Coleus forskohlii

Coleus forskohlii (Indian Coleus / Forskolin)

1. Identity: Botanical Classification, Chemical Names, and Natural Source

Coleus forskohlii is an Indian-origin medicinal plant and the sole natural source of the labdane terpenoid forskolin (molecular formula C₂₂H₃₄O₇). It is a perennial shrub of the Lamiaceae (mint) family, indigenous to India and Southeast Asia, with numerous reported applications in traditional medicine. The plant is native to the mountain regions of Nepal, India, and Thailand.

The commercial extract is formally derived from the root of Coleus forskohlii (synonym: Plectranthus barbatus) and is standardized to a percentage of the labdane diterpene forskolin, the primary bioactive molecule. Alternative names in the literature and on product labels include: Coleus forskohlii extract, Plectranthus barbatus extract, Indian coleus, makandi (Ayurvedic), coleonol, and forskolin (referring to the isolated diterpene).

The plant itself is a perennial aromatic herb with fleshy roots, purple tubular flowers, and green, ovate leaves with serrated margins. Forskolin is a naturally occurring labdane diterpenoid derived from the root of Coleus forskohlii. Coleus forskohlii is the only species known to contain forskolin.

The plant carries several common names in different traditions and languages. Regional folk names include Gaṇḍīra in Sanskrit, Makandi in Hindi, and Pashanabheda in some colloquial contexts. Coleus barbatus (another synonym) is used medicinally in Africa, Arabia, and Brazil, and the root tubers of the plant are also prepared and eaten as a condiment in India.

1.1 Chemical Characterization of Forskolin

Forskolin is a labdane diterpenoid isolated from the roots of Coleus forskohlii that has attracted sustained scientific and clinical interest due to its unique ability to directly activate adenylyl cyclase, leading to elevation of intracellular cyclic adenosine monophosphate (cAMP). Forskolin (1), 1-deoxyforskolin (2), and 1,9-dideoxyforskolin (3) are structurally related bioactive diterpenoids present in C. forskohlii. The 1,9-dideoxyforskolin analogue lacks the hydroxyl groups critical for adenylate cyclase activation and is considered pharmacologically inactive at that enzyme.

For the extraction of forskolin, tuberous roots of C. forskohlii are used, as they contain the highest concentration of this metabolite. The roots of the plant are the most sought-after part in phytotherapy; they are harvested in autumn, when their concentration in forskolin is at its strongest. The extract is obtained from the sun-dried tuberous roots of the plant by ethanol extraction.

1.2 Common Forms and Preparations

Commercial extracts are commonly standardized to 10–20% forskolin and dosed in supplements at approximately 25–100 mg forskolin per day, equivalent to approximately 250–1000 mg of extract depending on standardization. The preferred standardization in commercial preparations is approximately 5–20% forskolin, with 10% being most common. Preparations encountered in the scientific literature and on the supplement market include:

• Standardized root extract capsules or tablets (most common supplement form)
• Ophthalmic (eye drop) preparations for glaucoma applications
• Intravenous formulations (investigated in cardiac research settings, not available as supplements)
• Inhaled or nebulized forms (investigated in respiratory research)
• Traditional decoctions of dried root powder

In traditional Ayurvedic practice, the plant was typically administered as a decoction of the root or prepared as a herbal powder mixed with ghee or honey. Herbal ingredients are composed of a mixture of numerous compounds that are mostly still unidentified; chemical compositions within herbal ingredients vary depending on production areas, harvest time, and preparation methods of manufacturers. However, with standardized herbal extracts, the amounts of functional components in dietary supplements can be more reliably estimated.

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2. Traditional and Historical Use

2.1 Ayurvedic Medicine (India)

Ancient Hindu Ayurvedic texts described the use of extracts from Coleus species, and an isolated diterpene from Coleus forskohlii called forskolin was demonstrated to be a hypotensive agent with spasmolytic, cardiotonic, and platelet aggregation inhibitory activity. In Ayurvedic medicine, Coleus forskohlii—known traditionally as Makandi or Pashanabhedi—has been used for centuries to support heart health, respiratory function, and urinary tract conditions. Ancient Ayurvedic texts describe it as a remedy for chest pain (angina) and hypertension. It was also described as a treatment for intestinal spasm and convulsions, and it was used to dissolve urinary stones, treat fevers, and improve circulatory vigor.

