The phenolic compounds of methanolic extracts of Salvia pomifera and Salvia fruticosa were identified by liquid chromatography tandem mass spectrometry. Carnosic acid and its metabolite carnosol were the most abundant terpene phenolic compounds of S. fruticosa, while they were completely absent in S. pomifera. The main terpene phenolic constituent of S. pomifera was 12-O-methylcarnosic acid and its mass/mass fragmentation pathway was explained. The detailed mechanism of carnosic acid oxidation to carnosol was suggested. The effects of Salvia extracts and/or carnosic acid, the main diterpene phenolic component of S. fruticosa, on the proliferation and cell cycle of two melanoma cell lines (A375, Mel JuSo) and human fibroblast cell line (HFF) were investigated by MTT assay, PI-exclusion assay and flow cytometry cell cycle analysis. Extract of S. fruticosa more efficiently than S. pomifera extract reduced the proliferation of the human melanoma cells. Carnosic acid showed the most significant effect. The first evidence that carnosic acid affects microtubule dynamics and arrests the cell cycle in the G2/M phase was provided. Collectively, our results demonstrate that these two Salvia species are plants of medicinal interest with perspective for further investigation. Carnosic acid could be the compound responsible for the biological activities of S. fruticosa extracts.
- MeSH
- buněčné linie MeSH
- diterpeny abietanové chemie izolace a purifikace farmakologie MeSH
- epitelové buňky účinky léků patologie MeSH
- fenoly chemie izolace a purifikace farmakologie MeSH
- fibroblasty cytologie účinky léků MeSH
- inhibiční koncentrace 50 MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- lidé MeSH
- methanol chemie MeSH
- nádorové buněčné linie MeSH
- nadzemní části rostlin chemie MeSH
- oxidace-redukce MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemie izolace a purifikace farmakologie MeSH
- rostlinné extrakty chemie MeSH
- rozpouštědla chemie MeSH
- šalvěj chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Sanguinarine is a benzo[c]phenanthridine alkaloid with interesting cytotoxic properties, such as induction of oxidative DNA damage and very rapid apoptosis, which is not mediated by p53-dependent signaling. It has been previously documented that sanguinarine is reduced with NADH even in absence of any enzymes while being converted to its dihydro form. We found that the dark blue fluorescent species, observed during sanguinarine reduction with NADH and misinterpreted by Matkar et al. (Arch. Biochem. Biophys. 2008, 477, 43-52) as an anionic form of the alkaloid, is a covalent adduct formed by the interaction of NADH and sanguinarine. The covalent adduct is then converted slowly to the products, dihydrosanguinarine and NAD+, in the second step of reduction. The product of the reduction, dihydrosanguinarine, was continually re-oxidized by the atmospheric oxygen back to sanguinarine, resulting in further reacting with NADH and eventually depleting all NADH molecules. The ability of sanguinarine to diminish the pool of NADH and NADPH is further considered when explaining the sanguinarine-induced apoptosis in living cells.
The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.
- MeSH
- cyklooktany * chemie izolace a purifikace farmakologie MeSH
- doxorubicin farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- lidé MeSH
- lignany * chemie izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- P-glykoproteiny antagonisté a inhibitory MeSH
- polycyklické sloučeniny * chemie izolace a purifikace farmakologie MeSH
- Schisandra chemie MeSH
- semena rostlinná chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Rusko MeSH
A simple and rapid method for determination of six lignans found in plant cell cultures of Schisandra chinensis was developed and validated. The lignans were extracted from plant samples with methanol and the extracts were effectively cleaned by solid-phase extraction using Strata C18-E (Phenomenex) cartridges. Chromatographic separation was carried out on a Chromolith Performance RP-18e monolithic column (100 x 4.6 mm, Merck) using an isocratic mobile phase of acetonitrile and water in a 50:50 (v/v) ratio. The eluent was monitored at 220 nm. The baseline separation of schizandrin, gomisin A, deoxyschizandrin, gamma-schizandrin, gomisin N and wuweizisu C was achieved in a relatively short time period (20 min), which was made possible by the relatively high flow rate of the mobile phase (2 mL/min). The lower limit of quantitation was 0.1 mg/L for schizandrin and gomisin A, 0.3 mg/L for deoxyschizandrin, gamma-schizandrin, and gomisin N and 1 mg/L for wuweizisu C. The analysis of spiked samples containing six lignans provided absolute recoveries between 93 and 101% in all cases. The validated method was successfully applied to the determination of lignans in embryogenic plant cell cultures of Schisandra chinensis.
