Ancient Ayurvedic Herb Lowers Intraocular Pressure by Reducing Aqueous Inflow

Makandi (Coleus forskholii) is one of the most broadly useful herbs of Ayurveda, but until recently it was not well-known in the West. So wide-ranging are its therapeutic applications that it has been called a pharmacopaea in a single plant.

Coleus forskohlii has been an important traditional Ayurvedic herb for centuries. In 1973, researchers first isolated a particular active diterpene from Makandi's roots. Makandi is the only plant source thus far known for the substance. This substance is called forskolin.

A 1984 article by Caprioli et al in Investigative Ophthalmology & Visual Science found that Forskolin lowers the intraocular pressure of rabbits, monkeys, and humans. Similar work was reported the year before in the Lancet. (See Caprioli J and Sears M: Forskolin lowers intraocular pressure in rabbits, monkeys, and man. The Lancet 1:958, 1983.)

They stated,

“Forskolin and its analogues may represent a new class of anti-glaucoma drugs differing in its molecular mechanism from any previously used drug. Its effect on IOP should be additive with other glaucoma drugs, owing to its unique mode of action, and may even potentiate the effect of certain drugs, eg, epinephrine, which function (partially) through beta-receptor agonism. Tolerance may not occur because forskolin's action does not involve the cell surface receptor.”

That report got some attention, but not as much as I would have expected. In 2001, Alternative Medicine Review published a summary of the research on Makandi (Coleus Forskohlii).

See Alternative Medicine Review Volume 6, Number 2, 2001 for full details.

I am going to quote much of it here:

Forskolin from the plant Coleus forskohlii … decreases IOP by decreasing aqueous humor inflow.

Results of studies using topical forskolin applications to decrease IOP have been mixed. A study of 2-, 1-, and 0.5-percent forskolin solutions applied to the eyes of normal rabbits found significant, dose-dependent decreases in IOP within a half hour, peaking in 2-3 hours, and lasting up to 10 hours. On the other hand, a 1-percent forskolin solution failed to significantly decrease IOP in glaucomatous monkeys after two days of treatment.

To date, human studies on forskolin’s effect on IOP have been limited to healthy volunteers. Several studies have found it effective at lowering IOP and decreasing aqueous outflow in this population.

Meyer et al compared the effect of 1-percent forskolin versus placebo in 10 healthy volunteers in a randomized, crossover trial. In the first study, both the placebo group and the forskolin group experienced a decrease in IOP, which was attributed to the local anesthetic oxybuprocaine. In the second trial, proxymetacaine was used as the topical anesthetic and forskolin was found to significantly decrease IOP compared to placebo.

In 20 healthy volunteers one dose of a1-percent forskolin solution had no effect, whereas two instillations five minutes apart led to significant decreases in IOP and aqueous flow rate. In eight healthy subjects one drop of forskolin significantly decreased IOP and flow rate was diminished an average of 34 percent. Another study, however, did not find forskolin to have a significant effect at decreasing flow rate in a group of 15 healthy volunteers given one dose of 1-percent forskolin in each of three situations: during the day, at night while sleeping, and following pretreatment with timolol. (However, the effect on IOP was apparently not investigated during this study.)

While topical use of forskolin in animals and healthy humans appears promising, clinical studies on its use in glaucoma patients are lacking. Furthermore, while oral standardized extracts of Coleusforskohlii are known to raise cAMP as its mechanism of action in various disease conditions, it is not clear whether oral dosages have any effect on cAMP levels in the eye. More research on this important topic is needed. Forskolin eye drops are available through compounding pharmacies.

I have not found forskolin eye drops anywhere, and I looked extensively a couple years ago. At that time, I attemped to make my own eye wash using forskolin, but I had disasterous results. It seems the alcholol in the forskolin liquid extract did really bad things to my cornea. It also didn't lower my IOP. In fact, my IOP went up during this period.

Since then, I have used oral capsules of various brands and strengths at various times, and I have used an alchohol extract sold by Gaia Herbs several (lengthy) times. None of these products lowered my IOP as far as I could tell. I have been monitoring my IOP closely and it would have been apparent if forskolin significantly affected my IOP. That said, I would like to hear from others with different (or similar) experiences.

I think the Alternative Medicine Review article represents a good summary of what is currently known. I didn’t find any recent research that added to this understanding. However, on a side note, some of the newer publications indicate that researchers are looking for novel ways to mass produce the active ingredient (forskolin). Having recently reviewed in detail the issues related to Showa Denko’s L-Tryptophan manufacturing disaster, I don’t look forward to obtaining any of my forskolin from genetically transformed cultures induced by growth regulators.