For centuries, the leaves and root of Coleus have been a traditional remedy in India for digestive complaints, heart and lung conditions, asthma, insomnia, muscle spasm, convulsions, and skin disease. Ayurvedic practitioners used it to stimulate agni (digestive fire), balance vata and kapha doshas, and promote overall energetic vitality.

In Ayurveda, Coleus is known for its ability to "break stones" (Pashanabhedi) and regulate Vata and Kapha doshas. It is a traditional Ayurvedic herb gaining scientific attention for its active compound forskolin.

2.2 Other Traditional Cultures

Coleus barbatus (C. forskohlii) is used medicinally in Africa, Arabia, and Brazil. In Southern Siddha traditions, it is called "Makandi" and used for febrile conditions. The plant has a documented history in South Indian texts dating back to the 17th century CE; a Sanskrit manuscript found in Kerala refers to a "Kapila Srungii" herb used to stimulate the heart and improve digestion, believed by some scholars to be C. barbatus.

In the 1800s, British colonial botanists first classified the plant as Plectranthus barbatus and noted its use in traditional home remedies for coughs and chest congestion, sometimes mixed with honey or fresh ginger juice.

2.3 Modern Scientific Discovery

Since the 1970s, Coleus has been the subject of extensive research due to forskolin isolated from the roots being found to have remarkable therapeutic effects. In 1974, research carried out by Hoechst Pharmaceuticals and the Indian Central Drug Research Institute in a search for new drugs found that extracts of Coleus root reduced muscle spasms and lowered blood pressure. Chemical studies of alcoholic extracts of the tubers of C. barbatus led to isolation of the labdane diterpene forskolin (coleonol), which has become an important research tool in studying the roles of the enzyme adenylate cyclase and cyclic AMP in cellular physiology.

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3. Key Constituents and Active Compounds

3.1 Forskolin: Primary Bioactive

The pharmaceutical properties of forskolin are based on its ability to directly activate the adenylate cyclase enzyme, resulting in elevated levels of the second messenger cyclic adenosine monophosphate (cAMP). As initially shown by Seamon and Daly, the diterpene forskolin directly activates adenylyl cyclase (AC) and raises cyclic AMP levels in a wide variety of cell types.

Forskolin has been shown to be a powerful activator of the enzyme adenylate cyclase in various tissues. It is thought to act on the catalytic subunit and also on the coupling mechanism of guanine regulatory sites (Ns and Ni) with the catalytic subunit. It is now clear that forskolin elicits physiological responses which have been shown to be cAMP-dependent.

This receptor-independent signaling mechanism underlies a broad spectrum of pharmacological effects across cardiovascular, respiratory, metabolic, ophthalmic, dermatological, and oncological indications.

3.2 Secondary Diterpenes and Other Constituents

Forskolin (1), 1-deoxyforskolin (2), and 1,9-dideoxyforskolin (3) are structurally related bioactive diterpenoids present in C. forskohlii. The root also contains other labdane diterpenes (in addition to forskolin) and essential oil. The three main diterpenoids can be quantified by reversed-phase HPLC and are used as quality markers for standardization purposes.

3.3 Downstream Mechanisms of cAMP Elevation

Forskolin is a plant-derived compound that activates the enzyme adenylyl cyclase, which increases cyclic AMP (cAMP) inside cells. Elevated cAMP can activate hormone-sensitive lipase (HSL) in adipocytes (fat cells), which helps release stored fatty acids. Those fatty acids then enter mitochondria to be oxidized (burned) for energy.

Through direct activation of adenylate cyclase, forskolin raises intracellular cAMP and modulates lipolysis, smooth-muscle tone, and platelet function. Elevated intracellular cAMP also activates protein kinase A (PKA), which phosphorylates a broad array of downstream protein targets, accounting for the wide range of physiological effects observed across different tissue types.

Despite its broad pharmacological potential—including anti-glaucoma, anti-inflammatory, and anticancer activities—the clinical application of forskolin remains constrained by poor aqueous solubility, limited oral absorption, rapid metabolic clearance, and lack of intrinsic targeting capability.

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4. Scientific Evidence by Area of Use

4.1 Body Composition and Weight Management

Evidence strength: Preliminary; mixed results across studies; insufficient for firm conclusions.

A systematic literature review identified 7 clinical studies, including 4 randomized controlled trials (RCTs), examining the anti-obesity effect of forskolin or the extract of C. forskohlii root.

The most frequently cited human RCT was conducted by Godard et al. (2005). This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese men (BMI ≥ 26 kg/m²), with 30 subjects studied in a randomized, double-blind, placebo-controlled design for 12 weeks. Forskolin was shown to significantly decrease body fat percentage and fat mass as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). This trial used 250 mg of 10% forskolin extract twice daily (approximately 50 mg forskolin per day) over 12 weeks (PMID: 16020471).

A contrasting RCT examined effects in women. This study investigated the effects of Coleus forskohlii (CF) on body composition; 23 females supplemented their diet with ForsLean™ (250 mg of 10% CF extract) or a placebo two times per day for 12 weeks. CF tended to mitigate gains in body mass and scanned mass with no significant differences in fat mass. Results suggested that CF does not appear to promote weight loss but may help mitigate weight gain in overweight females with apparently no clinically significant side effects.

A further open-label trial examined a mixed-sex healthy population. An open-label study was conducted to evaluate the efficacy of CF root extract for weight management; 15 healthy volunteers participated in an 8-week study, receiving 500 mg of CF extract (10% forskolin) twice a day with meals. Twelve subjects (5 men and 7 women, mean age 32.0 ± 2.3 years) completed the study, and significant decreases compared to baseline were detected after 8 weeks for BMI, body weight, and fat content. This study lacked a placebo control, which limits its interpretability.

A randomized, double-blind, placebo-controlled trial examined metabolic syndrome risk factors. This study assessed the effects of supplementation with C. forskohlii extract on key markers of obesity and metabolic parameters in overweight and obese individuals; 30 participants were randomly assigned to receive either 250 mg of C. forskohlii extract or a placebo twice daily for 12 weeks, with all participants advised to follow a hypocaloric diet. 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.

An NIH Office of Dietary Supplements review notes that Coleus forskohlii (forskolin) has only been studied in a few short-term clinical trials, with current evidence showing no clear effect on body weight and limited safety data, underscoring the need for more rigorous research.

4.2 Glaucoma and Intraocular Pressure

Evidence strength: Moderate for ophthalmic (eye drop) application; studies are limited in size but directionally consistent.

Clinical evidence is considered strongest for glaucoma among the investigated indications. An open-label clinical trial enrolled 90 adult patients aged 18–60 years, suffering from open-angle glaucoma with an intraocular pressure (IOP) of more than 24 mmHg. The results demonstrated the efficacy of 1% forskolin (2 drops three times a day) in achieving fast onset of action and uniformity of hypotensive activity. Forskolin 1% eye drops were significantly effective in relieving signs and symptoms of open-angle glaucoma. Investigators concluded that forskolin 1% eye drops can be a safe alternative to beta-blockers in glaucoma patients with concomitant asthma.

Studies in humans on glaucoma have conflicting results overall, and while IOP-lowering has been demonstrated in some trials, the evidence base requires expansion through larger, controlled trials.

4.3 Asthma and Respiratory Function

Evidence strength: Preliminary; limited to a small number of trials; intravenous and inhaled formulations show more consistent effects than oral.

Potential therapeutic uses for asthma have been proposed because forskolin may help in relaxing smooth muscles and stabilizing inflammatory responses via cAMP elevation.

One single-blinded clinical trial directly compared oral forskolin with sodium cromoglycate. To determine the efficacy of forskolin in preventing asthma attacks, a single-blinded clinical study was performed in children and adult outpatients; 40 patients with mild persistent or moderate persistent asthma were randomly assigned to 6 months of treatment with forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 hours. The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%). Values of forced expiratory volume in 1 second and forced expiratory flow, mid-phase, were similar in the two groups during the treatment period. The investigators concluded that forskolin was more effective than sodium cromoglycate in preventing asthma attacks in patients with mild persistent or moderate persistent asthma. This study should be interpreted cautiously given its single-blind design, relatively small sample, and comparator (not placebo).

