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Forskolin

Scientific Name(s): Coleus barbatus, Coleus coerulescens, Coleus forskohlii auct., Plectranthus barbatus Andrews, Plectranthus forskalaei, Plectranthus forskohlii, Plectranthus grandis, Plectranthus kilimandschari
Common Name(s): Adel Inj, Asthma X-5, Ele-max, Forskolin, ForsLean, GlucoLean, HL-362, Indian coleus, Interex, Makandi, Mao hou qiao rui hua, Meta-Burn EF, NKH477, Pashanabhedi

Clinical Overview

Use

Forskolin has multiple sites of action and should be used with caution. Forskolin derivatives have been developed for use in cardiovascular conditions. Quality clinical trials are lacking to substantiate claims made of the weight loss properties of forskolin, and clinical studies conducted with oral and inhaled forskolin in patients with asthma are limited.

Dosing

Asthma: Oral forskolin has been studied using 10 mg daily over 2 to 6 months. Obesity/Metabolic syndrome: 250 mg of a 10% forskolin extract twice daily for 12 weeks has been studied.

Contraindications

Case reports are lacking.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. P. barbatus has been traditionally used as an emmenagogue and oral contraceptive.

Interactions

None well documented.

Adverse Reactions

Clinical trial data are generally lacking. Adverse events reported with the use of colforsin (a forskolin derivative) include tachycardia and arrhythmias. Forskolin should be avoided in patients with polycystic kidney disease.

Toxicology

Information is limited. Embryo-related toxicity has been reported.

Botany

P. barbatus is a perennial herb in a large genus of mints. Some of the species within the genus are difficult to distinguish, leading to unclear taxonomy. Synonyms include Plectranthus forskalaei, Plectranthus forskohlii, Plectranthus kilimandschari, Plectranthus grandis, Coleus forskohlii, Coleus barbatus, and Coleus coerulescens.

The plant is native to subtropical and tropical regions of India and East Africa, grows to a height of 60 cm, and has large, soft leaves. Clustered purple-blue flowers appear from fall to late spring.PLANTS 2007, Lukhoba 2006, Alasbahi 2010

History

This species and other related species have been used extensively in many traditional medical systems, including those of Brazil, eastern, and central Africa, as well as India and other Asian countries. Traditional medical uses include the treatment of digestive disorders (stomachache, gastric and intestinal spasm, nausea, as a purgative), skin (burns, wounds, insect bites, allergies), infections (eg, syphilis, ringworm), and other conditions, including neck stiffness, and rheumatism, and as an emmenagogue and oral contraceptive. Forskolin has also been used to treat heart, blood, and circulation conditions, and cancers. In the 1970s, the plant's cardiovascular activity was investigated, while the discovery that the diterpene forskolin directly activates adenylate cyclase (AC) was also made.Lukhoba 2006, Alasbahi 2010, Seamon 2981 Research is largely limited to the use of radiolabeled forskolin to quantify AC and to investigate analogs of forskolin. In India, the plant is cultivated for use in pickles.Alasbahi 2010, Insel 2003, Alasbahi 2010

Chemistry

The main constituents of P. barbatus are the diterpenoids and essential oil. Content of the essential oil depends on location and time of harvesting, and mainly consists of mono- and sesquiterpenes. Approximately 70 diterpenoids have been described in the leaves, roots, and whole plant, with forskolin (also known as coleonol) being one of the most active compounds.Alasbahi 2010

Because forskolin has been actively pursued as a drug development lead, many analytical chemistry studies exist, and commercially available preparations can be standardized by forskolin content.Alasbahi 2010 Tissue culture methods for forskolin production have also been successfully explored because the relatively modest content of forskolin in the plant has limited its development as a drug.Mersinger 1988, Mukherjee 2000

Uses and Pharmacology

The principle mechanism by which forskolin exerts its activity is by stimulation of AC, thereby increasing cellular cAMP, which is involved in processes such as glycogen and lipid metabolism. Chemical modification of forskolin at the 6- and 7-positions has led to semisynthetic compounds, with modest selectivity for particular cyclase isoforms, including the cardiac type 5 AC.

Stimulation of AC is thought to be the mechanism by which forskolin relaxes a variety of smooth muscles; however, forskolin has been found to act through other systems, including glucose transport and ion channels.Seamon 1981, Insel 2003, Alasbahi 2010, Iwatsubo 2003, Wessler 2003

Antithrombotic effect

Forskolin has been shown in vitro to inhibit platelet aggregation through AC stimulation, augmenting the effects of prostaglandins.Siegl 1982, Adnot 1982 An inhibitory effect on C-kinase activation in platelets has also been described.Alasbahi 2010

Animal data

Antithrombotic properties have been demonstrated in experiments in rats, rabbits, and sheep.Alasbahi 2010

Clinical data

Research reveals no clinical data regarding the use of forskolin for antithrombotic effects.

