Coleus Forskohlii and Forskolin Mechanism of action.

Coleus' New Role and wide applications.:

Coleus Forskohlii Extract CAS 66575-29-9 66428-89-5 photo picture image Forskolin is an extract from the roots of the Coleus forskohlii which directly activates the adenylate cyclase and raises cAMP(Cyclic Adenosine Monophosphate) levels in a variety of tissues. One of the emerging clinical applications for C. forskohlii is for nutritional support in weight management. The rationale for this novel application has been derived from the lipolytic mechanism (a biochemical pathway to metabolize lipids in the body) of forskolin fueled by forskolin-generated cyclic AMP and phosphorylation of hormone sensitive lipase (HSL). Forskolin used for improving lean body mass.

Maintaining or improving lean body mass while shedding extra pounds of adipose tissue has been advocated by the Centers for Disease Control. Lean body mass is important because it has been recently recognized as an independent, positive predictor of one's cardiovascular health and overall health.

The lipolytic potential of forskolin has been studied in vitro with human adipose tissue. One study compared the activity of HSL in adipose tissue and the regulatory effect of various compounds in young (25-33 year old) vs. middle-aged (52-62) men. No difference was observed in the lipase activity of adipose tissue, nor the number or function of beta-adrenergic receptors (receptors necessary for lipolytic response) in young vs. middle-aged subjects.

However, lipolysis induced by isoproterenol (beta-adrenergic receptor agonist), forskolin (post-receptor agonist), and theophylline (post-receptor agonist) was lower in middle-aged men compared to young men. These results indicate that the lipolytic response may decline with age mainly due to impairment in the post-receptor, but not necessarily the receptor mechanism.

The lipolytic potential of forskolin and other lipolytic agents may also depend on hereditary factors. Fat cells from 67 non-obese and 60 obese subjects, 19 to 60 years old, were studied. The family trait for obesity was present in 42 of the lean subjects and in 50 of the obese subjects.

Fat cells were incubated in vitro with isoprenaline (a non-selective beta-adrenoceptor agonist), forskolin and an analogue of cyclic AMP. The lipolytic response was significantly lower in obese subjects, both with and without genetic predisposition for being overweight and in non-obese subjects with a family trait for obesity compared to non-obese subjects without the trait.

The described lipolytic action stimulated in the cultures of fat cells may be partly responsible for forskolin's potential in weight loss. However, the proposed mechanism of forskolin in increasing lean body mass at the expense of body fat is currently attracting a good deal of attention.

Lean body mass consists of muscles, vital organs, bone, bone marrow, connective tissue and body water. Lean body mass can simply be described as total body weight minus fat. The proportion of lean body mass to fat not only determines the body's aesthetic look, but more importantly determines a person's physical fitness, health status and risk for morbidity (disease) and premature mortality.

Recently, a standardized extract of C. forskohlii was evaluated in a preliminary open-field clinical study on six overweight female volunteers receiving 250 mg of the extract (equivalent to 25 mg of forskolin) twice a day for eight weeks, half an hour before a meal. Each participant was asked to maintain her previous daily physical exercise and eating habits. In addition, physical activity was monitored based on a questionnaire before and during the trial.

During the eight-week trial, the mean values for body weight and fat content significantly decreased, whereas lean body mass significantly increased compared to the baseline values. No subjective or objective adverse effects were reported in the course of this study. However, a trend to lower systolic and diastolic blood pressure was noted. The pulse rate was maintained at the same level throughout the study.

Effects of Coleus on Cyclic AMP:

Increased cellular cyclic AMP results in inhibition of platelet activation, decreased likelihood of blood clots, reduced release of histamine, decreased allergy symptoms, increased force of contraction of the heart, relaxation of the arteries and other smooth muscles, increased thyroid function, increased fat metabolism, increased energy and possibly weight loss. Cyclic AMP and the chemicals it activates comprise a second messenger system that is responsible for carrying out the complex and powerful effects of hormones in the body.

In addition, asthma, eczema, psoriasis, angina, obesity and hypertension are believed to be associated with decreased Cyclic AMP.

Coleus and Glaucoma:

Glaucoma is a condition in which the pressure in the eye is too high, due to an imbalance between the formation of aqueous humor in the eye and its absorption in or drainage out of the eye. Eventually, as the pressure builds up, the blood vessels nourishing the optic nerve are constricted, resulting in irreversible damage to the nerve and impaired vision culminating in blindness, if left untreated.

