<i>Hypericum perforatum</i>: Which Constituents may Induce Intestinal MDR1 and CYP3A4 mRNA Expression?<i />

Gutmann, Heike; Poller, Birk; Büter, Karin Berger; Pfrunder, Arabelle; Schaffner, W.; Drewe, Jürgen

doi:10.1055/s-2006-931585

Cited by 50 publications
(27 citation statements)

References 19 publications

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“…This is in contrast to other substrates of P-gp such as dexamethasone and ritonavir (Gutmann et al, 2006;Narang et al, 2008;Perloff et al, 2004).…”

Section: And R-citalopram and Its Metabolites In Abcb1ab (-/-) Knocmentioning
confidence: 73%

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment
Karlsson¹,
Carlsson²,
Hiemke³
et al. 2013
European Neuropsychopharmacology
35
2
27
0
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According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10 mg/kg) or escitalopram (5 mg/kg). Serum and brain samples were collected 1-6 h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S-and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated.

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“…This is in contrast to other substrates of P-gp such as dexamethasone and ritonavir (Gutmann et al, 2006;Narang et al, 2008;Perloff et al, 2004).…”

Section: And R-citalopram and Its Metabolites In Abcb1ab (-/-) Knocmentioning
confidence: 73%

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“…St John's Wort may alter the expression of various membrane pumps and result in decreased bioavailability of a variety of drugs. Hypericin at a concentration of 10 mM induced mRNA expression of the Pgp gene MRD1 in the human colorectal carcinoma line LS180 (Gutmann et al, 2006). In contrast, Tian et al (2005) reported that only hyperforin and not hypericin (at 0.1 mM, 24 -48 h treatment) caused a time-/dose-dependent induction of Pgp protein by the same cell line.…”

Section: Photochemical Internalisationmentioning
confidence: 95%

Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells
Adigbli
¹
,
Wilson
²
,
Farooqui
³

et al. 2007
Br J Cancer
27
0
20
0
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Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; upon light activation the latter induces intracellular release of organellebound drug. We investigated whether co-administration of hypericin (photosensitiser) with mitoxantrone (MTZ, chemotherapeutic) plus illumination potentiates cytotoxicity in MDR cancer cells. We mapped the extent of intracellular co-localisation of drug/ photosensitiser. We determined whether PCI altered drug-excreting efflux pump P-glycoprotein (Pgp) expression or function in MDR cells. Bladder and breast cancer cells and their Pgp-overexpressing MDR subclones (MGHU1, MGHU1/R, MCF-7, MCF-7/R) were given hypericin/MTZ combinations, with/without blue-light illumination. Pilot experiments determined appropriate sublethal doses for each. Viability was determined by the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay. Intracellular localisation was mapped by confocal microscopy. Pgp expression was detected by immunofluorescence and Pgp function investigated by Rhodamine123 efflux on confocal microscopy. MTZ alone (0.1 -0.2 mg ml À1 ) killed up to 89% of drug-sensitive cells; MDR cells exhibited less cytotoxicity (6 -28%). Hypericin (0.1 -0.2 mM) effects were similar for all cells; light illumination caused none or minimal toxicity. In combination, MTZ /hypericin plus illumination, potentiated MDR cell killing, vs hypericin or MTZ alone. (MGHU1/R: 38.65 and 36.63% increase, Po0.05; MCF-7/R: 80.2 and 46.1% increase, Po0.001). Illumination of combined MTZ/hypericin increased killing by 28.15% (Po0.05 MGHU1/R) compared to dark controls. Intracytoplasmic vesicular co-localisation of MTZ/hypericin was evident before illumination and at serial times post-illumination. MTZ was always found in sensitive cell nuclei, but not in dark resistant cell nuclei. In illuminated resistant cells there was some mobilisation of MTZ into the nucleus. Pgp expression remained unchanged, regardless of drug exposure. Pgp efflux was blocked by the Pgp inhibitor verapamil (positive control) but not impeded by hypericin. The increased killing of MDR cancer cells demonstrated is consistent with PCI. PCI is a promising technique for enhancing treatment efficacy.

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“…It is known to be a strong inducer of hepatic and intestinal CYP450 enzymes as well as p-glycoproteins in the intestine through activation of pregnane X receptor (PXR) (4,(18)(19)(20)(21)(24)(25)(26)(27)(28)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). Hyperforin, its most active compound, has also been reported to be a potent activator of pregnane X receptor (PXR) (4,17-19, 40-44,48,51,52).…”

Section: St John's Wort (Sjw) (Hypericum Perforatum)mentioning
confidence: 99%

“…Hyperforin is the most active constituent of SJW, however, it has been demonstrated in many studies that there is great variability in the content of hyperforin among the commercial preparations of SJW, and also that SJW extracts with low hyperforin content (less than 1%) have not demonstrated any clinically relevant interactions (9,51,58,61,63,(65)(66)(67)(68)(69)(70)(71). Gödtel-Armbrust et al (2007) studied the CYP450 induction of LS174T cells by various extracts, commercial products and the purified SJW constituent hyperforin, observing that the content of hyperforin among the commercial preparations of SJW varied 62-fold (range 0.49-30.57 mg/dose) and that the magnitude of the induction correlated statistically significantly with the content of hyperforin in commercial SJW preparations and in dry extracts (69).…”

Section: St John's Wort (Sjw) (Hypericum Perforatum)mentioning
confidence: 99%

Herbal drugs and drug interactions
Dülger¹
2012
mpj
11
0
9
0
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Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

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Hypericum perforatum: Which Constituents may Induce Intestinal MDR1 and CYP3A4 mRNA Expression?

Cited by 50 publications

References 19 publications

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells

Herbal drugs and drug interactions

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