A methanolic extract of the whole plant of Isodon japonicus (Labiatae) showed potent inhibition on the LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 cells. Four known kaurane diterpenes were isolated by activity-guided fractionation and their structures were identified as kamebanin (1), kamebacetal A (2), kamebakaurin (3), excisanin A (4). All compounds also inhibited the LPS-induced NF-kappaB activation as assessed by NF-kappaB reporter assay and electrophoretic mobility shift assay (EMSA). Compounds 2-4 showed comparable inhibitory effects on the LPS-induced production of NO and PGE2, and activation of NF-kappaB without affecting cell viability. These results suggest that kaurane diterpenes could exert their inhibitory effects on the production of NO and PGE2 through the suppression of NF-kappaB activation, and be partially responsible for the anti-inflammatory activities of the genus Isodon.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine, and appears to play important roles in several psychiatric and neurological disorders. 1,2) MAO has been divided into two subtypes, MAO-A and MAO-B, on the basis of their amino acid sequence, substrate and inhibitor selectivity, and tissue distribution.2-4) MAO-A inhibitors are useful in the therapy of mental disorders, mainly as antidepressants, whereas MAO-B inhibitors are expected to be useful in the therapy of Parkinson's and Alzheimer's disease. 1,5) To date, a number of MAO inhibitors such as coumarins, xanthones, and isoquinoline alkaloids have been isolated from natural products or synthesized. 6-9)Piper longum L. (Piperaceae), a slender aromatic climber, is a native of the Indo-Malayan region and grows wild in the tropical rain forests of India. The extract of the crude drug "Piperis Longi Fructus," the fruits of P. longum, is frequently used in folk medicine to treat bronchial trouble and is used as a carminative and analgesic. 10,11) Piperine was the first amide isolated from Piper species and was reported to display central nervous system depression, antipyretic, and anti-inflammatory activity. 12,13) Moreover, previous studies have demonstrated that piperine and its derivatives present sedative-hypnotic, tranquilizing, and muscle-relaxing actions and can intensify the depressive action of other depressants.14) Based on the aforementioned evidence, it might be suggested that piperine could be useful for the control of CNS-related conditions, including mood disorders and moderate or mild depression states.In the present work, we have investigated the activityguided isolation and inhibitory effect of piperine on MAO activity in mouse brain. We also investigate the antidepressant-like activity of piperine in the in vivo tail suspension test. Results and DiscussionIn our ongoing search for naturally occurring MAO inhibitors, an ethanol extract of the fruits of P. longum exhibited strong inhibitory activity on mouse brain MAO. A bioassay-guided isolation of the extract yielded a known piperidine alkaloid, piperine, as an active component. The structure was identified by physicochemical and spectroscopic methods (mp, UV, IR, MS, 1 H-and 13 C-NMR) and by comparing the data obtained with those of published values (Fig. 1). 15,16) Piperine exhibited 38.0% inhibition of MAO activity at 8 mM, with an IC 50 value of 11.1 mM, which is comparable to iproniazid as a positive control (Table 1). According to the kinetic properties of MAO from the mouse brain, the values of K m and V max by using kynuramine were 72.2Ϯ5.60 mM and 3.97Ϯ0.18 nmol/min/mg protein, respectively (nϭ3) (data not shown).In order to verify the selectivity of the MAO activity, l-deprenyl-pretreated MAO preparation was used for the measurement of MAO-A activity, whereas a clorgyline-pretreated preparation was used for MAO-B. This result indicated that

Arctium lappa L. (Compositae), also known as "burdock," is a perennial herb that has been cultivated as a vegetable in many countries for a long time. The roots are widely used as a food, whereas the seeds are used in traditional Korean medicine as a diuretic, anti-inflammatory or detoxifying agent. 1)The genus Arctium is a rich source of dibenzylbutyrolactone lignans, some of which have antiproliferative and apoptotic effects,2) inhibit the binding of platelet-activating factor to rabbit platelets, 3) and induce differentiation against mouse myeloid leukemia cells. 4,5) The nitric oxide (NO) production inhibitory activities of three lignans, arctiin, arctigenin, and lappaol B, from the seeds of A. lappa were reported as a part of a larger study searching for anti-inflammatory substances from natural products.6) Further bioactivity-guided fractionation of this plant led to the isolation of a new sesquilignan, isolappaol C (1), along with four known sesqui-and dilignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5). This paper reports the isolation and structure elucidation of a new butyrolactone sesquilignan, isolappaol C, using spectroscopic method including 1D-and 2D-NMR as well as the inhibitory effects of compounds 1-5 on the NO production in LPS-stimulated murine macrophage RAW264.7 cells.Compound 1 was isolated as a white amorphous powder. The molecular formula was established as (Fig. 2). These data indicated that compound 1 is a demethylated derivative of lappaol D (3) at the position of C-4Ј. The absolute configuration at C-8 and C-8Ј of compound 1 were confirmed to be 8(R) and 8Ј(R) from the negative cotton effect at 234 nm in the circular dichroism (CD) spectrum of this compound.5) The relative stereochemistry of C-7Љ and C-8Љ was determined to be erythro by a comparison of the coupling constant between H-7Љ and H-8Љ (Jϭ5.6 Hz) with those of the erythro and threo isomers. 7,8) Therefore, the structure of compound 1 was determined to be a new sesquilignan, isolappaol C. However, the absolute configurations of the other chiral centers at C-7Љ and C-8Љ remain to be determined.Two known sesquilignans, lappaol C (2) and lappaol D (3), and two dilignans, lappaol F (4) and diarctigenin (5), were also isolated and identified by a comparison of the observed [a] D , UV, IR, 1 H-NMR, 13 C-NMR, DEPT, HMQC, HMBC, and FAB-MS data with the literature values. 4,[9][10][11][12] Nitric oxide is an inorganic gaseous molecule that is synthesized by the oxidation of L-arginine catalyzed by nitric oxide synthase (NOS) and is involved in a number of physiological and pathological processes in mammals. 13) In the NOS family, iNOS is expressed in a variety of cells including macrophages, endothelial cells, and smooth muscle cells in response to pro-inflammatory stimuli such as IL-1b, TNF-a, A new butyrolactone sesquilignan, isolappaol C (1), together with four known lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were isolated from the methanolic extract of the seeds from the ...

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).

A new flavan-3-ol glycoside, (-)-epicatechin-5-O-beta-D-glucosyl-3-benzoate (1), and two known compounds, (-)-epicatechin and (-)-epiafzelechin, were isolated from an EtOAc extract of Celastrus orbiculatus aerial parts that exhibited significant antioxidant effect in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay. The structure of 1 was elucidated by spectroscopic analyses, and compound 1 and its aglycon, (-)-epicatechin-3-benzoate (2), were found to be moderately active as antioxidants in the DPPH assay.