Two heretofore uncharacterised abietane diterpenes, sincoetsin C (1) and 3-hydroxyspirocoleon 7-O-β-D-glucoside (4), were isolated from a methanolic extract of Coleus blumei Benth. (Lamiaceae), along with the known compounds, scutellarioidone A (2) and spirocoleon 7-O-β-D-glucoside (3) using chromatographic techniques. Their structures were determined by 1D and 2D nuclear magnetic resonance including HSQC, HMBC, COSY and NOESY experiments, mass spectrometry (HR-MS) and other spectroscopic methods (UV, IR). Their antibacterial activity against the reference strain of methicillin-resistant Staphylococcus aureus subsp. aureus CCM 4750 (MRSA) was evaluated using optical absorption to obtain quantitative information on their growth. All isolated compounds displayed anti-MRSA 4750 activity at the concentration of 512 μg/mL. Sincoetsin C (1) was the abietane diterpene most active against MRSA 4750, with a minimum inhibitory concentration of 128 μg/mL.
- MeSH
- Coleus * chemie MeSH
- diterpeny abietanové izolace a purifikace farmakologie MeSH
- diterpeny * izolace a purifikace farmakologie MeSH
- fytonutrienty izolace a purifikace farmakologie MeSH
- methicilin rezistentní Staphylococcus aureus * účinky léků MeSH
- Staphylococcus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.
- MeSH
- antiflogistika chemie izolace a purifikace farmakologie MeSH
- arachidonát-5-lipoxygenasa metabolismus MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemie izolace a purifikace farmakologie MeSH
- inhibitory lipoxygenas chemie izolace a purifikace farmakologie MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- ovoce chemie MeSH
- proteomika * MeSH
- Publikační typ
- časopisecké články MeSH
This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results.
- MeSH
- acylkoenzym A chemie MeSH
- antioxidancia aplikace a dávkování chemie MeSH
- buněčné linie MeSH
- experimentální diabetes mellitus farmakoterapie MeSH
- fenoly aplikace a dávkování chemie izolace a purifikace MeSH
- flavonoidy aplikace a dávkování chemie izolace a purifikace MeSH
- hypercholesterolemie farmakoterapie MeSH
- hyperglykemie farmakoterapie MeSH
- lidé MeSH
- mediátory zánětu chemie MeSH
- myši inbrední NOD MeSH
- myši MeSH
- řebříček chemie MeSH
- rizikové faktory MeSH
- rostlinné extrakty aplikace a dávkování chemie MeSH
- simulace molekulového dockingu MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Eleven new C-geranylated flavonoids, tomentodiplacones L, M, and N (1, 2, 10), tomentodiplacol B (3), 3',4'-O-dimethyl-5'-hydroxydiplacone (4), mimulones F, G, and H (5, 6, 7), paulowniones A (8) and B (9), tomentone (11), and 3',4',5'-trimethoxyflavanone (12), together with 11 known flavonoids (13-23), were isolated from fruits of Paulownia tomentosa. The structures of the compounds isolated were determined by spectroscopic data interpretation. The ability of compounds 1-23, together with the nonprenylated flavanones eriodictyol (24) and naringenin (25), to reduce the production of the pro-inflammatory cytokine TNF-α in THP-1 cells after bacterial lipopolysaccharide stimulation was evaluated using an in vitro screening test. The preliminary structure-activity relationships of these derivatives were also studied, and the correlation of their TNF-α inhibitory activity with their lipophilicity was investigated. The mechanism of action of compounds with significant antiphlogistic potential (4, 7, 10, 14, 22) was investigated. These compounds reduced both the secretion of TNF-α and the level of its corresponding mRNA. Compounds 4, 7, 10, 14, and 22 inhibited the nuclear translocation of NF-κB, which controls the expression of TNF-α, by blocking the degradation of IκB.
- MeSH
- antiflogistika chemie izolace a purifikace farmakologie MeSH
- biologické modely MeSH
- flavanony chemie izolace a purifikace farmakologie MeSH
- lipopolysacharidy MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- NF-kappa B antagonisté a inhibitory MeSH
- ovoce chemie MeSH
- proteiny I-kappa B metabolismus MeSH
- TNF-alfa analýza antagonisté a inhibitory MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Chromatographic separation of root extracts of Morus alba and M. nigra led to the identification of the 2-arylbenzofurans moracin C (1), mulberrofuran Y (2), and mulberrofuran H (3), and the prenylated flavonoids kuwanon E (4), kuwanon C (5), sanggenon H (6), cudraflavone B (7), and morusinol (8), and the Diels-Alder adducts soroceal (9), and sanggenon E (10). The cytotoxicity and their antiphlogistic activity, determined as the attenuation of the secretion of TNF-α and IL-1β and the inhibition of NF-κB nuclear translocation in LPS-stimulated macrophages, were evaluated for compounds 1-10.
- MeSH
- antiflogistika farmakologie MeSH
- benzofurany chemie izolace a purifikace farmakologie MeSH
- benzopyrany chemie izolace a purifikace farmakologie MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- kůra rostlin chemie MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- makrofágy účinky léků MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- myši MeSH
- NF-kappa B účinky léků MeSH
- prenylace MeSH
- TNF-alfa farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Exhaustive chromatographic separation of the chloroform portion of the ethanolic extract obtained from Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits has led to isolation of ten C-6 geranylated flavanones tomentodiplacone C-I and mimulone C-E, featured by 3'-methoxy and 4'-hydroxy or 4'-hydroxy substitution of the B-ring of the flavonoid, respectively. The structures of these compounds were determined by using mass spectrometry (including HRMS) and 1D and 2D NMR spectroscopy. The absolute configurations of the compounds at C-2 were determined using circular dichroism. The obtained compounds showed the presence of a geranyl moiety functionalized by a carbonyl, hydroxyl or methoxyl group, or by formation of tetrahydrofuran or fused-pyrane ring, respectively. All of the flavanones described were isolated for the first time from a natural source. The antibacterial activities of selected compounds isolated along with the previously isolated geranylated flavanones were evaluated against a common panel of microbes and MRSA strains. The selected isolated compounds were tested for their ability to affect eukaryotic translation initiation via dual-luciferase reporter assay (firefly and renilla).
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- flavanony chemie farmakologie MeSH
- iniciace translace peptidového řetězce účinky léků MeSH
- luciferasy genetika MeSH
- Magnoliopsida chemie MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- ovoce chemie MeSH
- reportérové geny genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
