Coleus forskohlii

Alternative Medicine Review, March, 2006

Introduction

Coleus forskohlii is a botanical that has been used since ancient times in Hindu and Ayurvedic traditional medicine. The root portion of the plant has been traditionally used for medicinal purposes and contains the active constituent, forskolin. Forskolin was named after the Finnish botanist, Forskal. Historically, it has been used to treat hypertension, congestive heart failure, eczema, colic, respiratory disorders, painful urination, insomnia, and convulsions. Clinical studies of the plant and the forskolin constituent support these traditional uses, but also indicate it may have therapeutic benefit in asthma, angina, psoriasis, and prevention of cancer metastases.

Description

Coleus forskohlii is a perennial member of the mint (Lamiaceae) family and grows in the subtropical temperate climates of India, Nepal, Sri Lanka, and Thailand. Plant height is approximately 1-2 feet and its striking leaves are teardrop shaped, shimmering green framing a bright purple center; leaf color varies depending on the amount of shade. A cluster of stalked pale purple or blue flowers branches off a single stem. The rootstock is typically golden brown, thick, fibrous, and radially spreading. The roots are harvested in the fall, when forskolin is at its most concentrated and the color is the brightest.

Active Constituents

The diterpene forskolin, derived from the root of the plant, is the primary constituent of clinical interest in Coleusforskohlii. (2) It was discovered by Western scientists in 1974 and was initially referred to as coleonol. Since that time, as other coleonols and diterpenoids have been identified, the name was changed to forskolin. (3) Forskolin is responsible for virtually all pharmacological activities attributed to Coleus forskohlii; extracts of this constituent have been used in nearly all existing studies. There is evidence, however, that other plant constituents, such as volatile oils and other diterpenoids and coleonols, may contribute to the pharmacological activity and absorption of forskolin. (4) Detailed analysis reveals approximately 20 constituents in various parts of the plant, but forskolin and other coleonols are present only in the root portion?

Mechanisms of Action

Forskolin's primary mode of action is to increase cyclic adenosine monophosphate (cAMP) and cAMP-mediated functions, via activation of the enzyme adenylate cyclase. (6) Forskolin has been shown to increase cAMP formation in all eukaryotic cells except sperm, without hormonal activation of adenylate cyclase. (7) Forskolin's potentiation of cAMP in turn inhibits basophil and mast cell degranulation and histamine release, (8) lowers blood pressure (9) and intraocular pressure, (10) inhibits platelet aggregation, (11,12) promotes vasodilation, (9,13) bronchodilation, (14) and thyroid hormone secretion, (15,16) and stimulates lipolysis in fat cells. (17) Forskolin also has a positive inotropic action on cardiac tissue via increased cAMP levels. (18)

In addition to its cAMP-stimulating activity, forskolin inhibits the binding of platelet-activating factor (PAF), independently of cAMP formation. This may be a result of forskolin's direct effect on PAF or via interference with PAF binding to receptor sites. (12) Forskolin also appears to have an effect on several membrane transport proteins, and inhibits glucose transport in erythrocytes, adipocytes, platelets, and other cells. (19)

Clinical Indications

Intracellular cAMP levels are decreased in numerous diseases, including asthma, cardiovascular disease, eczema, psoriasis, hypertension, angina, and obesity; forskolin's ability to elevate cAMP has been shown to be of benefit in these circumstances.

Cardiovascular Disease

Both animal and clinical studies demonstrate forskolin significantly lowers blood pressure via relaxation of vascular smooth muscle. (9,18,20,21) 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. (20) 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. (21) Forskolin's ability to inhibit platelet aggregation is of additional benefit in cardiovascular disease. (11,22)

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. (13)