KC's guide to active ingridients in Clabs GB/WB

[kingcarlos]

juz to give info to ppl abt what they are taking and to stop noob abt asking questions lol

1st
Magensium Creatine Chelate

http://www.doctorphyto.com/Library/E..._and_Facts.htm

Magnesium and Energy

Magnesium plays an enormous role in energy metabolism. All energy for muscle contraction is derived from the hydrolysis of ATP. Magnesium is intimately linked to the metabolic cycle of ATP production and hydrolysis. There are three overlapping mutually supportive energy systems that provide the ATP needed for physical exercise:

1. Immediate (stored ATP, ADP plus phosphates)
2. Nonoxidative (glycolytic; usage of muscle starch)
3. Oxidative (Citric acid or "Krebs" cycle)

High intensity exercises are anaerobic and they rely on the Immediate energy system, which gets its ATP from:

* ATP existing in muscle sarcoplasm
* Myokinase reaction (ADP + Inorganic Phosphate)
* CPK Reaction (ADP plus Creatine Phosphate) Fig. 1

Creatine Chelated with Magnesium

Magnesium and creatine have been proven to provide beneficial effects in the same diverse areas of physiological activities. Since their biochemical roles are also closely interlaced in very specific reactions, researchers thought it logical to unite magnesium and creatine into a single compound. The formation of a chelate of creatine with magnesium using patented technology, can protect the creatine from this cyclization and make higher quantities of the physiologically active form of creatine available to the metabolic activities of the muscle cells and yield a higher energy status. Obviously, the Magnesium Creatine Chelate could serve to provide effective quantities of bioavailable magnesium, which along with its many other effects, will work intensely along with creatine to increase the muscle's ability to generate and recycle energy in the form of ATP.

Magnesium Chelate Study

In a controlled clinical study (available upon request), Magnesium Creatine Chelate was compared to creatine monohydrate, as well as creatine given along with magnesium. This study indicates that the Magnesium Creatine Chelate out performs creatine monohydrate, as well as creatine monohydrate given with magnesium by a wide margin. Magnesium Creatine Chelate enhances the body's ability to generate and regenerate the ATP needed to provide the energy needed for muscular performance.

In the study, Magnesium Creatine Chelate outperformed creatine, as well as combined creatine given with magnesium. Given the roles that magnesium and creatine play in the generation of energy needed for muscular performance, it would make sense that a substance that provides both magnesium and creatine in a synergistic form would outperform creatine alone.

[kingcarlos]

continued

www.albion-an.com/human/newsletter/dec1999.pdf
www.albion-an.com/human/newsletter/june1999.pdf
http://jrnlappliedresearch.com/artic...s1/ASHMEAD.htm

Supplements of either magnesium or creatine have been previously reported to improve ergogenic performance. This study compared ergogenic activity and recovery in rats by swimming them to exhaustion, resting them for 30 minutes, and then re-swimming them to exhaustion after previously receiving no creatine supplementation, creatine monohydrate (CM) alone, CM plus MgO, CM plus Mg amino acid chelate, or Mg creatine chelate supplements for 8 days. Daily doses of Mg and creatine were 5 mg and 100 mg, respectively, per kg body weight. The source of the Mg appeared to affect ergogenic performance. The Mg creatine chelate not only resulted in significantly (P < 0.01) greater swimming time to exhaustion, but it was the only Mg source that resulted in significant (P < 0.05) ergogenic recovery during the second swimming period. It was concluded that when Mg was chelated to CM in a 1:1 molar ratio, the resulting molecule allowed greater ergogenic activity than when the metabolites were supplied as admixtures with Mg coming from other sources.

Although most metabolic investigations have focused on creatine phosphate or ATP when considering muscle energy, it is important to not overlook the potential significance of magnesium. Stending-Lindberg et al.12 reported that high muscle magnesium significantly (P < 0.001) improved endurance during strenuous exercise. Other clinical and experimental data also suggest that oral magnesium supplementation enhances performance in athletes.13,14 Although acknowledging magnesium’s role in ergogenics, researchers have not reached total agreement on the value of supplemental magnesium. Some investigators have reported that oral magnesium supplementation had little effect on intramuscular magnesium concentrations, which suggests that the current magnesium status of the body will influence magnesium uptake.12,15

The source of the magnesium may have also impacted the magnitude of the effect of magnesium supplementation noted by these researchers. Different magnesium sources have different bioavailabilities. Limited data from animal studies suggest greater absorption of magnesium from an amino acid chelate source compared with MgO, MgSO4 or MgCl2.16–18 Investigators reported greater magnesium tissue uptakes from an oral dose of magnesium bisglycine chelate than with inorganic magnesium salts in human volunteers.19,20

In ergogenic studies involving animals, employment of different sources of magnesium has resulted in significant variations in physical performance. When dietary magnesium was provided as an amino acid chelate rather than as an inorganic salt, individual rats had a 2.5 times longer mean swimming time.21 In a similarly designed study, magnesium was fed as either a magnesium aspartate salt or as a magnesium aspartate chelate. Swimming time was increased twofold (P < 0.05) when the source of the magnesium was the aspartate chelate compared to the aspartate salt.22

Although magnesium and creatine have been studied individually, little has been published on the ergogenic effect of supplementing magnesium and creatine concurrently. The kinetic studies of Kuby et al.23 do not address supplementation but have reported that the level of creatine kinase activity depends on the ratio of magnesium to creatine as well as the concentration of each. Maximum creatine kinase activity was achieved at a 1:1 molar ratio of magnesium to creatine. An excess of either metabolite was inhibitory to the total kinase activity.23Although most metabolic investigations have focused on creatine phosphate or ATP when considering muscle energy, it is important to not overlook the potential significance of magnesium. Stending-Lindberg et al.12 reported that high muscle magnesium significantly (P < 0.001) improved endurance during strenuous exercise. Other clinical and experimental data also suggest that oral magnesium supplementation enhances performance in athletes.13,14 Although acknowledging magnesium’s role in ergogenics, researchers have not reached total agreement on the value of supplemental magnesium. Some investigators have reported that oral magnesium supplementation had little effect on intramuscular magnesium concentrations, which suggests that the current magnesium status of the body will influence magnesium uptake.12,15

The source of the magnesium may have also impacted the magnitude of the effect of magnesium supplementation noted by these researchers. Different magnesium sources have different bioavailabilities. Limited data from animal studies suggest greater absorption of magnesium from an amino acid chelate source compared with MgO, MgSO4 or MgCl2.16–18 Investigators reported greater magnesium tissue uptakes from an oral dose of magnesium bisglycine chelate than with inorganic magnesium salts in human volunteers.19,20

In ergogenic studies involving animals, employment of different sources of magnesium has resulted in significant variations in physical performance. When dietary magnesium was provided as an amino acid chelate rather than as an inorganic salt, individual rats had a 2.5 times longer mean swimming time.21 In a similarly designed study, magnesium was fed as either a magnesium aspartate salt or as a magnesium aspartate chelate. Swimming time was increased twofold (P < 0.05) when the source of the magnesium was the aspartate chelate compared to the aspartate salt.22

Although magnesium and creatine have been studied individually, little has been published on the ergogenic effect of supplementing magnesium and creatine concurrently. The kinetic studies of Kuby et al.23 do not address supplementation but have reported that the level of creatine kinase activity depends on the ratio of magnesium to creatine as well as the concentration of each. Maximum creatine kinase activity was achieved at a 1:1 molar ratio of magnesium to creatine. An excess of either metabolite was inhibitory to the total kinase activity.23Although most metabolic investigations have focused on creatine phosphate or ATP when considering muscle energy, it is important to not overlook the potential significance of magnesium. Stending-Lindberg et al.12 reported that high muscle magnesium significantly (P < 0.001) improved endurance during strenuous exercise. Other clinical and experimental data also suggest that oral magnesium supplementation enhances performance in athletes.13,14 Although acknowledging magnesium’s role in ergogenics, researchers have not reached total agreement on the value of supplemental magnesium. Some investigators have reported that oral magnesium supplementation had little effect on intramuscular magnesium concentrations, which suggests that the current magnesium status of the body will influence magnesium uptake.12,15

The source of the magnesium may have also impacted the magnitude of the effect of magnesium supplementation noted by these researchers. Different magnesium sources have different bioavailabilities. Limited data from animal studies suggest greater absorption of magnesium from an amino acid chelate source compared with MgO, MgSO4 or MgCl2.16–18 Investigators reported greater magnesium tissue uptakes from an oral dose of magnesium bisglycine chelate than with inorganic magnesium salts in human volunteers.19,20

In ergogenic studies involving animals, employment of different sources of magnesium has resulted in significant variations in physical performance. When dietary magnesium was provided as an amino acid chelate rather than as an inorganic salt, individual rats had a 2.5 times longer mean swimming time.21 In a similarly designed study, magnesium was fed as either a magnesium aspartate salt or as a magnesium aspartate chelate. Swimming time was increased twofold (P < 0.05) when the source of the magnesium was the aspartate chelate compared to the aspartate salt.22

