Inhibiting 15-pgdh: Taking The Prostglandin Protocol To The Next Level

pegasus2

Senior Member
My Regimen
Reaction score
4,736
Do you guys think if paralyzing immune system fully locally can have the same effect as an antiandrogen? I wonder if we can reduce everything that is coming after DHT like cytokines, prostaglandin ratio etcetc. and many more unexplored pathways

No
 

wislow9

Established Member
My Regimen
Reaction score
24
We now have access to a small molecule, potent inhibitor of 15-PGDH which metabolizes PGE1, PGE2 and PGF2a. It's called SW033291, and is available for purchase here. 15-PGDH is less active against PGD2, but for best effect you would combine this with a potent PGD2 inhibitor like ramatroban, TM30089, or OC000459. Combine these with exogenous PGE2, and you have the ultimate prostglandin protocol. Even better would be dimethyl PGE2, which is more stable and metabolism-resistant. A topical dose of .1% SW033291 should be effective.

If SW033291 by itself increase PGE2 , why you propose to use topical PGE2 or dimethyl PGE2 too ¿?
Prolonged use of PGE2 is not recommended . Can SW033291 works without using PGD2 inhibitors and PGE2 ¿? what do you think ¿?
 

pegasus2

Senior Member
My Regimen
Reaction score
4,736
If SW033291 by itself increase PGE2 , why you propose to use topical PGE2 or dimethyl PGE2 too ¿?
Prolonged use of PGE2 is not recommended . Can SW033291 works without using PGD2 inhibitors and PGE2 ¿? what do you think ¿?

It should work by itself, but it says right in the patent that you can get better results by combining it with prostglandins, and the study I linked in the OP clearly shows that the combination of SW and PGE2 is far more effective than either monotherapy in labor induction, and is similar to dmPGE2. As for PGD2 inhibitors, I don't know how much difference it will make. If you are genetically sensitive to PGD2 then I'd recommend using one, if not I wouldn't bother.
 

jared garnith

Established Member
My Regimen
Reaction score
73
What's the consensus on using exogenous pge2 and minoxidil at the same time? The pge2 I got from kane won't dissolve well in water and minoxidil is one of the only things with ethyl alcohol I can get? Some people said they'd cancel each other out because minoxidil acts on pge1 and would cancel out the pge2 but most studies I've found says it raises pge2 so I'm a bit confused.
 

John Difool

Senior Member
My Regimen
Reaction score
1,309
No surprises here. PGE2 won't dissolve in water. I hope you didn't waste too much of it to find out. Ethanol is fine but stability is limited so you can only do limited batches of a week or so.

I read the same about both cancelling out but I really don't think it matters that much. If you are paranoid about it, pour your pge2 in ethanol : PG 50/50 and use it at different times.
 

jared garnith

Established Member
My Regimen
Reaction score
73
No surprises here. PGE2 won't dissolve in water. I hope you didn't waste too much of it to find out. Ethanol is fine but stability is limited so you can only do limited batches of a week or so.

I read the same about both cancelling out but I really don't think it matters that much. If you are paranoid about it, pour your pge2 in ethanol : PG 50/50 and use it at different times.
Thanks for the reply luckily I didn't waste too much ugh read from a couple places about it dissolving in water but was skeptical should've dug deeper. Do you think vodka would be fine?
 

pegasus2

Senior Member
My Regimen
Reaction score
4,736
On the shipment? It went well. Thanks for checking.

These group buys are a joke. You never get people to commit and it takes forever to gather a few folks to get a little discount.

lol
 

pegasus2

Senior Member
My Regimen
Reaction score
4,736
Here's a good reason to use PGD2 inhibitors when wounding.

PGD2 has the capacity to inhibit follicle regeneration, and that the mechanism of this inhibition is through the Gpr44 receptor

Gpr44 KO mice had a 2-fold increase in regenerated follicles compared with wild-type

Gpr44 antagonists may be beneficial in androgenetic alopecia, our results suggest that formulations of Gpr44 antagonists may decrease scarring during wound healing. A specific example is ramatroban, an orally active, dual Gpr44, and thromboxane A2 receptor antagonist, which is approved in Japan for the treatment of allergic rhinitis in humans (Sugimoto et al., 2003). Future studies could examine the effect of ramatroban in stimulating hair follicle neogenesis.

https://pubmed.ncbi.nlm.nih.gov/23190891/
 
Last edited:

John Difool

Senior Member
My Regimen
Reaction score
1,309
PGD2 inhibitors like ramatroban, TM30089, or OC000459.
I am on TM and I need Melaton 3mg to sleep. Melaton 3 is great for hair. With 200mg of P4 I even have vivid dreams in technicolor.
 

pegasus2

Senior Member
My Regimen
Reaction score
4,736
Insomnia is the most obvious side effect of PGD2 inhibition.