Cancer

Experimental studies on various cancer cell lines have shown synergistic effects of forskolin in upregulating cellular responses.Lekmine 2008, Watanabe 2004, Watanabe 2005, Tong 2004, Li 2006, Kim 2004 A protective effect against ionizing radiationSolovjeva 2009 and UBV-induced apoptosisPasseron 2009 has been shown in vitro. Forskolin has been demonstrated to have an angiogenic effect via cAMP-dependent protein kinase pathways.Namkoong 2009

Cardiovascular effects

Animal data

Positive inotropic action has been demonstrated in isolated guinea pig, rabbit, and human heart tissue, and in vivo in cats and dogs. Forskolin augmented coronary blood flow in guinea pig hearts and increased heart rate and decreased blood pressure in dogs, cats, rabbits, and rats. A concentration-dependent inhibition of vascular contractility was demonstrated in rat aorta, and a vasodilator action in rats and rabbits has been shown.Alasbahi 2010

Clinical data

In human heart tissues, forskolin activated AC and demonstrated strong positive inotropic properties that were synergistic with isoproterenol.Bristow 2004 Older, small clinical studies have demonstrated that forskolin improves coronary blood flow and myocardial and left ventricular function and increases the blood flow in the cerebrum and kidneys.Alasbahi 2010

Due to poor water solubility and low oral bioavailability, clinical use of forskolin is limited and has led to development and study of colforsin (NKH477), a water-soluble derivative. Colforsin has a higher affinity for type 5 AC (myocardial AC), does not appear to cross the blood-brain barrier, and exerts a longer duration of action than forskolin. A colforsin preparation (Adehl) is approved for use in Japan, and limited studies have been conducted in cardiac surgery, heart failure, and cerebral vasospasm.Alasbahi 2010, Kikura 2004, Hayashida 2001, Suzuki 2006

CNS

The use of forskolin in studies involving the CNS is largely related to elucidating the role of cAMP in depression and other cellular processes.Cohen 2004, Gobert 2008, Seo 2009

Animal data

Radiolabeled forskolin was shown to bind to rat brain membranes in a saturable and specific manner.Seamon 1984 Forskolin demonstrated potent antidepressant activity in a rat forced swimming modelMaeda 1997 and prevented induced seizures in mice.Alasbahi 2010

Clinical data

Clinical trials are lacking; however, case studies using intravenous infusions of forskolin demonstrated a transient elevation in mood in some depressed and schizophrenic patients.Alasbahi 2010

Diabetes

Stimulation of the release of pancreatic insulin and glucagon by forskolin has been demonstrated in vitro.Alasbahi 2010 Influence of forskolin on glucose transport and the action of insulin in skeletal muscle has also been described.Niu 2003, Richmond 2009, Ding 2003 Clinical trials are lacking; however, studies in normal and diabetic rats have shown increases in blood glucose and serum insulin.Alasbahi 2010

Fertility

Due to its vasodilating properties, forskolin and analogs have been proposed for intercavernosal treatment of erectile dysfunction; however, only small clinical studies have been reported.Drewes 2003, Mulhall 1997 An in vitro study demonstrated increased bovine and human sperm motility with forskolin.Liu 2003

GI

Animal studies have shown that forskolin promotes gastric and pancreatic acid secretion, as well as relaxes intestinal smooth muscle.Alasbahi 2010

Immune

Forskolin has been shown to influence cellular immune responses in vitro and in animal experiments.Alasbahi 2010

Metabolic syndrome

A double-blind, randomized, placebo-controlled trial conducted in 41 overweight or obese participants evaluated the effect of C. forskohlii extract on appetite hormones and insulin sensitivity. C. forskohlii root extract 250 mg standardized to 10% forskolin was taken twice daily for 12 weeks. Of the 30 subjects who completed the trial, 6 were male. Subjects in the forskolin group exhibited significantly improved insulin levels (P=0.001) and insulin resistance (P=0.01) compared to controls; however, no significant differences were observed between groups for lipid parameters, blood glucose, or the appetite hormones ghrelin or leptin. The intervention was well tolerated.Loftus 2015

Obesity

A patent claiming promotion of lean body mass and antidepressant activity of a forskolin-containing extract was granted to the supplement company Sabinsa in 1998, and another patent was awarded in 2006.Alasbahi 2010, Majeed 1997

