Forskolin

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Forskolin
Forskolin.svg
Identifiers
CAS number 66428-89-5 YesY
PubChem 47936
ChemSpider 43607 YesY
UNII 1F7A44V6OU YesY
DrugBank DB02587
ChEBI CHEBI:42471 YesY
ChEMBL CHEMBL52606 YesY
Jmol-3D images Image 1
Properties
Molecular formula C22H34O7
Molar mass 410.50 g mol−1
Solubility soluble in organic solvents such as ethanol, chloroform and DMSO[1]
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Forskolin (also called Coleonol) is a labdane diterpene that is produced by the Indian Coleus plant (Coleus forskohlii). Forskolin is commonly used to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology. 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.[2] Cyclic AMP acts by activating cAMP-sensitive pathways such as protein kinase A and Epac.

Further information: function of protein kinase A

Biosynthesis[edit]

  • As with other members of the large diterpene family of natural products, forskolin is derived from geranylgeranyl pyrophosphate (GGPP). Forskolin, however, contains some unique functional elements, key among them is the presence of a tetrahydopyran derived heterocyclic ring. This ring is synthesized after the formation of the trans-fused carbon ring systems are formed by a carbocation mediated cyclization. The remaining tertiary carbocation is quenched by a molecule of water. After deprotonation, the remaining hydroxyl 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.[3] 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.

Chemical, biological and medical potential[edit]

  • Applied with rolipram, forskolin provides a route[further explanation needed] to inhibition of colon cancer cell growth and survival.[5] These two drugs also work together to induce long-term potentiation in neuronal populations.[6]
  • To date, there have been more than two clinical studies examining the effectiveness of forskolin as a weight loss aid. Only one has been subject to peer-review and published in a medical journal. This clinical study, sponsored by the Sabinsa Corporation - an herbal supplement manufacturer, also observed forskolin's role in significantly increasing lean mass, bone mass, and testosterone in the overweight and obese men involved.[7] This research has led to companies marketing forskolin as a bodybuilding supplement.
  • Clinical Studies with Forskolin Eye-Drops in Patients with Open Angle Glaucoma.[8][further explanation needed]
  • Forskolin may be helpful in controlling the underlying cause of glaucoma[9][10][11][12]

The sometimes successful use of forskolin to reduce intraocular pressure may be due to its unique ability to stimulate adenylate cyclase activity and increase cAMP which regulates and activates critical enzymes required for the cellular energy required to move fluid out of the eye.

  • Increase skin's natural resistance to burning under UV light (see links below)
  • Stimulate a tanning response when applied topically.[13]
  • Reduce urinary tract infections and enhance the ability of antibiotics to kill bacteria that normally survive.[14][15]

Forskolin can also be used to promote nerve repair by increasing cAMP concentrations. Forskolin can activate or upregulate the proliferation of Schwann cells in culture, together with Fibroblast growth factor or Transforming Growth Factor-Beta.[citation needed]

Various experimental studies are underway in using Forskolin as an adjuvant in treatment for diseases such as Parkinsons and/or nerve damage caused by trauma/accident.[citation needed]

Adverse Reactions[edit]

There are limited clinical trials about the adverse effects of forskolin. One study has shown that the lethal dose in rats (with the oral formulation) was >2,000 mg/kg. [16]

Safety in Pregnancy[edit]

There is limited information on forskolin’s use in pregnant women. The safety has not yet been determined.[17] Historically, Forskolin has been used to stimulate or promote menses in women as well as a form of oral birth control. [18] Forskolin should be used with caution or avoided altogether in women who are pregnant.[17]

References[edit]

  1. ^ "Forskolin" (pdf). Sigma Aldrich. 
  2. ^ "Forskolin For Weight Loss And Side Effects". www.ywdiet.com. Retrieved 7 December 2014. 
  3. ^ Dewick, P. M. (2009). Medicinal Natural Products (3rd ed.). Wiley. p. 232. ISBN 978-0470741689. 
  4. ^ In: "Innovative approaches in drug Research", A.F. Harms (Editor), Elsevier Science Publishers B.V., Amsterdam. 1986. p. 191-207; Forskolin - The Chemical Entity and Structure Activity Relationships of Forskolin and its Derivatives. de Souza N.J. In: Rupp, RH; de Souza, NJ; Dohadwalla, AN.(Eds). Proceedings of an international symposium on "Forskolin: Its Chemical, Biological and Medical Potential", Hoechst India Limited, Bombay. 1985. 5-12, 39-50;Structures and Sterochemistry of new Labdane diterpenoids from Coleus forskohlii Briq. Bhat, SV; Bajwa, BS; Dornauer, H; de Souza, NJ; Fehlhaber, HW. Tetrahedron Letters. 1977. 19: 1669.
  5. ^ McEwan, D. G.; Brunton, V. G.; Baillie, G. S.; Leslie, N. R.; Houslay, M. D.; Frame, M. C. (2007). "Chemoresistant KM12C Colon Cancer Cells Are Addicted to Low Cyclic AMP Levels in a Phosphodiesterase 4-Regulated Compartment via Effects on Phosphoinositide 3-Kinase". Cancer Research 67 (11): 5248–5257. doi:10.1158/0008-5472.CAN-07-0097. PMID 17545604. 
  6. ^ Otmakhov, N.; Khibnik, L.; Otmakhova, N.; Carpenter, S.; Riahi, S.; Asrican, B.; Lisman, J. (2004). "Forskolin-Induced LTP in the CA1 Hippocampal Region Is NMDA Receptor Dependent". Journal of Neurophysiology 91 (1): 1955–1962. doi:10.1152/jn.00941.2003. PMID 14702333. 
  7. ^ Godard, M. P.; Johnson, B. A.; Richmond, S. R. (2005). "Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men". Obesity Research 13 (8): 1335–1343. doi:10.1038/oby.2005.162. PMID 16129715. 
  8. ^ D.L. Pinto-Pereira. In: Rupp, RH; de Souza, NJ; Dohadwalla, AN.(Eds). Proceedings of an international symposium on "Forskolin: Its Chemical, Biological and Medical Potential", Hoechst India Limited, Bombay. 1985. pp. 183 - 191;
  9. ^ Wagh VD, Patil PN, Surana SJ, Wagh KVForskolin: Upcoming antiglaucoma molecule. J Postgrad Med. 2012 Jul;58(3):199-202
  10. ^ English, J. (January 2000). "Research preview for the new millenium". Vitamin Research News. 
  11. ^ Zeng, S.; Shen, B.; Wen, L.; Hu, B.; Peng, D.; Chen, X.; Zhou, W. (1995). "Experimental studies of the effect of Forskolin on the lowering of intraocular pressure". Yan Ke Xue Bao (Eye Science) 11 (3): 173–176. PMID 8758848. 
  12. ^ Head, K. A. (2001). "Natural Therapies for Ocular Disorders, Part Two: Cataracts and Glaucoma". Alternative Medicine Review 6 (2): 141–166. PMID 11302779. 
  13. ^ Amaro-Ortiz, A. (2013). "Pharmacologic induction of epidermal melanin and protection against sunburn in a humanized mouse model.". J. Vis. Exp. (79). doi:10.3791/50670. PMID 24056496. 
  14. ^ "Herbal treatment Forskolin may help knock out for urinary tract infections once and for all". News Medical. 2007-04-08. 
  15. ^ Bishop BL. et al. (May 2007). "Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.". Nat Med 13 (5): 625–30. doi:10.1038/nm1572. PMID 17417648. 
  16. ^ In: Huerta M, Urzúa Z, Trujillo X, González-Sánchez R, Trujillo-Hernández B. Forskolin compared with beclomethasone for prevention of asthma attacks: a single-blind clinical trial. J Int Med Res . 2010;38(2):661-668.
  17. ^ a b "Forskolin". Drugs.com. www.drugs.com. 
  18. ^ In:Lukhoba CW, Simmonds MS, Paton AJ. Plectranthus : a review of ethnobotanical uses. J Ethnopharmacol . 2006;103(1):1-24..

Further reading[edit]

External links[edit]