Forskolin

• How It Works

  Forskolin has not been shown to be an effective cancer therapy in human. Large scale clinical studies are needed to support its other uses.

  Forskolin is a root extract of the Indian plant Coleus forskohlii. It is thought to stimulate a cell enzyme called adenylate cyclase, causing higher-than-normal levels of cAMP, a molecule that is responsible for many cellular effects. Some of these effects include breakdown of fats, dilation of blood vessels and airways, inhibition of blood clotting, and improving heart function. An animal study showed that forskolin can cause tanning when applied directly to the skin without exposure to the sun. It has been proposed to be used in sunless tanning lotion to reduce skin cancer risks. Although these effects have been studied in the laboratory setting, very few clinical trials have been performed to test whether these effects also occur in humans. In a number of studies, forskolin was found to lower pressure in the eye but this effect remains controversial.

• Purported Uses
  • To treat asthma
    Forskolin may cause cellular changes that stimulate the dilation of airways.
  • To treat cancer
    Scientific evidence is limited to lab and animals studies. There are no human data to support this use.
  • To increase cardiac output in congestive heart failure
    Two clinical trials found positive effects of intravenous forskolin in patients with acute heart failure, but overall support for this use is not strong. Oral forms of this herb have not been tested in humans.
  • To treat glaucoma
    Studies in humans have conflicting results.
  • To lower high blood pressure
    Forskolin is known to cause cellular changes that lead to blood vessel dilation, which should lower blood pressure, but there is no proof from clinical trials that this effect occurs in humans.
  • For weight loss
    A small clinical study suggests forskolin may have benefits in obese men.
  • For tanning
    An animal study showed that forskolin causes tanning without sun exposure. Human studies have yet to be conducted.
• Patient Warnings

   

  • Forskolin formulations that are not designed for use in the eye (such as topical creams or extracts meant to be taken by mouth) should not be placed directly in the eye.
  • Acute poisoning after consumption of Coleus forskohlii products, possibly from contaminants, has been reported in Europe.
  • Forskolin preparations should not be used by patients with polycystic kidney disease.

   

• Do Not Take If
  • You are taking medication for high blood pressure such as beta-blockers, vasodilators, ACE inhibitors, or calcium channel blockers (Forskolin may lower your blood pressure even more).
  • You are taking warfarin or other blood thinners (Forskolin may have additive effects, increasing the risk of bleeding or bruising).
• Side Effects
  • Low blood pressure
  • Slow heart rate
• Special Point
  • Although forskolin is used to reduce intra-ocular pressure in glaucoma, no sterile eye drop formulation is available.
  • The intravenous form of forskolin is not available in the United States.
• Scientific Name

  Coleus forskohlii

• Clinical Summary

  Forskolin is a diterpene derived from the root of Coleus forskohlii. It is used for a variety of conditions, including cancer, obesity, glaucoma, asthma, and heart failure. Forskolin was shown in animal studies to promote the activation of adenylate cyclase and increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) ⁽¹⁾. Small clinical studies suggest that forskolin can benefit obese men in weight management ⁽²⁾. Forskolin eye drops may reduce intra-ocular pressure ⁽³⁾ and oral forskolin capsules help reduce asthma attacks ⁽⁴⁾. When administered intravenously or inhaled, forskolin has bronchodilation effect ^(5) (6). Forskolin also benefits cardiovascular health due to its inotropic ⁽⁷⁾, anti-inflammatory ⁽⁸⁾ and antiplatelet properties ⁽⁹⁾. One study found intra-arterial forskolin daropate to be an effective treatment for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage ⁽¹⁰⁾. Treatment of uropathogenic E.coli-infected mice with forskolin resulted in reduced number of bacteria via cyclic AMP-regulated exocytosis ⁽¹¹⁾.

  The anticancer effects of forskolin and its derivatives have also been studied in vitro ^(1) (23) and in animal models ⁽¹²⁾. When applied on the skin of mice, forskolin can stimulate the production of melanin in the absence of ultraviolet light ⁽¹²⁾. It has been proposed for use in sunless tanning lotions to reduce the risk of skin cancer by decreasing exposure to sun. In an in vitro study, an extract of forskolin was found to significantly reduce viral production in human lymphoid CEM-GFP cells infected with human immunodeficiency virus (HIV-1NL4) ⁽¹⁴⁾. These effects have yet to be confirmed in human studies.

  Cases of acute poisoning after the consumption of Coleus forskohlii products, possibly from contaminants, have been reported in Europe ⁽¹⁵⁾.

• Purported Uses
  • Allergies
  • Asthma
  • Cancer treatment
  • Congestive heart failure
  • Glaucoma
  • Hypertension
  • Weight loss
• Mechanism of Action

  Forskolin activates adenylate cyclase through direct stimulation of enzyme and by modulating enzyme activities. These lead to increase in intracellular concentrations of cyclic adenosine monophosphate (cAMP) ⁽¹⁾. This may explain the bronchodilation ^{(4) (5) (6)}, inotropic ⁽⁷⁾, vasodilatory ⁽¹⁶⁾ and antiplatelet ⁽¹¹⁾ effects of Forskolin. Forskolin has also been reported to increase cellular acetylcholinesterase and protect neuronal cells from organophosphate toxicity ⁽¹⁷⁾. It is thought to reduce body fat and has been studied as a weight loss agent ⁽²⁾.

