Scientific Name(s): Plectranthus barbatus . Lamiaceae (mint family)
Common Name(s): Forskolin , HL-362 , Indian coleus , makandi , mao hou qiao rui hua , NKH477 , and pashanabhedi . A forskolin derivative, Colforsin daropate , is registered for use in Japan as Adel Inj . The plant is a component of commercial preparations, including Asthma X-5 , Ele-max , Interex , Meta-Burn EF , GlucoLean , and ForsLean .
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.
Asthma : Oral forskolin has been studied using 10 mg daily over 2 to 6 months. Obesity : 250 mg of a 10% forskolin extract twice daily for 12 weeks has been studied.
Case reports are lacking.
Information regarding safety and efficacy in pregnancy and lactation is lacking. P. barbatus has been traditionally used as an emmenagogue and oral contraceptive.
None well documented.
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.
Information is limited. Embryo-related toxicity has been reported.
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. 1 , 2 , 3
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. 2 , 3 , 4 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. 3 , 5 , 6
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. 3
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. 3 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. 7 , 8
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. 4 , 5 , 6 , 9 , 10Antithrombotic effect
Forskolin has been shown in vitro to inhibit platelet aggregation through AC stimulation, augmenting the effects of prostaglandins. 11 , 12 An inhibitory effect on C-kinase activation in platelets has also been described. 6Animal data
Antithrombotic properties have been demonstrated in experiments in rats, rabbits, and sheep. 6Clinical data
Research reveals no clinical data regarding the use of forskolin for antithrombotic effects.Cardiovascular effects
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. 6Clinical data
In human heart tissues, forskolin activated AC and demonstrated strong positive inotropic properties that were synergistic with isoproterenol. 13 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. 6
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. 6 , 14 , 15 , 16CNS
Radiolabeled forskolin was shown to bind to rat brain membranes in a saturable and specific manner. 20 Forskolin demonstrated potent antidepressant activity in a rat forced swimming model 21 and prevented induced seizures in mice. 6Clinical 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. 6Obesity
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. 6 , 22Animal data
Animal models of obesity have been used by the patent holder to demonstrate decreases in body weight and fat. 6 In vitro studies suggest forskolin acts via cAMP but in a more complex manner than that of increased AC levels. 6 , 23Clinical 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. 6 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. 24 Adverse events were not reported. 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. 25Respiratory
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. 6 , 26Animal 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. 6Clinical 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. 26 , 27 Colforsin has also been evaluated as a bronchodilator in a limited number of studies. 28 , 29 , 30Skin
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. 6 , 31 , 32 , 33Clinical data
Case reports exist showing improvement of psoriatic symptoms and a decrease in erythema in patients with hyperplastic skin disorders. 6Other uses
Experimental studies on various cancer cell lines have shown synergistic effects of forskolin in upregulating cellular responses. 32 , 34 , 35 , 36 , 37 , 38 A protective effect against ionizing radiation 39 and UBV-induced apoptosis 33 has been shown in vitro. Forskolin has been demonstrated to have an angiogenic effect via cAMP-dependent protein kinase pathways. 40Diabetes
Stimulation of the release of pancreatic insulin and glucagon by forskolin has been demonstrated in vitro. 6 Influence of forskolin on glucose transport and the action of insulin in skeletal muscle has also been described. 41 , 42 , 43 Clinical trials are lacking; however, studies in normal and diabetic rats have shown increases in blood glucose and serum insulin. 6Fertility
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. 44 , 45 An in vitro study demonstrated increased bovine and human sperm motility with forskolin. 46GI
Animal studies have shown that forskolin promotes gastric and pancreatic acid secretion, as well as relaxes intestinal smooth muscle. 6Immune
Forskolin has been shown to influence cellular immune responses in vitro and in animal experiments. 6Ophthalmic
Forskolin has been used in animal and limited clinical studies in glaucoma, with only temporary effects reported. 6
Information regarding safety and efficacy in pregnancy and lactation is lacking. P. barbatus has been traditionally used as an emmenagogue and oral contraceptive. 2 , 47 Forskolin delayed spontaneous meiotic progression in human oocytes in an in vitro fertility study. 48
None reported, but interactions with CYP3A-dependent drugs are theoretically possible. 6 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. 6 As a consequence of gluconeogenesis, interference with medicines used in diabetes may be expected. 6
Forskolin-like substances have been identified in renal cyst fluid; therefore, forskolin should be avoided in patients with polycystic kidney disease. 49
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. 2 , 6 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. 25 Adverse events reported with the use of colforsin (a forskolin derivative) include tachycardia and arrhythmias. 6 , 15
Toxicology information is limited. The oral median lethal dose in rats has been reported to be more than 2,000 mg/kg body weight. 26 The hydroalcoholic extract of the plant has been shown to interfere with embryonic implantation and to delay fetal development. 47
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