Coleus Forskolii to reduce IgE, histamine, bp, and PAF???

[triffid113]

http://core.kmi.open.ac.uk/display/1034673

COLEUS (PLECTRANTHUS BARBATUS) – A MULTIPURPOSE MEDICINAL HERB

By SharmaYashaswini and Vasundhara M
Abstract

Plectranthus barbatus Andr. (Syn. Coleus forskohlii Briq.) is a perennial herb, belonging to the family Lamiaceae. Its tuberous roots are found to be a rich source of forskohlin (coleonol) used as a potential drug for hypertension, congestive heart failure, eczema, colic, respiratory disorders, painful urination, insomnia, and convulsions. Clinical studies of the plant further support these traditional uses, indicating therapeutic benefit in asthma, angina, psoriasis and prevention of cancer metastases. Forskolin directly activates almost all hormone sensitive adenylate cyclases in intact cells, tissues and even solubilised preparation of adenylate cyclase. Stimulation of adenylate cyclase is thought to be the mechanism by which forskolin relaxes a variety of smooth muscles. Forskolin, by increasing cAMP level in turn, inhibits basophil and mast cell degranulation and histamine release, lowers blood pressure and intraocular pressure and it inhibits platelet aggregation, promotes vasodilation, bronchodilation, and thyroid hormone secretion. Coleus acts as a natural source of drug for many major diseases implying that there is a great demand for production and processing of the crop. The paper deals with botany, medicinal uses, phytochemical, mechanism of action and case studies on coleus.
Topics: Coleus, cyclic AMP, forskolin, Plectranthus barbatus
Publisher: International Research Journal of Pharmacy

-----

Anyone try this for allergies? I have taken it to improve thyroid function but never thought to see if it would help with allergies. I think it's pricey so I have been hoarding my stash. Maybe it's time to really see what it can do (well next allergy season anyway).

 

[triffid113]

Inasmuch as Forskohlii influences cAMP, can anyone explain cAMP to me? I read references to it often but for some reason have never figured out what it is and how it works? Anyone?

the article above says that asthma and other allergies are caused by low cAMP and high PAE (cGMP?). Forskohlii's increase of cAMP inhibits mast degranulation and causes branchiodialtion. (In studies they inhaled the powder).

 

[A.B.]

Raising cAMP will have a stimulating effect, so it is not ideal when fatigue is present.

 

[triffid113]

Raising cAMP will have a stimulating effect, so it is not ideal when fatigue is present.

??? To me this requires explanation? Raising cAMP improves sensitivity to thyroid hormone which seems to me exactly what one needs when fatigued! (Unless one is hyperthyroid).

 

[triffid113]

This is what I find in poking around a bit so far...

Allergies…all about cAMP/cGMP?

Forskohlii, Spirulina, PAF (blood clotting effects of allergies)

Coleus Forskohlii improves the cells’ sensitivity to the thyroid hormone, thus it augments the thyroid actions. This is why I began taking it. When my thyroid went back close to normal, I stopped, and hoarded my supply as it is expensive. Now I find Forskohlii makes the cells more sensitive to many hormones!

Coleus Forskohlii works mainly through direct stimulation of cyclic AMP (adenosine monophosphate) production. Cyclic AMP is a cellular messenger that determines how cells react to hormonal signals. Forskohlii stimulates cAMP via enzyme: Adenyl Cyclase. Cyclic AMP (cAMP) is one of the most important secondary messengers in the cell. It is considered to be one of the most important cell regulating compounds.

One preliminary study found that forskolin was equally as effective as beclomethasone for the prevention of asthma attacks after two months of treatment in mild and moderate asthma sufferers.

Thorne says:


· Coleus Forskohlii decreases histamine release by increasing cAMP*


· supports normal respiratory and nasal function*

· helps maintain skin health*

· balances the cAMP/cGMP ratio*



Coenzyme-A technologies says:

Under normal circumstances, cAMP forms by adenylate cyclase activation due to hormonal stimulation at the cell receptor site. However, forskolin seems to bypass this reaction and allows for an increase in intracellular cAMP to occur.

Why is it important to increase cAMP levels? Well, there are several benefits of this to athletes including relaxation of the arteries and smooth muscles, lowering blood pressure, enhanced insulin secretion (which can help drive carbohydrates and protein into muscle cells for energy and recovery), increased thyroid hormone function (which can help enhance metabolic rate), and significantly increase lipolysis (fat burning). Forskolin also seems to benefit other cellular enzymes as well.

