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Forskolin
Forskolin
Forskolin
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Forskolin
Names
IUPAC name
(13R)-1α,6β,9α-Trihydroxy-11-oxo-8α,13-epoxylabd-14-en-7β-yl acetate
Systematic IUPAC name
(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-Ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxododecahydro-1H-naphtho[2,1-b]pyran-5-yl acetate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.060.354 Edit this at Wikidata
UNII
  • InChI=1S/C22H34O7/c1-8-19(5)11-14(25)22(27)20(6)13(24)9-10-18(3,4)16(20)15(26)17(28-12(2)23)21(22,7)29-19/h8,13,15-17,24,26-27H,1,9-11H2,2-7H3/t13-,15-,16-,17-,19-,20-,21+,22-/m0/s1 checkY
    Key: OHCQJHSOBUTRHG-KGGHGJDLSA-N checkY
  • InChI=1/C22H34O7/c1-8-19(5)11-14(25)22(27)20(6)13(24)9-10-18(3,4)16(20)15(26)17(28-12(2)23)21(22,7)29-19/h8,13,15-17,24,26-27H,1,9-11H2,2-7H3/t13-,15-,16-,17-,19-,20-,21+,22-/m0/s1
    Key: OHCQJHSOBUTRHG-KGGHGJDLBB
  • CC(=O)O[C@H]1[C@H]([C@@H]2[C@]([C@H](CCC2(C)C)O)([C@@]3([C@@]1(O[C@@](CC3=O)(C)C=C)C)O)C)O
Properties
C22H34O7
Molar mass 410.507 g·mol−1
Solubility Soluble in organic solvents such as ethanol, chloroform and DMSO[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Forskolin (coleonol) is a labdane diterpene produced by the plant Coleus barbatus (blue spur flower). Other names include pashanabhedi, Indian coleus, makandi, HL-362, mao hou qiao rui hua.[2] As with other members of the large diterpene class of plant metabolites, forskolin is derived from geranylgeranyl pyrophosphate (GGPP). Forskolin contains some unique functional elements, including the presence of a tetrahydropyran-derived heterocyclic ring.

Forskolin is commonly used in laboratory research to increase levels of cyclic AMP by stimulation of adenylate cyclase.[2]

The name comes from an obsolete name for the plant, Plectranthus forskolaei (see Coleus barbatus).

Mechanism of action

[edit]

Forskolin is used in biochemistry experiments to raise levels of cyclic AMP (cAMP) in studies of cell physiology.[2][3] Forskolin activates the enzyme adenylyl cyclase and increases intracellular levels of cAMP. cAMP is an important second messenger necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in the hypothalamus-pituitary gland axis, and for the feedback control of hormones via induction of corticotropin-releasing factor gene transcription.[4] Cyclic AMP acts by activating cAMP-sensitive pathways such as protein kinase A and EPAC1.

Chemistry

[edit]

It is defined as a category 4 chemical with acute dermal toxicity based on 2012 OSHA Hazard Communication Standard (29 CFR 1910.1200).[5]

Derivatives

[edit]

Its derivatives include colforsin daropate, NKH477,[6] and FSK88,[7] which may be more potent than forskolin at raising cAMP. These derivatives may have pharmaceutical utility against bronchoconstriction and heart failure.[8][9]

Chemical synthesis

[edit]

A total chemical synthesis has been reported. The key step of this chemical synthesis is photocyclization of a synthetic intermediate in presence of oxygen and methylene blue, followed by a singlet oxygen Diels-Alder reaction.[10]

Biosynthesis

[edit]

The heterocyclic ring is synthesized after the formation of the trans-fused carbon ring systems formed by a carbocation mediated cyclization. The remaining tertiary carbocation is quenched by a molecule of water. After deprotonation, the remaining hydroxy group is free to form the heterocyclic ring. This cyclization can occur either by attack of the alcohol oxygen onto the allylic carbocation formed by loss of diphosphate, or by an analogous SN2'-like displacement of the diphosphate.[11] This forms the core ring system A of forskolin.

