Forskolin: Natural Origin, Mechanism of Action and Safety

General Description

Forskolin, a bioactive compound from Coleus forskohlii roots, is notable for its health benefits and has been of clinical interest since 1974. It primarily works by increasing cyclic adenosine monophosphate levels, activating adenylate cyclase without cell surface receptor involvement. This action leads to various physiological effects, including reduced intraocular pressure, enhanced cardiovascular and respiratory functions, and improved cellular energy processes. Despite its benefits, forskolin may interact with certain medications, such as beta-agonists and anti-clotting drugs, and is not recommended for individuals with ulcers due to its potential to increase stomach acid. Generally safe at recommended dosages, forskolin has a stable shelf life of five years when stored properly.

Figure 1. Forskolin

Natural origin

Forskolin is a significant bioactive compound extracted from the roots of Coleus forskohlii, a plant belonging to the Lamiaceae or Labiatae family. It stands out among various compounds found in C. forskohlii for its health-related benefits and has been the subject of clinical interest since its discovery by Western scientists in 1974. Initially known as coleonol, the name was later changed to forskolin as further research identified additional related compounds. Forskolin is a labdane diterpene characterized by its chemical structure (7beta-Acetoxy-8, 13-epoxy-1a, 6b, 9a-trihydroxy-labd-14-en-11-one) and has a molecular weight of 410.5 g/mole. This compound appears as an off-white crystalline solid, soluble in organic solvents like DMSO, Ethanol, Methanol, and Dichloromethane and can be dissolved in water with ethanol. The plant from which forskolin is derived grows in various regions across India, including the Himalayas, Deccan Plateau, Eastern Ghats, and parts of the Western Ghats. It is known by several names in different Indian languages, reflecting its widespread recognition and use. Forskolin's extraction from only the root part of C. forskohlii underscores the specific localization of its pharmacologically active constituents. ¹

Mechanism of action

Forskolin's mechanism of action is primarily through the upregulation of cyclic adenosine monophosphate (cAMP) levels and the enhancement of cAMP-mediated functions. This is achieved by directly activating adenylate cyclase, an enzyme crucial for the conversion of ATP to cAMP. Forskolin's interaction with adenylate cyclase does not involve cell surface receptors but requires the presence of a guanine nucleotide-binding protein, G8, for optimal enzyme stimulation. It binds with high affinity to sites in rat brain and human platelet membranes, suggesting these sites are part of an activated adenylate cyclase complex. By increasing cAMP, forskolin regulates enzymes essential for cellular energy processes, including fluid movement out of the eye, thereby reducing intraocular pressure (IOP) and offering a novel approach to glaucoma treatment distinct from other drugs. Furthermore, forskolin's elevation of cAMP levels has broad biological implications, including inhibition of basophil and mast cell degranulation, reduction of blood pressure, promotion of vasodilation and bronchodilation, stimulation of thyroid hormone secretion and lipolysis, and a positive inotropic effect on the heart. It also influences neuron survival by affecting retinal ganglion cells' responsiveness to neurotrophins. Beyond its cAMP-stimulating activity, forskolin inhibits platelet-activating factor binding and affects membrane transport proteins, demonstrating a multifaceted pharmacological profile. ²

Safety

Forskolin is generally considered safe with an excellent safety profile when used at recommended dosages, exhibiting minimal toxicity or side effects. However, it can interact with certain medications and conditions, potentially enhancing the effects of beta-agonists like albuterol, and working synergistically with compounds such as epinephrine, ephedrine, and pseudoephedrine. This interaction may lead to a decreased requirement for beta-agonists. Additionally, forskolin may amplify the effects of anti-clotting medications, including warfarin, clopidogrel, aspirin, and anoxaparin, due to its ability to inhibit platelet aggregation and clotting. Individuals with ulcers should avoid forskolin, as it has the potential to increase stomach acid levels, posing a risk to those with this condition. When stored properly, forskolin maintains its stability and efficacy for up to five years, ensuring its long-term usability for those who can safely benefit from its pharmacological actions. ²

Reference

1. Wagh VD, Dehghan MH, Wagh KV, Salve SA, Tandale YN. Pharmacological potential and phytopharmaceutics of Coleus forskohlii (Makandi): A review. J GMP Ind Pharm 2009;3:50-54.

2. Wagh VD, Patil PN, Surana SJ, Wagh KV. Forskolin: upcoming antiglaucoma molecule. J Postgrad Med. 2012;58(3):199-202.