| 词条 | Hyperforin | ||||||||||||||||||||||||||||||||||
| 释义 |
| Verifiedfields = changed | verifiedrevid = 461774343 | IUPAC_name = (1R,5S,6R,7S)-4-Hydroxy-6-methyl-1,3,7-tris(3-methylbut-2-en-1-yl)-6-(4-methylpent-3-en-1-yl)-5-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dion | image = Hyperforin2DACS.svg | width = 225 | image2 = Hyperforin3Dan2.gif | width2 = 200 | tradename = | Drugs.com = | pregnancy_US = | legal_AU = | legal_UK = | legal_US = OTC | legal_status = Unscheduled | dependency_liability = Nil | routes_of_administration = Oral
| bioavailability = | metabolism = Hepatic and CYP3A & CYP2B | elimination_half-life = 9-19.64 hours | IUPHAR_ligand = 2764 | CAS_number = 11079-53-1 | PubChem = 114787 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01892 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = RM741E34FP | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 5834 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C07608 | ATC_prefix = none | 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 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 16736597 | ChEMBL_Ref = | ChEMBL = | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = IWBJJCOKGLUQIZ-HQKKAZOISA-N | C=35 | H=52 | O=4 | solubility = 0.66 | melting_point = 79-80 }}Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort).[1] Although hyperforin is purported to be responsible for pharmacological effects of St. John's wort;[1] there is only limited clinical evidence that hyperforin and St. John's wort affect depression.[3][4] OccurrenceHyperforin 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] ChemistryHyperforin 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.[9] PharmacokineticsSome 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.[10] 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.[11] Biochemistry{{primary sources|section|date=February 2016}}Hyperforin may be a constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort.[1][12] In vitro, it acted as a reuptake inhibitor of monoamines (MRI), 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.[13] In other laboratory studies, hyperforin induced cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor.[14]
Research on depressionTwo meta-analyses of clinical trials, one published in July 2016 and the other in March 2017, 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 long-term generalization of study results is limited by the short duration (4-12 weeks) of reviewed studies.[16][17] See also
References1. ^1 2 3 {{cite web |title=Hyperforin |url=https://pubchem.ncbi.nlm.nih.gov/compound/441298#section=Top |publisher=PubChem, US National Library of Medicine |accessdate=13 September 2018 |date=8 September 2018}} 2. ^{{cite journal | author = Beerhues L | year = 2006 | title = Hyperforin | url = | journal = Phytochemistry | volume = 67 | issue = 20| pages = 2201–7 | pmid = 16973193 | doi=10.1016/j.phytochem.2006.08.017}} 3. ^{{cite journal |vauthors=Smelcerovic A, Spiteller M |title=Phytochemical analysis of nine Hypericum L. species from Serbia and the F.Y.R. Macedonia |journal=Die Pharmazie |volume=61 |issue=3 |pages=251–2 |date=March 2006 |pmid=16599273 |doi= |url=}} 4. ^{{cite journal |author1=Bystrov NS |author2=Gupta ShR |author3=Dobrynin VN |author4=Kolosov MN |author5=Chernov BK |title=[Structure of the antibiotic hyperforin] |language=Russian |journal=Doklady Akademii Nauk SSSR |volume=226 |issue=1 |pages=88–90 |date=January 1976 |pmid=1248360 |doi= |url=}} 5. ^{{cite journal |vauthors=Bystrov NS, Chernov BK, Dobrynin VN, Kolosov MN |title=[The structure of hyperforin] |language= |journal=Tetrahedron Letters |volume=16 |issue=32 |pages=2791–2794 |year=1975 |month= |pmid= |doi=10.1016/S0040-4039(00)75241-5 |url=}} 6. ^{{cite journal |vauthors=Shimizu Y, Shi SL, Usuda H, Kanai M, Shibasaki M |title=Catalytic Asymmetric Total Synthesis of ent-Hyperforin |journal= Angew Chem Int Ed |volume=49 |issue=6 |pages=1103–6 |date=February 2010 | pmid= 20063336|doi=10.1002/anie.200906678| url=}} 