ABSTRACT
Four new prenylated xanthones, cudratricusxanthones J-M (1-4), were isolated from the CH2Cl2-soluble extract of the root bark of Cudrania tricuspidata, along with four known prenylated xanthones, isocudraxanthone K (5), cudraxanthone C (6), cudratricusxanthone A (7), and cudraxanthone L (8), and three known prenylated flavonoids, cudraflavone A (9), cudraflavanone A (10), and cudraflavone B (11). The structures of compounds 1-4 were elucidated using spectroscopic methods. Cudratricusxanthone A (7), cudraflavanone A (10), and cudraflavone B (11) showed moderate inhibitory effects on mouse brain monoamine oxidase (MAO) with IC50 values of 88.3, 89.7, and 80.0 microM, respectively.
Subject(s)
Monoamine Oxidase Inhibitors/isolation & purification , Moraceae/chemistry , Plants, Medicinal/chemistry , Xanthones/isolation & purification , Animals , Brain/enzymology , Mice , Molecular Structure , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Plant Bark/chemistry , Plant Roots/chemistry , Xanthones/chemistry , Xanthones/pharmacologyABSTRACT
Seven flavonoids were isolated from the whole plants and fruits of Cayratia japonica through the activity-guided isolation of a methanol extract using a monoamine oxidase (MAO) inhibition assay as a monitor. The chemical structures of the isolates were assigned as apigenin-7-O-beta-D-glucuronopyranoside (1), apigenin (2), luteolin (3), luteolin-7-O-beta-D-glucopyranoside (4), (+)-dihydroquercetin (taxifolin) (5), (+)-dihydrokaempferol (aromadendrin) (6) and quercetin (7). Among the isolated compounds, flavones such as apigenin (2) and luteolin (3), as well as the flavonol, quercetin (7) showed potent inhibitory effects against the MAO activity with IC50 values of 6.5, 22.6, and 31.6 microM, respectively. However, the flavone glycosides, apigenin-7-O-beta-D-glucuronopyranoside (1) and luteolin-7-O-beta-D-glucopyranoside (4), showed mild MAO inhibition (IC50 values: 81.7 and 118.6 microM, respectively). The flavanonol derivatives, taxifolin (5) and aromadendrin (6), also showed weak inhibition (IC50 values: 154.7 and 153.1 microM, respectively). Furthermore, quercetin (7) had a more potent inhibitory effect on MAO-A (IC50 value: 2.8 microM) than MAO-B (IC50 value: 90.0 microM). Apigenin (2) and luteolin (3) also preferentially inhibited MAO-A (IC50 values: 1.7 and 4.9 microM, respectively) compared with MAO-B (IC50 values: 12.8 and 59.7 microM, respectively).
Subject(s)
Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Brain/drug effects , Flavonoids/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Vitaceae , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/isolation & purification , Antidepressive Agents/chemistry , Antidepressive Agents/isolation & purification , Biological Assay/methods , Brain/enzymology , Chemical Fractionation/methods , Flavonoids/chemistry , Flavonoids/isolation & purification , In Vitro Techniques , Isoenzymes , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Molecular Structure , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/isolation & purification , Plant Extracts/chemistry , Solvents/chemistry , Structure-Activity RelationshipABSTRACT
As part of an ongoing search for plant-derived compounds that inhibit the activation of NF-kappaB, the methanol extract of the aerial parts of Isodon excisus was found to have significant inhibitory effects on the activation of NF-kappaB in murine macrophage RAW264.7 cells. Bioactivity-guided isolation of the extract yielded five new diterpenoids, excisusin A-E (1-5), along with seven known compounds, inflexarabdonin I (6), inflexarabdonin G (7), inflexin (8), inflexanin A (9), inflexanin B (10), inflexinol (11), and inflexarabdonin A (12). The structures were determined by analysis of the spectroscopic data including 2D NMR. All of the isolates were evaluated for their inhibitory effects on LPS-induced NF-kappaB activation and nitric oxide production in RAW264.7 cells.
Subject(s)
Diterpenes, Kaurane , Isodon/chemistry , Lipopolysaccharides/pharmacology , Macrophages/drug effects , NF-kappa B/antagonists & inhibitors , Nitric Oxide/antagonists & inhibitors , Plants, Medicinal/chemistry , Animals , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Korea , Mice , Molecular Conformation , Molecular StructureABSTRACT
A methylene chloride soluble fraction of the fruits of Cudrania tricuspidata significantly inhibited the mouse brain monoamine oxidase (MAO). Three known prenylated isoflavones were isolated and identified by activity-guided fractionation. Gancaonin A (1), 4'-O-methylalpinumisoflavone (2), and alpinumisoflavone (3) inhibited MAO activity in a concentration-dependent manner with IC50 values of 19.4, 23.9, and 25.8 microM, respectively. Of these, gancaonin A (1) showed a selective and potent inhibitory effect against MAO-B (IC50 0.8 microM) than MAO-A (IC50 >800 microM). The kinetic analysis using Lineweaver-Burk plots indicated that gancaonin A (1) competitively inhibited MAO-B.