The breakdown of fat for fuel (lipolysis) is actually regulated primarily by Acetyl CoenzymeA and secondary cAMP. Forskolin has been shown to not only enhance lipolysis but it may also inhibit fat storage from occurring.

One of the overlooked benefits of forskolin includes its stimulation of digestive enzymes, which can allow individuals to digest and assimilate their food better. It has been shown to increase nutrient absorption in the small intestine.

The recommended dosage for this supplement is 8-10 mg of active forskolin 2-3 times daily.





About the plant: Coleus forskohlii (Plectranthus barbatus) is a tropical plant in the mint family that has been used around the world for a variety of reasons, the most common of which was the treatment of cardiovascular ailments. Forskolin is found in highest concentrations in the root.

Dosage (according to nationalnutrition .ca): Weight loss: 125-250mg of extract standardized to 10-20% forskolin. Asthma: 10mg daily (Clinical doses may differ as recommended by your practitioner).

Phosphodiesterases​

As important as it is to elevate cyclic nucleotide levels, it is necessary for the cell to down-regulate the response via degradation of cAMP and cGMP through enzymes known as cyclic nucleotide phosphodiesterases. Phosphodiesterase (PDE5) is the target for the drug sildenafil citrate, or Viagra, used in the treatment of male impotence.

Suite101 says: Glycogen acts as an emergency supply of blood sugar, but can only be unlocked by cAMP. (!!!) [Of interest to those of us with low blood sugar issues, allergies, etc.]

Low cAMP and cGMP in nasal mucosa and saliva have been proven to coexist with lack of smell and taste.

The studies below show:

· increased breakdown of cAMP (via Phosphodiesterase) is present in atopic allergies.

· Disturbed cAMP/gCMP ratio (allergies) cause PAF with attendant cardiovascular risk.

· Spirulina corrects cAMP/cGMP ratio at 2g/day over time.



J Allergy Clin Immunol. 1982 Dec;70(6):452-7.

Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness.

Grewe SR, Chan SC, Hanifin JM.

Abstract

Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.

J Thromb Haemost. 2012 Feb;10(2):167-76. doi: 10.1111/j.1538-7836.2011.04576.x.

Novel roles of cAMP/cGMP-dependent signaling in platelets.

Smolenski A.

Source

UCD Conway Institute, UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, Ireland. albert.smolenski@ucd.ie

Abstract

Endothelial prostacyclin and nitric oxide potently inhibit platelet functions. Prostacyclin and nitric oxide actions are mediated by platelet adenylyl and guanylyl cyclases, which synthesize cyclic AMP (cAMP) and cyclic GMP (cGMP), respectively. Cyclic nucleotides stimulate cAMP-dependent protein kinase (protein kinase A [PKA]I and PKAII) and cGMP-dependent protein kinase (protein kinase G [PKG]I) to phosphorylate a broad panel of substrate proteins. Substrate phosphorylation results in the inactivation of small G-proteins of the Ras and Rho families, inhibition of the release of Ca(2+) from intracellular stores, and modulation of actin cytoskeleton dynamics. Thus, PKA/PKG substrates translate prostacyclin and nitric oxide signals into a block of platelet adhesion, granule release, and aggregation. cAMP and cGMP are degraded by phosphodiesterases, which might restrict signaling to specific subcellular compartments. An emerging principle of cyclic nucleotide signaling in platelets is the high degree of interconnection between activating and cAMP/cGMP-dependent inhibitory signaling pathways at all levels, including cAMP/cGMP synthesis and breakdown, and PKA/PKG-mediated substrate phosphorylation. Furthermore, defects in cAMP/cGMP pathways might contribute to platelet hyperreactivity in cardiovascular disease. This article focuses on recent insights into the regulation of the cAMP/cGMP signaling network and on new targets of PKA and PKG in platelets.

Spirulina & Allergies





1. Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients.



J Med Food. 2005 Spring;8(1):27-30. Mao TK, Van de Water J, Gershwin ME. Division of Rheumatology/Allergy and Clinical Immunology, University of

California at Davis, School of Medicine, Davis, California, USA.



