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 ::  Abstract
 :: Introduction
 ::  Description of F...
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 :: Acknowledgment
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Year : 2012  |  Volume : 58  |  Issue : 3  |  Page : 199-202

Forskolin: Upcoming antiglaucoma molecule

1 Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur, Maharashtra, India
2 Department of Botany, H. R. Patel Junior College of Science, Shirpur, Maharashtra, India

Date of Submission13-Dec-2011
Date of Decision26-Jan-2012
Date of Acceptance27-Mar-2012
Date of Web Publication26-Sep-2012

Correspondence Address:
V D Wagh
Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Near Karwand Naka, Shirpur, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.101396

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 :: Abstract 

Forskolin is the first pharmaceutical drug and product derived from a plant to be approved in India by the DCGI in 2006. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is a diterpenoid isolated from plant Coleus forskohlii (Lamiaceae). It is a lipid-soluble compound that can penetrate cell membranes and stimulates the enzyme adenylate cyclase which, in turn, stimulates ciliary epithelium to activate cyclic adenosine monophosphate, which decreases intraocular pressure (IOP) by reducing aqueous humor inflow. The topical application of forskolin is capable of reducing IOP in rabbits, monkeys, and humans. In its drug interactions, forskolin may act synergistically with epinephrine, ephedrine and pseudoephedrine. Whereas the effects of anti-clotting medications like warfarin, clopidogre, aspirin, anoxaparin, etc., may be enhanced by forskolin. Forskolin is contraindicated in the medications for people with ulcers as forskolin may increase acid level. Forskolin has a very good shelf-life of five years. Recently, its Ophthalmic inserts and in situ gels for sustained and delayed-release drug delivery systems were tested in New Zealand Albino Rabbits for its antiglaucoma efficacy. This drug review explains Forskolin as a drug, its antiglaucoma potential and recent findings of forskolin as an antiglaucoma agent. The literature search method used for this review was different databases and search engines like PubMed, International Pharmaceutical Abstracts, Google, Medicinal and Aromatic Plants (MAPA).

Keywords: Antiglaucoma drug, coleus forskohlii, forskolin, glaucoma, nanoparticles, ophthalmic insert

How to cite this article:
Wagh V D, Patil P N, Surana S J, Wagh K V. Forskolin: Upcoming antiglaucoma molecule. J Postgrad Med 2012;58:199-202

How to cite this URL:
Wagh V D, Patil P N, Surana S J, Wagh K V. Forskolin: Upcoming antiglaucoma molecule. J Postgrad Med [serial online] 2012 [cited 2023 Sep 26];58:199-202. Available from:

 :: Introduction Top

In India, since ancient times Coleus forskohlii has been used in Hindu and Ayurvedic traditional medicine. [1],[2] Forskolin was named after the Finnish botanist, Forskal. [3],[4] Coleus forskohlii is a perennial member of the mint or Lamiaceae (also known as Labiatae) family that was first discovered in the elower elevations of India. It was recorded in the ancient Sanskrit texts that Coleus forskohlii has been used as a medical herb to treat hypertension, congestive heart failure, eczema, colic, respiratory disorders, painful urination, insomnia, convulsions, asthma, angina, psoriasis and for prevention of cancer metastases. [3],[4],[5] The literature search method used was databases (PubMed, IPA, Google, MAPA) and websites and the following keywords were used while searching the literature "Coleus forskohlii", "Forskolin" and "Forskolin + Glaucoma".

 :: Description of Forskolin Top

Forskolin is an active constituent of Coleus forskohlii. Unlike the other coleus species C. forskohlii is used for health purposes. [6] Forskolin is a labdane diterpene which was derived as an active alkaloid from the roots of C. forskohlii. The synonyms used for forskolin are Colforsin and Coleonol. Detailed analysis reveals approximately 20 constituents in various parts of the plant, but forskolin and other coleonols are present only in the root portion. [7] Forskolin is the primary constituent of clinical interest in Coleus forskohlii. It was discovered by Western scientists in 1974. Initially it was referred to as coleonol. [8] The name was changed to forskolin as other coleonols and diterpenoids have been identified later. All pharmacological activities related to Coleus forskohlii are due to the active constituent named forskolin. [9]

