Forskolin
Encyclopedia
Forskolin is a labdane
diterpene
that is produced by the Indian Coleus plant (Coleus forskohlii). Forskolin is commonly used to raise levels of cyclic AMP (cAMP) in the study and research of cell
physiology. Forskolin resensitizes cell receptors by activating the enzyme adenylyl cyclase and increasing the intracellular levels of cAMP. cAMP is an important signal carrier necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in the hypothalamus/pituitary gland axis and for the feedback control of hormones. It acts by activating protein kinase A. Further reading: function of protein kinase A
Forskolin can also be used to promote nerve repair by increasing cAMP concentrations. Forskolin can activate or upregulate the proliferation of Schwann cells in culture, together with Fibroblast growth factor or Transforming Growth Factor-Beta.
Various experimental studies are underway in using Forskolin as an adjuvant in treatment for diseases such as Parkinsons and/or nerve damage caused by trauma/accident.
Labdane
Labdane is a natural bicyclic diterpene. It forms the structural core for a wide variety of natural products collectively known as labdanes or labdane diterpenes...
diterpene
Diterpene
Diterpenes are a type of terpenes composed of four isoprene units. They derive from geranylgeranyl pyrophosphate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol...
that is produced by the Indian Coleus plant (Coleus forskohlii). Forskolin is commonly used to raise levels of cyclic AMP (cAMP) in the study and research of cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
physiology. Forskolin resensitizes cell receptors by activating the enzyme adenylyl cyclase and increasing the intracellular levels of cAMP. cAMP is an important signal carrier necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in the hypothalamus/pituitary gland axis and for the feedback control of hormones. It acts by activating protein kinase A. Further reading: function of protein kinase A
Biosynthesis
- As with other members of the large diterpene family of natural products, forskolin is derived from geranylgeranyl pyrophosphate (GGPP). Forskolin, however, contains some unique functional elements, key among them is the presence of a tetrahydopyran derived heterocyclic ring. This ring is synthesized after the formation of the trans-fused carbon ring systems are formed by a carbocation mediated cyclization. The remaining tertiary carbocation is quenched by a molecule of water. After deprotonation, the remaining hydroxyl group is free to form the heterocyclic ring. This cyclization can occur either by attack of the alcohol oxygen onto the allylic carbocation formed by loss of diphosphate, or by an analogous SN2' like displacement of the diphosphate. This forms the core ring system A of forskolin.
- The remaining modifications of the core ring system A can putatively be understood as a series of oxidation reactions to form a poly-ol B which is then further oxidized and esterified to form the ketone and acetate ester moieties seen in forskolin. However, because the biosynthetic gene cluster has not been described this putative synthesis could be incorrect in the sequence of oxidation/esterification events, which could occur in almost any order.
Potential medical use
- Applied with rolipramRolipramRolipram is a PDE4-inhibitor. Like most PDE4-inhibitors, it is an anti-inflammatory drug. Rolipram is being studied as a possible alternative to current antidepressants. Recent studies show that rolipram may have antipsychotic effects...
, forskolin provides a route to inhibition of colon cancer cell growth and survival. These two drugs also work together to induce long-term potentiationLong-term potentiationIn neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
in neuronal populations. - Forskolin is a vasodilator.
- To date, there have been more than two clinical studies examining the effectiveness of forskolin as a weight loss aid. Only one has been subject to peer-review and published in a medical journal. This clinical study also observed forskolin's role in significantly increasing lean mass, bone mass, and testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
in the subjects involved. This research has led to companies marketing forskolin as a bodybuilding supplementBodybuilding supplementBodybuilding supplements are dietary supplements commonly used by those involved in bodybuilding and athletics. Bodybuilding supplements may be used to replace meals, enhance weight gain, promote weight loss or improve athletic performance...
. - Forskolin may be helpful to control the underlying cause of glaucomaGlaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
. The sometimes successful use of forskolin to reduce intraocular pressureIntraocular pressureIntraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...
may be due to its unique ability to stimulate adenylate cyclase activity and increase cAMPCyclic adenosine monophosphateCyclic adenosine monophosphate is a second messenger important in many biological processes...
which regulates and activates critical enzymes required for the cellular energy required to move fluid out of the eye. - Increase skin's natural resistance to burning under UV light (see links below)
- Stimulate a tanning response when applied topically.
- Reduce urinary tract infections and enhance the ability of antibiotics to kill bacteria that normally survive.
Forskolin can also be used to promote nerve repair by increasing cAMP concentrations. Forskolin can activate or upregulate the proliferation of Schwann cells in culture, together with Fibroblast growth factor or Transforming Growth Factor-Beta.
Various experimental studies are underway in using Forskolin as an adjuvant in treatment for diseases such as Parkinsons and/or nerve damage caused by trauma/accident.