Although magnesium and creatine have been studied individually, little has been published on the ergogenic effect of supplementing magnesium and creatine concurrently. The kinetic studies of Kuby et al.23 do not address supplementation but have reported that the level of creatine kinase activity depends on the ratio of magnesium to creatine as well as the concentration of each. Maximum creatine kinase activity was achieved at a 1:1 molar ratio of magnesium to creatine. An excess of either metabolite was inhibitory to the total kinase activity.23

This study shows that ergogenic improvements are possible when laboratory rat diets were supplemented concurrently with creatine and magnesium. It also showed that the source of magnesium may affect ergogenic activity. When creatine was supplemented alone, physical performance increased 30.6% in the first period and 49.7% in the second period over the control. When magnesium oxide was added to the creatine, physical performance increased 14.1% in the first period and 24.1% in the second period over the control. This increase was less than the creatine alone. The admixing of magnesium as an bisglycine chelate with the creatine resulted in a 28.2% increase in physical performance in the first period and a 45.2% increase in physical performance in the second period compared with the control group. This was somewhat equivalent to the creatine alone. Finally, when chelated magnesium creatine was supplemented, the physical performance increased 36.2% in the first period and 57.6% in the second period compared with the control group. These variations may be due to variations in the bioavailability of the magnesium source. This should be the subject of further investigation

[kingcarlos]

continued

http://www.hsrmagazine.com/articles/071feat4.html

In specific areas of muscle energy biochemistry, particularly in the generation of ATP, magnesium has overlapping effects with creatine. In fact, magnesium is intimately linked to the metabolic cycle of ATP production, and creatine requires magnesium for its energy producing cycle. Creatine MagnaPower™, developed by Albion Laboratories, is the first ingredient to link the two molecules together, creating a bioavailable chelate.

Magnesium and creatine are intimately intertwined in the energy producing CPK reaction (see figure 1). The majority of energy required for high intensity, anaerobic activity is derived from the CPK and the Myokinase reactions. The formation of ATP via the Myokinase reaction needs magnesium to catalyze the ATP formation and the CPK reactions require creatine and magnesium as well to cycle formation of the ATP needed for muscle contraction.

http://www.fda.gov/ohrms/dockets/dai...01/let7477.pdf
(official release by FDA)

http://hdlighthouse.org/see/supplements/creatine6.htm

[kingcarlos]

2nd

Betaine anhydrous

http://www.drugs.com/pdr/BETAINE_ANHYDROUS.html

www.orphan.com/Download/cystadane%20pi.pdf
http://www.umm.edu/altmed/ConsSupple...Betainecs.html

Betaine is a nutrient that plays an important role in the health of the cardiovascular system. Studies have suggested that betaine, along with other nutrients, helps to reduce potentially toxic levels of homocysteine (Hcy), a naturally occurring amino acid that can be harmful to blood vessels thereby contributing to the development of heart disease, stroke, and peripheral vascular disease (reduced blood flow to the legs and feet).

Betaine functions closely with other nutrients -- namely, S-adenosylmethionine (SAMe), folic acid, and vitamins B6 and B12 -- to break down Hcy and reduce toxic levels of this substance in the bloodstream. When betaine, or any of these related nutrients, becomes low in the body, Hcy levels may rise. Some people have a genetic condition called "homocystinuria," in which Hcy levels accumulate in the body. Betaine supplements are used to lower levels of Hcy in people with this inherited health condition.

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Research Division of the Department of Urology, University Hospital Charite, Humboldt University, D-10098 Berlin, Germany. henke@rz.charite.hu-berlin.de

Betaine improves the co-amplification of the two alternatively spliced variants of the prostate-specific membrane antigen mRNA as well as the amplification of the coding cDNA region of c-jun. It is suggested that betaine improves the amplification of these genes by reducing the formation of secondary structure caused by GC-rich regions and, therefore, may be generally applicable to ameliorate the amplification of GC-rich DNA sequences.

http://nar.oxfordjournals.org/cgi/co...ull/25/19/3957 (full text)

didnt find much helpful info on betaine anhydrous, instead found alot on betaine hydrochloride (Betaine-HCL). maybe Pt or Tank may want elaborate alil

[kingcarlos]

3rd Taurine Ethly Ester Di-HCL

-taurine with an ester attached

http://www.serve.com/BatonRouge/taurine_chmr.htm

For a long time, taurine was considered a nonessential nutrient for humans. However, in recent years it has become clear that Taurine is a very important amino acid involved in a large number of metabolic processes and can become essential under certain circumstances. Taurine is important in the visual pathways, the brain and nervous system, cardiac function, and it is a conjugator of bile acids. Basically, its function is to facilitate the passage of sodium, potassium and possibly calcium and magnesium ions into and out of cells and to stabilize electrically the cell membranes. Dr. G. E. Gaull (1984) suggests that since human never develop a high level of cysteinsulfinic acid decarboxylase, an enzyme necessary for the formation of taurine from the amino acid cysteine, people are probably all somewhat dependent upon dietary taurine. Under certain conditions of high stress or in disease states the need for taurine probably increases. Another important function of taurine is detoxification.Taurine is required for efficent fat absorption & solubilization. Studies also showed that dietary taurine supplementation ameliorates experimental renal disease including models of refractory nephrotic syndrome and diabetic nephropathy. The benefinical effects of taurine are mediated by its antioxidant action. (Trachtman H. and Sturman J.A., 1996, Amino Acids, 11:1-13). Taurine may also have an important role in renal development. One study with rats showed protective effect of taurine on TNBS-induced inflammatory bowel disease. With all these discoveries and more on the horizon taurine research is accelerating rapidly.

Taurine is extremely well-absorbed and a good blood level is readily obtained.

Like all nutrients, taurine enhances or decreases the action of other nutrients. Monosodium glutamate (MSG) is the sodium salt of the amino acid glutamic acid. If glutamic acid supplementation is given, as is sometimes done with alcoholics, it tends to reduce taurine. MSG itself can also reduce taurine levels. The amino acids beta-alanine and beta-hypotaurine, as well as the B-vitamin pantothenic acid, may also interfere with taurine’s functions. Zinc, on the other hand, enhances taurine’s effects. Zinc deficiency and combined vitamin A and zinc deficiency are associated with an increased excretion of taurine in the urine and with depleted taurine levels in the tissues where it is normally found. Cysteine and vitamin B6 are the most critical nutrients to support the manufacture of taurine in the body of human beings or those species that are able to synthesize enough.

Taurine, as the most abundant urinary metabolite after sulfate, is formed primarily from the amino acid cysteine. Pyridoxal phosphate (active vitamin B6) is necessary for this to take place. Taurine excretion is reduced in B6 deficiency, which suggests that adequate B6 intake is necessary for the production of taurine. Some taurine may be made directly from sulfate, thus bypassing the need for cysteine. Cysteine and B6 are useful to boost taurine levels without giving taurine directly when there is concern about an irritating effect on the digestive tract. Taurine is excreted in two ways. It is readily eliminated in the urine if body taurine levels are adequate. In times of taurine depletion, however, the kidney reabsorbs taurine and does not allow it to be lost in the urine. Taurine is also excreted in the bile, where it is bound to bile acids. It probably keeps bile acids soluble, preventing gallstone formation. Interesting: When a normal nutrient balance study is done on cats consuming diets adequate in taurine, the sum of the quantity of taurine recovered in feces and urine is considerably less than the taurine ingested, even disregarding synthesis. The reason for this disparity between taurine ingested and taurine excreted must be due to microbial degradation in the gut. Anaerobic bacteria deconjugate the bile acid and degrade taurine as well as modifying the structure of the steroid moiety to produce secondary bile acids. The metabolism in the gut is therefore important in determining the taurine status of cats.

The number of peptides with reported hormonal effects has skyrocketed. Recently, a hormone called glutataurine was discovered in the parathyroid gland of rats. Dr. L. Feuer and colleagues (1982, 1983) found that this peptide had highly selective action on adrenal hormones, which are involved in the body’s response to stress and on rat brain neurotransmitters. The nutritional basis of glandular therapies may be in the ingested peptides. Glutataurine has vitamin A-like effects. It antagonizes cortisone and thyroxine and increases the development of the thymus; increased levels of taurine have been found in hypothyroid patients. Dr. W. G. Lampson and his colleagues (1983) have found that taurine increases some of the effects of insulin. Because insulin can have hypoglycemic effects, taurine should be given with caution to patients with blood sugar problems. Taurine can inhibit the release of adrenalin from the adrenal gland. Taurine and hypotaurine have physiochemical properties similar to the sperm motility factor. A role for taurine and hypotaurine has been demonstrated in preparing the sperm of experimental animals for fertilization. Conceivably, some problems of infertility may be related to taurine deficiency.

In the mother, taurine increases blood levels of the hormone prolactin, which triggers the production and release of milk. Taurine is thus a useful supplement for nursing mothers, because it promotes lactation in the mother and better development in the infant. In a study of three groups of mouse pups on high-, normal- and low-protein diets, taurine added to the mother’s drinking water increased the pups’ survival rate by increasing the supply of milk. (The Healing Nutrients within, Braverman).

http://www.thorne.com/altmedrev/full...aurine3-2.html

Taurine comprises over 50 percent of the total free amino acid pool of the heart.9 It has a positive inotropic action on cardiac tissue,10 and has been shown in some studies to lower blood pressure.11,12 In part, the cardiac effects of taurine are probably due to its ability to protect the heart from the adverse effects of either excessive or inadequate calcium ion (Ca2+) levels.13 The consequence of Ca2+ excess is the accumulation of intracellular calcium, ultimately leading to cellular death. Taurine may both directly and indirectly help regulate intracellular Ca2+ ion levels by modulating the activity of the voltage-dependent Ca2+ channels, and by regulation of Na+ channels. Taurine also acts on many other ion channels and transporters. Therefore, its action can be quite non-specific.14 When an adequate amount of taurine is present, calcium-induced myocardial damage is significantly reduced, perhaps by interaction between taurine and membrane proteins.15 At least one study has suggested taurine's ability to function as a membrane stabilizer is related to its capacity to prevent suppression of membrane-bound NaK ATPase.16

Other research demonstrates taurine can protect the heart from neutrophil-induced reperfusion injury and oxidative stress. Because the respiratory burst activity of neutrophils is also significantly reduced in the presence of taurine, perhaps taurine's protective effect is mediated by its antioxidative properties.17

http://www.3dchem.com/molecules.asp?ID=22
http://www.findarticles.com/p/articl..._6/ai_71948215

[pu12en12g]

More on betaine:

What are some of the benefits of TMG?

TMG (Betaine Anhydrous) is a methyl donor with the following applications in human nutrition:

Anti-depression: By raising level of beneficial SAM (S-Adenosyl-Methionine).

Dose range: 500-1,500 mg daily

Body building: In the animal husbandry field, TMG is used to decrease fat and increase meat yield. While human studies have just started, a 200 pound individual with 20% body fat can expect to lose as much as 5 pounds of fat and gain as much as 12 pounds of muscle.

Dose range: 500-2,000 mg daily

Cardiac protection: Conversion of homocysteine to Methionine.

Dose range: 500-1,000 mg daily

General Health Preventative: As part of a formula for maintaining good health or disease prevention.

Dose range: 500-1,000 mg daily

Glutathione Elevation: In several different studies, TMG has been shown to increase hepatic Glutathione, the body's most important antioxidant.

Dose range: 500-1,500 mg daily

Homocysteine Lowering: Specific for that purpose. The supplement of choice for lowering homocystenuria,

Dose range: 500-1,000 mg daily.
As used by clinicians and hospitals with patient monitoring -up to 3 grams daily

Liver Disorders: As a part of liver-healing and protection formulas. Increases SAM levels in the liver, enables the liver to metabolize fat and protect against many challenges such as alcohol induced cirrhosis. TMG will also decrease bilirubin, alkaline phosphotase, and several other liver enzymes related to a large variety of liver disorders. Significant liver benefits have been shown in 20 studies.

Dose range: 500-1,500 mg. daily.

Longevity Formulations: As a part of a life extension formula. TMG has shown ability to protect interrogate of cellular DNA through methyl donation.

Dose range: 500-1,000 mg daily.

Methyl Donor Formulations: Along with B12, Folic acid, and Choline.

Dose range: 500-1,500 mg. daily.

Performance: Due to it's bi-polar nature, helps osmotic pressure in cells. For example it is used in salmon farming to protect fish against the problems of changing salt content. In humans, TMG maintains normal cellular electrolyte concentrations despite water and electrolyte losses during exercise. TMG also helps metabolize fats, which allows the body to burn fat rather than protein or muscle during exercise. The result is less cramping, increased endurance, and better utilization of fat stores,

Dose range: 1,000-2,000 mg daily.

Dietary betaine supplementation affects energy metabolism of pigs

This study provides evidence for a potential energy-sparing role of betaine in the metabolism of growing pigs. This study was performed under specific conditions of energy limitation in combination with a mild environmental stress. Under such conditions, betaine supplementation might enhance the energetic value of diets. Based on the reduced water consumption, the use of the osmotic properties of betaine seems promising when pigs are exposed to heat stress. The current results stress the importance of further research, for which environmental circumstances should be carefully chosen. To prevent accumulation of conflicting information, future studies should include measurements to elucidate further the mode of action of betaine.

http://jas.fass.org/cgi/reprint/81/5/1202

[kingcarlos]

4th Arginine Ethyl Ester

http://jpet.aspetjournals.org/cgi/co...act/255/3/1348
http://www.pubmedcentral.nih.gov/art...i?artid=284042

We have reported previously that N alpha-cocoyl-L-arginine ethyl ester (CAE) strongly inactivates hepatitis B surface antigen (HBsAg; Sugimoto and Toyoshima, Antimicrob. Agents Chemother. 16:329--332, 1979). Replacement of the L-arginine moiety of CAE by L-lysine did not decrease the HBsAg-inactivating effect of CAE, whereas replacement by some neutral amino acids and L-ornithine decreased it. Esterification of the carboxyl group of N alpha-acyl-L-arginine enhanced its inactivating effect. When the ethyl ester of CAE was converted to an amide group, the effect was appreciably decreased. Modification of the carboxyl group was essential for the inactivation. The effectiveness of N alpha-acyl-L-arginine ethyl ester depends upon the length of the acyl group, with the optimum length for the inactivation of HBsAg being C12 to C14. In addition to CAE, N alpha-lauroyl-L-lysine ethyl ester and N alpha-cocoyl-L-arginine amide were found to be strong inactivators of HBsAg. Significant inactivating effects on HBsAg were not observed in many anionic detergents containing an amino acid. These results suggest that for strongly inactivating HBsAg, a compound should contain a special amino acid, such as L-arginine, and a long acyl group and exhibit a cationic property.

http://www.serva.de/products/data/14600.02.shtml

http://www.pubmedcentral.nih.gov/art...i?artid=396133

The effect of pH on the hydrolysis of α-N-benzoyl-l-arginine ethyl ester (BAEE) and α-N-benzoyl-l-argininamide (BAA) by a proteolytic enzyme component purified from Ficus carica var. Kadota latex has been studied in detail over the pH range of 3 to 9.5. kcat (lim) values for the hydrolysis of BAEE and BAA were essentially identical (5.20 and 5.01 sec−1, respectively at 30°). kcat values for hydrolysis of BAEE and BAA were dependent on prototropic groups with apparent pK values of 4.24 and 8.53 and 4.10 and 8.59, respectively. kcat (lim) values for tht hydrolysis of BAEE and BAA were essentially identical (5.20 and groups of pK 4.33 and 8.60 and 4.55 and 8.51, respectively. Thus the pH optimum is 6.5 for both substrates. Km (app) values for BAEE and BAA were 3.32 × 10−2m and 6.03 × 10−2m respectively over the pH range of 3.9 to 8.0. These data are interpreted in terms of the involvement of a carboxyl and a sulfhydryl group in the active center of the enzyme. The data do not support the concept that deacylation of the acyl-enzyme is completely the rate controlling step in the hydrolyses. Rather, it appears that the magnitude of k2 and k3 are not greatly different.

http://jpet.aspetjournals.org/cgi/co...ract/254/1/289

L-arginine has been proposed to be the precursor of the endothelium- derived relaxing factor. In this study, we evaluated the pulmonary vascular effects of L-arginine-HCl and its benzoyl derivative N-alpha- benzoyl-L-arginine ethyl ester (BAEE) in the rat, in comparison with other vasodilators such as acetylcholine and sodium nitroprusside. In isolated pulmonary artery rings incubated with indomethacin (10 microM) and precontracted with phenylephrine (2 microM), BAEE (10(-6)-10(-5) M) significantly (P less than .05) relaxed the rings more than L-arginine. This effect was potentiated by the endothelium (P less than .05). The relaxing effect of BAEE (ED50 = 2.1 X 10(-6) M) and acetylcholine (ED50 = 2.4 X 10(-7) M) was significantly less potent than that of sodium nitroprusside (ED50 = 1.1 X 10(-8) M). Moreover, pretreatment with the soluble guanylate cyclase inhibitors methylene blue (10(-5) M) and hemoglobin (10(-5) M) antagonized BAEE-induced relaxation in intact pulmonary rings but had no effect on the relaxation elicited with atrial natriuretic peptide. In the isolated lung preparations perfused with the endoperoxide analog U46619 (5-10 nmol/min), sodium nitroprusside (10(-10)-10(-8) M) elicited potent vasodilation (ED50 = 2.8 X 10(-9) mol) whereas no vasodilation was observed with acetylcholine (10(-8)-10(-5) mol). BAEE (10(-6)-10(-5) M) decreased in a dose-dependent manner pulmonary perfusion pressure, and similar doses of L-arginine showed only a mild vasodilating effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[kingcarlos]