When administered intravenously or inhaled, forskolin had a bronchodilation effect. Forskolin may cause cellular changes that stimulate the dilation of airways.

4.4 Cardiovascular Effects

Evidence strength: Weak for oral administration; some positive signals from intravenous studies but not translatable to supplement use.

An isolated diterpene from Coleus forskohlii, called forskolin, was demonstrated to be a hypotensive agent with spasmolytic, cardiotonic, and platelet aggregation inhibitory activity. Two clinical trials found positive effects with intravenous forskolin for heart disease, but overall support for this use is not strong, and oral forms have not been adequately tested in humans.

Preliminary findings also suggest intraoperative infusion of forskolin may benefit cardiovascular health due to anti-inflammatory effects, or that intraarterial forskolin daropate may improve cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

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 with oral supplementation in humans.

4.5 Metabolic Syndrome and Insulin Sensitivity

Evidence strength: Preliminary; only a small number of RCTs, with some positive signals for insulin sensitivity but inconsistent effects on other metabolic markers.

In one clinical trial on 30 overweight and obese people, Coleus forskohlii (together with a low-calorie diet) reduced weight gain, insulin resistance, and blood cholesterol (by increasing HDL), suggesting that the intervention reduced the risk of metabolic syndrome. While some studies suggest that Coleus forskohlii might aid in weight loss and improve insulin resistance, scientific evidence supporting its efficacy for many proposed uses remains limited.

4.6 Testosterone and Hormonal Effects

Evidence strength: Very preliminary; single small RCT in men; not confirmed in women or larger populations.

In the Godard et al. (2005) RCT, serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). Results of RMR testing suggested that forskolin directly activated free fatty acid release, and there was a minimal, non-significant increase in RMR through increased thyroid hormone activity. Follow-up tests revealed no significant changes in RMR within either group, and there was no significant interaction seen across time among groups, refuting claims that forskolin can increase metabolic rate through increased thyroid hormone levels. This hormonal finding requires replication in larger trials before conclusions can be drawn.

4.7 Other Investigated Areas

Extremely limited research suggests that forskolin may reduce intraocular pressure and asthma symptoms, increase testosterone and bone mineral density, and improve metabolic health and body composition. Moreover, clinical trials against different types of cancers are progressing. Forskolin and its derivatives have shown anticancer effects in preclinical models. These areas remain investigational and evidence is currently insufficient to draw clinical conclusions.

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5. Body Systems Associated with Coleus forskohlii

Since ancient times, plants of the Coleus species have been used as an herbal medicine to treat various disorders of the cardiovascular, respiratory, gastrointestinal, and central nervous systems. The following body systems are associated with the plant based on traditional use and/or scientific investigation:

• Cardiovascular system: Demonstrated hypotensive, spasmolytic, cardiotonic, and platelet aggregation inhibitory activity of forskolin.
• Respiratory system: Potential for relaxing smooth muscles of the airway and stabilizing inflammatory responses.
• Ophthalmic system: Useful in reducing intraocular pressure in cases of glaucoma.
• Metabolic / Adipose: Activation of adenylyl cyclase increases cyclic AMP inside cells, which can activate hormone-sensitive lipase in adipocytes, releasing stored fatty acids.
• Endocrine (thyroid and adrenal): In vitro research indicates effects on thyroid cell metabolism and steroidogenesis pathways, though clinical significance in humans is uncertain.
• Gastrointestinal system: cAMP modulation in GI smooth muscle and secretory cells may alter motility and secretion; traditional use supports digestive benefit, though robust modern clinical evidence is sparse.
• Genitourinary: Traditional use for urinary stone dissolution and urinary tract support has been documented.

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6. Dosage Forms and Dosages Reported in Studies

Most clinical trials have administered 250 mg of Coleus forskohlii extract standardized to contain 10% forskolin twice per day, for a total daily dose of 500 mg of Coleus forskohlii extract, equivalent to 50 mg of forskolin.

