Coleus: a new development in the fight against Metabolic Syndrome X

Townsend Letter for Doctors and Patients, May, 2007 by Kerry Bone

Metabolic Syndrome X is now a recognized medical condition. The clinical features of this disorder typically include abdominal obesity and visceral fat, fatty liver, elevated hepatic transaminases (liver enzymes), dyslipidemia, and, eventually, hypertension. Sufferers of Metabolic Syndrome have a much greater risk of developing type 2 diabetes and usually exhibit high insulin levels and insulin resistance. (1,2) In the US, the incidence of Metabolic Syndrome has reached epidemic proportions, with somewhere between 30% to 40% of adults said to suffer from this condition. (3,4) Insulin resistance is probably the most significant underlying event in Metabolic Syndrome, and this, in turn, is thought to be closely linked to abdominal obesity and visceral fat. (5,6) Hence, any agent capable of addressing this fundamental issue of excess body fat will be a useful tool in the management of Metabolic Syndrome (together with other treatments and appropriate dietary and lifestyle modification).

Recent research on the Ayurvedic herb Coleus forskohlii suggests it could be such an agent. Controlled clinical trials with a standardized extract of Coleus have shown that it particularly seems to address the issue of excess body fat, as well as causing modest reductions in total body weight. This article provides a general review of the research on Coleus and its active component forskolin, including a summary of the results of the weight loss trials.

Background

An assumption of many in the scientific community is that non-toxic medicinal plants have little to offer to the development of new medicinal agents. However, recent events in natural products research, coupled with an ever-increasing refinement in pharmacological models, are beginning to reveal the subtle and relatively untapped therapeutic wealth of the plant kingdom. One notable development is Ginkgo biloba and PAF antagonism. Another is forskolin from the Indian plant Coleus forskohlii.

Since ancient times, preparations of Coleus species have been used in traditional Ayurvedic medicine. However, the use of Coleus forskohlii was only known to folk medicine. A large-scale screening of medicinal plants by the Indian Central Drug Research Institute in 1974 revealed the presence of a hypotensive and spasmolytic component of C. forskohlii, which was named coleonol. (7) Concurrent research by Hoescht India identified the same compound as forskolin. (8) Since the Hoescht scientists correctly assigned the chemical structure, their name generally has been adopted.

In 1981, it was shown that forskolin can activate, in a unique manner, the enzyme that produces cyclic adenosine monophosphate (AMP). (9) The promising new drug suddenly generated immense interest as a research tool for the study of biochemical systems involving cyclic AMP. From this point, there was an exponential increase in research on forskolin, and around 20,000 papers have been published to date.

Although this article will review much of the chemical and pharmacological information on forskolin, emphasis will also be given in the later stages to the clinical implications for the use of C forskohlii. At present, the research indicates that Coleus will be of value in the treatment of hypertension, mild congestive heart failure, asthma, hypothyroidism, psoriasis, digestive weakness, and glaucoma. Coleus may also be used as an antiplatelet herb, and, of course, to assist with a reduction of body fat.

Definition

Coleus forskohlii is a small member of the Lamiaceae (Labiatae or mint family), which grows as a perennial on the Indian plains and lower Himalayas. It is also cultivated as a garden ornamental, and the root is used as a condiment. The root contains an essential oil and diterpenes, especially 0.2 to 0.3% of the labdane diterpene forskolin. No other species of Coleus contains forskolin.

Cyclic AMP

Adenylate Cyclase Activation

Cyclic AMP (cAMP) was discovered in 1956, and its production is now known to be the final common pathway for many hormones and transmitter agents. In other words, the hormones or neurotransmitters do not enter the cell. They instead activate a receptor on the cell surface that is part of the adenylate cyclase enzyme complex. (10) This complex catalyses the production of cAMP in a cell. The cyclic AMP then activates c-AMP-dependent protein kinase (PKA), which results in changes in the cell's function. (10)

Figure 1 gives a schematic model of hormone-sensitive adenylate cyclase. The enzyme complex is composed of at least five different subunits, as shown. A stimulatory hormone binds to its receptor in the cell membrane. This results in activation of the catalytic subunit via coupling with the stimulatory guanine nucleotide regulatory component, and cAMP production is thereby increased. Similarly, an inhibitory hormone binding to its receptor results in deactivation of the catalytic subunit and decreased cAMP production. Forskolin appears to directly activate the catalytic subunit, an action that is unique. It may also activate the stimulatory Ns component. Research has shown that forskolin is able to markedly potentiate the effects of many hormones on biological responses in a synergistic fashion, suggesting that its activation of the catalytic subunit amplifies hormonal effects.