 :: Specifications of Forskolin Top

Forskolin is derived from the roots of Coleus forskohlii[10] belonging to family Lamiaceae or Labiatae.[5],[10] Its Sanskrit name is Pashanbedi, Makandi [11] and it is commonly known as Coleus, Karpuravali and Sughandabalu, (Hindi: Pathatchur; Kannada: Makandiberu; Gujarati: Maimul, Marathi: Garmai) [8],[10],[11] and its parts used are roots only. [7] Coleus forskohlii grows wild on sun-exposed arid and semi-arid hill slopes of the Himalayas in Uttar Pradesh, from Shimla eastward to Sikkim and Bhutan, the Deccan Plateau, Eastern Ghats, Eastern Plateau and rain shadow regions of the Western Ghats in India. [10]

Structure [8],[10]

Forskolin is the labdane diterpene produced by root portion of the Coleus forskohlii. Its chemical name is 7beta-Acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one. Its molecular weight [10] is 410.5 g/mole (anhydrous) and molecular formula [10] is C 22 H 34 O 7. Forskolin appears [10] as an off-white crystalline solid; having λ-max [10] at 210 nm, 305 nm and its melting point [10] is 228°C-230°C; while as it is soluble in DMSO, Ethanol, Methanol and Dichloromethane. It may be dissolved in 2% ethanol in water, by dissolving it first in ethanol and then subsequently diluting this solution with water [Figure 1]. [10]
Figure 1: Structure of Forskolin

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Mechanism 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. [12] Forskolin activation of adenylate cyclase accrues primarily though a direct action of the diterpene on the catalytic subunit of adenylate cyclase, however, Forskolin requires the presence of guanine nucleotide-binding protein, the G8 protein, for maximal stimulation of the enzyme. High-affinity binding sites for forskolin have been described in rat brain membranes and human platelet membranes, and these sites have structural requirement for forskolin analogues that are similar to those for activation of adenylate cyclase. It was suggested that these binding sites for forskolin are an activated complex of adenylate cyclase. [13]

Forskolin stimulates adenylate cyclase activity without interacting with cell surface receptors. Forskolin has the ability to stimulate adenylate cyclase activity and increase cyclic adenosine monophosphate (cAMP) which regulates and activates critical enzymes required for the cellular energy required to move fluid out of the eye. [13] Forskolin lowers the intraocular pressure (IOP) of rabbits, monkeys, and humans. In rabbits, net aqueous humor inflow decreases, outflow facility remains unchanged and ciliary blood flow increases. Forskolin has a different molecular mechanism from any previously used antiglaucoma drug. Its effect on IOP should be additive with other drugs because its tachiphylaxis might not occur because forskolin's action is not believed to involve the cell surface receptors. In vitro forskolin activates adenylate cyclase of crude particulate homogenates prepared from cultured human ciliary epithelia or from dissected ciliary epithelial processes of rabbit or human eyes. [13]

Forskolin has been shown to increase cAMP formation in all eukaryotic cells except sperm, without hormonal activation of adenylate cyclase. [14] Forskolin's potentiation of cAMP in turn inhibits basophil and mast cell degranulation and histamine release, [15] lowers blood pressure [16] and IOP, [17] inhibits platelet aggregation, [18],[19] promotes vasodilation, [16],[20] bronchodilation, [21] and thyroid hormone secretion, [22],[23] and stimulates lipolysis in fat cells. [24] Forskolin also has a positive inotropic action on cardiac tissue via increased cAMP levels. [25] The cAMP level is important for retinal ganglion cells neurotrophic responsiveness to neurotrophins which is important for neuron survival. cAMP may inhibit some forms of neurotrophin-mediated neuronal survival and suggests that a number of PI3-kinase-regulated processes in neurons may be inhibited by cAMP. [26]

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. [19] Forskolin also appears to have an effect on several membrane transport proteins, and inhibits glucose transport in erythrocytes, adipocytes, platelets, and other cells. [27]

Drug interactions, safety, contraindications and storage of forskolin

Forskolin may enhance the effects of beta-agonists such as albuterol. Forskolin may also act synergistically with epinephrine, ephedrine and pseudoephedrine. Decrease in needed dosage of beta-agonist may occur due to use of forskolin. The effect of anti-clotting medication like warfarin, clopidogre, aspirin, anoxaparin, etc., may be enhanced by the forskolin as it inhibits platelet aggregation and clotting. Coleus forskohlii have an excellent safety profile and generally are without toxicity or side-effects at the recommended dosage. As warnings and contraindications of forskolin ; avoid its use in the people with ulcers as forskolin may increase acid level. [14],[28] When stored as indicated, forskolin has a shelf-life of five years.

