Třezalka (Hypericum perforatum L.) je tradičně využívaná léčivá rostlina v alternativní i klasické medicíně. V současnosti jsou k dispozici poznatky o fyziologické aktivitě jednotlivých sloučenin, které třezalka syntetizuje ve svých pletivech. Nejvyšší pozornost je věnována hypericinu a hyperforinu. Tyto organické sloučeniny nacházejí uplatnění v léčbě depresivních stavů, v protinádorové (fotodynamické) terapii a jako antimikrobiální a virostatické agens. V předkládaném souhrnu jsou ve stručnosti prezentovány současné poznatky o analýze, fyziologickém účinku a praktickém využití hypericinu a hyperforinu ve farmakochemii a biomedicínských oborech.

St. John's Wort (Hypericum perforatum L.) is commonly accepted as a medicinal plant. The data on the physiological activities of the individual substances that are produced in different organs of H. perforatum are well known at present. The highest attention is focused on the characterization and phytochemical properties of hypericin and hyperforin. These organic compounds are used as antidepressant, anticarcinogenic (photodynamic), antimicrobial and virostatic agents. The review paper surveys the present knowledge of chemical and analytical methods for their identification and quantification, physiological activity, and pharmacological and biomedical applications of hypericin and hyperforin.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• depresivní poruchy farmakoterapie   terapie   MeSH
• lidé MeSH
• perylen analogy a deriváty   izolace a purifikace   terapeutické užití   MeSH
• rostlinné extrakty terapeutické užití   MeSH
• terpeny izolace a purifikace   terapeutické užití   MeSH
• třezalka chemie   MeSH
• virové nemoci farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• HYPERICIN, HYPOKRELINA,
• MeSH
• antitumorózní látky aplikace a dávkování   toxicita   MeSH
• buněčné linie MeSH
• fotochemoterapie metody   MeSH
• Hypocreales chemie   MeSH
• lékařská onkologie MeSH
• třezalka chemie   MeSH

• MeSH
• rostlinné extrakty analýza   chemie   MeSH
• třezalka chemie   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH

• MeSH
• perylen aplikace a dávkování   farmakologie   MeSH
• rostlinné přípravky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• třezalka chemie   metabolismus   MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• HYPERICIN (SLOVAKOFARMA),
• MeSH
• antitumorózní látky farmakologie   chemie   terapeutické užití   MeSH
• antivirové látky farmakologie   chemie   terapeutické užití   MeSH
• fotochemoterapie MeSH
• léčivé rostliny MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• floroglucinol analogy a deriváty   analýza   MeSH
• konzumní sacharóza MeSH
• kultivační média MeSH
• léčivé rostliny MeSH
• perylen analogy a deriváty   analýza   MeSH
• polyethylenglykoly MeSH
• terpeny analýza   MeSH
• třezalka metabolismus   růst a vývoj   MeSH
• vysokoúčinná kapalinová chromatografie MeSH

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80mm3 the mice were intraperitoneally injected with hypericin, either in a single dose (5mg/kg; 1 or 6h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70mW/cm2, 168 J/cm2). All tumours in control groups treated with hypericin alone as well as those irradiated with laser light alone had similar growth rates and none of these tumours regressed spontaneously. Complete remission of tumour in photodynamic therapy (PDT)-treated groups was similar (14-17% single dose vs. 33% fractionated dose), but the fractionated schedule of hypericin dosing was found to be more efficient than the single dose, measured by survival assay (p < 0.05). Our experimental model showed that fractionated administration of hypericin can produce a better therapeutic response than single administration

• MeSH
• antitumorózní látky fytogenní aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• fibrosarkom farmakoterapie   MeSH
• financování vládou MeSH
• fotochemoterapie MeSH
• fotosenzibilizující látky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• fytoterapie MeSH
• inbrední kmeny myší MeSH
• injekce intraperitoneální MeSH
• perylen analogy a deriváty   aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• světlo MeSH
• třezalka MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH

BACKGROUND/AIM: We report the incorporation of prospective anticancer agent hypericin into DNA and bovine serum albumin (BSA), respectively, with emphasis on comparison of the differences in interaction mode between hypericin and its model compound emodin. MATERIALS AND METHODS: Spectrophotometric methods were used for determination of the binding constants of the drug complex with biomacromolecules. Differential scanning calorimetry was applied for evaluation of drug-macromolecule complex thermal stability. RESULTS: The strength of interaction expressed by binding constants was found to be 4.0×104 l/mol for hypericin-DNA and 8.1×104 l/mol for emodin-DNA complex. Both molecules stabilize bovine serum albumin macromolecule and bind into the hydrophobic cavity in IIA subunit but their localization within the molecule is different. CONCLUSION: Anticancer agent hypericin and its derivative emodin interact with DNA with medium strength and are probably incorporated into the groove of DNA by hydrogen bonds. Bovine serum albumin can serve as a transport protein for hypericin since the binding force between both molecules is adequate.

• MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• DNA chemie   metabolismus   MeSH
• emodin chemie   farmakologie   MeSH
• molekulární struktura MeSH
• perylen analogy a deriváty   chemie   farmakologie   MeSH
• sérový albumin hovězí chemie   metabolismus   MeSH
• spektrální analýza MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Cancer stem-like cells (CSLCs) are considered a root of tumorigenicity and resistance. However, their identification remains challenging. The use of the side population (SP) assay as a credible marker of CSLCs remains controversial. The SP assay relies on the elevated activity of ABC transporters that, in turn, can be modulated by hypericin (HYP), a photosensitizer and bioactive compound of St. John's Wort (Hypericum perforatum), a popular over-the-counter antidepressant. Here we aimed to comprehensively characterize the SP phenotype of cancer cells and to determine the impact of HYP on these cells. METHODS: Flow cytometry and sorting-based assays were employed, including CD24-, CD44-, CD133-, and ALDH-positivity, clonogenicity, 3D-forming ability, ABC transporter expression and activity, and intracellular accumulation of HYP/Hoechst 33342. The tumorigenic ability of SP, nonSP, and HYP-treated cells was verified by xenotransplantation into immunodeficient mice. RESULTS: The SP phenotype was associated with elevated expression of several investigated transporters and more intensive growth in non-adherent conditions but not with higher clonogenicity, tumorigenicity or ALDH-positivity. Despite stimulated BCRP level and MRP1 activity, HYP reversibly decreased the SP proportion, presumably via competitive inhibition of BCRP. HYP-selected SP cells acquired additional traits of resistance and extensively eliminated HYP. CONCLUSIONS: Our results suggest that SP is not an unequivocal CSLC-marker. However, SP could play an important role in modulating HYP-treatment and serve as a negative predictive tool for HYP-based therapies. Moreover, the use of supplements containing HYP by cancer patients should be carefully considered, due to its proposed effect on drug efflux and complex impact on tumor cells, which have not yet been sufficiently characterized.

• MeSH
• ABC transportér z rodiny G, člen 2 metabolismus   MeSH
• aldehyddehydrogenasa metabolismus   MeSH
• analýza přežití MeSH
• buněčné klony MeSH
• buněčné sféroidy účinky léků   metabolismus   patologie   MeSH
• fenotyp MeSH
• karcinogeneze účinky léků   metabolismus   patologie   MeSH
• lidé MeSH
• myši SCID MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky účinky léků   metabolismus   patologie   MeSH
• nádorové proteiny metabolismus   MeSH
• nádory metabolismus   patologie   MeSH
• P-glykoprotein metabolismus   MeSH
• perylen analogy a deriváty   farmakologie   MeSH
• substrátová specifita účinky léků   MeSH
• vedlejší populace buněk účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

By means of fluorescence spectroscopy we have studied the kinetics of interaction of a photosensitizer hypericin (Hyp) with high-density lipoproteins (HDL). Hyp is incorporated into HDL molecules as monomer till ratio Hyp/HDL ∼8:1 and above this ratio forms non-fluorescent aggregates. This number is different from that found in the case of Hyp incorporation into low-density lipoprotein (LDL) molecules (8:1 vs 30:1). The difference is mainly attributed to the smaller size of HDL in comparison with LDL molecule. Biphasic kinetics of Hyp association with HDL was observed. The rapid phase of incorporation is completed within seconds, while the slow one lasts several minutes. The kinetics of the association of Hyp molecules with free HDL, Hyp/HDL=10:1 complex and the redistribution of Hyp from Hyp/HDL=70:1 complex to free HDL molecules reveal a qualitative similar characteristics of these processes with those observed for the interaction of Hyp with LDL. However, the incorporation of Hyp into HDL in the "slow" phase is more rapid than to LDL and extend of Hyp penetration into lipoproteins in the fast phase is also much higher in the case of HDL. The lower concentration of cholesterol molecules in outer shell of HDL particles is probably the determining factor for the more rapid kinetics of Hyp incorporation to and redistribution from these molecules when comparing with LDL particles.

• MeSH
• buněčné linie MeSH
• chemie farmaceutická MeSH
• fluorescenční spektrometrie MeSH
• fotosenzibilizující látky chemie   MeSH
• lipoproteiny HDL chemie   MeSH
• lipoproteiny LDL chemie   MeSH
• perylen analogy a deriváty   chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH