11 replies to this topic

[malbecman]

Just found this pub, thought it might be of interest since some people have reported using luteolin +/- resveratrol.

Well, too bad it isn't just a PDE5 inhibitor.

Better watch out for some of those other effects from PDE 1-4, though (read the end of the abstract)....


Eur J Pharmacol. 2009 Oct 22. [Epub ahead of print]
Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia.
Yu MC, Chen JH, Lai CY, Han CY, Ko WC.

Department of Internal Medicine, Taipei Municipal Wan-Fang Hospital, Taiwan.
The aim of the present study was to investigate the mode of action of luteolin on phisphodiesterase (PDE) 1-5, and the possible adverse effects, such as nausea, vomiting, and gastric hypersecretion, determined by replacing [(3)H]-rolipram binding and reversing xylazine/ketamine-induced anesthesia. The reversing effect was reported to occur through a presynaptic alpha(2)-adrenoceptor inhibition and trigger vomiting in ferrets. In contrast, clonidine, an alpha(2)-adrenoceptor agonist, prevented emesis induced by PDE4 inhibitors in ferrets. According to the Lineweaver-Burk analysis, luteolin (3-30muM) competitively inhibited PDE1-5 activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5muM, respectively, which did not significantly differ from each other. The equilibrium dissociation constant (K(d)) and maximal density (B(max)) for [(3)H]-rolipram binding at high-affinity rolipram binding sites of guinea pig brain cell membranes were 10.1nM and 3.7pmol/g of tissue, respectively. The EC(50) (PDE4(H)) values of luteolin and Ro 20-1724, a selective PDE4 inhibitor, for displacing 2nM [(3)H]-rolipram binding were 11.2muM and 45.6nM, respectively. The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724 were calculated to be 0.6, and 0.004, respectively. Both luteolin (10-30mumol/kg, s.c.) and Ro 20-1724 (0.1-1mumol/kg, s.c.) significantly reversed the xylazine/ketamine-induced anesthesia in mice. Although luteolin non-selectively and competitively inhibited PDE1-5, only PDE4 inhibition contributed to a reversing effect. In conclusion, because of the low therapeutic (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as nausea, vomiting and gastric hypersecretion should be carefully monitored, whenever luteolin is used for treating allergies, asthma or chronic obstructive pulmonary disease.

PMID: 19853596

[bixbyte]

Just found this pub, thought it might be of interest since some people have reported using luteolin +/- resveratrol.

Well, too bad it isn't just a PDE5 inhibitor.

Better watch out for some of those other effects from PDE 1-4, though (read the end of the abstract)....


Eur J Pharmacol. 2009 Oct 22. [Epub ahead of print]
Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia.
Yu MC, Chen JH, Lai CY, Han CY, Ko WC.

Department of Internal Medicine, Taipei Municipal Wan-Fang Hospital, Taiwan.
The aim of the present study was to investigate the mode of action of luteolin on phisphodiesterase (PDE) 1-5, and the possible adverse effects, such as nausea, vomiting, and gastric hypersecretion, determined by replacing [(3)H]-rolipram binding and reversing xylazine/ketamine-induced anesthesia. The reversing effect was reported to occur through a presynaptic alpha(2)-adrenoceptor inhibition and trigger vomiting in ferrets. In contrast, clonidine, an alpha(2)-adrenoceptor agonist, prevented emesis induced by PDE4 inhibitors in ferrets. According to the Lineweaver-Burk analysis, luteolin (3-30muM) competitively inhibited PDE1-5 activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5muM, respectively, which did not significantly differ from each other. The equilibrium dissociation constant (K(d)) and maximal density (B(max)) for [(3)H]-rolipram binding at high-affinity rolipram binding sites of guinea pig brain cell membranes were 10.1nM and 3.7pmol/g of tissue, respectively. The EC(50) (PDE4(H)) values of luteolin and Ro 20-1724, a selective PDE4 inhibitor, for displacing 2nM [(3)H]-rolipram binding were 11.2muM and 45.6nM, respectively. The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724 were calculated to be 0.6, and 0.004, respectively. Both luteolin (10-30mumol/kg, s.c.) and Ro 20-1724 (0.1-1mumol/kg, s.c.) significantly reversed the xylazine/ketamine-induced anesthesia in mice. Although luteolin non-selectively and competitively inhibited PDE1-5, only PDE4 inhibition contributed to a reversing effect. In conclusion, because of the low therapeutic (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as nausea, vomiting and gastric hypersecretion should be carefully monitored, whenever luteolin is used for treating allergies, asthma or chronic obstructive pulmonary disease.