While there are no clinically proven alternative therapies for glaucoma, there are several treatments that may be beneficial and coleus is one of them. Clinical studies have shown that topical application of one percent forskolin eye drops resulted in significant decreases in intraocular pressure for up to five hours. Limited clinical experience suggests that oral forskolin appears to offer significant potential for sufferers of glaucoma. An Indian pharmaceutical company is currently engaged in clinical trials of a forskolin eye drop product.

Glaucoma is characterized by elevated intraocular pressure (IOP). Several animal and human studies have demonstrated the ability of forskolin to lower IOP, possibly via cAMP activation and a reduction in aqueous flow.

Caprioli et al demonstrated a significant decrease in IOP in rabbits, monkeys, and humans administered a topical forskolin suspension (1% forskolin). This effect was present at one hour post application and remained significant for at least five hours.In one clinical trial of 20 young, healthy volunteers, two 50 [micro]L topical instillations of one-percent forskolin were applied to one eye while the other eye served as control, receiving only the topical vehicle. At one-hour post instillation, the IOP fell 2.4 [+ or -] 1.3 mmHg and aqueous flow rate was reduced by 13 percent in the treatment eye compared to the control. Both results were statistically significant.

In a randomized, double-blind, placebo-controlled, cross-over trial with two separate arms, 10 healthy, non-smoking men were given a forskolin (1%) suspension in one eye and placebo in the other eye; proxymetacaine (0.5%) was the local anesthetic. The forskolin suspension resulted in decreases in IOP, but the differences between the forskolin treatment and placebo treatment at eight hours post application were statistically insignificant. Six men participated in a second arm of the study and a different local anesthetic (0.4% oxybuprocaine) was used. In this study arm a highly significant 25-percent reduction of IOP was observed at six hours post application. The different results in the two arms may be attributable to the different topical anesthetics used prior to forskolin application.These results suggest forskolin may be of benefit in reducing IOP in glaucoma patients.
Coleus Forskohlii Extract CAS 66575-29-9 66428-89-5 photo picture image

Coleus and Depression:

Depression is believed to be associated with an imbalance of neurotransmitters in the brain, serotonin and dopamine primarily. Where there is a shortage of serotonin, the supplements 5-HTP or tryptophan or the SSRI drugs like prozac or Zoloft may be beneficial. If the catecholamine neurotransmitters (epinephrine, norephinephrine) are deficient the amino acids L-Phenylalanine or L-Tyrosine, or monoamine oxidase inhibitors like GeroVital (GH3) or Deprenyl are may be helpful. Recent research has also been evaluating drugs that increase Cyclic AMP as a means of elevating the catecholamines. Since forskolin elevates Cyclic AMP, it may improve neurotransmitter function and thereby relieve depression. Clinical trials using coleus to treat depression have not been done.

Coleus with Asthma and Allergies:

Coleus is an effective smooth muscle relaxer, resulting in bronchodilation, decreased airway resistance, increased vital capacity and increased forced expiratory volume. This action is the result of the increase in Cyclic AMP caused by coleus. Many asthma medications increase Cyclic AMP by inhibiting the enzymes that cause its breakdown. Thus, coleus and the traditional asthma drugs are likely to act synergistically. Therefore, one should consult their physician before combining them.

Asthma and other allergic conditions are characterized by decreased cAMP levels in bronchial smooth muscle, as well as high levels of PAE In response to allergenic stimuli, mast cells degranulate, histamine is released, and bronchial smooth muscle contracts. Forskolin's activation of cAMP inhibits human basophil and mast cell degranulation, resulting in subsequent bronchodilation.

Research has demonstrated aerosolized dry forskolin powder results in significant relaxation of bronchial muscles and relief of asthma symptoms. In one randomized, double-blind, placebo-controlled trial, 16 asthma patients were given a single inhaled (aerosolized) 10-mg dose of dry forskolin powder, an asthma medication (0.4 mg fenoterol), or placebo. Both fenoterol and forskolin administration resulted in significant, equivalent bronchodilation, but patients taking fenoterol experienced marked finger tremor response and a decrease in plasma potassium levels. These side effects were not observed in patients receiving forskolin.

In six asthmatics (ages 18-64 years), nebulized forskolin administration (1 mg and 5 mg per metered dose) resulted in an increase in forced expiratory volume. Two patients experienced immediate relief from bronchoconstriction and shortness of breath; the remaining four patients reported relief after 10-15 minutes. Blood pressure and heart rate remained stable in all patients and no tremors, palpitations, or other adverse effects were reported.

Coleus and Hypothyroidism:

Forskolin has demonstrated the ability to increase thyroid hormone production and stimulate thyroid hormone release.

Coleus and Cancer Metastases:

Reserch has shown coleus to be a potent inhibitor of tumor colonization in mice. It is theoretically possible that coleus could be used in humans to prevent or inhibit tumor metastases.Many metastasizing tumor cell lines induce platelet aggregation both in vitro and in vivo. Upon aggregation, platelets release substances that promote tumor growth.Researchers have demonstrated forskolin's ability to block platelet aggregation via its stimulation of platelet adenylate cyclase and increase of intracellular cAME Agarwal and Parks gave 82 [micro]g forskolin to mice 30-60 minutes prior to injection with a highly metastatic melanoma cell line (B16 F10). Forskolin reduced tumor colonization in the lungs by 70 percent.

Coleus and Immune Enhancement:

Forskolin appears to exhibit potent immune system enhancement by activating macrophages and lymphocytes.

Coleus and Psoriasis:

In psoriasis, cells divide about 1,000 times faster than normal. Coleus helps to alleviate psoriasis by normalizing the cAMP /cGMP ratio. Like asthma, psoriasis is characterized by decreased levels of cAMP in the skin in relation to another regulating substance, cyclic guanosine monophosphate (cGMP). This imbalance results in a much higher rate of cell division--1,000 times greater than normal, resulting in psoriatic outbreaks. Although study details are not available, Ammon et al reported an improvement in symptoms of psoriasis in four patients supplemented with forskolin. The ability of forskolin to regulate cAMP levels in skin cells has been shown to have therapeutic benefit for sufferers of psoriasis.
Coleus Forskohlii Extract CAS 66575-29-9 66428-89-5 photo picture image

Cardiovascular Effects of Coleus:Cardiovascular Disease

Coleus forskohlii has traditionally been used to treat hypertension, congestive heart failure, and angina. Coleus's basic cardiovascular action is to lower blood pressure, while simultaneously increasing the contractility of the heart. This is believed to be due to forskolin's Cyclic AMP-elevating ability, which results in relaxation of the arteries, and increased force of contraction of the heart muscle. A preliminary trial found that coleus reduced blood pressure and improved heart function in people with cardiomyopathy. Coleus also increases cerebral blood flow, indicating that it may be beneficial in cerebral vascular insufficiency, and in enhancing post-stroke recovery. The platelet aggregation-inhibiting effects of coleus also adds to its value in cardiovascular disorders.

Both animal and clinical studies demonstrate forskolin significantly lowers blood pressure via relaxation of vascular smooth muscle.In a small study of seven patients with dilated cardiomyopathy, intravenous forskolin administered at 3 [micro]g/kg/minute significantly reduced diastolic blood pressure (17%) without increasing myocardial oxygen consumption; left ventricular function also improved.In a similar study (patient sample size not available), 4 [micro]g/kg/ minute of intravenous forskolin given to dilated cardiomyopathy patients resulted in decreased vascular resistance and a 19-percent improvement in left ventricle contractility. Heart rate increased an average of 16 percent in study patients. Subjects also exhibited a 20-percent reduction in arterial pressure accompanied by symptomatic flush.Forskolin's ability to inhibit platelet aggregation is of additional benefit in cardiovascular disease.

Forskolin also demonstrates a direct effect on cerebrovascular vasodilation via cAMP activation. In rabbits, intravenous infusion of 10 [micro]g/kg/min forskolin increased blood flow to the brain from 39 [+ or -] 5 to 56 [+ or -] 9 mL/min. This change was accompanied by a small decrease in mean arterial pressure, although cerebral oxygen consumption remained stable. These results indicate forskolin may be useful in cases of cerebral vascular insufficiency and post-stroke.

Coleus and Weight Loss:

In vitro (studies done in the lab) studies show that coleus stimulates fat metabolism. Researchers have found that many obese people have lower than normal Cyclic AMP production. Because of these considerations, coleus may, theoretically, be a weight loss agent, especially for those with reduced Cyclic AMP production. In a recent study, six overweight women took 25 mg of coleus (250 mg capsules of 10% standardized forskolin extract) twice daily for eight weeks. At the end of the eight-week trial, the participants lost a mean of ten pounds, and reduced their percentage of body fat by nearly 8%. Blood pressure levels also trended lower during the trial.

