Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two enzymes sensitive to various chemical compounds having ability to bind to crucial parts of these enzymes. Boldine is a natural alkaloid and it was mentioned in some older works that it can inhibit some kinds of AChE. We reinvestigated this effect on AChE and also on BChE using acetyl (butyryl) thiocholine and Ellman's reagents as standard substances for spectrophotometric assay. We found out IC50 of AChE equal to 372 μmol/l and a similar level to BChE, 321 μmol/l. We conclude our experiment by a finding that boldine is cholinesterase inhibitor; however we report significantly weaker inhibition than that suggested in literature. Likewise, we tried to investigate the mechanism of inhibition and completed it with in silico study. Potential toxic effect on cholinesterases in real conditions is also discussed.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• aporfiny chemie   farmakologie   MeSH
• butyrylcholinesterasa chemie   metabolismus   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• molekulární modely MeSH
• sekundární metabolismus * MeSH
• substrátová specifita účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Boldine is an aporphine alkaloid widely consumed in the folk medicine of some regions. Its anticancer potential has been shown but not yet elucidated. We compared the antitumor effect of orally and parenterally applied boldine in mice bearing solid Ehrlich tumor. We also explored the effects of boldine on breast adenocarcinoma MCF-7 cells in vitro. Repeated i. p. injections of 30, 60, or 90mg boldine/kg, either alone or combined with doxorubicin, slowed tumor growth in vivo. The latter two doses also prolonged the post-therapeutic survival of the mice. When fed food supplemented with boldine at a dose of 90mg/kg, the tumor-bearing mice survived significantly longer, but there was no effect on tumor size. Interestingly, continuous p. o. administration did not produce detectable levels of boldine in plasma or tissue samples, in contrast to high but short-lived concentrations after i. p. injections. There was neither antagonism nor synergism between boldine and doxorubicin, except a possible synergism of i. p. boldine 90mg/kg combined with doxorubicin when compared with doxorubicin alone.Boldine was cytotoxic to MCF-7 cells and reduced their viability and proliferation in vitro. Exposure to boldine decreased bromodeoxyuridine incorporation and histone H3 phosphorylation but did not induce apoptosis. Boldine treatment resulted in p38, ERK, and JNK activation in the mitogen-activated protein kinase pathway in a dose-dependent manner. Since bioavailability in mice seems to be different from that reported in rats, pharmacokinetic studies in humans are needed to evaluate the role of boldine in the beneficial effects of Boldo infusions. Copyright Georg Thieme Verlag KG Stuttgart . New York.

• MeSH
• adenokarcinom * farmakoterapie   MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• aporfiny farmakologie   terapeutické užití   MeSH
• doxorubicin MeSH
• experimentální nádory mléčných žláz * farmakoterapie   MeSH
• fytoterapie MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine.

• MeSH
• ABC transportéry nedostatek   genetika   metabolismus   MeSH
• aplikace orální MeSH
• aporfiny aplikace a dávkování   metabolismus   farmakologie   MeSH
• buňky Hep G2 MeSH
• buňky MDCK MeSH
• cholagoga a choleretika aplikace a dávkování   metabolismus   farmakologie   MeSH
• ethinylestradiol farmakologie   MeSH
• genetická transkripce účinky léků   MeSH
• glutathion metabolismus   MeSH
• hepatobiliární exkrece MeSH
• intravenózní infuze MeSH
• játra účinky léků   metabolismus   MeSH
• kinetika MeSH
• lidé MeSH
• osmóza MeSH
• potkani inbrední LEW MeSH
• potkani transgenní MeSH
• potkani Wistar MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům genetika   metabolismus   MeSH
• psi MeSH
• receptory cytoplazmatické a nukleární agonisté   genetika   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• transfekce MeSH
• upregulace MeSH
• žluč metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Plant and folk medicine represent nowadays a source of either new therapeutic substances or substrates for drug synthesis. One such promising group for possible further exploitation is the family of aporphine alkaloids containing boldine and related compounds. In this mini-review we focus on boldine and its newly described effects, which predominantly arise from its antioxidant properties. Moreover, we try to compare its antiproliferative properties with other better known members of the aporphine group.

• MeSH
• antioxidancia farmakologie   MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• aporfiny farmakologie   MeSH
• lidé MeSH
• proliferace buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• alkaloidy terapeutické užití   MeSH
• antioxidancia MeSH
• aporfiny farmakokinetika   farmakologie   izolace a purifikace   MeSH
• peroxidace lipidů účinky záření   MeSH

• MeSH
• antioxidancia farmakologie   MeSH
• aporfiny farmakologie   MeSH
• cytochrom P-450 CYP1A1 antagonisté a inhibitory   MeSH
• jaterní mikrozomy enzymologie   účinky léků   MeSH
• léčivé rostliny chemie   MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH