Coleus forskohlii

Coleus forskohlii Information

Coleus forskohlii is a plant that is part of the mint family. Native to the subtropical regions of India, Myanmar and Thailand, it is a spice and medicinal herb with a long history of usage in Ayurvedic medicine. The root of the plant contains the highest levels of the active ingredient, forskolin. Forskolin is a potent activator of the enzyme adenylate cyclase, which activates cyclic adenosine monophosphate (cAMP) in the cell. Through a multi-step process, this increases the concentration of the active form of hormone-sensitive lipase, resulting in a greater release of fatty acids from the body's adipose tissues. Forskolin also has a thyroid-stimulating action, which contributes to thermogenesis and an increase in the basal metabolic rate. These properties allow it to enhance the effects of the ephedrine/caffeine combination.

Traditional medicine has used Coleus forskohlii to help with cardiovascular disease, abdominal colic, respiratory disorders, painful urination, insomnia, and convulsions.

How Does Coleus forskohlii Work?

The basic mechanism of action of forskolin is the activation of an enzyme, adenylate cyclase, which increases cyclic adenosine monophosphate (cAMP) in cells. Cyclic AMP is perhaps the most important cell-regulating compound. Once formed it activates many other enzymes involved in diverse cellular functions. Under normal situations cAMP is formed when a stimulatory hormone (e.g., epinephrine) binds to a receptor site on the cell membrane and stimulates the activation of adenylate cyclase. This enzyme is incorporated into all cellular membranes and only the specificity of the receptor determines which hormone will activate it in a particular cell. Forskolin appears to bypass this need for direct hormonal activation of adenylate cyclase via transmembrane activation. As a result of this activation of adenylate cyclase intracellular cAMP levels rise. The physiological and biochemical effects of a raised intracellular cAMP level include: inhibition of platelet activation and degranulation; inhibition of mast cell degranulation and histamine release; increased force of contraction of heart muscle; relaxation of the arteries and other smooth muscles; increased insulin secretion; increased thyroid function; and increased lipolysis. Recent studies have found forskolin to possess additional mechanisms of action independent of its ability to directly stimulate adenylate cyclase and cAMP dependent physiological responses. Specifically forskolin has been shown to inhibit a number of membrane transport proteins and channel proteins through a mechanism that does not involve the production of cAMP. The result is again a transmembrane signaling that results in activation of other cellular enzymes. Research is underway in the attempt to determine the exact receptors to which the forskolin is binding. Another action of forskolin is on antagonizing the action of platelet-activating factor (PAF) by interfering with PAF binding to receptor sites. PAF plays a central role in many inflammatory and allergic processes including neutrophil activation, increasing vascular permeability, smooth muscles contraction including bronchoconstriction, and reduction in coronary blood flow. After treatment of platelets with forskolin prior to PAF binding, a 30% to 40% decrease in PAF binding was observed. The decrease in PAF binding caused by forskolin was concomitant with a decrease in the physiological responses of platelets induced by PAF. However, this forskolin-induced decrease in PAF binding was not a consequence of cAMP formation as the addition of a cAMP analog could not mimic the action of forskolin. Additionally, the inactive analog of forskolin, dideoxyforskolin, which does not activate adenylyl cyclase, also reduced PAF binding was due to a direct effect of this molecule and its analog on the PAF receptor itself or to components of the post receptor signaling for PAF.