5th

glycocyamine

http://www.findarticles.com/p/articl...20/ai_98488370

Breaking research has revealed that you might be able to get more out of supplemental creatine by using glycocyamine, the primary building block (precursor) of creatine. Better yet, this nutrient might also boost endogenous (the body's own) creatine production, answering the prayers of creatine nonresponders who have been looking for a way to get the incredible effects of creatine monohydrate.

http://www.jem.org/cgi/content/abstract/81/5/423
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Of the six phosphagen kinases found in animals, the primary structure is known only for creatine kinase. Here we report three cDNA-derived or chemically determined amino acid sequences of two kinds of phosphagen kinases: a glycocyamine kinase from the polychaete Neanthes diversicolor (Annelida) and arginine kinase from the abalone Nordotis madaka (Mollusca) and the shrimp Penaeus japonicus (Arthropoda). Like vertebrate creatine kinases are monomers. These enzymes consist of 350 to 390 amino acid residues, and have a calculated molecular mass of 39,900 to 44,500 Da. Neanthes glycocyamine kinase shows 50 to 58% sequence similarity with vertebrate and invertebrate creatine kinases, having the greatest similarity (57 to 58%) with vertebrate mitochondrial creatine kinase isoform. It shows lower, but significant similarity (37 to 39%) with invertebrate arginine kinases. The sequence similarity between Nordotis and Penaeus arginine kinases is 51%. A phylogenetic tree constructed from 14 amino acid sequences of phosphagen kinases showed that they can be separated into three major clusters corresponding to creatine kinase, glycocyamine kinase and arginine kinase. The cluster of glycocyamine kinase is apparently closer to that of creatine kinase than arginine kinase. The cluster of creatine kinase is composed of several subclusters, each corresponding to three vertebrate isoforms and the invertebrate enzyme.

[kingcarlos]

6th

4-Hydroxyisoleucine

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Citation

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 microM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

http://diabetes.diabetesjournals.org...tract/47/2/206

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

http://www.integritynut.com/sp1.htm

http://doi.wiley.com/10.1002/ejoc.200300434
http://doi.wiley.com/10.1002/1099-06...4%3E3.0.CO;2-6

[kingcarlos]

Red acid

REDuction Complex™ 1000mg
FlaxSeed Oil Powder, Bioactive Fatty-Acid Ethanolamide (Oleoylethanolamide) (OEA), Hypolipidemic Fatty Acid Analogue (Tetradecylthioacetic Acid)

Ethanolamide

http://jpet.aspetjournals.org/cgi/co...ract/301/3/900

Pharmacological Characterization of the Anandamide Cyclooxygenase Metabolite: Prostaglandin E2 Ethanolamide

Ruth A. Ross, Susan J. Craib, Lesley A. Stevenson, Roger G. Pertwee, Andrea Henderson, John Toole and Heather C. Ellington

Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland

Anandamide can be metabolized by cyclooxygenase-2 to produce prostaglandin E2 (PGE2) ethanolamide. The purpose of this study was to investigate the pharmacology of this novel compound. Radioligand binding experiments in membranes from human embryonic kidney cells transfected with PGE2 receptor subtypes EP1, EP2, EP3, and EP4 revealed that PGE2 ethanolamide has pKi values of 5.61 ± 0.1, 6.33 ± 0.01, 6.70 ± 0.13, and 6.29 ± 0.06, respectively, compared with 8.31 ± 0.16, 9.03 ± 0.04, 9.34 ± 0.06, and 9.10 ± 0.04 for PGE2. PGE2 inhibits electrically evoked contractions of the guinea pig vas deferens (EP3 receptor-mediated), with a pEC50 value of 9.09 ± 0.06, compared with that of 7.38 ± 0.09 for PGE2 ethanolamide. In the guinea pig trachea, 100 nM PGE2 and 1 µM PGE2 ethanolamide produced contractions of 51.8 ± 10.6 and 38.9 ± 5.6% (of the histamine Emax), respectively. The EP1 receptor antagonist SC-51089 (10 µM) prevented the contractions induced by both compounds. In the presence of 10 µM 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089), PGE2 caused a concentration-related relaxation of histamine-induced contractions of this tissue (EP2 receptor-mediated), the pEC50 value being 8.29 ± 0.17 compared with that of 7.11 ± 0.18 for PGE2 ethanolamide. In the rabbit jugular vein, PGE2 induces relaxation (EP4 receptor-mediated) with a pEC50 of 9.35 ± 0.25, compared with 7.05 ± 0.4 for PGE2 ethanolamide. In dorsal root ganglion neurons in culture, 3 µM PGE2 ethanolamide evoked an increase in intracellular calcium concentration in 21% of small-diameter capsaicin-sensitive neurons. We conclude that this compound is pharmacologically active, however its physiological relevance has yet to be established.

Inflammatory Diseases Unit, Roche Bioscience, Palo Alto, California 94303, USA.

Because of its structural similarity to polyunsaturated fatty acids, anandamide could serve as substrate for enzymes such as lipoxygenases and cyclooxygenases, which metabolize polyunsaturated fatty acids to potent bioactive metabolites. Here the ability of recombinant human cyclooxygenase-1 (hCOX-1) and cyclooxygenase-2 (hCOX-2) to metabolize anandamide was studied. Baculovirus-expressed and -purified hCOX-2, but not hCOX-1, effectively oxygenated anandamide. Reverse phase high pressure liquid chromatography analysis of the products derived from 1-14C-labeled anandamide showed that the products formed are similar to those formed with arachidonic acid as substrate. The major prostanoid product derived from anandamide was determined by mass spectrometry to be prostaglandin E2 ethanolamide. Incubation of anandamide with lysates and the intact cell line expressing COX-2 but not that of COX-1 produced prostaglandin E2 ethanolamide. These results demonstrate the existence of a COX-2-mediated pathway for anandamide metabolism, and the metabolites formed represent a novel class of prostaglandins.

Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK AB25 2ZD. r.ross@abdn.ac.uk

Anandamide can be metabolized by cyclooxygenase-2 to produce prostaglandin E(2) (PGE(2)) ethanolamide. The purpose of this study was to investigate the pharmacology of this novel compound. Radioligand binding experiments in membranes from human embryonic kidney cells transfected with PGE(2) receptor subtypes EP(1), EP(2), EP(3), and EP(4) revealed that PGE(2) ethanolamide has pK(i) values of 5.61 +/- 0.1, 6.33 +/- 0.01, 6.70 +/- 0.13, and 6.29 +/- 0.06, respectively, compared with 8.31 +/- 0.16, 9.03 +/- 0.04, 9.34 +/- 0.06, and 9.10 +/- 0.04 for PGE(2). PGE(2) inhibits electrically evoked contractions of the guinea pig vas deferens (EP(3) receptor-mediated), with a pEC(50) value of 9.09 +/- 0.06, compared with that of 7.38 +/- 0.09 for PGE(2) ethanolamide. In the guinea pig trachea, 100 nM PGE(2) and 1 microM PGE(2) ethanolamide produced contractions of 51.8 +/- 10.6 and 38.9 +/- 5.6% (of the histamine E(max)), respectively. The EP(1) receptor antagonist SC-51089 (10 microM) prevented the contractions induced by both compounds. In the presence of 10 microM 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089), PGE(2) caused a concentration-related relaxation of histamine-induced contractions of this tissue (EP(2) receptor-mediated), the pEC(50) value being 8.29 +/- 0.17 compared with that of 7.11 +/- 0.18 for PGE(2) ethanolamide. In the rabbit jugular vein, PGE(2) induces relaxation (EP(4) receptor-mediated) with a pEC(50) of 9.35 +/- 0.25, compared with 7.05 +/- 0.4 for PGE(2) ethanolamide. In dorsal root ganglion neurons in culture, 3 microM PGE(2) ethanolamide evoked an increase in intracellular calcium concentration in 21% of small-diameter capsaicin-sensitive neurons. We conclude that this compound is pharmacologically active, however its physiological relevance has yet to be established.