The remaining modifications of the core ring system A can putatively be understood as a series of oxidation reactions to form a poly-ol B which is then further oxidized and esterified to form the ketone and acetate ester moieties seen in forskolin. However, because the biosynthetic gene cluster has not been described, this putative synthesis could be incorrect in the sequence of oxidation/esterification events, which could occur in almost any order.

Weight loss

[edit]

Although forskolin has been used in preliminary weight loss research, the low quality of the studies and inconclusive results prevented any determination of effects.[12]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Forskolin

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from Grokipedia
Forskolin is a labdane diterpenoid compound with the molecular formula C₂₂H₃₄O₇, primarily isolated from the roots of the plant Coleus forskohlii (synonym Plectranthus barbatus), a member of the family native to subtropical and tropical regions of , the , and . This naturally occurring substance, chemically known as 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxylabd-14-en-11-one, was first identified in 1974 and serves as the main bioactive constituent of the plant. Forskolin functions as a potent activator of the enzyme , which catalyzes the conversion of ATP to (cAMP), thereby elevating intracellular cAMP levels and influencing various cellular processes such as activity, signaling, and . In traditional Ayurvedic medicine, extracts from C. forskohlii have been used for centuries to treat conditions including , , heart disorders, and digestive issues. Pharmacologically, forskolin's ability to boost cAMP has positioned it as a candidate for therapeutic applications in diverse areas, including the treatment of through intraocular pressure reduction, congestive by enhancing cardiac contractility, and via bronchodilation. Recent research has explored its potential in management, where supplementation with C. forskohlii extract containing forskolin has shown modest effects on , including reduced fat mass and increased in some clinical studies. Additionally, preclinical investigations indicate neuroprotective effects against pathology, antidiabetic benefits improving glycemic control and reproductive function, and anticancer properties through modulation of signaling pathways, including recent 2025 studies showing efficacy against aggressive and . Antiviral activity has also been demonstrated against viruses such as by inhibiting viral replication. Despite these promising effects, clinical evidence remains limited for many applications, and forskolin is commonly available as a rather than an approved pharmaceutical in most regions.

History and Discovery

Initial Isolation

Forskolin was first isolated in 1974 by researchers at the Central Drug Research Institute (CDRI) in , , including J. S. Tandon and colleagues, from the tuberous roots of forskohlii Briq. (synonym Plectranthus barbatus Andrew), a traditionally used in Ayurvedic medicine. This isolation occurred as part of a large-scale screening program for bioactive compounds from Indian medicinal , targeting hypotensive and spasmolytic activities. The compound, initially named coleonol, was obtained through bioassay-guided fractionation of ethanolic root extracts, yielding a crystalline solid with significant cardiovascular effects in preliminary animal tests. In 1977, a team at Hoechst India Limited, led by Sujata V. Bhat, conducted detailed chemical analysis and fully elucidated the structure of coleonol, renaming it forskolin to honor the 18th-century Swedish naturalist Peter Forsskål, who first described the plant genus. Through spectroscopic methods including NMR, , and IR, they characterized forskolin as a labdane-type diterpenoid with the formula C22H34O7, featuring a unique tricyclic structure with hydroxyl groups at C-1, C-6, and C-9, an acetoxy at C-7, a at C-11, and an bridge between C-8 and C-13. This structural determination confirmed its novelty among known diterpenes and highlighted its potential as a lead for pharmaceutical development. Hoechst Pharmaceuticals initiated early pharmacological screening of forskolin in the mid-1970s, revealing its potent activation of adenylate cyclase and elevation of intracellular cyclic AMP levels in various tissues, independent of G-protein coupling. These studies, conducted on isolated membranes and intact cells, demonstrated dose-dependent effects on cardiac contractility, relaxation, and platelet aggregation inhibition, laying the groundwork for its investigation as a therapeutic agent.