Spirulina represents a blue-green alga that is widely produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. We have previously shown that the in vitro culture of Spirulina with human peripheral blood mononuclear cells (PBMCs) modulated the production of cytokines. In the present study, we evaluated the impact of a Spirulina-based dietary supplement (Earthrise Nutritionals, Inc., Irvine, CA) on patients with allergic rhinitis by assessing the production of cytokines [interleukin (IL)-4, interferon (IFN)-gamma, and IL-2] critical in regulating immunoglobulin E-mediated allergy. In a randomized double-blinded crossover study versus placebo, allergic individuals were fed daily with either placebo or Spirulina, at 1,000 mg or 2,000 mg, for 12 weeks. PBMCs isolated before and after the Spirulina feeding were stimulated with phytohemagglutinin (PHA) prior to determining the levels of cytokine from cell culture supernatants. Although Spirulina seemed to be ineffective at modulating the secretion of Th1 cytokines (IFN-gamma and IL-2), we discovered that Spirulina, administered at 2,000 mg/day, significantly reduced IL-4 levels by 32% from PHA-stimulated cells. These results indicate that Spirulina can modulate the Th profile in patients with allergic rhinitis by suppressing the differentiation of Th2 cells mediated, in part, by inhibiting the production of IL-4. To our knowledge, this is the first human feeding study that demonstrates the protective effects of Spirulina towards allergic rhinitis.

 

[A.B.]

??? To me this requires explanation? Raising cAMP improves sensitivity to thyroid hormone which seems to me exactly what one needs when fatigued! (Unless one is hyperthyroid).

Fatigue in the sense of exhaustion. Doing more work when exhausted is not good. Stimulants tend to do just that, leading to long term worsening.

 

[Valentijn]

??? To me this requires explanation? Raising cAMP improves sensitivity to thyroid hormone which seems to me exactly what one needs when fatigued! (Unless one is hyperthyroid).

It's probably different for you, since you've said yourself in the past that you don't have ME, but ME patients trying to do anything to stimulate usually end up regretting it. At best there's a brief period of stimulation followed by a crash.

That seems to work alright for some people, if they need the stimulation to work and then can go home and crash then recover quickly enough (mild cases?). But for most of us it probably just means more bouncing back and forth between over-activity and worsening crashes, with little benefit during the period of increased energy, and drastically reduced abilities during the crash.

 

[triffid113]

Actually I have said I think CFS runs in my family and I am beating it by taking 40 supplements a day, just barely. Have you ever tried forslean? You sound like me about allergies...I have had them worse than anyone my allergist has ever met, worse than anyone I ever met has ever seen (so like I was popular for them in my whole school of 4,000 in High School), and I was so tired of hearing people telling me to try netti pots and Allarest ad nauseum that I got down on the idea of trying new things (so once a year I tried something new, didn't work, and gave up). It wasn't until I had 10 good years of Flonase and then it stopped working that I turned to the internet, found new strategies, and found things that work substantially (if nowhere as good as Flonase). I get being tired of trying new things...but did you ever think that the reason you get energy and then burn out from trying 'stimulants' might be running out f cAMP? So maybe taking something like forslean periodically, say at meal times, might do the trick? I get that it takes energy to even think about trying something new and I don't kow that this is the first thing I would try. It's just a thing. A possibility.

 

[triffid113]

When I have allergies my thyroid goes out, my adrenal gland goes out, my high blood pressure goes low and I have to eat salt or pass out. I cannot even think of doing the tiniest chore because I am so tired (but of course seeing the chore left undone is tiring too). And I find caffeine helps 3%...like it helps for a few minutes, so it seems like it will help but doesn't really long term. But I also become extremely depressed and I crave cheese and together with the fact that caffeine helps slightly and that I am always low dopamine makes me think I am using up dopamine to make epinephrine and running out and my body is trying to resupply tyrosine and fake dopamine (caffeine excites dopamine receptors or something like that). Anyway, out of all this exhaustion, what I WANT is a stimulant that WORKs. Not a drug with side effects. Not a caffeine. So Spirulina raises cAMP (thus is a stimulant) and so far I have seen no negatives (except that it's not as good as Flonase) but I did not take it for 3 months before allergy season like you are supposed to - instead I took massive quantities at the last minute. And this year the allergy season was shorter due to the monsoon-ish rains. So only over time will I see if the spirulina thing is going to work for me. (the low dose 2g/day forever). At 2g/day it does not feel like a stimulant. If it is, there is no dropping off the cliff on the other side like with caffeine. I have never noticed any negative (nor really positive) effects of forskohlii either. I took whatever the bottle said, but now that I have read several articles - one saying 10mg/day for allergies, one saying 10 mg 3x/day for allergies, I will have to try it again next time. I just took it to give my hypothyroid that little bit extra recovery. Normally my thyroid recovers fairly promptly after allergy season is over. Anything to speed that along is sooo welcome though as I have to get a lot of living done in the time left between allergies.

 

[triffid113]

I hope the PAF message was not lost. I have become aware this year that my allergies cause platelet aggregation which raises cardiovascular risk. It appears that in correcting cAMP, forskohlii lowers PAF.

I am extremely concerned about the link between allergies, PAF, and cardiovascular risk and thus in any substance that purports to correct this, such as forskohlii, spirulina, or ??

Other unusual things to be improved by forskohlii are said to be depression and digestion. So there are other reasons to take a special interest in this herb.

 

[triffid113]

I find one troubling bit of info: Cyclic AMP is synthesized from ATP by the action of the enzyme adenylyl cyclase.

Which may mean if you don't have the ATP to spare you can't make cAMP. idk yet how forskoholii works - I mean does it require ATP to start with or somehow supply the ATP to make this happen? Because if the ATP is required up front right away I can see that this might be a dead end. Ema says she takes forskohlii so I've asked her about how it works with CFS.

Cyclic AMP (cAMP) is synthesized from ATP by the action of the enzyme adenylyl cyclase.
Cyclic AMP serves as the secondary messenger for:

• adrenaline
• glucagon [THIS seems a likely reason that an allergic person (me) would be hypoglycemic my whole life...allergies mean low cAMP]
• luteinizing hormone (LH)

Cyclic GMP (cGMP)

Cyclic GMP is synthesized from the nucleotide GTP using the enzyme guanylyl cyclase.
Cyclic GMP serves as the second messenger for

• atrial natriuretic peptide(ANP)
• nitric oxide(NO)
• the response of the rods of the retina to light.

 

[alex3619]

Resveratrol also increases cAMP, though perhaps not in all cell types. Its also probably less dangerous. I avoided forskolin in my research as I am not convinced its safe in larger doses. Mind you I am not convinced resveratrol is either.

Ca++ and cAMP form an axis - two intracellular messengers that are inversely related. As cAMP goes up, Ca++ goes down. So some of the impact is from decreased ionized calcium in the cell. These two affect many hormones and metabolici processes. This is not a simple subject, and I only know a tiny bit of it.

http://www.cell.com/abstract/S0092-8674(12)00030-X?script=true

 

[Thinktank]

Certain probiotics also increase cAMP.

 

[triffid113]

And due to something someone else said about rhodiola, it apparently increases cAMP too:

http://www.mdpi.com/1420-3049/16/4/3371

Salidroside Attenuates Hydrogen Peroxide-Induced Cell Damage Through a cAMP-Dependent Pathway

Shuang Guan, Wei Wang, Jing Lu, Wenhui Qian, Guoren Huang, Xuming Deng and Xuelin Wang 1,*


Abstract: Salidroside, a major component of Rhodiola rosea L., has shown various pharmacological functions, including antioxidant effects, but the signal transduction pathway of its antioxidant effects is not very clear. In this study, we found that salidroside could attenuate hydrogen peroxide (H2O2)-induced HL-7702 cell damage, inhibit H2O2-induced cytosolic free Ca2+ ([Ca2+]i) elevation, scavenge reactive oxygen species (ROS) and increase 3’-5’-cyclic adenosine monophosphate (cAMP) level in a dose-dependent manner, but it couldn’t influence 3’-5’-cyclic guanosine monophosphate (cGMP) levels. Therefore, these results indicated that the antioxidant effects of salidroside were associated with down-regulation of [Ca2+]i, ROS occur via a cAMP-dependent pathway.

So looks like it would have an effect in allergies too,

(But the trick is knowing how much it takes, as it can take quite a lot over quite a long time. So for Spirulina it takes 2g over 3 months (which I have not tried, but I can say that 10.5 g/day works with only 1 day buildup).

Thanks, Alex, I am seeing this connection to Ca+, however the above study makes it sound like too much Ca+ is the problem, Ca+ produced by H2O2. Like you, I don't know enough. But I am reading up a bit.

 

[triffid113]

I caught a cold yesterday and all my colds turn to allergy attacks so I tried 300mg coleus forskohlii. I could feel it but only about 10%, not hardly worth an honorable mention. idk how it works if taken over time though. I wonder if I took 10 different herbs that raise cAMP if it additively would knock out my allergies??? I already take SO many pills!

 

[triffid113]

I am also concerned with allergy-raised PAF, so here is a cAMP raising herb that lowers PAF:

Thromb Haemost. 1982 Dec 27;48(3):301-6.
The effect of a medicinal Chinese herb on platelet function.