[kingcarlos]

continued

The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs
Hans Wahn, Jürgen Wolf, Florian Kram, Stefan Frantz, and Jens A. Wagner

Department of Internal Medicine I/Center of Cardiovascular Medicine, University of Würzburg, Germany

Submitted 5 July 2005 ; accepted in final form 25 July 2005

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.9 ± 3.4 mmHg, 5 µM, and +39.5 ± 10.8 mmHg, 0.4 µM, respectively). 2-AG induced lung edema. The CB1 receptor antagonist AM-251 (0.1 and 5 µM) and the VR1 vanilloid receptor antagonist capsazepine (10 µM) failed to reduce anandamide's effects. The metabolically stable anandamide and 2-AG analogs R-methanandamide and noladin ether, {Delta}9-tetrahydrocannabinol, and the synthetic cannabinoid HU-210, which is no arachidonic acid product, were without effect. The unspecific cyclooxygenase (COX) inhibitor aspirin (100 µM, P < 0.001) and the specific COX-2 inhibitor nimesulide (10 µM, P < 0.01) completely prevented pulmonary hypertension after 5 µM anandamide. COX-2 RNA was detected in rabbit lungs. The synthetic thromboxane receptor antagonist SQ 29,548 was without effect, but the specific EP1 prostanoid receptor antagonist SC-19220 (100 µM) inhibited the pressure increase after anandamide (P < 0.05). PCR analysis detected fatty acid amidohydrolase (FAAH), an enzyme that degrades endocannabinoids, in rabbit lung tissue. Furthermore, the specific FAAH inhibitor methyl arachidonyl fluorophosphonate (0.1 µM) blocked pressure effects of anandamide (P < 0.01). Finally, anandamide (99 ± 55 pmol/g) and 2-AG (19.6 ± 8.4 nmol/g) were found in native lungs. We conclude that anandamide increases pulmonary arterial pressure via COX-2 metabolites following enzymatic degradation by FAAH into arachidonic acid products.

pulmonary hypertension; cannabinoid receptors; vanilloid receptors; prostaglandins

The discovery of the endogenous cannabimimetic lipid mediators, anandamide and 2-arachidonoyl glycerol, opened the door to the discovery of other endogenous lipid mediators similar in structure and function. The majority of these compounds do not bind appreciably to known cannabinoid receptors; yet some of them produce cannabimimetic effects while others exert actions through novel mechanisms that remain to be elucidated. This review explores the growing diversity of recently discovered putative lipid mediators and their relationship to the endogenous cannabinoid system. The possibility that there remain many unidentified signalling lipids coupled with the evidence that many of these yield bioactive metabolites due to actions of known enzymes (e.g. cyclooxygenases, lipoxygenases, cytochrome P450s) suggests the existence of a large and complex family of lipid mediators about which only little is known at this time. The elucidation of the biochemistry and pharmacology of these compounds may provide therapeutic targets for a variety of conditions including sleep dysfunction, eating disorders, cardiovascular disease, as well as inflammation and pain.
Keywords:

Cannabinoid, lipid mediator, acyl ethanolamide, arachidonoyl glycine, arachidonoyl dopamine, oleoyl dopamine, cyclooxygenase
Abbreviations:

2-AG, 2-arachidonoyl glycerol; anandamide, N-arachidonoyl ethanolamide; CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; FAAH, fatty acid amide hydrolase; GABA, arachidonoyl-italic gamma-aminobutyric acid; NADA, N-arachidonoyl dopamine; NAGly, N-arachidonoyl glycine; noladin ether, 2-arachidonoyl glycerol ether; OEA, oleoyl ethanolamide; OLDA, oleoyl dopamine; PALDA, palmitoyldopamine; PEA, palmitoyl ethanolamide; SEA, stearoyl ethanolamide; STEARDA, stearoyldopamine; TRPV1, transient receptor potential type vanilloid 1 receptor

http://www.nature.com/bjp/journal/v1.../0706093a.html

[kingcarlos]

Oleoylethanolamide

http://www.jlr.org/cgi/content/short/C300008-JLR200v1

Food intake is inhibited by oral oleoylethanolamide
Mie Julin Nielsen, Gitte Petersen, Arne Astrup, and Harald S. Hansen

Department of Pharmacology, Danish University of Pharmaceutical Sciences, Copenhagen 2100

Corresponding Author: hsh@dfh.dk

Oleoylethanolamide may be an endogenous regulator of food intake, and intraperitoneal injection of this compound decreases food intake in 24 h-starved rats (Rodriguez de Fonseca et al. 2001 Nature 414, 209-212). It is generally believed that this kind of lipid amides is rapidly catabolized in the gastrointestinal tract thereby preventing their use as oral anti-obesity compounds. We now show that oral oleoylethanolamide inhibits food intake dose-dependently 90 min after food presentation to starved rats. Food intake was reduced 15.5% (P < 0.01) by administration of 10 mg/kg of oleoylethanolamide. [3H]-Oleoylethanolamide was used to assess the degree of catabolism in the gastro-intestinal tract. The endogenous level of this acylethanolamide was increased 11 times in the intestinal tissue (i.e. 3.91 ± 0.98 nmol/g tissue, mean ± SEM) 90 min after food presentation as a result of the finding of 0.48% of the dose as intact oleoylethanolamide. These findings reveal unexpected properties of orally administered oleoylethanolamide, which may have the potential of a cheap and safe anti-obesity drug.

http://www.weightloss-news.com/did_alpha_sample.htm#oea

www.cmcr.ucsd.edu/geninfo/11_Fu.pdf
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Department of Pharmacology, Georgetown University, Washington, DC 20057, USA. gpa3@georgetown.edu

The fatty acid oleoylethanolamide (OEA) is a satiety factor that excites peripheral vagal sensory nerves, but the mechanism by which this occurs and the molecular targets of OEA are unclear. In this study the ability of OEA to modulate the capsaicin receptor (TRPV1) was explored. OEA alone did not activate TRPV1 expressed in Xenopus oocytes under control conditions, but produced a differential modulation of agonist-evoked responses. OEA enhanced proton-gated TRPV1 currents, inhibited anandamide-evoked currents and had no effect on capsaicin-evoked responses. Following stimulation of protein kinase C (PKC), OEA alone directly activated TRPV1 channel with an EC50 of approximately 2 microm at room temperature. This effect was due to direct phosphorylation of TRPV1 because no responses to OEA were observed with mutant channels lacking critical PKC phosphorylation sites, S502A/S800A. In sensory neurons, OEA-induced Ca2+ rises that were selective for capsaicin-sensitive cells, inhibited by the TRPV1 blocker, capsazepine, and occurred in a PKC-dependent manner. Further, after PKC stimulation, OEA activated TRPV1 channels in cell-free patches suggesting a direct mode of action. Thus, TRPV1 represents a potential target for OEA and may contribute to the excitatory action of OEA on sensory nerves.

Department of Pharmacology, Georgetown University, Washington, DC 20057, USA. gpa3@georgetown.edu

The fatty acid oleoylethanolamide (OEA) is a satiety factor that excites peripheral vagal sensory nerves, but the mechanism by which this occurs and the molecular targets of OEA are unclear. In this study the ability of OEA to modulate the capsaicin receptor (TRPV1) was explored. OEA alone did not activate TRPV1 expressed in Xenopus oocytes under control conditions, but produced a differential modulation of agonist-evoked responses. OEA enhanced proton-gated TRPV1 currents, inhibited anandamide-evoked currents and had no effect on capsaicin-evoked responses. Following stimulation of protein kinase C (PKC), OEA alone directly activated TRPV1 channel with an EC50 of approximately 2 microm at room temperature. This effect was due to direct phosphorylation of TRPV1 because no responses to OEA were observed with mutant channels lacking critical PKC phosphorylation sites, S502A/S800A. In sensory neurons, OEA-induced Ca2+ rises that were selective for capsaicin-sensitive cells, inhibited by the TRPV1 blocker, capsazepine, and occurred in a PKC-dependent manner. Further, after PKC stimulation, OEA activated TRPV1 channels in cell-free patches suggesting a direct mode of action. Thus, TRPV1 represents a potential target for OEA and may contribute to the excitatory action of OEA on sensory nerves.

Department of Pharmacology, Georgetown University, Washington, DC 20057, USA. gpa3@georgetown.edu

The fatty acid oleoylethanolamide (OEA) is a satiety factor that excites peripheral vagal sensory nerves, but the mechanism by which this occurs and the molecular targets of OEA are unclear. In this study the ability of OEA to modulate the capsaicin receptor (TRPV1) was explored. OEA alone did not activate TRPV1 expressed in Xenopus oocytes under control conditions, but produced a differential modulation of agonist-evoked responses. OEA enhanced proton-gated TRPV1 currents, inhibited anandamide-evoked currents and had no effect on capsaicin-evoked responses. Following stimulation of protein kinase C (PKC), OEA alone directly activated TRPV1 channel with an EC50 of approximately 2 microm at room temperature. This effect was due to direct phosphorylation of TRPV1 because no responses to OEA were observed with mutant channels lacking critical PKC phosphorylation sites, S502A/S800A. In sensory neurons, OEA-induced Ca2+ rises that were selective for capsaicin-sensitive cells, inhibited by the TRPV1 blocker, capsazepine, and occurred in a PKC-dependent manner. Further, after PKC stimulation, OEA activated TRPV1 channels in cell-free patches suggesting a direct mode of action. Thus, TRPV1 represents a potential target for OEA and may contribute to the excitatory action of OEA on sensory nerves.

