Hyperforin

Hyperforin
	IUPAC name (1R,5S,7R,8S)-4-hydroxy-8-methyl-3,5,7-tris(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-1-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione
Identifiers
CAS number	11079-53-1
ChemSpider	16736597
UNII	RM741E34FP
DrugBank	DB01892
KEGG	C07608
ChEBI	CHEBI:5834
ChEMBL	CHEMBL1237210
Jmol-3D images	Image 1
	SMILES CC(C)C(=O)[C@@]21C(=O)[C@@](C[C@H](C\C=C(/C)C)[C@@]1(C)CC\C=C(/C)C)(C\C=C(/C)C)C(=O)C(\C\C=C(/C)C)=C2\O ;
	InChI InChI=1S/C35H52O4/c1-22(2)13-12-19-33(11)27(16-14-23(3)4)21-34(20-18-25(7)8)30(37)28(17-15-24(5)6)31(38)35(33,32(34)39)29(36)26(9)10/h13-15,18,26-27,38H,12,16-17,19-21H2,1-11H3/t27-,33+,34+,35-/m0/s1 ; Key: IWBJJCOKGLUQIZ-HQKKAZOISA-N InChI=1/C35H52O4/c1-22(2)13-12-19-33(11)27(16-14-23(3)4)21-34(20-18-25(7)8)30(37)28(17-15-24(5)6)31(38)35(33,32(34)39)29(36)26(9)10/h13-15,18,26-27,38H,12,16-17,19-21H2,1-11H3/t27-,33+,34+,35-/m0/s1; Key: IWBJJCOKGLUQIZ-HQKKAZOIBJ ;
Properties
Molecular formula	C35H52O4
Molar mass	536.78 g/mol
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

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Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort).

[edit] Occurrence

Hyperforin has only been found in significant amounts in Hypericum perforatum (St John's wort),^[1] where it accumulates in oil glands, pistils, and fruits, probably as a plant defense against herbivory.^[2] Other Hypericum species contain low amounts of hyperforin.^[3]

[edit] Chemistry

The structure of hyperforin was elucidated by a research group from the Shemyakin Institute of Bio-organic Chemistry (USSR Academy of Sciences in Moscow) and published in 1975.^[4]^[5] Hyperforin is a prenylated phloroglucinol derivative. An enantioselective total synthesis of hyperforin was reported in 2010.^[6]

Hyperforin is unstable in the presence of light and oxygen.^[7]

[edit] Pharmacology

Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.^[8] It acts as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC₅₀ values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range.^[9] It appears to exert these effects by activating the transient receptor potential ion channel TRPC6.^[10] Activation of TRPC6 induces the entry of sodium and calcium into the cell which causes inhibition of monoamine reuptake.^[10]

Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).^[11]

Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax) in human volunteers were reached 3.5h after administration of an extract containing 14.8 mg hyperforin. Biological half-life (t½) and mean residence time were 9h and 12h respectively with an estimated steady state plasma concentration of 100 ng/ml (approx. 180 nM/L) for 3 doses/d. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.^[12]

[edit] Antibiotic

Hyperforin has antibiotic properties and is active against methicillin-resistant strains of Staphylococcus aureus (MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 μg/ml,^[13] as well as against other gram-positive bacteria.^[14]

[edit] See also

[edit] Further reading

Beerhues L (October 2006). "Molecule of Interest: Hyperforin". Phytochemistry 67 (20): 2201–7. doi:10.1016/j.phytochem.2006.08.017. PMID 16973193.

[edit] References

^ Umek A, Kreft S, Kartnig T, Heydel B (May 1999). "Quantitative phytochemical analyses of six hypericum species growing in slovenia". Planta medica 65 (4): 388–90. doi:10.1055/s-2006-960798. PMID 17260265.
^ Beerhues L. (2006). “Hyperforin.” Phytochemistry 67 (20): 2201-7. PMID 16973193
^ Smelcerovic A, Spiteller M (March 2006). "Phytochemical analysis of nine Hypericum L. species from Serbia and the F.Y.R. Macedonia". Die Pharmazie 61 (3): 251–2. PMID 16599273.
^ Bystrov NS, Gupta ShR, Dobrynin VN, Kolosov MN, Chernov BK (January 1976). "[Structure of the antibiotic hyperforin]" (in Russian). Doklady Akademii Nauk SSSR 226 (1): 88–90. PMID 1248360.
^ Bystrov NS, Chernov BK, Dobrynin VN, Kolosov MN (1975). "[The structure of hyperforin]". Tetrahedron Letters 16 (32): 2791–2794. doi:10.1016/S0040-4039(00)75241-5.
^ Shimizu Y, Shi S-L, Usuda H, Kanai M, Shibasaki M (February 2010). "Catalytic Asymmetric Total Synthesis of ent-Hyperforin". Angew Chem Int Ed 49 (6): 1103–6. doi:10.1002/anie.200906678.
^ Liu F, Pan C, Drumm P, Ang CY (February 2005). "Liquid chromatography-mass spectrometry studies of St. John's wort methanol extraction: active constituents and their transformation". Journal of pharmaceutical and biomedical analysis 37 (2): 303–12. doi:10.1016/j.jpba.2004.10.034. PMID 15708671.
^ Newall, Carol A.; Joanne Barnes; Anderson, Linda R. (2002). Herbal medicines: a guide for healthcare professionals. London: Pharmaceutical Press. ISBN 0-85369-474-5.
^ Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sci. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
^ ^a ^b Leuner K, Kazanski V, Müller M, et al. (December 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.
^ Moore LB, Goodwin B, Jones SA, et al. (June 2000). "St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor". Proceedings of the National Academy of Sciences of the United States of America 97 (13): 7500–2. doi:10.1073/pnas.130155097. PMC 16574. PMID 10852961. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16574.
^ Biber A, Fischer H, Römer A, Chatterjee SS. (1998). “Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers.” Pharmacopsychiatry 31 Suppl 1:36-43. PMID 9684946
^ Reichling J, Weseler A, Saller R (July 2001). "A current review of the antimicrobial activity of Hypericum perforatum L". Pharmacopsychiatry 34 Suppl 1: S116–8. doi:10.1055/s-2001-15514. PMID 11518059.
^ Schempp CM, Pelz K, Wittmer A, Schöpf E, Simon JC (June 1999). "Antibacterial activity of hyperforin from St John's wort, against multiresistant Staphylococcus aureus and gram-positive bacteria". Lancet 353 (9170): 2129. doi:10.1016/S0140-6736(99)00214-7. PMID 10382704.