Wang Z, Roberts JM, Grant PG, Colman RW, Schreiber AD.
Abstract

We investigated the effect of the Chinese herb Injectio Salvia Miltiorrhizae (ISM) on human platelet function in vitro. ISM inhibited platelet aggregation and serotonin release induced by either ADP or epinephrine in a dose dependent manner. This effect of ISM was observed with both gel-filtered platelets (ID50 = 8-30 micrograms ISM/ml gel-filtered platelets) and platelets in plasma (ID50 = 400-900 micrograms ISM/ml of platelet-rich plasma). The active molecule(s) in ISM was heat stable, resistant to acid, base and proteolysis and fractionated on Sephadex 6-25 at MW approximately 280. ISM did not interact with the platelet alpha-adrenergic receptor, but increased cAMP in intact platelets. The results are consistent with the concept that ISM inhibition of platelet aggregation and release is mediated by an increase in platelet cAMP. The exact mechanism whereby ISM increases platelet cAMP appears to be that of inhibition of cyclic AMP phosphodiesterase. The effect of ISM on platelet function is one mechanism which might explain the therapeutic effect of ISM in experimental and clinical coronary artery disease.

 

[triffid113]

And here's a not so rosy picture of life as a chronic producer of low cAMP:

According to Sears cyclic AMP levels are chronically diminished by elevated insulin levels, which puts a damper on a multitude of hormone systems (Ref.1).
For instance, all the steroid hormones (testosterone, estrogen, progesterone) require cyclic AMP for their production. It is an important second messenger that is an intermediary between the hormones and the cell metabolism.
Growth hormone release and release of thyroid stimulating hormone need cyclic AMP before they can be released from the pituitary gland. Thyroid hormone will not be released into the blood stream without cyclic AMP and the sleep inducing melatonin hormone will not be produced from serotonin without cyclic AMP.
What does this mean in practical terms? It means that if we eat the wrong foods such as the typical North American diet with lots of starch in foods such as pasta, bread, potatoes, rice and refined cereal as well as sugar in its various disguises, the chances are that many people end up with chronically low cyclic AMP levels. This in turn will turn off our energies and cause a low sex drive. It also can be a cause of infertility as the female hormone cycles are interfered with. Interference with thyroid function from low cyclic AMP levels causes slow mentation, weight gain and low energy (hypothyroidism symptoms). It also can cause sleeplessness and make us more prone to mental depression. If this sounds familiar, it is because this is what is happening to a lot of people.

 

[triffid113]

Resveratrol also increases cAMP, though perhaps not in all cell types. Its also probably less dangerous. I avoided forskolin in my research as I am not convinced its safe in larger doses. Mind you I am not convinced resveratrol is either.

Ca++ and cAMP form an axis - two intracellular messengers that are inversely related. As cAMP goes up, Ca++ goes down. So some of the impact is from decreased ionized calcium in the cell. These two affect many hormones and metabolici processes. This is not a simple subject, and I only know a tiny bit of it.

http://www.cell.com/abstract/S0092-8674(12)00030-X?script=true[/quote]

Alex, I'm curious what you think of berberine, which raises AMPK?

 

[alex3619]

triffid113 , I do not know enough about berberine to say much. I can say that as a downregulator of COX-2 it might have a good impact on inflammation. However COX-2 may help fight infection. This is a substance I might have a more detailed look at sometime though.

This is worrying though, and might indicate those with ME should not take berberine:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464622/

An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases AMP/ATP ratio.

 

[triffid113]

triffid113 , I do not know enough about berberine to say much. I can say that as a downregulator of COX-2 it might have a good impact on inflammation. However COX-2 may help fight infection. This is a substance I might have a more detailed look at sometime though.

This is worrying though, and might indicate those with ME should not take berberine:

Berberine raises AMPK, which is AMP kinase.
Protein kinases are a group of enzymes
which catalyze the phosphorylation of other proteins.
The activity of some of these protein kinases
is dependent upon the presence of cyclic AMP. ATP
is used as the phosphate source.

[So, ATP is needed for forskohlii to make cAMP, and cAMP activates AMPK, which in order to work phosporhylating other proteins, requires another ATP].

Good point. But you know methylation needs ATP too...so do many processes. idk the relative amount of ATP needed...like if this is a big drain or an ordinary little one. Just don't know. I mean it might be that once we look closely enough that every process needs ATP...