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Citation

Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-alpha. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-alpha agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.

http://jp.physoc.org/cgi/content/abstract/564/2/541

Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1
Xiangbin Wang1, Rosa Linda Miyares1 and Gerard P Ahern1

1 Department of Pharmacology, Georgetown University, 3900 Reservoir Road NW, Washington, DC 20057, USA

Oleoylethanolamide (OEA) is an endogenous lipid that regulates feeding and body weight. Although the effects of OEA are believed to depend on activation of vagal sensory afferent neurones, the mechanisms involved in exciting these neurones are unclear. Here we show that OEA directly excited nodose ganglion neurones, the cell bodies of vagal afferents. OEA depolarized these neurones and evoked inward currents that were restricted to capsaicin-sensitive cells. These currents were fully blocked by the TRPV1 inhibitor, capsazepine, and no responses to OEA were observed in neurones cultured from TRPV1-null mice. Similarly, OEA induced a rise in Ca+ concentration in wild-type but not TRPV1-deficient neurones, and responses to OEA were greater at 37°C compared to room temperature. Significantly, OEA administration in mice induced visceral pain-related behaviours that were inhibited by capsazepine and absent in TRPV1-null animals. Further, OEA reduced 30-min food intake in wild-type but not in TRPV1-null mice. Thus, the acute behavioural effects of OEA may result from visceral malaise via the activation of TRPV1.

[kingcarlos]

continued

http://www.jbc.org/cgi/content/abstract/278/33/30429

From the Department of Pharmacology, Georgetown University, Washington, D. C. 20057

The fatty acid oleoylethanolamide (OEA) is a satiety factor that excites peripheral vagal sensory nerves, but the mechanism by which this occurs and the molecular targets of OEA are unclear. In this study the ability of OEA to modulate the capsaicin receptor (TRPV1) was explored. OEA alone did not activate TRPV1 expressed in Xenopus oocytes under control conditions, but produced a differential modulation of agonist-evoked responses. OEA enhanced proton-gated TRPV1 currents, inhibited anandamide-evoked currents and had no effect on capsaicin-evoked responses. Following stimulation of protein kinase C (PKC), OEA alone directly activated TRPV1 channel with an EC50 of ~2 µM at room temperature. This effect was due to direct phosphorylation of TRPV1 because no responses to OEA were observed with mutant channels lacking critical PKC phosphorylation sites, S502A/S800A. In sensory neurons, OEA-induced Ca2+ rises that were selective for capsaicin-sensitive cells, inhibited by the TRPV1 blocker, capsazepine, and occurred in a PKC-dependent manner. Further, after PKC stimulation, OEA activated TRPV1 channels in cell-free patches suggesting a direct mode of action. Thus, TRPV1 represents a potential target for OEA and may contribute to the excitatory action of OEA on sensory nerves.

www.ccicht.ca/November_2004.pdf
www.pwsnotes.org/Medical_Research

[kingcarlos]

Hypolipidemic Fatty Acid Analogue (Tetradecylthioacetic Acid)



http://www.jlr.org/cgi/content/abstract/36/3/535

Tetradecylthioacetic acid (a 3-thia fatty acid) decreases triacylglycerol secretion in CaCo-2 cells

A Gedde-Dahl, T Ranheim, CA Drevon, S Skrede, RK Berge and AC Rustan
Department of Pharmacology, University of Oslo, Norway.

The effects of the hypolipidemic fatty acid analogue tetradecylthioacetic acid (TTA) on synthesis and secretion of lipoproteins in CaCo-2 cells were studied. Radiolabeled tetradecylthioacetic acid was absorbed and metabolized as efficiently as oleic acid, although a discrepancy in the metabolic fate was evident. Whereas tetradecylthioacetic acid was incorporated into cell- associated triacylglycerol to the same extent as normal fatty acids (e.g., oleic acid and palmitic acid), the amount of triacylglycerol secreted from cells incubated with tetradecylthioacetic acid was 8 to 10 times lower than the amount secreted from cells incubated with palmitic acid and oleic acid, respectively. On the other hand, there was an enhanced incorporation of tetradecylthioacetic acid into cell- associated and secreted phospholipids. Despite incorporation of tetradecylthioacetic acid into cellular triacylglycerol, unlike oleic acid, tetradecylthioacetic acid did not stimulate production of triacylglycerol-rich particles. Ultracentrifugation of basolateral media from cells incubated with tetradecylthioacetic acid revealed low amounts of triacylglycerol in the triacylglycerol-rich fraction (p < 1.006 g/ml), suggesting secretion of lipoproteins with a higher density than chylomicrons. However, the present study shows that the stimulated triacylglycerol secretion caused by oleic acid was inhibited in the presence of TTA. The decreased rate of triacylglycerol secretion from these cells was not accompanied by a stimulation of fatty acid oxidation. Based on these findings, we therefore suggest that tetradecylthioacetic acid mainly affects secretion of lipoproteins in CaCo-2 cells.

[kingcarlos]

Red Sweat Complex™ 650mg
L-tyrosine, Natural Caffeine, Green Tea Extract (60% EGCG), Coleus Forskohlii (20% Forskolin), Evodia Rutaecarpa (95% Evodiamine Extract), Cocoa Bean (Extracted for 99% Theobromine), Salvia Sclaria (96% sclareolides), Bioperine® (Piper Nigrum), Vinca Minor (Extracted for 99% Vinpocetine), Huperzia Serrata (Extracted for 99% Huperzine A)

L-tyrosine

Tyrosine for depression:
a double-blind trial
by
Gelenberg AJ, Wojcik JD, Falk WE,
Baldessarini RJ, Zeisel SH, Schoenfeld D, Mok GS
Department of Psychiatry,
University of Arizona, Tucson 85724.
J Affect Disord 1990 Jun; 19(2):125-32

ABSTRACT

We treated 65 outpatients with RDC major depression in a randomized, prospective, double-blind comparison of oral L-tyrosine, 100 mg/kg/day, imipramine, 2.5 mg/kg/day, or placebo for 4 weeks. Tyrosine increased and imipramine decreased 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion significantly, but there was no evidence that tyrosine had antidepressant activity. The only side effect to achieve statistical significance was greater dry mouth with imipramine. MHPG excretion and plasma amino acid concentrations failed to predict or correlate with clinical improvement.

http://www.pdrhealth.com/drug_info/n...lty_0256.shtml
http://www.umm.edu/altmed/ConsSupple...yrosinecs.html

Tyrosine is a nonessential amino acid that is synthesized in the body from phenylalanine. As a building block for several important brain chemicals, tyrosine is needed to make epinephrine, norepinephrine, serotonin, and dopamine, all of which work to regulate mood. Deficiencies in tyrosine, therefore, have been associated with depression. Tyrosine also aids in the production of melanin (pigment responsible for hair and skin color) and in the function of organs in the body responsible for making and regulating hormones, including the adrenal, thryroid, and pituitary glands. Tyrosine is also involved in the synthesis of enkephalins, substances that have pain-relieving effects in the body.

Low levels of tyrosine have been associated with low blood pressure, low body temperature, and an under active thyroid. This does not mean, however, that taking tyrosine supplements will avoid these particular circumstances.

Because tyrosine binds unstable molecules (called free radicals) that can potentially cause damage to the cells and tissues, it is considered a mild antioxidant. Thus, tyrosine may be useful for people who have been exposed to harmful chemicals (such as from smoking) and radiation.

Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors.

Adinolfi E, Kim M, Young MT, Di Virgilio F, Surprenant A.

Institute of Molecular Physiology, Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.

The purinergic P2X7 receptor not only gates the opening of a cationic channel, but also couples to several downstream signaling events such as rapid membrane blebbing, microvesicle shedding, and interleukin-1beta release. Protein-protein interactions are likely to be involved in most of these signaling cascades; and recently, a P2X7 receptor-protein complex comprising at least 11 distinct proteins has been identified. We have studied one of these interacting proteins, HSP90, in human embryonic kidney cells expressing either human or rat P2X7 receptors as well as in rat peritoneal macrophages using biochemical (immunoprecipitation and Western blotting) and functional (membrane blebbing and currents) assays. We found that HSP90 was tyrosine-phosphorylated in association with the P2X7 receptor complex, but not in the cytosolic compartment. The HSP90 inhibitor geldanamycin decreased tyrosine phosphorylation of HSP90 and produced a 2-fold increase in the sensitivity of P2X7 receptors to agonist. Protein expression and tyrosine phosphorylation of a mutant P2X7 receptor in which a tyrosine in the C-terminal domain was substituted with phenylalanine (Y550F) were not changed, but tyrosine phosphorylation of HSP90 associated with this mutant P2X7 receptor complex was significantly greater than that associated with the wild-type complex. P2X7-Y550F receptors showed a 15-fold lower sensitivity to agonist, which was reversed by geldanamycin. We conclude that selective tyrosine phosphorylation of P2X7 receptor-associated HSP90 may act as a negative regulator of P2X7 receptor complex formation and function.
Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors.

Adinolfi E, Kim M, Young MT, Di Virgilio F, Surprenant A.

Institute of Molecular Physiology, Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.