Traditional and Early Research

forskohlii, known in as Makandi or Gandira, has been utilized in Ayurvedic for millennia to address various ailments, particularly heart conditions, , and disorders. It has been utilized in traditional Ayurvedic for millennia to address various ailments, particularly heart conditions, , and disorders such as eczema and through its purported balancing effects on bodily humors. These traditional uses stem from the plant's roots and tubers, often prepared as decoctions or powders to promote vitality and detoxification. By the , European botanists and physicians began exploring species, including introductions from colonial botanical collections in , for their potential properties. Interest focused on the plant's ability to relieve muscle spasms and intestinal cramps, drawing from initial observations of its calming effects in herbal preparations. This period marked the transition of from an exotic ornamental to a subject of preliminary medicinal inquiry in Western pharmacopeias, though systematic studies remained limited. In the early , pharmacological investigations shifted toward animal models to validate traditional claims, with crude extracts of forskohlii demonstrating notable cardiovascular benefits. Studies conducted in during the 1970s at institutions like the Central Drug Research Institute highlighted the extracts' capacity to regulate , exhibiting hypotensive effects in experimental animals without significant . These findings, based on oral and intravenous administrations, laid the groundwork for later isolations, including the identification of forskolin in 1974.

Natural Occurrence and Biosynthesis

Plant Sources

Forskolin is primarily sourced from the roots of Coleus forskohlii (synonym Plectranthus barbatus), a perennial herb in the family native to subtropical regions of , , and . This plant thrives in warm, temperate climates and is found growing wild on slopes at elevations up to 2,300 meters. The roots serve as the main storage site for forskolin, with negligible amounts in other parts like stems or leaves. Forskolin concentrations in dried roots typically range from 0.01% to 1.0% by dry weight, with higher levels influenced by factors such as cultivar, subtropical growing conditions, and between 5.5 and 7. Optimal production occurs in well-drained, sandy soils rich in , where environmental stresses like moderate can enhance diterpenoid accumulation. Variability across accessions highlights the importance of selecting high-yielding genotypes for consistent output. Recent advances include aeroponic cultivation systems, which as of have achieved forskolin contents of up to 1.03 mg/g (0.103%) dry weight after 18 weeks, offering improved efficiency and reduced resource consumption compared to traditional methods. Commercial cultivation of forskohlii is prominent in and , driven by demand for dietary supplements, with farming focused on root harvest after 5-7 months of growth. Extraction from these roots yields standardized products containing 10-20% pure forskolin, achieved through solvent-based methods that isolate the compound efficiently from crude plant material. In , contract farming systems cover thousands of hectares, supporting global supply chains while emphasizing sustainable practices to prevent overharvesting of wild populations.

