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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/02 10:53:44」(JST)

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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 resensitizes cell receptors by activating the enzyme adenylyl cyclase and increasing the intracellular levels of cAMP. cAMP is an important signal carrier 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. Cyclic AMP acts by activating cAMP-sensitive pathways such as protein kinase A and Epac. Further reading: 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.^[2] 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]

Forskolin-An Example of Innovative Drug Research on Natural Products. de Souza N.J.

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.

Potential medical use[edit]

Applied with rolipram, forskolin provides a route^{[further explanation needed]} to inhibition of colon cancer cell growth and survival.^[3] These two drugs also work together to induce long-term potentiation in neuronal populations.^[4]
Forskolin is a vasodilator.
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 also observed forskolin's role in significantly increasing lean mass, bone mass, and testosterone in the overweight and obese men involved.^[5] This research has led to companies marketing forskolin as a bodybuilding supplement.
Forskolin and Aqueous Humor Flow. Dr. M. L. Sears. 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. 148-152;

Glaucoma and Forskolin.Dr. J. Caprioli.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. 153-174; Pharmacodynamics of Forskolin Eye-drops in healthy subjects. Dr. P.U.Witte. 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. 175-182; Clinical Studies with Forskolin Eye-Drops in Patients with Open Angle Glaucoma. D. (Mrs.) 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;

Forskolin may be helpful in controlling the underlying cause of glaucoma^[6]^[7]^{[citation needed]}^[8]^[9]

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.^[10]
Reduce urinary tract infections and enhance the ability of antibiotics to kill bacteria that normally survive.^[11]^[12]^{[citation needed]}

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.

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.

References[edit]

^ "Forskolin" (pdf). Sigma Aldrich.
^ Dewick, P. M. (2009). Medicinal Natural Products (3rd ed.). Wiley. p. 232. ISBN 978-0470741689.
^ 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.
^ 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.
^ 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.
^ Wagh VD, Patil PN, Surana SJ, Wagh KVForskolin: Upcoming antiglaucoma molecule. J Postgrad Med. 2012 Jul;58(3):199-202
^ English, J. (January 2000). "Research preview for the new millenium". Vitamin Research News.
^ 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.
^ Head, K. A. (2001). "Natural Therapies for Ocular Disorders, Part Two: Cataracts and Glaucoma". Alternative Medicine Review 6 (2): 141–166. PMID 11302779.
^ Template:Url = http://www.ncbi.nlm.nih.gov/pubmed/24056496
^ "Herbal treatment Forskolin may help knock out for urinary tract infections once and for all". News Medical. 2007-04-08.
^ 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.

External links[edit]

Scientific American: Sunless Suntan Proves Possible
Research on suntanning effect of forskolin extract from Plectranthus barbatus
New Scientist: Herbal remedy could flush out bladder infections

UpToDate Contents

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1. 心筋における興奮収縮連関 excitation contraction coupling in myocardium

English Journal

Transcriptional and functional studies of Human Endogenous Retrovirus envelope EnvP(b) and EnvV genes in human trophoblasts.

Vargas A, Thiery M, Lafond J, Barbeau B.AbstractHERV (Human Endogenous Retrovirus)-encoded envelope proteins are implicated in the development of the placenta. Indeed, Syncytin-1 and -2 play a crucial role in the fusion of human trophoblasts, a key step in placentation. Other studies have identified two other HERV env proteins, namely EnvP(b) and EnvV, both expressed in the placenta. In this study, we have fully characterized both env transcripts and their expression pattern and have assessed their implication in trophoblast fusion. Through RACE analyses, standard spliced transcripts were detected, while EnvV transcripts demonstrated alternative splicing at its 3' end. Promoter activity and expression of both genes were induced in forskolin-stimulated BeWo cells and in primary trophoblasts. Although we have confirmed the fusogenic activity of EnvP(b), overexpression or silencing experiments revealed no impact of this protein on trophoblast fusion. Our results demonstrate that both env genes are expressed in human trophoblasts but are not required for syncytialization.
Virology.Virology.2012 Mar 30;425(1):1-10. Epub 2012 Jan 25.
HERV (Human Endogenous Retrovirus)-encoded envelope proteins are implicated in the development of the placenta. Indeed, Syncytin-1 and -2 play a crucial role in the fusion of human trophoblasts, a key step in placentation. Other studies have identified two other HERV env proteins, namely EnvP(b) and
PMID 22277806

Saturated fatty acid exposure induces androgen overproduction in bovine adrenal cells.