Subject(s)
Fruit/chemistry , Maclura , Monoamine Oxidase Inhibitors/isolation & purification , Animals , Brain/enzymology , Dose-Response Relationship, Drug , Isoflavones/chemistry , Isoflavones/isolation & purification , Isoflavones/pharmacology , Kinetics , Methylene Chloride/chemistry , Mice , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plants, Medicinal/chemistryABSTRACT
A lignan derivative, (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (DHDA), was isolated from Kalopanax septemlobus L. and was observed to have neuritogenic activity. DHDA at 50 microM caused a marked induction of neurite outgrowth and an enhancement of nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells. However, it did not exhibit any neurotrophic action. At 50 microM, DHDA enhanced NGF-induced neurite-bearing activity. This activity was partially blocked by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and by GF109203X, a protein kinase C (PKC) inhibitor. These results suggest that DHDA can induce neurite outgrowth and enhance NGF-induced neurite outgrowth from PC12 cells by amplifying up-stream steps such as MAPK and PKC.
Subject(s)
Lignin/analogs & derivatives , Neurites/drug effects , Animals , Araliaceae , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Indoles/pharmacology , Lignin/antagonists & inhibitors , Lignin/isolation & purification , Lignin/pharmacology , MAP Kinase Signaling System/drug effects , Maleimides/pharmacology , Medicine, East Asian Traditional , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Nerve Growth Factor/pharmacology , Neurites/physiology , PC12 Cells , Plant Bark/chemistry , Plant Stems , Plants, Medicinal , Protein Kinase C/antagonists & inhibitors , RatsABSTRACT
Skin hyperpigmentations such as melasma, freckles and senile lentigines can be subjectively treated by depigmenting agents. In our ongoing study to find melanogenesis inhibitors from natural sources, Piper longum L (fruits, Piperaceae) was discovered to have an inhibitory effect on alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis in melanoma B16 cells. Piperlonguminine has been identified as the melanogenesis inhibitor from P. longum by activity-guided extraction and isolation. The compound showed dose-dependent inhibitory effects with 85.1 +/- 4.9% inhibition at 25 microM, 62.1 +/- 6.1% at 12.5 microM, 36.4 +/- 4.6% at 6.3 microM and 18.4 +/- 5.1% at 3.1 microM on alpha-MSH-induced melanogenesis, showing an IC50 value of 9.6 microM. As a positive control, kojic acid exhibited an IC50 value of 44.6 microM on the melanogenesis. As to the mode of action, piperlonguminine showed an inhibitory effect on alpha-MSH-induced tyrosinase synthesis, documented by Western immunoblot analysis. However, piperlonguminine did not show an inhibitory effect on tyrosinase activity or a direct depigmenting effect of melanin.
Subject(s)
Dioxolanes/pharmacology , Phytotherapy , Piper , Plant Extracts/pharmacology , alpha-MSH/antagonists & inhibitors , alpha-MSH/drug effects , Animals , Cell Line, Tumor/drug effects , Dioxolanes/administration & dosage , Dioxolanes/therapeutic use , Dose-Response Relationship, Drug , Fruit , Melanins/biosynthesis , Mice , Monophenol Monooxygenase/biosynthesis , Pigmentation Disorders/drug therapy , Plant Extracts/administration & dosage , Plant Extracts/therapeutic useABSTRACT
The inhibitory compound of monoamine oxidase (MAO) activity was isolated from the CH(2)Cl(2) fraction of the fructus of Evodia rutaecarpa and identified as 1-methyl-2-undecyl-4(1H)-quinolone (1). Compound 1 showed a selective inhibition of type B MAO (MAO-B) activity with the IC(50) value of 15.3 microM using a substrate kynuramine, but did not inhibit type A MAO (MAO-A) activity. The kinetic analysis using Lineweaver-Burk plots indicated that compound 1 competitively inhibited MAO-B activity with the K(i) value of 9.91 microM. The inhibition of MAO-B by compound 1 was found to be irreversible by dialysis of the incubation mixture. These results suggest that compound 1 is a potent irreversible inhibitor of MAO-B, and may regulate catecholamine content in the neurons.
Subject(s)
Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/metabolism , Quinolones/chemistry , Quinolones/pharmacology , Animals , Brain/drug effects , Brain/enzymology , Evodia , Fruit , Mice , Monoamine Oxidase Inhibitors/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Quinolones/isolation & purificationABSTRACT
Furanoligularenone (1), a known eremophilane, was identified from Ligularia fischeri (Compositae) together with 3-oxo-8alpha-hydroxy-10alphaH-eremophila-1,7(11)-dien-12,8beta-olide (2) and 3-oxo-8alpha-methoxy-10alphaH-eremophila-1,7(11)-dien-12,8beta-olide (3), by its potent inhibition of LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 cells. Compound 1 also suppressed the expression of iNOS and COX-2 mRNA and protein in a dose-dependent manner. Taken together, compound 1 inhibits the production of NO and PGE2 at the transcription of iNOS and COX-2 genes, and would be responsible for the anti-inflammatory activities of the Ligularia fischeri.