- MeSH
- cyklooktany chemie MeSH
- extrakce na pevné fázi metody MeSH
- lignany chemie MeSH
- methanol chemie MeSH
- molekulární struktura MeSH
- reprodukovatelnost výsledků MeSH
- Schisandra chemie MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Using exhaustive chromatographic separation we have isolated (-)-tigloyl-deangeloyl-gomisin F as a novel dibenzocyclooctadiene lignan from schisandra chinensis. With the help of HPLC, we further isolated (+)-schisandrin, (+)-deoxyschisandrin, (+)-γ-schisandrin, (-)-gomisin J, (+)-gomisin A, (-)-gomisin N, (-)-tigloyl-gomisin P, (-)-wuweizisu C, (-)-gomisin D, rubrisandrin A, (-)-gomisin G, (+)-gomisin K (3) and (-)-schisantherin C. A full NMR description of (-)-schisantherin C was carried out with the aim to confirm previous reports of its structure. Compounds isolated were identified on the basis of UV, IR, (1)H- and (13)C-NMR and MS. The cytotoxicity of lignans was tested for the BY-2 cell line alone and as a synergistic effect with the cytotoxic agent camptothecin. Lignans showed various toxicity and synergistic and antagonistic effects on camptothecin-induced cytotoxicity. Cytotoxicity against colon cancer cell line LoVo was also tested.
- MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- chemická frakcionace MeSH
- cytotoxiny chemie izolace a purifikace toxicita MeSH
- lidé MeSH
- lignany chemie izolace a purifikace toxicita MeSH
- nádorové buněčné linie MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- proliferace buněk účinky léků MeSH
- rostlinné extrakty chemie MeSH
- Schisandra chemie MeSH
- tabák účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The in vitro antiradical activity of Schisandra chinensis lignans was investigated using DPPH, ABTS+, Fenton reaction inhibition and tyrosine-nitration inhibition assays, as were the in vivo antidiabetic activities of selected lignans in an animal model of alloxan-induced diabetes. Different degrees of antiradical activity were found, depending upon the structural parameters of the tested compounds. Unfortunately, the compounds showed no antidiabetic activity in concentration range tested.
- MeSH
- antioxidancia farmakologie MeSH
- lignany farmakologie MeSH
- modely u zvířat MeSH
- myši inbrední ICR MeSH
- myši MeSH
- rostlinné extrakty farmakologie MeSH
- scavengery volných radikálů farmakologie MeSH
- Schisandra chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A panel of nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gamma-schizandrin and wuweizisu C was examined for their effect on multidrug resistance, as well as their anti-proliferative activities. COR-L23/R, a multidrug resistant sub-line, which has been reported to over-express multidrug resistance-associated protein (MRP1), was used for the experiments together with its parent cell line COR-L23 (human lung cell carcinoma). We found that lignans deoxyschizandrin and gamma-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin to COR-L23/R cells. Deoxyschizandrin and gamma-schizandrin also significantly enhanced the accumulation of doxorubicin in drug resistant cells. Both lignans alone had no effect on the cell cycle; however, when combined with sub-toxic doses of doxorubicin, they induced cell cycle arrest in the G2/M phase, which is typical for toxic doses of doxorubicin. Our results suggest that deoxyschizandrin and gamma-schizandrin potentiate the cytotoxic effect of doxorubicin in doxorubicin resistant lung cancer cells COR-L23/R by increasing the accumulation of doxorubicin inside the cells. The common structural feature of both active lignans is the R-biaryl configuration and the absence of a hydroxy group at C-8. Unlike the reversal effect, the cytotoxicity of lignans with the R-biaryl configuration was similar to that observed for lignans with the S-biaryl configuration.
- MeSH
- buněčné dělení účinky léků MeSH
- chemorezistence účinky léků MeSH
- cyklooktany aplikace a dávkování farmakologie chemie MeSH
- daunomycin aplikace a dávkování farmakologie metabolismus MeSH
- G2 fáze účinky léků MeSH
- lidé MeSH
- lignany aplikace a dávkování farmakologie chemie MeSH
- mnohočetná léková rezistence účinky léků MeSH
- nádorové buněčné linie MeSH
- nádory plic farmakoterapie metabolismus MeSH
- protinádorová antibiotika aplikace a dávkování farmakologie metabolismus MeSH
- velkobuněčný karcinom farmakoterapie metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