The purinergic P2X7 receptor not only gates the opening of a cationic channel, but also couples to several downstream signaling events such as rapid membrane blebbing, microvesicle shedding, and interleukin-1beta release. Protein-protein interactions are likely to be involved in most of these signaling cascades; and recently, a P2X7 receptor-protein complex comprising at least 11 distinct proteins has been identified. We have studied one of these interacting proteins, HSP90, in human embryonic kidney cells expressing either human or rat P2X7 receptors as well as in rat peritoneal macrophages using biochemical (immunoprecipitation and Western blotting) and functional (membrane blebbing and currents) assays. We found that HSP90 was tyrosine-phosphorylated in association with the P2X7 receptor complex, but not in the cytosolic compartment. The HSP90 inhibitor geldanamycin decreased tyrosine phosphorylation of HSP90 and produced a 2-fold increase in the sensitivity of P2X7 receptors to agonist. Protein expression and tyrosine phosphorylation of a mutant P2X7 receptor in which a tyrosine in the C-terminal domain was substituted with phenylalanine (Y550F) were not changed, but tyrosine phosphorylation of HSP90 associated with this mutant P2X7 receptor complex was significantly greater than that associated with the wild-type complex. P2X7-Y550F receptors showed a 15-fold lower sensitivity to agonist, which was reversed by geldanamycin. We conclude that selective tyrosine phosphorylation of P2X7 receptor-associated HSP90 may act as a negative regulator of P2X7 receptor complex formation and function.
Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors.

Adinolfi E, Kim M, Young MT, Di Virgilio F, Surprenant A.

Institute of Molecular Physiology, Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.

The purinergic P2X7 receptor not only gates the opening of a cationic channel, but also couples to several downstream signaling events such as rapid membrane blebbing, microvesicle shedding, and interleukin-1beta release. Protein-protein interactions are likely to be involved in most of these signaling cascades; and recently, a P2X7 receptor-protein complex comprising at least 11 distinct proteins has been identified. We have studied one of these interacting proteins, HSP90, in human embryonic kidney cells expressing either human or rat P2X7 receptors as well as in rat peritoneal macrophages using biochemical (immunoprecipitation and Western blotting) and functional (membrane blebbing and currents) assays. We found that HSP90 was tyrosine-phosphorylated in association with the P2X7 receptor complex, but not in the cytosolic compartment. The HSP90 inhibitor geldanamycin decreased tyrosine phosphorylation of HSP90 and produced a 2-fold increase in the sensitivity of P2X7 receptors to agonist. Protein expression and tyrosine phosphorylation of a mutant P2X7 receptor in which a tyrosine in the C-terminal domain was substituted with phenylalanine (Y550F) were not changed, but tyrosine phosphorylation of HSP90 associated with this mutant P2X7 receptor complex was significantly greater than that associated with the wild-type complex. P2X7-Y550F receptors showed a 15-fold lower sensitivity to agonist, which was reversed by geldanamycin. We conclude that selective tyrosine phosphorylation of P2X7 receptor-associated HSP90 may act as a negative regulator of P2X7 receptor complex formation and function.

http://www.umm.edu/altmed/ConsSupple...yrosinecs.html

Antidepressant Medications, Monoamine Oxidase Inhibitors (MAOIs)
Tyrosine may cause a severe increase in blood pressure in people taking MAOIs (such as phenelzine, tranylcypromine, pargyline, and selegiline). This severe increase in blood pressure (also called "hypertensive crisis") can lead to a heart attack or stroke. For this reason, individuals taking MAOIs should foods and supplements containing tyrosine.

Appetite suppressant Medications

In a rat study, L-tyrosine increased the appetite-suppressant effects of phenylpropanolamine, ephedrine, and amphetamine. More research is needed to determine whether L-tyrosine produces similar results in humans.

Morphine
Although the application for humans is unclear, animal studies suggest that tyrosine increases the pain-relieving effects of morphine.

Levodopa
Tyrosine should not be taken at the same time as levodopa, a medication used to treat Parkinson's disease because levodopa may interfere with the absorption of tyrosine.

[kingcarlos]

green tea extract

http://thyroid.about.com/cs/dietweightloss/a/greentea
http://www.umm.edu/altmed/ConsHerbs/GreenTeach.html
http://www.raysahelian.com/greentea.html

http://www.news-medical.net/?id=7673

A new study tested the effect of regularly taking green tea extract (GTE) and found that over 10 weeks, endurance exercise performance was boosted up to 24% with 0.5% GTE supplementation, and 8% with 0.2% by-weight addition to food.

Reporting in the online edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology researchers at the Biological Sciences Laboratories of Kao Corp., Tochigi, Japan, said the 8-24% increase in swimming time-to-exhaustion was "accompanied by lower respiratory quotients and higher rates of fat oxidation."

The results "indicate that GTE is beneficial for improving endurance capacity and support the hypothesis that the stimulation of fatty acid utilization is a promising strategy for improving endurance capacity," according to the study entitled, "Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice." Research was conducted by Takatoshi Murase, Satoshi Haramizu, Akira Shimotoyodome, Azumi Nagasawa and Ichiro Tokimitsu, working at Kao Corp., a Japanese maker of healthcare products, including green tea beverages.

http://www.physorg.com/news2849.html
Green tea extract boosts exercise endurance 8-24 percent ...

http://www.atkins.com/research-libra...dy-composition

Dulloo, A.G., Duret, C., Rohrer, D., et al., “Efficacy of a Green Tea Extract Rich in Catechin Polyphenols and Caffeine in Increasing 24-h Energy Expenditure and Fat Oxidation in Humans,” American Journal of Clinical Nutrition, 70(6), 1999, pages 1040-1045.
Summary:


BACKGROUND: Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system.

OBJECTIVE: We investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans.

DESIGN: Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch, and dinner.

RESULTS: Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen. Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P < 0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines.

CONCLUSIONS: Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.

http://www.pdrhealth.com/drug_info/n...gre_0319.shtml

[kingcarlos]

Coleus Forskohlii (20% Forskolin)

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells.

Okuda H, Morimoto C, Tsujita T.

2nd Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Japan.

Forskolin (7 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxy-labd-14-ene-11-one) induced both cyclic AMP production and lipolysis in intact fat cells, but stimulated lipolysis without increasing cyclic AMP at a concentration of 10(-5) M. Homogenization of fat cells elicited lipolysis without elevation of cyclic AMP. Forskolin did not stimulate lipolysis in the homogenate. Forskolin stimulated both cyclic AMP production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. However, at a concentration of 10(-6) M, it induced lipolysis without increase in the cyclic AMP content in this cell-free system. In the cell-free system, homogenization of the lipid droplets resulted in marked increase in lipolysis to almost the same level as that with 10(-4) M forskolin without concomitant increase in cyclic AMP. Addition of forskolin to a cell-free system consisting of homogenized lipid droplets and lipase did not stimulate lipolysis further. Phosphodiesterase activities were found to be almost the same both in the presence and absence of forskolin in these reaction mixtures. Although 10(-3) M forskolin produced maximal concentrations of cyclic AMP: 6.7 x 10(-7) M in fat cells and 2.7 x 10(-7) M in the cell-free system, 10(-4) M cyclic AMP did not stimulate lipolysis in the cell-free system. In a cell-free system consisting of lipid droplets and the lipase, pyrophosphate inhibited forskolin-induced cyclic AMP production, but decreased forskolin-mediated lipolysis only slightly. Based on these results, mechanism of lipolytic action of forskolin was discussed.

PMID: 1314877 [PubMed - indexed for MEDLINE]

http://www.raysahelian.com/coleusforskohlii.html

http://www.kroger.com/hn/Herb/Coleus.htm
http://www.actahort.org/members/show...knrarnr=675_32
http://www.fda.gov/ohrms/dockets/dai...2098-vol97.pdf

[Bane]

Since you are at it,please post the established effective dosages

[kingcarlos]

Since you are at it,please post the established effective dosages

of what? lol. what up bro. RA got ton of researches and im not that free too. i ll try to complete it b4 i went to HK or after it

[kingcarlos]

Evodia Rutaecarpa

http://www.ingentaconnect.com/conten...00010/art00013
Wu-Chu-Yu, the unripe fruit from Evodia rutaecarpa, has long been utilized in
... normal rats that received vehicle, Evodia rutaecarpa or aminoguani- ...

http://www.raysahelian.com/evodiamine.html

Evodiamine is an extract from a plant called Evodiae Fructus. There have been many studies with this compound, but almost all have been done either in a laboratory on isolated cells or in rodents. No published human trials could be found. Evodiamine has been promoted as a weight loss agent.
Based on the available studies, we can say that evodiamine
Raises body temperature
Inhibits the growth and metastases of certain cancer cells in vitro
Influences the metabolism of certain drugs
Influences the secretion of catecholamines from the adrenal glands

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide release.

Chiou WF, Ko HC, Chen CF, Chou CJ.