In vitro and animal studies demonstrate lipolysis in fat cells is stimulated by forskolin via activation of adenylate cyclase and increased levels of cAME In a study involving 34 women, researchers discovered adipocytes from morbidly obese women have decreased adenylate cyclase activity, compared to adipocytes from normal weight women. In a small study, six overweight women were given 250 mg Coleusforskohlii, standardized to contain 10-percent forskolin, twice daily for eight weeks. Average weight loss at the end of the trial was 10 pounds, with an eight-percent reduction in body fat. Blood pressure tended to be lower in all women during the trial. No adverse effects were reported, indicating Coleus forskohlii might be safe and effective for losing weight and body fat.More research with a larger study population is indicated.

Coleus forskohlii: Fat-Fighting and More

Coleus forskohlii, is a member of the mint family (Lamiaceae). As part of a long-standing tradition in India, C. forskohlii roots have been used as a marinated food, or pickle, that is commonly eaten as part of a vegetarian meal. Upon closer investigation into the plant's pharmacological properties, it was revealed that C. forskohlii roots contain forskolin, a compound that belongs to the chemical class of diterpenes.

It is the only plant-derived compound presently known to directly stimulate the enzyme adenylate cyclase, and subsequently cyclic AMP. Cyclic AMP is also nicknamed the 'second messenger,' referring to its broad range of activity in the body's life-sustaining reactions.

In the last 20 years, forskolin has been successfully evaluated in numerous clinical studies, including bronchial asthma, cardiovascular health, glaucoma, sexual dysfunction in men and dermatological diseases. In the cited clinical studies, no adverse effects of forskolin administration were reported in spite of the fact that different doses, forms of administration and routes of administration were employed in these studies.

A toxicological study performed by a specialized, independent, U.S.-based laboratory indicates that an extract of C. forskohlii roots standardized to 10 percent forskolin is a relatively safe product with an oral LD50 above 2,000 mg/kg (2,000 mg/kg did not produce any mortality in experimental animals). The AMES test, a bacteria mutagenicity test, performed at the same time as the LD50 study, did not show mutagenic properties in the same C. forskohlii extract.

an subjects have demonstrated that supplementation with a standardized grade of Coleus Forskohlii can help patients lose up to 10 lbs. In just 8 weeks. Subjects also increased their lean mass, which further speeds up the resting metabolic rate.

Multi-ingredient Formulas:

Coleus forskohlii extracts are typically encountered in the marketplace as part of multi-ingredient, nutraceutical formulations. Plausible combinations in such formulations would include other botanical, mineral or chemical compounds to provide synergistic or additional, potentially helpful actions. Such existing formulations may, for example, include a combination of extracts from ma huang (aerial plant parts), green tea, guarana seed or Citrus aurantium fruit.

The combination of Coleus extract (166.6 mg) with ephedrine (ma huang extract) and caffeine (guarana seed extract), in doses of 20mg and 200mg, respectively, can theoretically provide an additive action. The effect of ephedrine administered together with caffeine in 20mg/200mg dose respectively was evaluated in several clinical studies and found to be effective in the management of human obesity. Conversely, administration of these compounds separately to obese individuals was clinically ineffective.

There is also published evidence derived from an in vitro study on the feasibility of combining forskolin with caffeine. Based on this study, such a combination could, theoretically increase alertness, allay drowsiness and fatigue and increase intellectual performance. However, it should be noted that the promising theoretical premise for combining forskolin with other ingredients should be supported by clinical data.

Increasing Lean Body Mass:

The health-promoting value of increasing lean body mass can be directly appreciated due to the known benefits derived from physical exercise in building lean body mass and stamina.

Consider that lean body mass correlates positively with the performance of an incremental treadmill exercise test and that the percentage of fat in the abdomen is significantly less in athletes than non-exercising controls. Because abdominal fatty tissue is a significant risk factor for cardiovascular disease, exercise (as well as any other means) that results in increased lean body mass may have a positive impact on long-term cardiovascular health and life span.

It has been postulated that by stimulating cyclic AMP, forskolin may increase the circulation of anabolic hormones and enhance their utilization which would theoretically lead to increased lean body mass.

Studies have shown that selective inhibitors of phosphodiesterase (PD) enzymes (group of enzymes inactivating cyclic AMP) and forskolin are potent activators of the hypothalamo-pituitary-adrenal (HPA) axis when given orally or intraperitoneally to rodents. The content of cyclic AMP in hypothalamic tissue increased in response to forskolin. At the same time CRH (corticotropin or ACTH releasing hormone) was released, and steroid hormones were synthesized.

The selective inhibitors of PD enzymes worked synergistically with forskolin in increasing steroidogenesis. Forskolin also has a stimulatory effect on the cyclic AMP of testicular Leydig cells. This effect is similar to that of the LH (luteinizing hormone) which controls Leydig cell steroidogenesis by stimulation of the androgen pathways mainly through adenylate cyclase and cyclic AMP mediated mechanisms.

Cancer, Thyroid Application:

Cyclic AMP-dependent kinase activation and phosphorylation of steroidogenic proteins presumably causes an increase in testosterone production. Despite the steroidogenic properties of forskolin, a prolonged increase of cyclic AMP levels produced by forskolin in the culture medium of human prostatic cancer cells inhibited cellular growth of the cancer. This inhibition of cellular growth by forskolin generated cyclic AMP suggests a possible new, safe approach to prostatic carcinoma therapy.

An additional contribution of forskolin to the anabolic and lean body mass building mechanism is due to its stimulation of adenylate cyclase in the human thyroid. Forskolin stimulation is additive with that of TSH (thyroid stimulating hormone) and also differs from TSH stimulation of adenylate cyclase. Forskolin may also produce an anabolic effect by increasing the thyroid hormone dependent regulation of the uncoupling protein (UCP) and through its role in thermogenesis.

Studies were performed in brown adipocytes obtained from the brown fat of euthyroid (normal function of thyroid) or hypothyroid (decreased function of thyroid) rats. T3 and T4 thyroid hormones significantly enhance the effect of forskolin, UCP and thermogenesis. In fat cells from hypothyroid rats, forskolin failed to stimulate UCP; but after exposure to T3 or T4, cells recovered full responsiveness to forskolin.

The active principle of Coleus forskohlii, forskolin, emerges as a versatile nutraceutical, that is relatively safe for human consumption, and has many clinically proven applications. However, one of the promising applications of forskolin relates to management of weight loss and improving lean body mass.

While sensible, daily exercise remains the primary method to maintain and increase lean body mass, the combined effects of exercise with forskolin supplementation could contribute to, and further optimize, lean body mass. It should be emphasized that healthy functioning of the body depends not so much on a lower fat content, but rather on obtaining a higher percentage of lean body mass.
Coleus Forskohlii Extract CAS 66575-29-9 66428-89-5 photo picture image

Increase And Stimulate Thyroid Hormone Production!

Forskohlii (Coleus forskohlii), a member of the mint family, grows on the sun-exposed, dry slopes of India and is used in traditional Ayurvedic practices. Forskolin is a pharmacologically active compound found in Coleus forskohlii which has been used in over 5000 research studies since 1981. This product is guaranteed to contain 1% forskolin.

Forskohlin a plant used since antiquity in Hindu and Ayurvedic traditional medicine is the source of an amazing compound of unique biological importance. The plant, Coleus forskohlii, is where the compound forskolin comes from. Forskolin has started showing up in many of the most advanced thermogenics and fat burners on the market due to it natural fat-loss-enhancing properties. Forskolin has also been touted as a life extension/longevity/anti-aging health product due to studies showing it's positive effects on the heart, lungs, and blood pressure.

Forskolin has been shown to increase thyroid hormone production as well as stimulate thyroid hormone release. As we know, the thyroid is responsible for metabolic rate via the hormones it releases. Therefore, increasing production of the thyroid results in an increase in metabolism. But, that's not all forskolin is good for!

Reference:

1.Coleus Forskohlii and Forskolin Mechanism of action.

This article written and edited via herbalist of MDidea Extracts Professional. They run a range of online descriptions about this herb,including general information related and summarized updating discoveries from findings of professional scientisits this field related.Describe style aimed to form a useful detecting literature space where the intertwined threshold and related questions raise out and visualize themselves.

♣ last edit date:20th,Oct.2010.