For completeness, I will provide some bontanical background information as well as the complete abstract and a few additional sections from the article by Caprioli et al discussed above. I'll start with the abstract.

Forskolin lowers intraocular pressure by reducing aqueous inflow.

Invest Ophthalmol Vis Sci. 1984 Mar;25(3):268-77.

Forskolin is a diterpene derivative of the plant Coleus forskohlii that stimulates adenylate cyclase activity without interacting with cell surface receptors. Forskolin lowers the intraocular pressure of rabbits, monkeys, and humans. In rabbits, net aqueous humor inflow decreases, outflow facility remains unchanged, and ciliary blood flow increases. Tolerance to the intraocular pressure lowering effect did not occur in rabbits after topical doses given every 6 hr for 15 days. 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. This activation is not blocked by timolol. The stimulation of adenylate cyclase by isoproterenol in vitro is potentiated in the presence of forskolin. Forskolin represents a potentially useful class of anti-glaucoma agents differing in molecular mechanism of action from previously used drugs.

With intravenous doses less than 0.5mg/kg, only small transient volumetric changes in IOP were recorded in the cannulated eyes. Doses of 0.5mg/kg in three rabbits caused a steady state IOP decrease of 3 to 5 mmHg with the onset at approximately45 min and recovery to baseline occurring at approximately200 min.Intravitreal injection or topical administration of forskolin in suspension significantly reduces IOP in rabbits by reducing aqueous inflow without any increase in outflow facility.

Topical administration of forskolin in monkeys and in normal human volunteers also caused significant decreases in IOP.16Intravenous administration of forskolin in rabbits produced a steady state decrease in intraocular pressure only after doses large enough to approximate the intraocular concentrations probably achieved after topical administration. Iris-ciliary body blood flow increased by approximately2.5-fold 1 hr after topical forskolin, while choroidal flow remained unchanged. This increase probably was caused by a direct vasodilatory effect in the ciliary body. The increase in blood flow and decrease in net aqueous flow mimic the cholera toxin effect.

Forskolin and its analogues may represent a new class of anti-glaucoma drugs differing in its molecular mechanism from any previously used drug. Its effect on IOP should be additive with other glaucoma drugs, owing to its unique mode of action, and may even potentiate the effect of certain drugs, eg, epinephrine, which function (partially) through beta-receptor agonism. Tachyphylaxis or tolerance may not occur because forskolin's action does not involve the cell surface receptor.

Slight modification of the molecule may increase its water solubility and corneal penetration, reducing the dose delivered to the surface of the eye and enhancing its effectivity. More work in this area is warranted to determine forskolin's potential therapeutic usefulness.

Bontanical Background Information

Botanical Name: Coleus forskohlii
Plant Family: Lamiaceae/Labatiae (mint family)
Common name: Makandi (Sanskrit) Also known as Mainmul, Sughandabalu and Karpuravali (Hindi: Patharchur; Kannada: Makandiberu)
Origin: A perennial plant which grows on the Indian plains and the lower Himalayas

Makandi grows wild on the Indian plains and the lower Himalayas on sun-exposed arid and semi-arid hill slopes of Uttar Pradesh (India), where it thrives from Simla eastward to Sikkim and Bhutan, the Deccan Plateau, the Eastern Ghats, the Eastern Plateau and the rainshadow regions of the Western Ghats in India. It has also been cultivated as an ornamental plant around the world and its root is used as a spice in Thailand, Myanmar and throughout Southeastern Asia. Makandi is one of 150 Coleus species commonly cultivated, but among a very few of these the roots (and to a lesser extent, the stems) of C. forskohlii are used for therapeutic purposes.

Originally published at http://freeradicalfederation.com/archive/2006/08/23/MakandiLowersIntraoc... on Wednesday, August 23, 2006 1:17 PM.

Notes from “Makandi (C. forskholii): A Pharmacopaea in a Single Root” By William A. Courson. I copied these from here. (As is apparent, I used a lot of information from Courson's article. I didn't ask for permission, so if it turns out that I copied too much [I'm not sure what the limit is], then I will have to remove it.)