National Research Institute of Chinese Medicine, NO. 155-1, SEC. 2, Li-Nung Street, Shipai, Taipei, Taiwan. wfchiou@cma23.nricm.edu.tw

Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg(-1), i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO2- plus NO3-). Pretreatment with ethanol extract of E. rutaecarpa (25, 50 and 100 mg kg(-1), i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg(-1), i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia.

PMID: 12396303 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

The effect of Evodia rutaecarpa extract on cytokine secretion by human mononuclear cells in vitro.

Chang CP, Chang JY, Wang FY, Tseng J, Chang JG.

Department of Molecular Medicine & Chinese Medicine, Taipei Municipal Jen-Ai Hospital, Taiwan.

The effect of Evodia rutaecarpa extract on cytokine secretion by human mononuclear cells in vitro was investigated. Evodia rutaecarpa extract of various concentrations in mononuclear cell culture medium showed biphasic effects on the secretion of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) by the mononuclear cells. Generally speaking, a low to medium level of Evodia rutaecarpa extract, in concentrations ranging from 10% to 30%, showed significant stimulating effects on the secretion of IL-1 beta, IL-6, TNF-alpha and GM-CSF. On the other hand, high level of Evodia rutaecarpa extract, with concentration more than 40%, lost its stimulating effects. Moreover, reaction time affected the stimulating effects of Evodia rutaecarpa extract on cytokine secretion by mononuclear cells. Mononuclear cell culture medium containing Evodia rutaecarpa extract that was allowed to react for 18 or 24 hours showed significantly better stimulating effects than that reacted for 1 or 3 hours.

PMID: 7572779 [PubMed - indexed for MEDLINE]

http://www.ingentaconnect.com/conten...00013/art01215
http://www.thieme-connect.de/DOI/DOI.../s-2005-871270

Effects of Evodia rutaecarpa and Rutaecarpine on the Pharmacokinetics of Caffeine in Rats

Tung-Hu Tsai1, 2, Chun-Hao Chang3, Lie-Chwen Lin1
1 National Research Institute of Chinese Medicine, Taipei, Taiwan
2 Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
3 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
Abstract

To assess possible herb-drug interactions, rutaecarpine (an herbal ingredient of Evodia rutaecarpa; 25 mg/kg/day, p. o.), the ethanol extract of Evodia rutaecarpa (1 g/kg/day, p. o.), and an herbal preparation of Evodia rutaecarpa (Wu-Chu-Yu-Tang; 1 g/kg/day) were individually pretreated daily for three consecutive days in rats and on the fourth day caffeine was administered (2 mg/kg, i. v.). Caffeine concentrations in blood, brain and bile were concurrently measured by microdialysis coupled to a liquid chromatographic system. Pharmacokinetic data were calculated by a non-compartmental model. The results indicate that the caffeine crosses the blood-brain barrier and goes through hepatobiliary excretion. The caffeine level was significantly decreased by the pretreatment of rutaecarpine, the extract of Evodia rutaecarpa and herbal preparation Wu-Chu-Yu-Tang. This finding should be very important whenever herb-drug interactions would be possible for a herbal remedy.

http://taylorandfrancis.metapress.co...P525372487.pdf

[kingcarlos]

Cocoa Bean (Extracted for 99% Theobromine)

http://www.greatvistachemicals.com/p...eobromine.html

Theobromine is a chemical stimulant frequently confused with caffeine, but has very different effects on the human body. It is a mild, lasting stimulant with a mood improving effect. Theobromine is found in cocoa and chocolate, in doses that are safe for humans to consume in large quantities, but can be lethal for animals such as dogs and horses, as they metabolize theobromine more slowly. Theobromine belongs to a class of alkaloid molecules known as methylxanthines. Methylxanthines naturally occur in as many as sixty different plant species and include caffeine (the primary methlyxanthine in coffee) and theophylline (the primary methylxanthine in tea). Theobromine is the primary methylxanthine found in products of the cocoa tree, theobroma cacao.

Theobromine affects humans similarly to caffeine, but on a much smaller scale. Theobromine is mildly diuretic (increases urine production), is a mild stimulant, and relaxes the smooth muscles of the bronchi in the lungs. In the human body, theobromine levels are halved between 6-10 hours after consumption.
Theobromine has been used as a diuretic, meaning that it increases urine production in the body. This is particularly useful after a person has experienced cardiac failure. Cardiac failure can sometimes result in an accumulation of bodily fluids. Theobromine is also known for its ability to dilate blood vessels making it a commonly prescribed treatment for people suffering from high blood pressure. Its ability to dilate has also been distorted and used with digitalis to relieve dilation.

http://www.3dchem.com/molecules.asp?ID=155
http://www.newstarget.com/002530.html
www.scielo.br/pdf/jbchs/v10n6/a04v10n6.pdf
http://www.cnpp.usda.gov/FENR/FENRv1...nrv13n2p47.pdf
Comparison of children’s intakes of caffeine and theobromine, ... Contribution of food groups to caffeine and theobromine for children, ...

[kingcarlos]

Salvia Sclaria (96% sclareolides)

http://www.ingentaconnect.com/conten...00003/art00009
Clary sage (Salvia sclarea L., 2n ˆ 22) exists commonly as a ... clonal micropropagation
of Salvia sclarea. Vsesoiuznyi Nauchno- ...

http://journals.tubitak.gov.tr/agric...1-4-0309-2.pdf
evaluations of Salvia sclarea infected by BBWV-I. Ill Farmaco 56:. 219-227. ...
inflammatory and peripheral analgesic actions of Salvia sclarea oil ...

www.theida.com/pdf/Clary%20sage.pdf (specific description of the plant)

[kingcarlos]

Bioperine® (Piper Nigrum) ----black pepper extract

www.ias.ac.in/currsci/aug102001/246.pdf
http://www.fda.gov/ohrms/dockets/dai...0658-vol81.pdf

limited info on it

Vinca Minor (Extracted for 99% Vinpocetine)

http://www.priory.com/med/vinpocetine.htm
http://www.thorne.com/pdf/journal/7-..._monograph.pdf (specific info on dosage, effect and time to take it)
http://www.fda.gov/ohrms/dockets/dai...00/let4881.pdf (must read)

http://www.fda.gov/ohrms/dockets/doc...918-vol141.pdf
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study.

Szakall S, Boros I, Balkay L, Emri M, Fekete I, Kerenyi L, Lehel S, Marian T, Molnar T, Varga J, Galuska L, Tron L, Bereczki D, Csiba L, Gulyas B.

PET Centre, Debrecen University Medical School, Hungary.

The effects of vinpocetine (Cavinton) on the cerebral glucose metabolism of chronic stroke patients are studied with positron emission tomography. The regional and global cerebral metabolic rates of glucose (CMRglu) and the kinetic constants related to them are quantified before and after single-dose intravenous vinpocetine treatment. These measurements are completed with transcranial Doppler sonography and single photon emission computed tomography to explore the possible mechanisms underlying the resulting changes in glucose uptake and metabolism in the brain. The authors' findings indicate that a single-dose vinpocetine treatment, although it does not affect significantly the regional or global metabolic rates of glucose, improves significantly the transport of glucose (both uptake and release) through the blood-brain barrier in the whole brain, the entire contralateral hemisphere, and in the brain tissue around the infarct area of the symptomatic hemisphere. These changes are in accord with increased blood flow in the entire contralateral hemisphere as well as decreased blood flow velocity and increased peripheral vessel resistance in the entire symptomatic hemisphere.

PMID: 9780850 [PubMed - indexed for MEDLINE]

[kingcarlos]

Huperzia Serrata (Extracted for 99% Huperzine A)


http://www.digitalnaturopath.com/treat/T411921.html
http://www.brainlightning.com/huperzine.html

An extract from a variety of the Chinese club moss, Huperzia serrata. Studies carried out in China indicated that the active substance Huperzine A, is a promising new treatment for Alzheimer’s disease. Other studies indicate that Huperzine A is a superior acetylcholine esterase (AChE) inhibitor with excellent penetration into the CNS and a remarkable in vivo half-life. Two double-blind clinical trials carried out in China demonstrate that Huperzine A is both safe and effective for the long term treatment of Alzheimer's dementia. In addition to its activity as an AChE inhibitor, recent findings suggest that Huperzine A has other neuroprotective functions:

1) Huperzine A inhibits glutamate-induced cytotoxicity in cultures of rat neonatal hippocampal and cerebella neurons;

2) Huperzine A promotes dendrite outgrowth of neuronal cultures.

http://www.pdrhealth.com/drug_info/n...hup_0141.shtml
www.ust.hk/~bri/dimer%20leaflet.pdf

http://www.blackwell-synergy.com/doi...4.2005.00130.x
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment.

Ye JW, Cai JX, Wang LM, Tang XC.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P.R. China.

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0. 1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

PMID: 9918593 [PubMed - indexed for MEDLINE]

http://www.masonvitamins.com/Web%20L...on/1335-30.pdf (dosages)