Animal data

Animal models of obesity have been used by the patent holder to demonstrate decreases in body weight and fat.Alasbahi 2010 In vitro studies suggest forskolin acts via cAMP but in a more complex manner than that of increased AC levels.Alasbahi 2010, Okuda 1992

Clinical data

Quality clinical trials are lacking to substantiate claims made of the antiobesity properties of forskolin. Two older studies suggested that topically applied forskolin cream reduced localized fat in the thighs of obese women without the need for diet or exercise.Alasbahi 2010 A small (N = 30), randomized clinical trial conducted in obese men found a decrease in body fat, increase in bone mass, and a trend toward changes in lean body mass following 12 weeks of forskolin versus placebo. An increase in serum testosterone was also demonstrated. Adverse events were not reported.Godard 2005 A trial conducted among women at the same dosage found no changes in body fat and concluded that forskolin does not promote weight loss. No changes in various metabolic markers or laboratory indices were found, except for changes in white blood count, serum calcium, ALT, and uric acid levels.Henderson 2005

Ophthalmic

Forskolin has been used in animal and limited clinical studies in glaucoma, with only temporary effects reported.Alasbahi 2010

Respiratory

In addition to smooth muscle relaxant properties, forskolin also exerts activity on inflammatory mediators, including interleukins and histamine, and on calcium ion influx, leading to its evaluation in asthma.Alasbahi 2010, Huerta 2010

Animal data

In guinea pigs, forskolin blocked bronchospasm caused by inflammatory mediators (histamine, leukotriene-4) and antigens. Relaxation of the bronchioles has also been demonstrated in isolated ovine tissue.Alasbahi 2010

Clinical data

Limited single-blinded clinical studies have been conducted with oral and inhaled forskolin in patients with asthma and in healthy volunteers. Oral forskolin performed better than sodium chromoglycate in preventing asthma attacks in children and adults with mild/moderate persistent asthma, while inhaled forskolin was not superior to beclomethasone in lung function improvement. Adverse events were not reported.Huerta 2010, González-Sánchez 2006 Colforsin has also been evaluated as a bronchodilator in a limited number of studies.Wajima 2002, Wajima 2003, Bauer 1993

Skin

Animal data

Studies in animals have shown various effects of forskolin, including induction of melatonin production in the pineal glands, increased melanin in hair follicles leading to an increase in pigmentation, increased hair growth, and a protective effect against ultraviolet B light (UBV)-induced apoptosis.Alasbahi 2010, Chen 2009, Lekmine 2008, Passeron 2009

Clinical data

Case reports exist showing improvement of psoriatic symptoms and a decrease in erythema in patients with hyperplastic skin disorders.Alasbahi 2010

Dosing

Asthma

Oral forskolin has been studied using 10 mg daily over 2 to 6 months.Huerta 2010, González-Sánchez 2006

Obesity

250 mg of a 10% forskolin extract twice daily for 12 weeks has been studied.Godard 2005, Henderson 2005

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. P. barbatus has been traditionally used as an emmenagogue and oral contraceptive.Lukhoba 2006, Almeida 2000 Forskolin delayed spontaneous meiotic progression in human oocytes in an in vitro fertility study.Shu 2008

Interactions

None reported, but interactions with CYP3A-dependent drugs are theoretically possible. Forskolin exhibits cardiovascular properties and may have additive effects with anticoagulants, antihypertensives, and vasodilators. Potentiation of the antiplatelet effect of prostaglandins and aspirin has been demonstrated in vitro. As a consequence of gluconeogenesis, interference with medicines used in diabetes may be expected.Alasbahi 2010

Adverse Reactions

Forskolin-like substances have been identified in renal cyst fluid; therefore, forskolin should be avoided in patients with polycystic kidney disease.Putnam 2007

Large doses in mice have been reported to have a depressant action on the CNS, and perianal dermatitis has been reported with the use of whole plant extracts.Lukhoba 2006, Alasbahi 2010 Clinical trial data are generally lacking; however, a clinical trial found no changes in various metabolic markers or laboratory indices, except for changes in white blood count, serum calcium, ALT, and uric acid levels.Henderson 2005 Adverse events reported with the use of colforsin (a forskolin derivative) include tachycardia and arrhythmias.Alasbahi 2010, Hayashida 2001

Toxicology

Toxicology information is limited. The oral median lethal dose in rats has been reported to be more than 2,000 mg/kg body weight.Huerta 2010 The hydroalcoholic extract of the plant has been shown to interfere with embryonic implantation and to delay fetal development.Almeida 2000

References

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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