Specific dosages from cited studies are as follows:

• The Godard et al. RCT in overweight and obese men used 250 mg of 10% extract twice daily for 12 weeks (PMID 16129715).
• The Henderson et al. study in overweight women used 250 mg of 10% CF extract (ForsLean™) two times per day for 12 weeks.
• An open-label trial used 500 mg of CF extract (10% forskolin) twice a day with meals for 8 weeks.
• A randomized, double-blind, placebo-controlled trial used 250 mg of C. forskohlii extract (10% standardized) twice daily for 12 weeks.
• The asthma clinical trial (Gonzalez-Sanchez et al., 2006) used 10 mg/day of oral forskolin in capsules for 6 months.
• The glaucoma open-label study used 1% forskolin eye drops, 2 drops three times a day.

Commercial extracts are commonly standardized to 10–20% forskolin and dosed in supplements at approximately 25–100 mg forskolin per day, equivalent to approximately 250–1000 mg extract depending on standardization.

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7. Safety Considerations and Drug Interactions

7.1 General Tolerability

In the 12-week Henderson et al. female trial, no clinically significant interactions were seen in metabolic markers, blood lipids, muscle and liver enzymes, electrolytes, red cells, white cells, hormones (insulin, TSH, T3, and T4), heart rate, blood pressure, or weekly reports of side effects. No significant adverse events were reported during that study that could be attributed to the supplementation protocol, suggesting that CF supplementation does not appear to be associated with any significant clinical side effects at those dosages.

7.2 Gastrointestinal Adverse Events

A post-marketing nationwide online survey of Coleus forskohlii extract (CFE) users was conducted to evaluate safety in real-world conditions, noting that pharmacological actions of chemicals often differ between species and that it is ideal to set the optimal amount based on human data. Gastrointestinal symptoms (diarrhea, nausea and vomiting, and constipation) accounted for 92.0% of reported adverse events in the survey. Twenty-seven products containing CFE were identified; five of them were reported to cause diarrhea, with suggested intake amounts of 250 mg/day to 1000 mg/day of CFE.

7.3 Cardiovascular and Hemodynamic Concerns

Safety concerns include hypotension and increased bleeding risk when combined with anticoagulants or antiplatelet drugs. Caution is warranted regarding low blood pressure (hypotension) when used in conjunction with medications such as beta-blockers, vasodilators, and/or calcium channel blockers.

7.4 Drug Interactions

Forskolin has documented moderate interactions with at least 73 different drugs and mild interactions with at least 88 different drugs, according to Medscape's drug interaction database. Key categories of interactions include:

• Anticoagulants and antiplatelet agents: Nabumetone and forskolin both increase anticoagulation; use with caution and monitor. Similar concerns apply to naproxen and other NSAIDs used concurrently.
• Antihypertensives: Risk of additive hypotension with beta-blockers, vasodilators, and calcium channel blockers.
• Antidiabetic agents: Coleonol, a compound found in Coleus root, may stimulate insulin release, potentially producing pharmacodynamic synergism with blood-glucose-lowering agents.

Caution is advised when using simultaneously with anticoagulants, antihypertensives, or vasodilators, and in individuals suffering from ulcers or diabetes.

7.5 Cytochrome P450 Interactions

Research has been conducted to evaluate the effect of C. forskohlii and its major constituents on cytochrome P450 (CYP3A, CYP2B, and CYP2C) mRNA expression in rat hepatocytes; the extract was subjected to standardization with respect to forskolin, 1-deoxyforskolin, and 1,9-dideoxyforskolin. These findings in rat hepatocytes suggest a potential for herb–drug metabolic interactions, though human clinical data on CYP-mediated interactions are limited.

7.6 Special Populations

Scientific evidence supporting efficacy for many proposed uses of Coleus forskohlii remains limited. The compound's endocrine-modulating activity (via cAMP elevation and effects on steroidogenesis genes) warrants caution in populations with hormone-sensitive conditions. Safety in pregnancy and lactation has not been established in clinical studies.

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References

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