Xiang Hua Han

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 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.

ent-Kaurane Diterpenoids from Isodon japonicus

Five ent-kaurane diterpenoids, 6beta,7beta,14beta-trihydroxy-1alpha,19-diacetoxy-7alpha,20-epoxy- ent-kaur-16-en-15-one (1), 1alpha,6beta,7beta-trihydroxy-11alpha,19-diacetoxy-7alpha,20-epoxy-ent-kaur-16-en-15-one (2), 6-hydroxy-1alpha,19-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (3), 19-hydroxy-1alpha,6-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (4), and 6-aldehyde-1alpha,19-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (5), along with 10 known ent-kaurane diterpenoids, pseurata C (6), longikaurin C (7), effusanin C (8), longikaurin B (9), longikaurin D (10), effusanin D (11), excisanin B (12), lasiokaurin (13), megathyrin A (14), and loxothyrin A (15), were isolated from the aerial parts of Isodon japonicus. Their structures were determined on the basis of spectroscopic (1D-, 2D-NMR and MS) and chemical evidence. The isolates were evaluated for their inhibitory effects on LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells.

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.

Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase

We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with IC50 values of 3.6 and 139.2 μM, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B (IC50 value: 1.6 μM) than MAO-A (IC50 value: 27.1 μM). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and 1.3 μM, respectively.

Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages

The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 μM.

Antioxidative oligostilbenes from Caragana sinica

Two new oligostilbenes, caragasinins A (5) and B (10), and eight known compounds, kobophenol A (1), (+)-α-viniferin (2), (+)-ampelopsin F (3), pallidol (4), (+)-isoampelopsin F (6), miyabenol C (7), carasinaurone (8) and caraphenol B (9) were isolated from the ethylacetate-soluble extract of the roots of Caragana sinica. The structures of the isolates were determined on the basis of extensive spectroscopic analysis including 1D, 2D NMR and HRESI-MS. These compounds were assessed for antioxidant activities. Caragasinin A (5), caraphenol B (9), and caragasinin B (10) showed moderate DPPH scavenging activity and lipid peroxidation inhibitory activities with IC(50) values ranging from 34.7±1.0 to 89.1±2.3μM.

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.

Phenanthrenes from Dendrobium nobile and their inhibition of the LPS-induced production of nitric oxide in macrophage RAW 264.7 cells.

Bioactivity-guided isolation of the methanol extract of the stems of Dendrobium nobile yielded a new phenanthrene together with nine known phenanthrenes and three known bibenzyls. Their structures were elucidated by analysis of the spectroscopic data including 2D-NMR. All of the isolates were evaluated for their potential to inhibit the LPS-induced production of nitric oxide in murine macrophage RAW 264.7 cells. Compounds 1-4, 7-13 inhibited nitric oxide production with the IC(50) values ranging from 9.6 microM to 35.7 microM.

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.