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[pmid17260265-0] Umek A, Kreft S, Kartnig T, Heydel B (May 1999). "Quantitative phytochemical analyses of six hypericum species growing in slovenia". Planta medica 65 (4): 388–90. doi:10.1055/s-2006-960798. PMID 17260265.

[1] Beerhues L. (2006). “Hyperforin.” Phytochemistry 67 (20): 2201-7. PMID 16973193

[pmid16599273-2] Smelcerovic A, Spiteller M (March 2006). "Phytochemical analysis of nine Hypericum L. species from Serbia and the F.Y.R. Macedonia". Die Pharmazie 61 (3): 251–2. PMID 16599273.

[pmid1248360-3] Bystrov NS, Gupta ShR, Dobrynin VN, Kolosov MN, Chernov BK (January 1976). "[Structure of the antibiotic hyperforin]" (in Russian). Doklady Akademii Nauk SSSR 226 (1): 88–90. PMID 1248360.

[doi10.1016.2FS0040-4039.2800.2975241-5-4] Bystrov NS, Chernov BK, Dobrynin VN, Kolosov MN (1975). "[The structure of hyperforin]". Tetrahedron Letters 16 (32): 2791–2794. doi:10.1016/S0040-4039(00)75241-5.

[10.1002.2Fanie.200906678-5] Shimizu Y, Shi S-L, Usuda H, Kanai M, Shibasaki M (February 2010). "Catalytic Asymmetric Total Synthesis of ent-Hyperforin". Angew Chem Int Ed 49 (6): 1103–6. doi:10.1002/anie.200906678.

[pmid15708671-6] Liu F, Pan C, Drumm P, Ang CY (February 2005). "Liquid chromatography-mass spectrometry studies of St. John's wort methanol extraction: active constituents and their transformation". Journal of pharmaceutical and biomedical analysis 37 (2): 303–12. doi:10.1016/j.jpba.2004.10.034. PMID 15708671.

[isbn0-85369-474-5-7] Newall, Carol A.; Joanne Barnes; Anderson, Linda R. (2002). Herbal medicines: a guide for healthcare professionals. London: Pharmaceutical Press. ISBN 0-85369-474-5.

[pmid9718074-8] Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sci. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.

[pmid17666455-9] Leuner K, Kazanski V, Müller M, et al. (December 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455.

[pmid10852961-10] Moore LB, Goodwin B, Jones SA, et al. (June 2000). "St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor". Proceedings of the National Academy of Sciences of the United States of America 97 (13): 7500–2. doi:10.1073/pnas.130155097. PMC 16574. PMID 10852961. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16574.

[11] Biber A, Fischer H, Römer A, Chatterjee SS. (1998). “Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers.” Pharmacopsychiatry 31 Suppl 1:36-43. PMID 9684946

[pmid11518059-12] Reichling J, Weseler A, Saller R (July 2001). "A current review of the antimicrobial activity of Hypericum perforatum L". Pharmacopsychiatry 34 Suppl 1: S116–8. doi:10.1055/s-2001-15514. PMID 11518059.

[pmid10382704-13] Schempp CM, Pelz K, Wittmer A, Schöpf E, Simon JC (June 1999). "Antibacterial activity of hyperforin from St John's wort, against multiresistant Staphylococcus aureus and gram-positive bacteria". Lancet 353 (9170): 2129. doi:10.1016/S0140-6736(99)00214-7. PMID 10382704.

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Hyperforin

Contents

[edit] Occurrence

[edit] Chemistry

[edit] Pharmacology

[edit] Antibiotic

[edit] See also

[edit] Further reading

[edit] References

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