PMID: 19853596

Dear Malbecman,

Well, too bad it isn't just a PDE5 inhibitor.

= A Constant Erection


Luteolin is a Flavone extracted from Ragweed pollen, peanuts, celery, thyme, dandelion, rinds, leaves ....
PDE4 inhibitor that just happens to be extracted from plants that some people are allergic.
IMHO, You might choke to death on Luteolin if you have asthma.

This is now off my supplement List.

Thank You for the Abstract.

Bix

Edited by bixbyte, 06 November 2009 - 11:51 PM.

[maxwatt]

Just found this pub, thought it might be of interest since some people have reported using luteolin +/- resveratrol.

Well, too bad it isn't just a PDE5 inhibitor.

Better watch out for some of those other effects from PDE 1-4, though (read the end of the abstract)....


Eur J Pharmacol. 2009 Oct 22. [Epub ahead of print]
Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia.
Yu MC, Chen JH, Lai CY, Han CY, Ko WC.

Department of Internal Medicine, Taipei Municipal Wan-Fang Hospital, Taiwan.
The aim of the present study was to investigate the mode of action of luteolin on phisphodiesterase (PDE) 1-5, and the possible adverse effects, such as nausea, vomiting, and gastric hypersecretion, determined by replacing [(3)H]-rolipram binding and reversing xylazine/ketamine-induced anesthesia. The reversing effect was reported to occur through a presynaptic alpha(2)-adrenoceptor inhibition and trigger vomiting in ferrets. In contrast, clonidine, an alpha(2)-adrenoceptor agonist, prevented emesis induced by PDE4 inhibitors in ferrets. According to the Lineweaver-Burk analysis, luteolin (3-30muM) competitively inhibited PDE1-5 activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5muM, respectively, which did not significantly differ from each other. The equilibrium dissociation constant (K(d)) and maximal density (B(max)) for [(3)H]-rolipram binding at high-affinity rolipram binding sites of guinea pig brain cell membranes were 10.1nM and 3.7pmol/g of tissue, respectively. The EC(50) (PDE4(H)) values of luteolin and Ro 20-1724, a selective PDE4 inhibitor, for displacing 2nM [(3)H]-rolipram binding were 11.2muM and 45.6nM, respectively. The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724 were calculated to be 0.6, and 0.004, respectively. Both luteolin (10-30mumol/kg, s.c.) and Ro 20-1724 (0.1-1mumol/kg, s.c.) significantly reversed the xylazine/ketamine-induced anesthesia in mice. Although luteolin non-selectively and competitively inhibited PDE1-5, only PDE4 inhibition contributed to a reversing effect. In conclusion, because of the low therapeutic (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as nausea, vomiting and gastric hypersecretion should be carefully monitored, whenever luteolin is used for treating allergies, asthma or chronic obstructive pulmonary disease.

PMID: 19853596

Dear Malbecman,

Well, too bad it isn't just a PDE5 inhibitor.

= A Constant Erection


Luteolin is a Flavone extracted from Ragweed pollen, peanuts, celery, thyme, dandelion, rinds, leaves ....
PDE4 inhibitor that just happens to be extracted from plants that some people are allergic.
IMHO, You might choke to death on Luteolin if you have asthma.

This is now off my supplement List.

Thank You for the Abstract.

Bix

Curiously, quercetin, also a PDE inhibitor, is being used to treat asthma. Luteolin has been used in Taiwan to treat asthma. If you luteolin in 98 pure, there are unlikely to be allergens present.

[bixbyte]

Just found this pub, thought it might be of interest since some people have reported using luteolin +/- resveratrol.

Well, too bad it isn't just a PDE5 inhibitor.

Better watch out for some of those other effects from PDE 1-4, though (read the end of the abstract)....


Eur J Pharmacol. 2009 Oct 22. [Epub ahead of print]
Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [(3)H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia.
Yu MC, Chen JH, Lai CY, Han CY, Ko WC.

Department of Internal Medicine, Taipei Municipal Wan-Fang Hospital, Taiwan.
The aim of the present study was to investigate the mode of action of luteolin on phisphodiesterase (PDE) 1-5, and the possible adverse effects, such as nausea, vomiting, and gastric hypersecretion, determined by replacing [(3)H]-rolipram binding and reversing xylazine/ketamine-induced anesthesia. The reversing effect was reported to occur through a presynaptic alpha(2)-adrenoceptor inhibition and trigger vomiting in ferrets. In contrast, clonidine, an alpha(2)-adrenoceptor agonist, prevented emesis induced by PDE4 inhibitors in ferrets. According to the Lineweaver-Burk analysis, luteolin (3-30muM) competitively inhibited PDE1-5 activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5muM, respectively, which did not significantly differ from each other. The equilibrium dissociation constant (K(d)) and maximal density (B(max)) for [(3)H]-rolipram binding at high-affinity rolipram binding sites of guinea pig brain cell membranes were 10.1nM and 3.7pmol/g of tissue, respectively. The EC(50) (PDE4(H)) values of luteolin and Ro 20-1724, a selective PDE4 inhibitor, for displacing 2nM [(3)H]-rolipram binding were 11.2muM and 45.6nM, respectively. The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724 were calculated to be 0.6, and 0.004, respectively. Both luteolin (10-30mumol/kg, s.c.) and Ro 20-1724 (0.1-1mumol/kg, s.c.) significantly reversed the xylazine/ketamine-induced anesthesia in mice. Although luteolin non-selectively and competitively inhibited PDE1-5, only PDE4 inhibition contributed to a reversing effect. In conclusion, because of the low therapeutic (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as nausea, vomiting and gastric hypersecretion should be carefully monitored, whenever luteolin is used for treating allergies, asthma or chronic obstructive pulmonary disease.

PMID: 19853596

Dear Malbecman,

Well, too bad it isn't just a PDE5 inhibitor.

= A Constant Erection


Luteolin is a Flavone extracted from Ragweed pollen, peanuts, celery, thyme, dandelion, rinds, leaves ....
PDE4 inhibitor that just happens to be extracted from plants that some people are allergic.
IMHO, You might choke to death on Luteolin if you have asthma.

This is now off my supplement List.

Thank You for the Abstract.

Bix

Curiously, quercetin, also a PDE inhibitor, is being used to treat asthma. Luteolin has been used in Taiwan to treat asthma. If you luteolin in 98 pure, there are unlikely to be allergens present.

_________________________________________________________________

Quercetin is a Flavone that is found in Onions, Tomatoes, apples, capers, tea...
Quercetin might cause bladder cancer in cattle with HPV
Quercetin I do not see this Flavone having PDE inhibitor properties?
Do you have a reference?

See drug interaction and occurrences

http://en.wikipedia.org/wiki/Quercitin

Luteolin is a Flavone that is found in Peanuts (not referenced, listed extracted from peanuts on my COA), ragweed pollen, leaves, barks ....
Luteolin might cause allergic reactions and or asthma.
Luteolin is extracted from substances people are allergic.
Luteolin is a PDE 1 to PDE 5 inhibitor.

http://en.wikipedia.org/wiki/Luteolin


Maybe it would be wise to avoid these Flavones.

____________________________________________________________________________

[niner]

Luteolin is most often found in leaves, but it is also seen in celery, thyme, dandelion, rinds, barks, clover blossom and ragweed pollen.[1] It has also been isolated from Salvia tomentosa.[3] Dietary sources include celery, green pepper, thyme, perilla, camomile tea, carrots, olive oil, peppermint, rosemary and oregano.[4][5]

Just because it's found in ragweed pollen doesn't mean that's what they extract it from. Extractions are going to be done from a crop that can be grown easily and has a high concentration of luteolin, along with low concentrations of anything undesirable. I don't think there is any reason to avoid it if it is coming from a reputable producer. Note that resveratrol is found in peanuts, but that doesn't mean people with peanut allergies have to avoid it, since it all comes from knotweed or cell culture.

