1079 replies to this topic

[sedentary]

Cell senescence is for the most part a perfectly healthy process. However once they have survived their purpose they turn dysfunctional and start to send out SASP. The ideal senolytic culls selectively the dysfunctional ones.

 

whats the ideal senolytic? sure as hell aint fisetin. and im not sure ill be messing around with senescence since ive read about their importance.

Edited by sedentary, 28 September 2019 - 09:54 PM.

[Michael]

I've moved the studies on aging, cancer, and senescence into the existing thread on this study.

[bhangchai]

 

 

My experience with Fisetin was indicative of one, a known senolytic effect - delayed wound healing: a minor nick on a wart took 5.5hours to clot. 

 

 

 

 

 

 

 

 

I have also noticed a delay of wound healing, but your specific example of a nick not clotting, in my opinion, may only show a difference in ability of blood to clot similar to the effect of taking aspirin...

[MikeDC]

It is not like senescent cells are waiting for you to have a wound so they can help to heal it. Senescent cells are created when you have a wound.

[ambivalent]

It is not like senescent cells are waiting for you to have a wound so they can help to heal it. Senescent cells are created when you have a wound.

 

No this isn't true as I understood it, I don't have the link to hand but it is in the thread, when I have time I will dig it up. Specifically, senescent cells are utilised to signal wound healing it has been documented iirc. There was a senolytic drug used  in the 80s from which patients had bled to death. I quickly found a paper (which I can't link) titled: An essential role senescent cells for optimal wound healing through secretion of PDF-GAA

 

which is consistent with your observation of s-cells created* and then utilised to heal wounds, but for your claim to be complete, it would rather suggest then senolytics are active in preventing the creation of senescent cells some time after administration, not just there in the clean up process. Either way it is a risk. 

 

* assuming that is what is meant by 'appear'.

 

@bhangchai that may well be true, though I've not experienced it, but I didn't take any aspirin.

[sedentary]

interesting study; https://www.nutraing...ve-decline-risk

it seems to associate consumption of pelargonidin, but not fisetin with reduced cognitive decline. ill assume its combination of probably this and that plus many more to be found in the next 20 years. so, why would someone just buy fisetin by itself and use it? makes no sense to me, sorry

[lost69]

https://www.actinovo...aqs#Customizing

 

they require 10L minimum, are there members interested in getting liposomal fisetin?

 

i asked them the cost of custom production liposomal fisetin

[lost69]

https://www.actinovo...aqs#Customizing

 

they require 10L minimum, are there members interested in getting liposomal fisetin?

 

i asked them the cost of custom production liposomal fisetin

 

they just answered to my request and they require 5L order as a minimum.i guess if few members make single orders to reach 5L we can get it done.

group orders are too messy and it s not worth it
 

[JR7]

they just answered to my request and they require 5L order as a minimum.i guess if few members make single orders to reach 5L we can get it done.

group orders are too messy and it s not worth it
 

I would buy 

 

 

Edited by JR7, 05 October 2019 - 09:45 PM.

[Oakman]

I would buy 

 

I might, but at what cost?

[Krell]

https://www.actinovo...aqs#Customizing

 

they require 10L minimum, are there members interested in getting liposomal fisetin?

 

i asked them the cost of custom production liposomal fisetin

 

Interested depending on cost
 

[tintinet]

https://www.actinovo...aqs#Customizing

 

they require 10L minimum, are there members interested in getting liposomal fisetin?

 

i asked them the cost of custom production liposomal fisetin

 

 

Interested

[lost69]

i asked the cost, after we have the cost i will ask if it is possible to make many single prepaid orders to reach 5L

 

i made a group order for stearic acid from sigma aldrich and i don t have time for such a thing again so i hope they can do single prepaid orders

[Ms02138]

Also perhaps interested--like everyone, wondering what the price would be?

 

[Andey]

Interested

[Andey]

Their common price is around 25 euro for 250ml of solution.

For a quercetin(similar compound) 250 ml contains 6.25 grams of it. 

6.25 of Fisetin if bought from Swanson at retail prices would be around 24$.

 

Looks like it could cost below 50 euro then, but it depends whether they would apply some markup for a custom substance and processing. 

[ambivalent]

Given my MO, I am naturally interested too; however, I would like to query the rationale given we seem to have sufficient bio-availability to subvert the healing process, is it sensible to reach deeper than this? 

[Oakman]

Their common price is around 25 euro for 250ml of solution.

For a quercetin(similar compound) 250 ml contains 6.25 grams of it. 

6.25 of Fisetin if bought from Swanson at retail prices would be around 24$.

 

Looks like it could cost below 50 euro then, but it depends whether they would apply some markup for a custom substance and processing. 