Biosynthetic Pathway

Forskolin biosynthesis in Coleus forskohlii commences with the linear isoprenoid precursor geranylgeranyl diphosphate (GGPP), which is cyclized to form the labdane-type skeleton characteristic of the compound. This process involves two : copalyl diphosphate (CfTPS2, a class II ) converts GGPP to (13R)-copalyl diphosphate, followed by class I CfTPS3, which catalyzes the cyclization to 13R-manoyl oxide, the first dedicated intermediate in the pathway. The subsequent elaboration of 13R-manoyl oxide to forskolin requires a complex cascade of oxidations and acetylations, primarily mediated by monooxygenases from the CYP76AH subfamily. Key among these is CfCYP76AH15, which performs iterative reactions including at C-11 to initiate formation at that position, followed by at C-1; this enzyme's multifunctional nature enables sequential modifications on the substrate. Additional P450s, including CfCYP76AH8, CfCYP76AH9, CfCYP76AH10, and CfCYP76AH11, contribute further hydroxylations at C-6, C-7, and C-9, along with oxidation steps that establish the polyhydroxylated and keto functionalities essential to forskolin's structure. In total, five such P450 enzymes drive these oxidative transformations, often in a non-specific or overlapping manner to achieve regioselective oxygenation. Acetylation of the hydroxyl groups at C-6 and C-7 occurs after oxidation, catalyzed by BAHD-family acetyltransferases such as CfACT1 (also denoted CfAAT1D in some contexts), which transfers from in a regiospecific manner; this step completes the diacetylated motif unique to forskolin. The full pathway, reconstituted in , confirms that a minimal set of CfTPS2, CfTPS3, three P450s (e.g., CfCYP76AH15, CfCYP76AH11, CfCYP76AH8), and one acetyltransferase suffices for conversion to forskolin, though native production involves the broader set for efficiency. This biosynthetic route is localized to specialized root cork cells—suberized structures akin to trichomes—in C. forskohlii roots, where the enzymes colocalize with intracellular oil bodies that store the lipophilic product. Pathway flux is upregulated by stress signals, including ; exogenous application of (500 μM) to hairy root cultures increases forskolin yield by up to 2.5-fold, indicating jasmonate-mediated transcriptional regulation of key genes like those encoding the P450s. Since the initial reconstitution, advances in have enhanced heterologous production in engineered yeast, with optimized strains achieving forskolin titers exceeding 100 mg/L as of 2021. These developments, including of CYP enzymes for improved activity and specificity, offer a promising sustainable approach to meet commercial demand without relying solely on cultivation.

Chemical Properties

Molecular Structure

Forskolin possesses the molecular formula C22_{22}H34_{34}O7_7 and a molecular weight of 410.51 g/mol. It is classified as a labdane diterpenoid, featuring a characteristic ring system fused to a ring, along with a group and three free hydroxyl functionalities plus an ester derived from a fourth hydroxyl group. This heterotricyclic structure includes an exocyclic and positions for oxidation that contribute to its chemical complexity. The full systematic IUPAC name, reflecting its , is [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzochromen-5-yl] , highlighting eight chiral centers including those at C-3, C-4a, C-5, C-6, C-6a, C-10, C-10a, and C-10b. This configuration is essential to its three-dimensional architecture, with the core providing rigidity and the ring incorporating an linkage. In its pure form, forskolin manifests as a white to off-white crystalline powder with a of 228–232 °C. It exhibits good solubility in polar organic solvents, such as (∼6 mg/mL) and (up to 160 mg/mL), but limited in (<0.1 mg/mL).

Derivatives and Synthesis

Forskolin derivatives have been developed to improve , stability, and targeted therapeutic while retaining its ability to activate . One notable derivative is 6-acetyl-7-deacetylforskolin, also known as isoforskolin, which features an at the 6-position and a free hydroxy at the 7-position; this modification results in retained but reduced activity compared to forskolin in stimulating adenylate cyclase. Another key derivative is NKH477, or colforsin daropate , a water-soluble analog designed for intravenous administration that exhibits enhanced potency in activating cardiac . This compound serves as a for treating by improving cardiac contractility through elevated cyclic AMP levels. Total synthesis of forskolin enables production independent of natural sources and allows for analog creation. The first total synthesis was accomplished by E. J. Corey and colleagues in through a multi-step process involving stereoselective cyclizations to construct the complex labdane diterpene framework, culminating in the racemic compound after 20 steps. Subsequent approaches have refined efficiency, but Corey's route remains seminal for demonstrating feasibility despite the molecule's stereochemical challenges. Semi-synthetic methods focus on modifying naturally isolated forskolin or its precursors to enhance pharmaceutical properties. Regioselective , such as of 7-desacetylforskolin at specific hydroxy positions, produces with improved stability for and delivery, as seen in the preparation of water-soluble variants like those with aminoacyl groups at the 6- or 7-position. These modifications preserve core bioactivity while addressing limitations of the parent compound's .

