Hyperforin

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Hyperforin
Hyperforin2DACS.svg
Hyperforin3Dan2.gif
Clinical data
Dependence
liability
Nil
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • US: OTC
  • In general: unscheduled
Pharmacokinetic data
Metabolism Hepatic and CYP3A & CYP2B
Elimination half-life 9-19.64 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ECHA InfoCard 100.112.565 Edit this at Wikidata
Chemical and physical data
Formula C35H52O4
Molar mass 536.784973
3D model (JSmol)
Melting point 79–80 °C (174–176 °F)
Solubility in water 0.66 mg/mL (20 °C)
 ☒N☑Y (what is this?)  (verify)

Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort).[1] Hyperforin is attributed to provide the main antidepressant effect of St. John's wort,[1] although there is little clinical evidence that hyperforin and St. John's wort have any effect on depression.

Occurrence[edit]

Hyperforin has only been found in significant amounts in Hypericum perforatum with other related species such as Hypericum calycinum containing lower levels of the phytochemical.[1] It accumulates in oil glands, pistils, and fruits, probably as a plant defensive compound.[2] Other Hypericum species contain low amounts of hyperforin.[3]

Chemistry[edit]

Hyperforin is a prenylated phloroglucinol derivative. 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] A total synthesis of the non-natural enantiomer of hyperforin was reported in 2010[6] and a total synthesis of the natural enantiomer was disclosed in 2012.[7]

Hyperforin is unstable in the presence of light and oxygen.[8]

Pharmacokinetics[edit]

Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax) in human volunteers were reached 3.5 hours after administration of an extract containing 14.8 mg hyperforin. Biological half-life (t1/2) and mean residence time were 9 hours and 12 hours, respectively, with an estimated steady state plasma concentration of 100 ng/mL (approx. 180 nM) for 3 doses per day. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.[9]

In healthy male volunteers, 612 mg dry extract of St. John's wort produced hyperforin pharmacokinetics characterised by a half life of 19.64 hours.[10]

Biochemistry[edit]

Hyperforin may be a constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.[1][11] In vitro, it acted as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 μg/mL for all compounds, with the exception of glutamate, which is in the 0.5 μg/mL range.[12] In other laboratory studies, hyperforin induced cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor.[13]

Reuptake Inhibition
Neurotransmitter IC50 (nanomoles)[12]
Norepinephrine 80 ± 24
Dopamine 102 ± 19
GABA 184 ± 41
5-HT 205 ± 45
Glutamate 829 ± 687
Choline 8500
Binding affinity (human receptors)
Receptor Ki (nanomoles)
DRD1 595.8[14]
Natural and semi-synthetic analogues of Hyperforin
Aristoforin
Hyperforin trimethoxybenzoate
Tetrahydrohyperforin
Octahydrohyperforin
Hyperforin nicotinate

Research[edit]

Two meta-analyses of clinical trials evaluating the efficacy of St. John's wort for treating mild-to-moderate depression indicated a response similar to selective serotonin reuptake inhibitors and with better tolerance, although the quality of the studies reviewed was limited by low numbers of subjects and short durations of treatment.[15][16]

See also[edit]

References[edit]

  1. ^ a b c d "Hyperforin". PubChem, US National Library of Medicine. 8 September 2018. Retrieved 13 September 2018. 
  2. ^ Beerhues L (2006). "Hyperforin". Phytochemistry. 67 (20): 2201–7. doi:10.1016/j.phytochem.2006.08.017. PMID 16973193. 
  3. ^ 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. 
  4. ^ Bystrov NS; Gupta ShR; Dobrynin VN; Kolosov MN; Chernov BK (January 1976). "[Structure of the antibiotic hyperforin]". Doklady Akademii Nauk SSSR (in Russian). 226 (1): 88–90. PMID 1248360. 
  5. ^ 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. 
  6. ^ Shimizu Y, Shi SL, 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. PMID 20063336. 
  7. ^ Sparling B, Moebius D, Shair M (December 2012). "Enantioselective Total Synthesis of Hyperforin" (Submitted manuscript). J Am Chem Soc. 135 (2): 644–7. doi:10.1021/ja312150d. PMID 23270309. 
  8. ^ 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. 
  9. ^ Biber, A; Fischer, H; Römer, A; Chatterjee, SS (June 1998). "Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers". Pharmacopsychiatry. 31 (Suppl 1): 36–43. doi:10.1055/s-2007-979344. PMID 9684946. 
  10. ^ Schulz, HU; Schürer, M; Bässler, D; Weiser, D (2005). "Investigation of the Bioavailability of Hypericin, Pseudohypericin, Hyperforin and the Flavonoids Quercetin and Isorhamnetin Following Single and Multiple Oral Dosing of a Hypericum Extract Containing Tablet". Arzneimittelforschung. 55 (1): 15–22. doi:10.1055/s-0031-1296820. PMID 15727160. 
  11. ^ Newall, Carol A.; Joanne Barnes; Anderson, Linda R. (2002). Herbal medicines: a guide for healthcare professionals. London: Pharmaceutical Press. ISBN 978-0-85369-474-8. 
  12. ^ a b 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. 
  13. ^ 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 16574Freely accessible. PMID 10852961. 
  14. ^ "Hyperforin". BindingDB. Retrieved 5 March 2015. 
  15. ^ Ng QX, Venkatanarayanan N, Ho CY (March 2017). "Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis". Journal of Affective Disorders. 210: 211–221. doi:10.1016/j.jad.2016.12.048. PMID 28064110. 
  16. ^ Cui YH, Zheng Y (2016). "A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults". Neuropsychiatric Disease and Treatment. 12: 1715–23. doi:10.2147/NDT.S106752. PMC 4946846Freely accessible. PMID 27468236.