I've been thinking about the potential of using the prostglandin protocol for skin rejuvenation too. After all, PGD2 increases scarring during wound healing, and PGE2 induces regeneration in all kinds of tissue.

inhibiting 15-PDGH can aid in abnormal wound healing. Hypertrophic scars can form after severe burns or poor wound healing conditions lead to excessive proliferation of fibroblasts, producing excessive extracellular matrix. Administration of TD88, a 15-PDGH inhibitor, leads to increased Type IV collagen and decreased wound healing factors (PDGF, CTGF, TIMP-2) at the injury site, preventing the excessive wound scarring that occurs with suppression of PGE2.2 Inhibiting 15-PDGH allows for improved reepithelization on wounded surfaces.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725599/

If anyone has burns or acne scars you may want to give microneedling + SW + PGE2 + TM a try, along with tretinoin and hyaluronic acid. Be careful of cancer though.

15-PDGH knockout mice have been shown to have a 7.6-fold increase in colon tumors and confers carcinogen susceptibility to normally resistant mice, concomitant with a doubling of 15-PGDH
 
Last edited:

John Difool

Senior Member
My Regimen
Reaction score
1,309
For skin I use a combo of versabase cream with Estradiol Estriol Estrone Progesterone melted in a few drops of solvent. Ii added Tretinoid the past month and BETA. Skin is smooth no more acne, pores are shrinking, redness is gone.
 

pegasus2

Senior Member
My Regimen
Reaction score
4,736
Is anyone else using this? I'm curious how well SW+PGE2 alone works with microneedling.

Here's another patent for a first generation 15-PGDH inhibitor for hair growth. They tested it and found it grew hair even without exogenous PGE2, and this is less potent than SW033291. SW is too experimental for most, but the potential of this drug to promote hair growth is hard to match.

Surprisingly, the applicant has now demonstrated that an enzyme which is specifically involved in the degradation of these prostaglandins is present in the dermal papilla of the hair, which is a critical compartment for the life of the hair. Indeed, the applicant has now proved the presence of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) at this level. It has additionally shown that the specific inhibition of 15-PGDH has a beneficial effect on the hair density and/or growth.

https://patents.justia.com/patent/20080206320

"We have developed a drug that acts like a vitamin for tissue stem cells, stimulating their ability to repair tissues more quickly. The drug heals damage in multiple tissues, which suggests to us that it may have applications in treating many diseases."

these benefits emerged without any adverse side effects, even at SW033291 doses much higher than would be required for 15-PGDH inhibition.

SW033291 healed virtually all the ulcers in the animals' colons and prevented colitis symptoms. In mice where two-thirds of their livers had been removed surgically, SW033291 accelerated regrowth of new liver nearly twice as fast as normally happens without medication
Because bone marrow, colon, and liver are significantly different tissues, the investigators believe the pathway by which SW033291 speeds tissue regeneration is likely to work as well for treating diseases of many other tissues of the body.

https://www.sciencedaily.com/releases/2015/06/150611144438.htm

It's been shown to have a strong effect on lung tissue as well in pulmonary fibrosis, and in kidneys. In every cell line it's tried it's been a miracle drug for stem cell proliferation. It's even suggested as a treatment for canities.

https://www.nature.com/articles/s41598-020-68336-0
https://www.frontiersin.org/articles/10.3389/fphys.2020.00138/full

Dr Dusko Ilic of King's College London calls the results remarkable, but is cautious about the potential for tumor proliferation. They hope to use the drug to regenerate livers in liver cancer patients, but he dismisses the idea as too risky:

The drug seems to be too good to be true. The data presented show remarkable improvement in regeneration of multiple tissues. However, the study is performed only in mice and it would be encouraging to see a similar effect in other larger animal before even thinking about clinical trial in humans. What does worry me and curbs my enthusiasm is the fact that all the mouse disease models are actually otherwise healthy animals. For example, they show that after resection of two-thirds of the liver mass, mice treated with the experimental drug show increased rate of regeneration as compared with control. When would one remove 2/3 of liver in human patients? The most often is in a case of malignant tumour. Giving drug to such patients would be too risky – if any tumour cell survived, it is likely that their proliferation would be potentiated. Thus, we may end up causing more harm to the patients. The drug might be more useful in patients who have had part of their liver removed after trauma-related injury, rather than from a tumour, but the same issue would still apply and we would have to be sure that nothing else was wrong with any organ in the body."

Prof. Alison at QMUL appears more optimistic:

“Although these studies were in mice, all three models are well validated, and with no adverse side-effects in the short-term. Obviously more experimental studies are needed before early clinical trials can start, but if successful, I see no reason why such an approach cannot be translated to the clinic quite quickly. The inhibitor may also have utility in other areas of significant human morbidity, for example, diabetic leg ulcers.”
https://www.sciencemediacentre.org/...n-drug-promoting-tissue-regeneration-in-mice/




 
Top