Pharmacology

Mechanism of Action

Forskolin exerts its primary biological effects through direct activation of adenylate cyclase (AC), a membrane-bound enzyme that catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP). Unlike typical G-protein-coupled receptor agonists, forskolin binds directly to the catalytic unit of AC, bypassing the need for G-protein intermediaries such as Gsα, and thereby elevates intracellular cAMP levels independently of receptor stimulation. This unique mechanism was first demonstrated in studies using rat brain membranes and intact cells, where forskolin rapidly and reversibly stimulated AC activity without requiring exogenous guanyl nucleotides or being inhibited by G-protein antagonists. The increase in cAMP triggered by forskolin activates (PKA), which in turn downstream targets, modulating various cellular processes through altered protein function and gene expression. This pathway can be summarized as: forskolin binds to AC → elevated cAMP → PKA activation → of substrates. Forskolin's action potentiates the effects of other AC stimulators, such as hormones or , by facilitating conformation changes that enhance catalytic efficiency. Forskolin displays high potency toward specific AC isoforms, particularly the transmembrane types V and VI, which are predominant in cardiac and vascular tissues. In cell-based assays, forskolin achieves half-maximal activation () of these isoforms at concentrations around 5-10 μM, enabling robust cAMP elevation in relevant physiological contexts. This isoform selectivity underscores forskolin's utility as a tool for dissecting AC signaling in targeted tissues.

Physiological Effects

Forskolin exerts its physiological effects primarily through the elevation of intracellular (cAMP) levels, which activates () and leads to downstream events in various tissues. This mechanism results in tissue-specific responses, including modulation of tone and metabolic activity, without directly involving receptor binding. In the cardiovascular system, forskolin induces by relaxing vascular cells, primarily through PKA-mediated of myosin light chain kinase, which inhibits its activity and reduces contraction. It also promotes positive inotropy in cardiac myocytes by enhancing calcium influx via PKA of L-type calcium channels, increasing their open probability and thereby boosting contractility; studies in isolated heart preparations have shown dose-dependent increases in contractile force. These effects contribute to improved and reduced systemic in experimental models. Forskolin demonstrates bronchodilatory effects in the by relaxing airway through PKA activation, which decreases intracellular calcium levels and promotes muscle relaxation. Additionally, it inhibits release from mast cells and by elevating cAMP, thereby reducing allergic bronchoconstriction; studies on tissue have reported inhibition of -induced contractions. These actions lead to widened airways and decreased bronchial reactivity in animal models of . Metabolically, forskolin stimulates in adipocytes by activating (HSL) via PKA , facilitating the breakdown of triglycerides into free fatty acids and for energy mobilization. Furthermore, it potentiates effects by directly stimulating adenylate cyclase in follicular cells, enhancing secretion of thyroxine (T4) and (T3); experiments in dog lobes showed forskolin at 10 μM increasing T4 release comparably to . This amplification supports elevation without altering synthesis pathways.

Therapeutic Applications

Weight Loss and Metabolic Effects

Forskolin promotes fat reduction and lean body mass increase primarily through elevation of intracellular (cAMP) levels, which activates hormone-sensitive to enhance in . This mechanism may also contribute to mild thermogenic effects, though clinical studies have not consistently shown increases in . A seminal 2005 randomized, double-blind, -controlled trial by Godard et al. involving 30 and obese men demonstrated these effects, with participants receiving 250 mg of 10% forskolin extract (providing 25 mg forskolin) twice daily for 12 weeks. The forskolin group experienced a significant reduction in of 4.14% and fat mass of 4.52 kg, alongside a nonsignificant increase in of 3.71 kg, compared to . Additional mechanisms include improved insulin sensitization, as evidenced by a 2015 in 30 overweight and obese subjects, where the same dosage of forskolin extract for 12 weeks significantly lowered insulin levels and indices. Reviews of available trials suggest modest outcomes, typically around 1-2 kg in individuals over 8-12 weeks, though results vary by study population and are often confounded by concurrent diet or exercise interventions. Recent reviews as of 2023 indicate limited and inconsistent evidence for substantial weight loss efficacy, with poor oral bioavailability and low water solubility noted as potential limitations.