(1) Ammon H.P.T. et al.: "Forskolin: From Ayruvedic Remedy to a Modern Agent,” Planta Medica (1985) Vol. 51, pp. 473-477

(2) Reddy, C.S., R.B. Desireddy & V. Ciddi: “A Review on Forskolin: A Cyclic AMP Modulator from Tissue Cultures of Coleus Forskholii,” Pharmacognosy Magazine, (July-October 2005) V. 1, No. 3, p. 85

(3) “Coleus forskholii: Origin and Botanical Traits,” Online at http://www.tnsmpb.tn.gov.in/images/COLEUS%20FORSKOHLII.pdf (September 29, 2005),
Tamil Nadu State Medicinal Plant Board, State Government of Tamil Nadu (India)

(4) Himalaya Health Care Products, Online at himalayahealthcare.com/aboutayurveda/cahc.htm (September 29, 2005)

(5) “Medicinal Plants: Ayurvedic Herbal Medicines,” National Institute of Ayurvedic Medicine, Online at www.niam.com/corp-web/mediplnt.htm (September 29, 2005)

(6) Families.com, Online at www.encyclopedias.families.com/coleus-509-510-gea2 (September 29, 2005)

(7) Loc.cit., Note 3

(8) October 3, 2005: Personal correspondence from Dr. Kenneth Lakuma Opiro of Uganda, in the author’s possession

(9) Saleem, A.M., P.B. Dhasan & M.R.M. Rafiullah: “Isolation of Forskolin from Stem of Coleus Forskholli,” Pharmacognosy Magazine, (July-October 2005) V. 1, No. 3, p. 89

(10) Chavez, M: Research Perspectives in Asthma: A Rationale for the Therapeutic Application of Magnesium, Pyridoxine, Coleus forskholii and Ginkgo biloba in the Treatment of Adult and Pediatric Asthma,” The Internist (September 1998) V.5, No.3, pp.14–16

(11) Dubey MP, R.C. Srimal, S. Nityanand S, & B.N. Dhawan: Pharmacological studies on coleonol, a hypotensive diterpene from Coleus forskohli, Journal of Ethnopharmacology (1981) Vol. 3, pp. 1–13.

(12) Agrawal, D.P.: “The Himalayan Medicine System and its Materia Medica,” Online at www.indianscience.org/essays/20-%20E-Himalayan%20Medicine%20System%20fine12.pdf, p. 14 (September 29, 2005)

(13) Duke, J.A.: The Green Pharmacy Herbal Handbook (Saint Martin’s Press, 2000) p. 109

(14) Loc.cit., Note 12

(15) Ahmad, F. et al.: “Insulin and Glucagon Releasing Activity of Coleonol (Forskolin) and its Effect on Blood Glucose Level in Normal and Alloxan Diabetic Rats,” Acta Diabetologica (1991) pp.71-77

(16) Head, K.A.: “Natural Therapies for Ocular Disorders, Part Two: Cataracts and Glaucoma,” Alternative Medicine Review (2001) pp. 141-66

(17) Pole, Sebastian, Lic. OHM, Ayur.H.C., “Herbal Ayurveda,” (online on August 20, 2005 at http://www.herbalayurveda.com/herbdetail.asp?ID=49)

(18) Ibid.

(19) Thallon, Cheryl: “Coleus Forskholii,” (Online on August 20, 2005 at http://www.organicfood.co.uk/vms/coleusforskholii.html)

(20) Allen, D.O. et al.: “Relationships Between Cyclic AMP Levels and Lipolysis in Fat Cells After Isoproterenol and Forskolin Stimulation,” The Journal of Pharmacology and Experimental Therapeutics (1986) Vol. 238(2) pp. 659-664

(21) Haye, B. et al.: “Chronic and Acute Effects of Forskolin on Isolated Thyroid Cell Metabolism,” Molecular and Cellular Endocrinology (1985) Vol. 43, pp. 41-50

(22) Yajima H. et al.: “cAMP Enhances Insulin Secretion by an Action on the ATP-Sensitive K+ Channel-Independent Pathway of Glucose Signaling in Rat Pancreatic Islets,” Diabetes (1999) Vol. 48, No. 5, pp.1006-12

(23) Loc.cit., Note 19
(24) Loc.cit., Note 3
(25) Loc.cit., Note 19
(26) Loc.cit., Note 12
(27) Loc.cit., Note 16

(28) Abel,R: The Eye Care Revolution (Kensington Health, 1999) quoted in Meyers, Stephen: “Natural Healing for Aging Vision,” HSR: Health Supplement Retailer (online Sept. 17, 2005 at www.hsrmagazine.com/articles/231feat2.html)

(29) Coleus forskholii, website of Global Herbal Supplies, Inc., (Queensland, Australia); Online at www.globalherbalsupplies.com/herb_information/coleus_forskohlii.htm (September 29, 2005)

(30) Loc.cit., Note 13

(31) “Statement concerning the safety of products containing the Ayurvedic Herb Coleus Forskolii (July 20, 2005),” Irish Medicines Board, Government of Ireland; Online at

http://www.imb.ie/safety.asp?nav=2,37&action=view&safety_item_id=44

(October 1, 2005)