  In vitro and animals studies have shown forskolin and its derivative can inhibit cell proliferation, and induce cell cycle arrest and apoptosis in human gastric cancer cells ^(18) (19). Forskolin was also found to inhibit melanoma cell-induced platelet aggregation and reduce lung metastasis ⁽¹³⁾. Forskolin upregulates the expression of cytochrome P450 3A (CYP3A) family through the pregnane-X-receptor that regulates the CYP3A genes ^(20) (21).

• Warnings

  Forskolin may have a role in promoting cyst enlargement in patients with polycystic kidney disease. It is therefore recommended that these patients avoid the use of all preparations containing this compound ⁽²²⁾.

• Adverse Reactions

  Reported: Hypotension, tachycardia ⁽¹⁾, headache ⁽¹⁰⁾

• Herb-Drug Interactions

  Anti-hypertensives: Forskolin may have additive hypotensive effect with beta-blockers, vasodilators, calcium channel blockers, etc. ⁽⁷⁾.
  Anticoagulants: Forskolin may cause bleeding due to additive platelet inhibition ⁽⁹⁾.
  Forskolin can induce CYP3A gene expression and can potentially increase the metabolism of drugs that are substrates of related microsomal enzymes ^(20) (21).

• References

  1. Seamon KB, Padgett W, Daly JW. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A, 1981. 78(6):3363-7.

  2. Godard MP, Johnson BA, Richmond SR. Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men. Obes Res, 2005. 13(8):1335-43.

  3. Meyer BH, et al. The effects of forskolin eye drops on intra-ocular pressure. S Afr Med J, 1987. 71(9):570-1.

  4. Gonzalez-Sanchez R, et al. Forskolin versus sodium cromoglycate for prevention of asthma attacks: a single-blinded clinical trial. J Int Med Res, 2006. 34(2):200-7.

  5. Wajima Z, et al. Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans. Crit Care Med, 2002. 30(4):820-6.

  6. Bauer K, et al. Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma. Clin Pharmacol Ther, 1993. 53(1):76-83.

  7. Metzger H, Lindner E. The positive inotropic-acting forskolin, a potent adenylate cyclase activator. Arzneimittelforschung, 1981. 31(8):1248-50.

  8. Hayashida N, et al. Antiinflammatory effects of colforsin daropate hydrochloride, a novel water-soluble forskolin derivative. Ann Thorac Surg, 2001. 71(6):1931-8.

  9. Christenson JT, Thulesius O, Nazzal MM. The effect of forskolin on blood flow, platelet metabolism, aggregation and ATP release. Vasa, 1995. 24(1):56-61.

  10. Suzuki S, Ito O, Sayama T, Goto K. Intra-arterial colforsin daropate for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neuroradiology. 2010 Sep;52(9):837-45.

  11. Bishop BL, Duncan MJ, Song J, et al. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007.

  12. Agarwal KC, Parks RE, Jr. Forskolin: a potential antimetastatic agent. Int J Cancer, 1983. 32(6):801-4.

  13. D’Orazio JA, et al. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature, 2006. 443(7109):340-4.

  14. Sabde S, Bodiwala HS, Karmase A, et al. Anti-HIV activity of Indian medicinal plants. J Nat Med. 2011 Mar 3.

  15. Daykin A. Acute Poisoning From Coleus Forskohlii Containing Products, Letter to Herbalists, UK. 2005. (Accessed on March 18, 2009)

  16. Baumann G, et al. Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy—a comparative study with dobutamine and sodium nitroprusside. J Cardiovasc Pharmacol, 1990. 16(1):93-100.

  17. Curtin BF, et al. Forskolin, an inducer of cAMP, up-regulates acetylcholinesterase expression and protects against organophosphate exposure in neuro 2A cells. Mol Cell Biochem, 2006.

  18. Li Z, Wang J. A forskolin derivative, FSK88, induces apoptosis in human gastric cancer BGC823 cells through caspase activation involving regulation of Bcl-2 family gene expression, dissipation of mitochondrial membrane potential and cytochrome c release. Cell Biol Int, 2006.

  19. Sun B, Geng S, Huang X, et al. Coleusin factor exerts cytotoxic activity by inducing G0/G1 cell cycle arrest and apoptosis in human gastric cancer BGC-823 cells. Cancer Lett. 2011 Feb 1;301(1):95-105.

  20. Dowless MS, et al. Cyclic AMP-independent activation of CYP3A4 gene expression by forskolin. Eur J Pharmacol, 2005. 512(1):9-13.

  21. Ding X, Staudinger JL. Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. J Pharmacol Exp Ther, 2005. 312(2):849-56.

  22. Putnam WC, Swenson SM, Reif GA, et al. Identification of a forskolin-like molecule in human renal cysts. J Am Soc Nephrol. 2007 Mar;18(3):934-43.

  23. Follin-Arbelet V, Misund K, Hallan Naderi E, Ugland H, Sundan A, Blomhoff HK. The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM.Sci Rep. 2015 Aug 26;5:13001.