[bixbyte]

Luteolin is most often found in leaves, but it is also seen in celery, thyme, dandelion, rinds, barks, clover blossom and ragweed pollen.[1] It has also been isolated from Salvia tomentosa.[3] Dietary sources include celery, green pepper, thyme, perilla, camomile tea, carrots, olive oil, peppermint, rosemary and oregano.[4][5]

Just because it's found in ragweed pollen doesn't mean that's what they extract it from. Extractions are going to be done from a crop that can be grown easily and has a high concentration of luteolin, along with low concentrations of anything undesirable. I don't think there is any reason to avoid it if it is coming from a reputable producer. Note that resveratrol is found in peanuts, but that doesn't mean people with peanut allergies have to avoid it, since it all comes from knotweed or cell culture.

_________________________________________________________


I have a couple problems with Quercetin and Luteolin.
And I Also think Quercetin and Luteolin should be addressed as separate issues.


1. Research that states Luteolin is a PDE1 to PDE5 inhibitor? But dominates as a PDE-4.
2. Luteolin also knocked out a certain anesthesia called Ketamine.

Ketamine is prescribed only for children and animals not adults because its side effect includes nightmares.
PDE-5 inhibitors are known.
PDE-1 to PDE-4 are not well known.

Therefore, I believe luteolin needs further study.

--------------------

1. Should I tweak my Resveratrol with Quercetin if this supplement might be carcinogenic?

Research states certain strains of HPV and Quercetin = Cancer:

"In cattle, there is a synergystic interaction between bovine papillomavirus-2 infection and exposure to quercetin, promoting bladder neoplasia, clinically presenting as enzootic haematuria. "

--------------------

Resveratrol acts as a modulator of certain medications.
Why do I want to take the chance of modulating Quercetin or Luteolin?
I think the supplement vendors have it backwards.
Personally, I would supplement on Resveratrol and avoid the Quercetin and Luteolin.


Alex

[Anthony_Loera]

Hi BixByte,

Your study is interesting, I will check it out some more.
It appears (as it sometimes happens) we get studies that appear to conflict with each other... such as the breast cancer study with Resveratrol and Quercetin seems to conflict with the one you mentioned (in the broad sense).

Maybe the inclusion of resveratrol makes all the difference?

Hmm..

A

Edited by Anthony_Loera, 30 November 2009 - 07:22 PM.

[2tender]

Looking at the chemical structure of Resveratrol and Quercetin, they seem similar. Thats probably not a revelation, nor is it a fact that they may enhance each other if taken together as quite a few people are, and have been doing. Bixbyte, I appreciate the fact that you always present whats contrary to a positive premise. People need to look at this from every angle, differing points of view enhance accurate perception.

Edited by 2tender, 01 December 2009 - 12:39 PM.

[bdelfin]

The bigger worry about a lifetime of taking high doses of quercetin is damage to chromosomal structures due to endoreduplication. Granted, 500 mg. would give a peak concentration of 4 microM, and they found strong concern at 30 microM, but they never tested lower doses...

As for luteolin -- I never felt any ill effects from it back when I took it at 4 or 8 mg. a day, but a friend of mine just started taking olive leaf extract, so I'm going to give her a heads up. Thanks, malbecman.

[bdelfin]

Wait a minute -- I read that a study of quercetin absorption found a peak concentration of 0.8 microM when consuming apples containing 100 mg. of quercetin. If luteolin has similar absorption, wouldn't it require 355 mg. of luteolin to reach the 3 microM that was the lowest concentration in the study? What kinds of risks would the amounts typically consumed, say 4-8 mg., really have?

[niner]

Wait a minute -- I read that a study of quercetin absorption found a peak concentration of 0.8 microM when consuming apples containing 100 mg. of quercetin. If luteolin has similar absorption, wouldn't it require 355 mg. of luteolin to reach the 3 microM that was the lowest concentration in the study? What kinds of risks would the amounts typically consumed, say 4-8 mg., really have?

That is a good observation. Also note that peak concentration is only reached fleetingly, and it's all downhill from there. If you want to obtain an effective concentration for a reasonable amount of time, your peak will need to be even higher. I doubt that 4-8mg has any risk whatsoever. It's not enough for a PDE effect, you won't put a crimp in your clubbing on ketamine, and you will certainly not choke to death. What is this, the hysteria thread?

[bdelfin]

What is this, the hysteria thread?

Hmm, not a bad idea. Actually, we could use a hysteria forum. Think of how much it would do to clean up certain threads...