 

There's a much, much less expensive alternative to Swanson I've found.

 

https://www.amazon.c...70457096&sr=8-6

 

For, say, 10 grams (of 50% Fisetin powder), $12.50 for $2.50/g actual Fisetin, or 100 grams @$87, or $1.74/gram, or even less, $1.34/ gram @ 500 grams

 

Perhaps lipo Fisetin is more bioavailable, but at these prices, why not just take more regular, rather than spending $$$ just to get extra bioavailability?

[sedentary]

whats the other 50% in there?

[Oakman]

whats the other 50% in there?

If you go to purebulk, you can see the label that says..per serving...

 

Fisetin 150 mg 
(from 300 mg Cotinus Coggygria P.E.) (branch)

[lost69]

answer you have to sign a non disclosure agreement before we send quotation, so we go nowhere

 

i use swanson, it is 3000mg per bottle 12usd, 5000mg (only 50% is fisetin) 87usd, if i m correct swanson is the cheapest

 

fisetin source is Novusetin®, the same for swanson or drbest.i buy other stuff from pure bulk not fisetin

[Oakman]

answer you have to sign a non disclosure agreement before we send quotation, so we go nowhere

 

i use swanson, it is 3000mg per bottle 12usd, 5000mg (only 50% is fisetin) 87usd, if i m correct swanson is the cheapest

 

fisetin source is Novusetin®, the same for swanson or drbest.i buy other stuff from pure bulk not fisetin

 100 grams equaling 50 grams fistein @$87 .... not 5000 mgs

[lost69]

 100 grams equaling 50 grams fistein @$87 .... not 5000 mgs

 

oh you right, purebulk definitely the cheapest.

 

did anybody got some kind of test using purebulk?

 

i got BP lowering (130/90 to 90-70) and high sensibility C reactive protein lowering (last result 0.16).but now they stay there even if i stay weeks without senolytics so i can t check purebulk.fisetin dose 0.6g for 3 days but added other senolytic supp so confounding factors included

 

did anybody check these on purebulk and got results?anybody tried improving absorption from purebulk?

Edited by lost69, 08 October 2019 - 02:14 PM.

[dlewis1453]

 

 

i got BP lowering (130/90 to 90-70) and high sensibility C reactive protein lowering (last result 0.16).but now they stay there so i can t check purebulk.fisetin dose 0.6g for 3 days but added other senolytic supp so confounding factors included

 

 

 

Hi Lost, 

 

Just to clarify, did you lower your blood pressure from 130/90 to 90/70 by taking just fisetin, or did you take other senolytics as well? 

[lost69]

Hi Lost, 

 

Just to clarify, did you lower your blood pressure from 130/90 to 90/70 by taking just fisetin, or did you take other senolytics as well? 

 

i was taking c60 and gdf11 since 2016, first no effect on BP and second a little effect, fisetin and other mild senolytics added lately i have to check but i believe end of 2018 or early 2019.

 

fisetin+quercetin+delta tocopherols made a sharp decrease on BP, at first there was a tendency to go up to 120/80 after a week or so and later with more cysles of this it stayed there

 

i also started stemcell renewal during this period end 2018-2019 so this can be a confounding factor, gdf11 (which i stopped 1-2 moths ago) no and c60 also
 

Edited by lost69, 08 October 2019 - 02:46 PM.

[Nate-2004]

Back to bio-availability, I know a lot of things have low bio-availability. I found a published study showing that, in humans, EGCG has terrible bio-availability and used various combinations to try and improve its uptake. So for that what was found is that if it is taken in a fasted state, with a small amount (200mg) of vitamin C, black pepper extract, and fish oil, that this achieved the highest levels of egcg detected in the blood stream. Glucuronidation, oxidation and certain proteins can greatly diminish its uptake. 

 

So is fisetin the same way? It's a flavinol not a catichin, but perhaps it's got similar issues? If you can find out *why* it isn't absorbed then perhaps that problem would be solved. Especially if glucuronidation is the issue. Not sure about the sulfation, that could be solved by something (chlorate?) that inhibits sulfation but what?