Forskolin and its antiglaucoma potential glaucoma [8],[29]

Glaucoma is a condition in which the pressure in the eye is too high (>22 mm/Hg), due to an imbalance between the aqueous humor formation and draining out of the eye. Increase in IOP results in irreversible damage to the nerve and impaired vision culminating in blindness, if left untreated. There are no clinically proven alternative therapies for glaucoma, but there are several beneficial treatments and coleus is one of them. Forskolin reduces IOP by reducing aqueous humor inflow with no change in outflow facility which indicates the potential of forskolin as a therapeutic agent in the treatment of glaucoma. Reduction in IOP by forskolin was studied with animals like monkeys, rabbits and in healthy human volunteers also.

Recent findings of forskolin as an antiglaucoma agent

Glaucoma is a progressively degenerative disease of the optic nerve and is the second leading cause of blindness in the world affecting 67 million people globally. Sami Labs is the first pharmaceutical company which derived a product from a plant to be approved in India, it is also the first such eye care product worldwide. The drug Forskolin Ophthalmic Solution has been accorded approval by the Drug Controller General of India in August 2006; developed by the Bangalore-based Sami Labs, a subsidiary of Sabinsa, this eye drops' formulation will be available in the market under the brand name "Ocufors 2%". [30] Hoechst had identified the efficacy of forskolin in the treatment of glaucoma but they could not make an effective formulation and subsequently dropped the studies midway through. According to the company's official press release, "Ocufors" is 30 per cent more effective than the most popular drug for glaucoma in the market with no side-effects.

Wagh et al., formulated forskolin ophthalmic drug delivery systems to test its efficacy in New Zealand albino rabbits for its antiglaucoma efficacy. [31] Ophthalmic Inserts [32] of forskolin extract (OIE) and pure forskolin 98% (OIF) were prepared as matrix-controlled delivery with the aim of achieving once a day administration. Ophthalmic Insert Drug Delivery System (OIDDS) for forskolin showed a significant reduction in IOP up to 24 h and an increased corneal residence time up to 12 h with sustained therapeutic action which is a desirable feature for an antiglaucoma agent. [31],[33],[34],[35],[36],[37] Gupta et al., prepared forskolin nanocrystals and stabilized by poloxamer 407. Their investigations proven that the pH and thermoreversible polymeric in situ gel forming nanosuspensions with ability of controlled drug release exhibits a greater potential for glaucoma therapy. [38]

Forskolin and rutin are the main ingredients of a food supplement, when given in a open-label pilot study to 16 patients with Primary Open Angle Glaucoma under treatment with different topical drugs and with stable IOP were given additional treatment with the food supplement for 40 days, and their IOP values measured at enrolment, at the end of treatment and 40 days after treatment interruption. This association treatment resulted in a further decrease of IOP by roughly 20% of the initial value. The effect was reversible upon suspension of the treatment. [39]

Thus, forskolin is a wonder drug with a proven antiglaucoma drug candidature. Though the forskolin eye drops have crossed all clinical trial phases there is a necessity to undergo human volunteer studies for newly developed ophthalmic dosage form and drug delivery systems. It is the need of the hour to explore Forskolin drug for its applications and therapeutic efficacy in other diseases also. There might be a perfect solution to increase the solubility of forskolin either by different solubility enhancement techniques in the formulation industry or by nanoparticles, nanocrystals, nanosuspension, nanoemulsion and nanocomposites in nanotechnology.

 :: Acknowledgment Top

The author Vijay D Wagh, is thankful to Indian Council of Medical Research for its assistance as Senior Research Fellowship to him, for this research work. The authors are also thank Sami Labs Pvt. Ltd, Bangalore, Karnataka, India for the gift sample of Forskolin (98% pure).