7. ^{{cite journal |vauthors=Sparling B, Moebius D, Shair M |title=Enantioselective Total Synthesis of Hyperforin |journal= J Am Chem Soc |volume=135|issue= 2|pages= 644–7|date=December 2012 | pmid=23270309 |doi=10.1021/ja312150d| url=http://nrs.harvard.edu/urn-3:HUL.InstRepos:12563735|type=Submitted manuscript }} 8. ^{{cite journal |vauthors=Nicolaou KC, Carenzi GE, Jeso V |title=Construction of highly functionalized medium-sized rings: synthesis of hyperforin and perforatumone model systems |journal=Angewandte Chemie International Edition in English |volume=44 |issue=25 |pages=3895–9 |date=June 2005 |pmid=15892032 |doi=10.1002/anie.200500776 |url=}} 9. ^{{cite journal |author1=Liu, F |author2=Pan, C |author3=Drumm, P |author4=Ang, CY |title=Liquid chromatography-mass spectrometry studies of St. John's wort methanol extraction: active constituents and their transformation |journal=Journal of Pharmaceutical and Biomedical Analysis |volume=37 |issue=2 |pages=303–12 |date=February 2005 |pmid=15708671 |doi=10.1016/j.jpba.2004.10.034 |url=}} 10. ^{{cite journal|author1=Biber, A |author2=Fischer, H |author3=Römer, A |author4=Chatterjee, SS |title=Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers|doi=10.1055/s-2007-979344|pmid=9684946|volume=31|issue=Suppl 1|pages=36–43|journal=Pharmacopsychiatry|date=June 1998}} 11. ^{{cite journal|title=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|journal=Arzneimittelforschung|volume=55|issue=1|pages=15–22|doi=10.1055/s-0031-1296820|pmid=15727160|author1=Schulz, HU |author2=Schürer, M |author3=Bässler, D |author4=Weiser, D |year=2005}} 12. ^{{cite book |author1=Newall, Carol A. |author2=Joanne Barnes |author3=Anderson, Linda R. |title=Herbal medicines: a guide for healthcare professionals |publisher=Pharmaceutical Press |location=London |year=2002 |pages= |isbn=978-0-85369-474-8 |oclc= |doi=}} 13. ^1 {{cite journal |vauthors=Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE |title=Hyperforin as a possible antidepressant component of hypericum extracts |journal=Life Sci. |volume=63 |issue=6 |pages=499–510 |year=1998 |pmid=9718074 |doi=10.1016/S0024-3205(98)00299-9}} 14. ^{{cite journal |vauthors=Moore LB, Goodwin B, Jones SA, etal |title=St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=97 |issue=13 |pages=7500–2 |date=June 2000 |pmid=10852961 |pmc=16574 |doi=10.1073/pnas.130155097 |url=}} 15. ^{{cite web|title=Hyperforin|url=http://www.bindingdb.org/bind/searchby_r1l.jsp?constrain=0&reactant1=hyperforin&tag=r1l&loMW=&hiMW=&loKI=&hiKI=&loIC=&hiIC=&lodG=&hidG=&anDor=and&submit=Search|website=BindingDB|accessdate=5 March 2015}} 16. ^1 {{cite journal|last=|first=|vauthors=Ng QX, Venkatanarayanan N, Ho CY|date=March 2017|title=Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis|url=|journal=Journal of Affective Disorders|volume=210|pages=211–221|doi=10.1016/j.jad.2016.12.048|pmid=28064110|quote=27 clinical trials with a total of 3808 patients were reviewed [...] For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits.|via=}} 17. ^1 {{cite journal|last=|first=|vauthors=Cui YH, Zheng Y|date=|year=2016|title=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|url=|journal=Neuropsychiatric Disease and Treatment|volume=12|pages=1715–23|doi=10.2147/NDT.S106752|pmc=4946846|pmid=27468236|quote=A total of 3,126 patients with depression were included. St John’s wort extract did not differ from SSRIs in clinical response, remission, and mean reduction in Hamilton Rating Scale for Depression score. [...] Both St John’s wort extract and SSRIs are effective in treating mild-to-moderate depression. St John’s wort extract is safer than SSRIs.|via=}} External links
| title = Pharmacodynamics | titlestyle = background:#ccccff | list1 ={{Leukotriene signaling modulators}}{{Prostanoid signaling modulators}}{{Transient receptor potential channel modulators}}{{Xenobiotic-sensing receptor modulators}} }} 3 : Antidepressants|Pregnane X receptor agonists|Chemicals in Hypericum |
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