have chemo-preventive and antioxidant activities in different tissues via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of SFN on Duchenne muscular dystrophy. Four-week-old mdx mice were treated with SFN by gavage (2 mg·kg body wt⁻¹·day⁻¹ for 8 wk), and our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 with a Nrf2-dependent manner. SFN significantly increased skeletal muscle mass, muscle force (∼30%), running distance (∼20%), and GSH-to-GSSG ratio (∼3.2-fold) of mdx mice and decreased the activities of plasma creatine phosphokinase (∼45%) and lactate dehydrogenase (∼40%), gastrocnemius hypertrophy (∼25%), myocardial hypertrophy (∼20%), and malondialdehyde levels (∼60%). Furthermore, SFN treatment also reduced the central nucleation (∼40%), fiber size variability, and inflammation and improved the sarcolemmal integrity of mdx mice. Collectively, these results show that SFN can improve muscle function and pathology and protect dystrophic muscle from oxidative damage in mdx mice associated with Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

 

[e Volution]

I've been supplementing BroccoMax by Jarrow Formulas after a combination of listening to Dr Rhonda Patrick's podcasts, and moving to a city with pollution levels higher than I would like. I'd love to know what the best supplement is currently (easily) available on the market right now. I do plan to get into the broccoli seeds/sprouts route at some point but too busy right now. 

[mrkosh1]

The best supplement is probably going to your grocery store, talking to your produce manage to find out the exact day their sprouts arrive, and make arrangements to buy some every time a new produce truck arrives.

 

I'm highly surprised about the quantity of sulforaphane that can be obtained by eating (zero processing) around four ounces of raw broccoli sprouts. On the very low end, they will contain around 30 milligrams of sulforaphane. Other studies I've read have given estimates of twice that amount or more from about two ounces. Basically, the content in sprouts is variable (depending upon the cultivar and growing conditions and how long they were allowed to grow) but it can be very significant.

 

Just consuming about four ounces of sprouts have pushed some people's plasma content of sulforaphane to 2 umol or slightly higher. Other people end up having less in their plasma. Again, this is highly variable. To optimize this, soaking for four minutes in 60C water and then blending them and allowing the sulforaphane to form in the blender will maximize the sulforaphane. Since the heating process can almost triple the amount of sulforaphane formed and blending it would increase it more, literally just one ounce might be all you need for a modest dose of sulforaphane!

 

What I've been finding online is that the beneficial effects of sulforaphane on "normal" cells and stem cells seem to be maximized at levels that are almost always below 5umol. I know that you cannot exactly compare in-vitro data to in-vivo data, but going by many in-vitro tests, above 5umol is where cytotoxic effects can start showing up. Interestingly, I've read a couple papers on the effects on non-cancerous stem cells where the optimum is 1 umol or lower!

 

We really need more human trials to learn the optimum dosage in humans. Right now, it is just a guess. When I start consuming sprouts, I think I'm going to stick with one (or a maximum of two) ounces heated to 60C and blended.

 

 

[Harkijn]

Broccoli sprouts are no doubt number one.But as an additional means of keeping up sulforaphane levels I would like to sing a song of praise for the humble watercress. No processing is needed: just rinse, cut, wait and eat as a salad , perhaps together with some mustard powder. Delicious!

 

An interesting aside: elsewhere on this website Reason today points to an animal study that links aging to a large extend to cumulative damage to pericytes in the gut. The researchers say the search is now on for substances that protect our pericytes.

http://en.dgist.ac.k...contentNo=33894

 

But we know that a very good candidate is sulforaphane, as documented by you in this thread. For completeness' sake I add a link about this:

http://www.sciencedi...271531714001481

[mrkosh1]

No processing is required for broccoli sprouts either. Just chewing them very well is enough. However, when I start sprouting, I'll want to get the most for every dollar of seeds I purchase. So to get the most sulforaphane, I'll pre-process them. Basically, if the numbers in the literature are close to being correct, it could allow for someone to get the same health benefits from one ounce of sprouts as they normally would from four or maybe five. 

[Nate-2004]

I just started on broccoli extract, especially considering that I *hate* broccoli. It tastes the worst of all things I have ever eaten. I have that dreaded gene that causes people to find green vegetables bitter. I'll be trying this out for the next 30 days and will let you know how it goes. For reference, here is what I bought.

Edited by Nate-2004, 20 January 2017 - 06:31 AM.

[albedo]

 

 

Is it possible to supplement a broccoli extract with myrosinase enzymes in case it doesn't include it?
I've ordered two brands with sulforaphane, one including a bland with these enzymes and the other only sulforaphane from extract, so would it be effective in getting benefits from the latter if I take it with the former?

This one is advocated by Fahey in the Rhonda Patrick interview: http://www.nutramaxs...a-day-p430.aspx

I've not tried it but am tempted. Another strategy is to grind broccoli seeds and disguise them in a meal or smoothie.

 

 

Also consider the  French supplement which performed very positively on Fahey's trials: http://www.prostapha...rostaphane.html

It is not available in US yet though as he said during the (excellent) interview.

 

I am going to give this a try: http://www.prostaphane.com/. As focus seems in particular on prostate health and I keep a log of both inflammation and PSA biomarkers maybe I can use those to monitor a possible impact. Have you considered the other possible clinically relevant biomarkers you can look at? Thanks.

[mrkosh1]

This is the reference I have been about how broccoli seeds should be sprouted.

 

http://www.superfood...coli-seeds.html

 

Broccoli seeds themselves actually have substantially high levels of glucoraphanin, but additionally contain the antimetabolite erucic acid which inhibits its absorption if consuming the seeds directly. This acid is broken down during the sprouting process, in turn making the sprouts a viable source of this sulforaphane-producing antioxidant compared to the seeds or the more mature versions of the plant.

 

https://sweetwaterhr...ag/erucic-acid/

 

Rape is a member of the mustard/cabbage family. It has pretty, bright yellow flowers. It’s grown for its seeds—but unprocessed rapeseed has never been used for food, as has mustard seed. That’s because the seeds contain as much as 45% erucic acid, which is a poison. Insects won’t eat the seeds, and natural, unprocessed rapeseed is poisonous to humans and other animals. It causes deposits of fatty acids in the heart and thickening of the cardiac walls, which can lead to valve dysfunction and heart failure. Erucic acid can cause these effects even in quantities as small as 2%, which is the percentage of erucic acid allowed in canola oil in the United States. Rapeseed also contains glycosides, which interfere with thyroid functioning.

 

---

 

It sounds like there is a good reason for growing the sprouts instead of grinding the seeds.

[mrkosh1]

https://eurekamag.co...p?pdf=003705597

 

Determination and Health Implication of the Erucic

Acid Content of Broccoli Florets, Sprouts, and Seeds

 

UTH

ABSTRACT: The erucic acid content of broccoli florets, sprouts, and seeds was found to be about 0.8, 320, and

12100 mg/100 g, respectively. Using the erucic acid limit established for canola oil in the U.S.A. and Canada as

a guideline, the estimated dietary intake of erucic acid from florets and sprouts was considered of little conse-

quence, whereas in seeds a relatively small amount (about 35 g/wk) equaled our calculated exposure limit for

erucic acid. Additionally, the most complete fatty acid distribution yet published for the various forms of broccoli

are presented.

Keywords: broccoli florets, broccoli sprouts, broccoli seeds, erucic acid, fatty acid distributio