 

 

https://www.ncbi.nlm...les/PMC3689181/

 

Pharmacokinetics and Bioavailability of Fisetin

 

Shia et al. have investigated the metabolism and pharmacokinetics of fisetin in rats (60). The activities of fisetin and its serum metabolites against 2,2′-azobis (2-amidinopropane hydrochloride) (AAPH)-induced hemolysis were evaluated and compared on an equimolar basis. After intravenous administration of fisetin (10 mg/kg body weight), the mean serum concentration–time profiles of metabolites showed that fisetin declined rapidly. The sulfates/glucuronides and glucuronides were largely at higher concentrations than the parent compounds at all time points, suggesting that fisetin was rapidly and extensively biotransformed by conjugation metabolism in the liver, mainly sulfation. Following oral dose (50 mg/kg body weight), fisetin levels were maintained after the first pass through the intestine and liver as shown by presence of the parent compound in serum. The (AUC)0-2880 of fisetin sulfates/glucuronides was 2.2-fold that of fisetin glucuronides, demonstrating that fisetin was rapidly and extensively metabolized to sulfates and glucuronides. Interestingly, it was observed that less sulfation occurred in enterocytes than in hepatocytes when serum levels of metabolites were compared after intravenous dose (60). It was shown that after treatment of 50 mg/kg body weight of fisetin, Cmaxand AUC0-2880 values of fisetin sulfate/glucuronide were 27-fold and 59-fold greater than the Cmax and AUC0-4320 values of 5-OH-flavone sulfate/glucuronide, respectively, following 40 mg/kg body weight of 5-OH-flavone. After an equal dose, the AUC0-4320 of 7-OH-flavone sulfate/glucuronide was found to be even lower than that of 5-OH-flavone sulfate/glucuronide (60). There was significant inhibition of AAPH-induced hemolysis by both fisetin and its serum metabolites, signifying that fisetin sulfates/glucuronides retain free-radical scavenging activity due to the presence of residual phenolic groups after conjugation metabolism (60).

It has been reported that the maximum fisetin concentration reached 2.5 μg/ml at 15 min, and the plasma concentration declined biphasically with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h after administration of fisetin at a dose of 223 mg/kg intraperitoneally in mice (68). These studies clearly demonstrate that the metabolism of fisetin has a significant role in its biological responses and anticancer activities. Ragelle et al. conducted a study to incorporate fisetin into a nanoemulsion to improve its pharmacokinetics and therapeutic efficacy (53). It has been shown that the fisetin nanoemulsion injected intravenously showed no significant difference in systemic exposure compared to free fisetin in mice, but when given intraperitoneally as compared to free fisetin, a 24-fold increase in the relative bioavailability of fisetin was found. The antitumor activity of the fisetin nanoemulsion in Lewis lung carcinoma-bearing mice occurred at lower doses compared to free fisetin (53).

 

Edited by Nate-2004, 08 October 2019 - 07:45 PM.

[sedentary]

If you go to purebulk, you can see the label that says..per serving...

 

Fisetin 150 mg 
(from 300 mg Cotinus Coggygria P.E.) (branch)

 

why did they extract it from a plant nobody has even heard of. whats wrong with extracting it from strawberries? i know it will take A LOT of them but they are widely available all over the world everywhere and are cheap in comparison to those most hard to find exotic plants. i just dont get it.

[Oakman]

why did they extract it from a plant nobody has even heard of. whats wrong with extracting it from strawberries? i know it will take A LOT of them but they are widely available all over the world everywhere and are cheap in comparison to those most hard to find exotic plants. i just dont get it.

 

Well, knowledge is power... and understanding. If you research a bit, this plant is not just any old plant, it has been medicinally evaluated for various purposes. I'm just guessing, but it seems it is far more economical to use this plant for fisetin, rather than picking strawberries and extracting. Read the link and you'll see what potential this plant has.

 

"Phytochemical analysis of the C. coggygria methanol extract of the heartwood, performed by Valianou et al. (2009) indicated the presence of 3′,4′,6-trihydroxyaurone (sulfuretin), 3′,4′,7- trihydroxyflavonol (fisetin), 3′,4′,7-trihydroxyflavanol (fustin), 3′,4′,5,7-tetrahydroxyflavonol (quercetin), 3′,4′,5,7-tetrahydroxyflavanol (taxifolin), 4′,7-dihydroxyflavanol, 3′,4′,7- trihydroxyflavanone (butin), 4′,7-dihydroxyflavanone (liquiritigenin), trans-2′,3,4,4′- tetrahydroxychalcone (butein), 4′,5,7-trihydroxyflavanone, and trans-2′,4,4′-trihydroxychalcone (isoliquiritigenin)."

 

Cotinus coggygria Scop.: An overview of it Chemical Constituents, Pharmacological and Toxicological Potential

[Colorow]

I also would be interested

[OP2040]

I'm on day 2 of my yearly senolytic intervention.  This time I'm including my wife as a second experiment.  I did not include dasatinib, and went with my usual protocol:

F (1G) + Q (1G) + C (2.25G) + Bioperine (15mg)  X  3 days

 

So far nothing to report, and frankly I'm getting rather jaded with all of it.  Maybe some folks are correct.  If you don't see/feel something then chances are what you're doing probably is a dud.   I feel like I have no choice but to include dasatinib next year for that reason.  Or maybe just try it again soon, as in very soon.