Furohyperforin, a Prenylated Phloroglucinol from St. John's Wort (Hypericum perforatum)

Verotta, Luisellá; Appendino, Giovanni; Belloro, Emanuela; Jakupovic, Jasmin; Bombardelli, Ezio

doi:10.1021/np980470v

Cited by 90 publications

(50 citation statements)

References 10 publications

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“…However, traditional preparations such as teas and tinctures of the herb contain little or no hyperforin (Meier, 2001). Furohyperforin, the major oxidation product of hyperforin, occurs in the aerial parts at about 5% of the hyperforin concentration (Verotta et al, 1999). In addition, oxepahyperforin (Verotta et al, 2000) and other oxidation analogues of hyperforin have also been isolated and elucidated (Shan et al, 2001).…”

Section: Phloroglucinolsmentioning

confidence: 99%

A review of the antibacterial activity of Hypericum perforatum L.

Saddiqe

Naeem

Maimoona

2010

Journal of Ethnopharmacology

309

186

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Section: Phloroglucinolsmentioning

confidence: 99%

A review of the antibacterial activity of Hypericum perforatum L.

Saddiqe

Naeem

Maimoona

2010

Journal of Ethnopharmacology

309

186

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“…Hyperforin (2.0 to 4.5 %), adhyperforin (0.2 to 1.9 %) (Brondz et al 1982 ;Ollivier et al 1985 ;Ayuga & Rebuelta 1986 ;American Herbal Pharmacopeia 1997), oxygenated analogues of hyperforin (Trifunovic et al 1998 ;Verotta et al 1999Verotta et al , 2000.…”

Section: Prenylated Phloroglucinolsmentioning

confidence: 99%

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

Barnes

Anderson

Phillipson

2001

Journal of Pharmacy and Pharmacology

688

462

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The chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for St John's wort. Many pharmacological activities appear to be attributable to hypericin and to the flavonoid constituents ; hypericin is also reported to be responsible for the photosensitive reactions that have been documented for St. John's wort. With regard to the antidepressant effects of St John's wort, hyperforin, rather than hypericin as originally thought, has emerged as one of the major constituents responsible for antidepressant activity. Further research is required to determine which other constituents contribute to the antidepressant effect.Evidence from randomised controlled trials has confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression. There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted). Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine longterm safety. St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication.Concerns have been raised over interactions between St John's wort and certain prescribed medicines (including warfarin, ciclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, triptans, oral contraceptives) ; advice is that patients taking these medicines should stop taking St John's wort, generally after seeking professional advice as dose adjustment of conventional treatment may be necessary.

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“…This instability is due to the enolized ␤-dicarbonyl system present in the molecule. Several previous studies dealt with the chemical modification of its structure by acylation, alkylation, and oxidation but not with a chemical simplification of hyperforin to identify new stable and potent hyperforin analogs (Tada et al, 1992;Verotta et al, 1999Verotta et al, , 2000Verotta et al, , 2004. It is noteworthy that the core structure of hyperforin, the phloroglucinol, is rather stable.…”

mentioning

confidence: 99%

Simple 2,4-Diacylphloroglucinols as Classic Transient Receptor Potential-6 Activators—Identification of a Novel Pharmacophore

Leuner

Heiser²,

Derksen³

et al. 2009

Mol Pharmacol

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The naturally occurring acylated phloroglucinol derivative hyperforin was recently identified as the first specific canonical transient receptor potential-6 (TRPC6) activator. Hyperforin is the major antidepressant component of St. John's wort, which mediates its antidepressant-like properties via TRPC6 channel activation. However, its pharmacophore moiety for activating TRPC6 channels is unknown. We hypothesized that the phloroglucinol moiety could be the essential pharmacophore of hyperforin and that its activity profile could be due to structural similarities with diacylglycerol (DAG), an endogenous nonselective activator of TRPC3, TRPC6, and TRPC7. Accordingly, a few 2-acyl and 2,4-diacylphloroglucinols were tested for their hyperforin-like activity profiles. We used a battery of experimental models to investigate all functional aspects of TRPC6 activation, including ion channel recordings, Ca 2ϩ imaging, neurite outgrowth, and inhibition of synaptosomal uptake. Phloroglucinol itself was inactive in all of our assays, which was also the case for 2-acylphloroglucinols. For TRPC6 activation, the presence of two symmetrically acyl-substitutions with appropriate alkyl chains in the phloroglucinol moiety seems to be an essential prerequisite. Potencies of these compounds in all assays were comparable with that of hyperforin for activating the TRPC6 channel. Finally, using structure-based modeling techniques, we suggest a binding mode for hyperforin to TRPC6. Based on this modeling approach, we propose that DAG is able to activate TRPC3, TRPC6, and TRPC7 because of higher flexibility within the chemical structure of DAG compared with the rather rigid structures of hyperforin and the 2,4-diacylphloroglucinol derivatives.

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Furohyperforin, a Prenylated Phloroglucinol from St. John's Wort (Hypericum perforatum)

Abstract: Furohyperforin, an oxygenated analogue of the prenylated phloroglucinol hyperforin, was isolated from the aerial parts of Hypericum perforatum. Its structure was elucidated as 2 on the basis of extensive NMR investigations.

Cited by 90 publications

References 10 publications

A review of the antibacterial activity of Hypericum perforatum L.

A review of the antibacterial activity of Hypericum perforatum L.

St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties

Simple 2,4-Diacylphloroglucinols as Classic Transient Receptor Potential-6 Activators—Identification of a Novel Pharmacophore

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