Bellanger S, Battista MC, Fink GD, Baillargeon JP.SourceDivision of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
Steroids.Steroids.2012 Mar 10;77(4):347-53. Epub 2012 Jan 9.
BACKGROUND: Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenemia, from ovarian and adrenal origin, and is characterized by insulin resistance (IR). Studies found that raising in vivo non-esterified fatty acid (NEFA) levels, which induces lipotoxicity, increases androgen levels and
PMID 22245830

Downregulation of PKD1 by shRNA results in defective osteogenic differentiation via cAMP/PKA pathway in human MG-63 cells.

Qiu N, Zhou H, Xiao Z.SourceInstitute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, China; Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38165.
Journal of cellular biochemistry.J Cell Biochem.2012 Mar;113(3):967-76. doi: 10.1002/jcb.23426.
Mutations and/or deletions of Pkd1 in mouse models resulted in attenuation of osteoblast function and defective bone formation; however, the function of PKD1 in human osteoblast and bone remains uncertain. In the current study, we used lentivirus-mediated shRNA technology to stably knock down PKD1 i
PMID 22034075

Japanese Journal

Dopamine D_1 Agonist Facilitates Long‐term Depression Induction by Callosal Low‐frequency Stimulation in Rat Anterior Cingulate Cortex

Sakuragi Sokichi
愛知教育大学研究報告. 自然科学編 60, 63-69, 2011-03-01
… The facilitative effect of SKF-38393 on LTD induction was not mimicked by forskolin, an adenylcyclase activator, but was partially mimicked by phorbol 12, 13-didecanoate, which is known to activate the intracellular PKC pathway. …
NAID 80021880058

Activities of bone morphogenetic proteins in prolactin regulation by somatostatin analogs in rat pituitary GH3 cells

Tsukamoto Naoko,Otsuka Fumio,Miyoshi Tomoko,Inagaki Kenichi,Nakamura Eri,Suzuki Jiro,Ogura Toshio,Iwasaki Yasumasa,Makino Hirofumi
Molecular and Cellular Endocrinology 332(1-2), 163-169, 2011-01-30
… In GH3 cells activated by forskolin, BRC suppressed forskolin-induced PRL secretion with reduction in cAMP levels. … OCT did not affect forskolin-induced PRL level, while SOM230 reduced PRL secretion and PRL mRNA expression induced by forskolin. … BMP-4 treatment enhanced the reducing effect of SOM230 on forskolin-induced PRL level while BMP-4 did not affect the effects of OCT or BRC. …
NAID 120003497020

Inactivation of Membrane Surface Ecto-5′-nucleotidase by Sodium Nitroprusside in C6 Glioma Cells

Kumasaka Tadanori,Matsuoka Isao,Mashiko Hirobumi,Niwa Shin-ichi,Kimura Junko
Journal of Pharmacological Sciences 117(1), 45-53, 2011
… When cells were incubated with sodium nitroprusside (SNP), phorbol 12-myristate 13-acetate, forskolin, lipopolysaccharide, or interferon-γ, only SNP inhibited NT5E activity in a time- and concentration-dependent manner (IC50 = 1.2 μM). …
NAID 130001011765

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「フォルスコリン」

Forskolin
	IUPAC name (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f]chromen-5-yl acetate
Identifiers
CAS number	66428-89-5
PubChem	47936
ChemSpider	43607
UNII	1F7A44V6OU
DrugBank	DB02587
ChEBI	CHEBI:42471
ChEMBL	CHEMBL52606
Jmol-3D images	Image 1
	SMILES 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 ;
	InChI 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 ; Key: OHCQJHSOBUTRHG-KGGHGJDLSA-N 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 ;
Properties
Molecular formula	C22H34O7
Molar mass	410.50 g mol−1
Solubility	soluble in organic solvents such as ethanol, chloroform and DMSO
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

　　[★]

英: forskolin
関: ホルスコリン

[1] "Forskolin" (pdf). Sigma Aldrich.

[Dewick-2] Dewick, P. M. (2009). Medicinal Natural Products (3rd ed.). Wiley. p. 232. ISBN 978-0470741689.

[McEwan_et_al.-3] 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.

[Otmakhov_et_al.-4] 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.

[Godard_et_al.-5] 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.

[6] Wagh VD, Patil PN, Surana SJ, Wagh KVForskolin: Upcoming antiglaucoma molecule. J Postgrad Med. 2012 Jul;58(3):199-202

[7] English, J. (January 2000). "Research preview for the new millenium". Vitamin Research News.

[8] 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.

[9] Head, K. A. (2001). "Natural Therapies for Ocular Disorders, Part Two: Cataracts and Glaucoma". Alternative Medicine Review 6 (2): 141–166. PMID 11302779.

[10] Template:Url = http://www.ncbi.nlm.nih.gov/pubmed/24056496

[11] "Herbal treatment Forskolin may help knock out for urinary tract infections once and for all". News Medical. 2007-04-08.

[Bishop_BL._et_al._.282007.29-12] 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.

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