Jai Seup Ro

Monoamine oxidase inhibitory components fromCayratia japonica

Seven flavonoids were isolated from the whole plants and fruits ofCayratia 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-β-D-glucuronopyranoside (1), apigenin (2), luteolin (3), luteolin-7-O-β-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 μM, respectively. However, the flavone glycosides, apigenin-7-O-β-D-glucuronopyranoside (1) and luteolin-7-O-β-D-glucopyranoside (4), showed mild MAO inhibition (IC50 values: 81.7 and 118.6 μM, respectively). The flavanonol derivatives, taxifolin (5) and aromadendrin (6), also showed weak inhibition (IC50 values: 154.7 and 153.1 μM, respectively). Furthermore, quercetin (7) had a more potent inhibitory effect on MAO-A (IC60 value: 2.8 μM) than MAO-B (IC50 value: 90.0 μ.M). Apigenin (2) and luteolin (3) also preferentially inhibited MAO-A (IC50 values: 1.7 and 4.9 μM, respectively) compared with MAO-B (IC50 values: 12.8 and 59.7 μM, respectively).

Monoamine oxidase inhibitory components from the roots of Sophora flavescens

In our search for monoamine oxidase (MAO) inhibitors from natural resources, we found that the methanol extract of the roots ofSophora flavescens showed an inhibitory effect on mouse brain monoamine oxidase (MAO). Bioactivity-guided isolation of the extract yielded two known flavonoids, formononetin (1) and kushenol F (2), as active compounds along with three inactive compounds, oxymatrine (3), trifolirhizin (4), and β-sitosterol (5). Formononetin (1) and kushenol F (2) showed significant inhibitory effects on MAO in a dose-dependent manner with IC50 values of 13.2 and 69.9 μM, respectively. Formononetin (1) showed a slightly more potent inhibitory effect against MAO-B (IC50: 11.0 μM) than MAO-A (IC50: 21.2 μM). Kushenol F (2) also preferentially inhibited the MAO-B activity than MAO-A activity with the IC50 values of 63.1 and 103.7 μM, respectively.

Monoamine oxidase inhibitory constituents from the fruits of Cudrania tricuspidata.

A methylene chloride soluble fraction of the fruits ofCudrania 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-methylalpinumi-soflavone (2), and alpinumisoflavone (3) inhibited MAO activity in a concentration-dependent manner with IC50 values of 19.4, 23.9, and 25.8 μM, respectively. Of these, gancaonin A (1) showed a selective and potent inhibitory effect against -B (IC50 0.8 μ?) than -A (IC50 >800 μM). The kinetic analysis using Lineweaver-Burk plots indicated that gancaonin A (1) competitively inhibited MAO-B.

Inhibition of type A monoamine oxidase by coptisine in mouse brain

The inhibitory effects of coptisine, a protoberberine isoquinoline alkaloid, on type A and type B monoamine oxidase (MAO-A and MAO-B) activities in mouse brain were investigated. Coptisine showed an inhibitory effect on MAO-A activity in a concentration-dependent manner using a substrate kynuramine, but coptisine did not inhibit MAO-B activity. Coptisine exhibited 54.3% inhibition of MAO-A activity at 2 microM. The values of Km and Vmax of MAO-A were 151.9 +/- 0.6 microM and 0.40 +/- 0.03 nmol/min/mg protein, respectively (n=5). Coptisine competitively inhibited MAO-A activity with kynuramine. The Ki value of coptisine was 3.3 microM. The inhibition of MAO-A by coptisine was found to be reversible by dialysis of the incubation mixture. These results suggest that coptisine is a potent reversible inhibitor of MAO-A, and that coptisine functions to regulate the catecholamine content.

Monoamine oxidase inhibitory coumarins from the aerial parts of Dictamnus albus.

The methanol extract from the aerial parts ofDictamnus albus was active in inhibiting monoamine oxidase (MAO) from the mouse brain. Activity-guided fractionation led to the isolation of four known coumarins, 7-(6′R-hydroxy-3′, 7′-dimethyl-2′E, 7′-octadienyloxy) coumarin (1), auraptene (2), umbelliferone (3), and xanthotoxin (4), as active compounds along with an inactive alkaloid, skimmianine (5). Compounds1 and2 inhibited MAO activity in a concentration-dependent manner with IC50 values of 0.7 and 1.7 μM, respectively. Compounds1 and2 showed a slight and potently selective inhibitory effect against MAO-B (IC50 0.5 and 0.6 μM, respectively) compared to MAO-A (IC50 1.3 and 34.6 μM, respectively). According to kinetic analyses derived by Lineweaver-Burk reciprocal plots, compounds1 and2 exhibited a competitive inhibition to MAO-B.

Inhibitory Effect of Inflexinol on Nitric Oxide Generation and iNOS Expression via Inhibition of NF-κB Activation

Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae) have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 μM) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-κB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases.

Kaurane diterpenoids from Isodon excisus inhibit LPS-induced NF-κB activation and NO production in macrophage RAW264.7 cells

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.

Induction of neurite outgrowth by (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol from PC12 cells.

A lignan derivative, (-)-(7R, SSJ-dihydrodehydrodiconiferyl alcohol (DHDA), was isolated fromKalopanax septemlobus L. and was observed to have neuritogenic activity. DHDA at 50 μ? 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 neu-rotrophic action. At 50 μ?, DHDA enhanced NGF-induced neurite-bearing activity. This activity was partially blocked by the mitogen-activated protein kinase inhibitor PD98059 and by GF109203X, a protein kinase 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 and PKC.

Acetophenones from the roots ofCynanchum wilfordii HEMSLEY

Two acetophenones, cynandione A (1) and cynanchone A (2), were isolated from the roots ofCynanchum wilfordii. Their structures were identified by comparison of their physicochemical and spectral data with reported values.

Monoamine oxidase inhibitory naphthoquinones from the roots of Lithospermum erythrorhizon.

Activity-guided fractionation of a hexane-soluble extract of the roots ofLithospermum erythrorhizon, using a mouse brain monoamine oxidase (MAO) inhibition assay, led to the isolation of two known naphthoquinones, acetylshikonin and shikonin, and a furylhydroquinone, shikonofuran E. These compounds were shown to inhibit MAO with IC50 values of 10.0, 13.3, and 59.1 μM, respectively. Although no specificity for MAO-A and MAO-B was shown by acetylshikonin and shikonin, a Lineweaver-Burk plot analysis indicated that the inhibition was competitive for both MAO-A and MAO-B activity.