Other Medical Uses

Forskolin and its derivatives, such as colforsin daropate, have demonstrated bronchodilatory properties that may benefit patients with asthma by reducing bronchospasm through activation of adenylate cyclase and elevation of intracellular cAMP levels. In a single-blinded clinical trial involving patients with mild to moderate persistent asthma, oral forskolin at 10 mg daily was more effective than sodium cromoglycate in preventing asthma attacks, with significant improvements in pulmonary function tests including forced expiratory volume in one second compared to placebo. This derivative is approved for intravenous use in Japan, where it has been applied in clinical settings to manage acute respiratory complications associated with bronchoconstriction. In the treatment of , topical application of forskolin effectively lowers (IOP) by enhancing cAMP-mediated reduction in aqueous humor production within the ciliary . An open-label evaluating 1% forskolin in patients with open-angle reported a mean IOP reduction of 4.5 mm Hg in the right eye and 5.4 mm Hg in the left eye after four weeks, corresponding to approximately 20% decrease from baseline, with no significant adverse effects beyond mild ocular irritation. This positions forskolin as a potential alternative for patients intolerant to beta-blockers, particularly those with concomitant . Forskolin derivatives like colforsin daropate have been investigated for cardiovascular applications, particularly in , due to their positive inotropic and vasodilatory effects via cAMP elevation in cardiac myocytes. In , colforsin daropate is clinically used for perioperative acute following , where it improves and reduces without excessive . Preclinical and early support its role in enhancing in congestive models. Forskolin shows promise in managing through its ability to promote relaxation of corpus cavernosum . Intracavernosal administration of forskolin in a pilot study of men with vasculogenic impotence resulted in successful erections in 75% of cases, comparable to papaverine-phentolamine combinations. Furthermore, studies indicate synergistic effects with phosphodiesterase type 5 (PDE5) inhibitors like , where forskolin amplifies cAMP signaling to enhance cGMP-mediated in penile tissue. Emerging research explores forskolin's anti-inflammatory potential for conditions like . In a rat model of imiquimod-induced , ethanolic extract of forskohlii significantly reduced disease severity scores, epidermal thickness, and pro-inflammatory cytokines (TNF-α, IL-17), while boosting enzymes such as . These findings suggest a role for cAMP modulation in suppressing keratinocyte hyperproliferation, though human clinical trials are needed to confirm efficacy. Preclinical studies as of 2024 also indicate potential anticancer effects of colforsin daropate in MYC-driven high-grade serous ovarian through inhibition of signaling pathways, but clinical evidence is lacking.

Safety and Regulation

Side Effects and Toxicity

Forskolin use is generally well-tolerated at typical supplemental doses, but common side effects include , , and flushing, particularly when administered intravenously or at oral doses exceeding 50 mg daily. These cardiovascular effects stem from forskolin's ability to activate adenylate cyclase, leading to increased cyclic AMP levels and . Forskolin is contraindicated during and due to insufficient data and potential risks to the or . It should also be avoided by individuals with , as it may promote enlargement. Gastrointestinal disturbances, such as diarrhea and upset stomach, are also frequently reported, affecting approximately 10% of users in post-marketing surveys of forskohlii extracts containing forskolin. Other mild reactions may include , , , and restlessness, though these are less consistently documented across studies. In terms of toxicity, forskolin exhibits low in animal models, with an oral LD50 exceeding 2 g/kg in rats. Severe adverse events are rare but can include arrhythmias, particularly in patients with pre-existing cardiac conditions, as evidenced by isolated perfused heart studies and case reports of following supplement ingestion. Long-term data on forskolin are limited, with chronic use potentially linked to elevated liver enzymes or in high-dose scenarios, as suggested by user surveys and animal hepatotoxicity studies; however, human clinical evidence remains sparse and inconclusive. No clear evidence supports dependency with prolonged use.