 :: References Top

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17.Caprioli J, Sears M, Bausher L. Forskolin lowers intraocular pressure by reducing aqueous inflow. Invest Ophthalmol Vis Sci 1984;25:268-77.  Back to cited text no. 17
18.Agarwal KC, Parks RE Jr. Synergistic inhibition of platelet aggregation by forskolin plus PGE1 or 2-fluoroadenosine: Effects of 2, 5-dideoxyadenosine and 5-methylthioadenosine. Biochem Pharmacol 1982;31:3713-6.  Back to cited text no. 18
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21.Lichey I, Friedrich T, Priesnitz M, Biamino G, Usinger P, Huckauf H. Effect of forskolin on methacholine-induced bronchoconstriction in extrinsic asthmatics. Lancet 1984;2:167.  Back to cited text no. 21
22.Haye B, Aublin JL, Champion S. Chronic and acute effects of forskolin on isolated thyroid cell metabolism. Mol Cell Endocrinol 1985;43:41-50.  Back to cited text no. 22
23.Roger PP, Servais P, Dumont JE. Regulation of dog thyroid epithelial cell cycle by forskolin and adenylate cyclase activator. Exp Cell Res 1987;172:282-92.  Back to cited text no. 23
24.Okuda H, Morimoto C, Tsujita T. Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells. J Lipid Res 1992;33:225-31.  Back to cited text no. 24
25.Lindner E, Dohadwalla AN, Bhattacharya BK. Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohlii: Forskolin. Arzneimittelforschung 1978;28:284-9.  Back to cited text no. 25
26.Steven P, Soren I, Zhengui X, Daniel RS. Brain-Derived Neurotrophic Factor Protection of CorticalNeurons from Serum Withdrawal-Induced Apoptosis Is Inhibited by cAMP. J Neurosci 2003;23:4420-7.  Back to cited text no. 26
27.Mills I, Moreno FJ, Fain JN. Forskolin inhibition of glucose metabolism in rat adipocytes independent of adenosine 3, 5-monophosphate accumulation and lipolysis. Endocrinology 1984;115:1066-9.  Back to cited text no. 27
28.Kavitha C, Rajamani K, Vadivel E. Coleus Forskohlii: A comprehensive review on morphology, phytochemistry and pharmacological aspects. J Med Plants Res 2010;4:278-85.  Back to cited text no. 28
29.Patient guide by The Glaucoma Foundation. Available from: [Last accessed on 2011 Aug 17].  Back to cited text no. 29
30.Wagh VD, Inamdar B, Wagh KV, Samanta MK. The effect of Forskolin ophthalmic inserts on intraocular pressure in rabbit eyes. Int J Pharm Pharm Sci 2009;1:146-55.  Back to cited text no. 30
31.Wagh VD. Development and evaluation of ophthalmic drug delivery systems for natural forskolin and its analogues in the treatment of glaucoma. Ph. D. Dissertation, The Tamilnadu, Dr. M.G.R. Medical University, Chennai, India; 2007.  Back to cited text no. 31
32.Tandale YN, Wagh VD. Formulation and evaluation of dorzolamide hydrochloride polymeric film. Int J PharmTech Res 2011;3:1817-24.  Back to cited text no. 32
33.Wagh VD, Inamdar B, Samanta MK. Polymers used in ocular dosage form and drug delivery systems. Asian J Pharm 2008;1:12-7.  Back to cited text no. 33
34.Wagh VD, Wagh KV, Pati PP, Samanta MK. Formulation and evaluation of ophthalmic insert drug delivery system (OIDDS) of forskolin. Asian J Pharm 2008;1:222-4.  Back to cited text no. 34
35.Wagh VD, Wagh KV, Samanta MK. Formulation and evaluation of ophthalmic insert drug delivery system of forskolin. J Pharm Res 2009;2:12-25.  Back to cited text no. 35
36.Wagh VD, Samanta MK. Formulation development and evaluation of HPMC based Ophthalmic Inserts Drug Delivery System (OIDDS) of forskolin. Indian J Pharm 2010;1:10-3.  Back to cited text no. 36
37.Wagh VD, Pathare YS. Herbal medicines and nutritional supplements used in the treatment of glaucoma: A review. Res J Pharm Biol Chem Sci 2012;3:331-9.  Back to cited text no. 37
38.Gupta S, Samanta MK, Raichur AM. Dual-Drug delivery system based on in situ gel forming nanosuspensions of forskolin to enhance antiglaucoma efficacy. AAPS PharmSciTech 2010;11:322-35.  Back to cited text no. 38
39.Pescosolido N, Librando A. Oral administration of an association of forskolin, rutin and vitamins B1 and B2 potentiates the hypotonising effects of pharmacological treatments in POAG patients. Clin Ter 2010;161:e81-5.  Back to cited text no. 39


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30 Inhibitors of Bacillus anthracis edema factor
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Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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