Drug Interactions and Dosage

Forskolin is typically administered orally as a in doses ranging from 100 to 300 mg per day of extract standardized to 10-20% forskolin content, equivalent to 10-50 mg of pure forskolin daily, often divided into two doses. Clinical studies on metabolic effects have commonly used 250 mg of a 10% forskolin extract twice daily, providing 25 mg of forskolin per dose. For acute cardiovascular applications, intravenous administration of forskolin or its colforsin daropate has been studied at rates of 0.5-1.0 μg/kg/min following an initial , though such uses are investigational and not standard in . Oral of forskolin is limited due to poor , with absorption estimated to be low, though formulations combining it with bioavailability enhancers like from may improve uptake by inhibiting metabolic enzymes. Forskolin exhibits several potential drug interactions due to its effects on cardiovascular function, platelet aggregation, and . It may potentiate the hypotensive effects of antihypertensive medications, such as beta-blockers and , potentially leading to excessive reduction. Similarly, forskolin can enhance the bronchodilatory actions of beta-agonists like epinephrine or , increasing the risk of additive cardiovascular stimulation. Contraindications exist with anticoagulants and antiplatelet drugs, as forskolin inhibits platelet aggregation and may heighten bleeding risk. Additionally, forskolin from forskohlii extract may induce CYP3A enzyme expression in some models, potentially accelerating the of substrates for this pathway, though is inconsistent and clinical relevance remains unclear. In the United States, forskolin is not approved by the FDA as a pharmaceutical drug but is widely available over-the-counter as a under the Dietary Supplement Health and Education Act of 1994. No FDA GRAS notices have been issued for forskolin or Coleus forskohlii extracts, though some manufacturers have self-affirmed GRAS status for food use based on safety data. In the , Coleus forskohlii extracts are subject to regulations under Regulation (EU) 2015/2283, requiring pre-market authorization for use in food supplements if not historically consumed in the region; while not explicitly listed as authorized as of November 2025, they are commercially available with varying compliance to safety assessments. Users should consult regulatory databases for the latest status in specific jurisdictions.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Forskolin
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC5388535/
  3. https://pubmed.ncbi.nlm.nih.gov/23023353/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC11397331/
  5. https://pubmed.ncbi.nlm.nih.gov/27739063/
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC10856047/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC2129145/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC4913438/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC10439998/
  10. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70158
  11. https://www.uclahealth.org/news/release/treatment-strategy-reprograms-brain-cancer-cells-halting
  12. https://pubmed.ncbi.nlm.nih.gov/20186655/
  13. https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-2007-969566.pdf
  14. https://sujatavbhat.com/images/pdf/natural-products-2.pdf
  15. https://pubmed.ncbi.nlm.nih.gov/6345959/
  16. https://academicjournals.org/journal/JMPR/article-full-text-pdf/DD448E315429.pdf
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC4471649/
  18. https://www.ayurvana.fr/en/blog/post/the-coleus-plant.html
  19. https://elifesciences.org/articles/23001
  20. https://www.mdpi.com/1420-3049/27/24/8986
  21. https://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra26190f
  22. https://www.chemijournal.com/archives/2020/vol8issue4/PartAH/8-4-340-314.pdf
  23. https://www.mdpi.com/1420-3049/29/17/4215
  24. https://www.phytojournal.com/archives/2018/vol7issue5/PartAV/7-5-402-401.pdf
  25. https://www.ijpsonline.com/articles/effect-of-solvents-and-extraction-methods-on-forskolin-content-from-icoleus-forskholiii-roots.pdf
  26. https://www.entrepreneurindia.co/blog-description/13610/venturing%2Bcoleus%2Bforskohlii%2Bextract%2Bmarket
  27. https://doi.org/10.7554/eLife.23001
  28. https://www.ijpsnonline.com/index.php/ijpsn/article/view/577
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC9113163/
  30. https://lktlabs.com/product/forskolin/
  31. https://pubmed.ncbi.nlm.nih.gov/6681845/
  32. https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5232
  33. https://karger.com/pha/article/69/3/127/271162/A-Forskolin-Derivative-Colforsin-Daropate
  34. https://pubs.acs.org/doi/10.1021/ja00219a059
  35. https://pubs.acs.org/doi/10.1021/jo00273a039
  36. https://pubmed.ncbi.nlm.nih.gov/8996857/
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC319568/
  38. https://www.ncbi.nlm.nih.gov/books/NBK27958/
  39. https://pmc.ncbi.nlm.nih.gov/articles/PMC2692545/
  40. https://www.mdpi.com/2076-3417/9/19/4089
  41. https://www.ahajournals.org/doi/pdf/10.1161/01.str.17.6.1299
  42. https://link.springer.com/article/10.1007/s003950050222
  43. https://pubmed.ncbi.nlm.nih.gov/2530974/
  44. https://www.sciencedirect.com/science/article/abs/pii/0014299984901699
  45. https://www.sciencedirect.com/science/article/pii/0014579384813277
  46. https://pubmed.ncbi.nlm.nih.gov/6327383/
  47. https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2005.162
  48. https://pmc.ncbi.nlm.nih.gov/articles/PMC4663611/
  49. https://www.healthline.com/nutrition/forskolin-review
  50. https://www.ncbi.nlm.nih.gov/books/NBK576386/
  51. https://www.drugs.com/npp/forskolin.html
  52. https://pubmed.ncbi.nlm.nih.gov/16749416/
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC4487936/
  54. https://pubmed.ncbi.nlm.nih.gov/26155078/
  55. https://pubmed.ncbi.nlm.nih.gov/11712370/
  56. https://pubmed.ncbi.nlm.nih.gov/7616388/
  57. https://pubmed.ncbi.nlm.nih.gov/9334594/
  58. https://doi.org/10.1124/jpet.105.092544
  59. https://journals.lww.com/aptb/fulltext/2024/14090/coleus_forskohlii_shows_anti_psoriatic_activity_in.2.aspx
  60. https://www.science.org/doi/10.1126/scisignal.ado8303
  61. https://www.rxlist.com/forskolin/generic-drug.htm
  62. https://www.webmd.com/vitamins-and-supplements/forskolin-uses-and-risks
  63. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/forskolin
  64. https://pmc.ncbi.nlm.nih.gov/articles/PMC6521622/
  65. https://www.sigmaaldrich.com/sds/sigma/f3917
  66. https://cdn.caymanchem.com/cdn/msds/11018m.pdf
  67. https://pubmed.ncbi.nlm.nih.gov/2558825/
  68. https://www.drugs.com/npc/forskolin.html
  69. https://www.heartlungcirc.org/article/S1443-9506%2824%2901315-5/fulltext
  70. https://www.researchgate.net/publication/228063629_Dietary_Coleus_forskohlii_extract_generates_dose-related_hepatotoxicity_in_mice
  71. https://reference.medscape.com/drug/coleus-forskohlii-colforsin-forskolin-344584
  72. https://www.sciencedirect.com/science/article/abs/pii/S1043661803003281
  73. https://www.sciencedirect.com/science/article/pii/S2590098620300142
  74. https://www.verywellhealth.com/everything-you-need-to-know-about-forskolin-7853493
  75. https://pubmed.ncbi.nlm.nih.gov/38803590/
  76. https://www.sciencedirect.com/science/article/pii/S2225411014000418
  77. https://www.nrdc.org/sites/default/files/safety-loophole-for-chemicals-in-food-list.pdf
  78. https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2012.2663
  79. https://ec.europa.eu/food/food-feed-portal/screen/novel-food-catalogue/search
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