Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K.

Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine ß-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 µM, and 43.9 µM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 µM, and 42.5 µM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 µM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 µM and this value was higher than that of deprenyl (0.046 µM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 µM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

Monoamine Oxidase and Dopamine ß-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides.

This research was designed to determine what components of Gardenia jasminoides play a major role in inhibiting the enzymes related antidepressant activity of this plant. In our previous research, the ethyl acetate fraction of G. jasminosides fruits inhibited the activities of both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B), and oral administration of the ethanolic extract slightly increased serotonin concentrations in the brain tissues of rats and decreased MAO-B activity. In addition, we found through in vitro screening test that the ethyl acetate fraction showed modest inhibitory activity on dopamine-ß hydroxylase (DBH). The bioassay-guided fractionation led to the isolation of five bio-active compounds, protocatechuic acid (1), geniposide (2), 6'-O-trans-p-coumaroylgeniposide (3), 3,5-d-ihydroxy-1,7-bis (4-hydroxyphenyl) heptanes (4), and ursolic acid (5), from the ethyl acetate fraction of G. jasminoides fruits. The isolated compounds showed different inhibitory potentials against MAO-A, -B, and DBH. Protocatechuic acid showed potent inhibition against MAO-B (IC50 300 µmol/L) and DBH (334 µmol/L), exhibiting weak MAO-A inhibition (2.41 mmol/L). Two iridoid glycosides, geniposide (223 µmol/L) and 6'-O-trans-p-coumaroylgeniposide (127µmol/L), were selective MAO-B inhibitor. Especially, 6'-O-trans-p-coumaroylgeniposide exhibited more selective MAO-B inhibition than deprenyl, well-known MAO-B inhibitor for the treatment of early-stage Parkinson's disease. The inhibitory activity of 3,5-di-hydroxy-1,7-bis (4-hydroxyphenyl) heptane was strong for MAO-B (196 µmol/L), modest for MAO-A (400 µmol/L), and weak for DBH (941 µmol/L). Ursolic acid exhibited significant inhibition of DBH (214 µmol/L), weak inhibition of MAO-B (780 µmol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders.

Major constituents and antimicrobial activity of Korean herb Acorus calamus.

The constituents and antimicrobial activity of the essential oil from Acorus calamus were analysed. Methyl isoeugenol and cyclohexanone were identified as the major constituents of the essential oil. The essential oil was tested for antimicrobial activity against bacteria and yeast, and has shown strong antibiotic activities against most of the tested microbes, except Escherichia coli. The hexane extract has shown a similar pattern of antimicrobial activity as the essential oil. Methyl isoeugenol, the most abundant constituent in the essential oil, has also shown similar antimicrobial activity, except against Bacillus subtilis. The essential oil as well as the hexane extract and methyl isoeugenol have shown antimicrobial activity against Propionibacterium acne, which is known to be involved in acne vulgaris.

Effects of swimming exercise and soybean supplementation on the immune functions of rats fed a high-fat diet.

1. In the present study, the effects of swimming exercise and soybean supplementation on the immune functions of rats fed a high-fat diet were examined. 2. Thirty-four male rats were randomly divided into four groups: (i) HS, a high-fat diet sedentary group (n = 8); (ii) HE, a high-fat diet exercised group (n = 9); (iii) SS, a soybean diet sedentary group (n = 8); and (iv) SE, a soybean diet exercised group (n = 9). The high-fat diet was composed of 35% carbohydrate, 20% protein and 35% fat. For the soybean diet, 3% crude soybean extract was substituted for the protein, carbohydrate and fat according to the energy content of the diet. In the exercise groups, rats swam for 60 min/day, 5 days/week for 4 weeks. 3. The subpopulation of CD4(+) cells and the CD4(+)/CD8(+) ratio did not differ significantly between the high-fat diet and soybean diet groups. However, the subpopulation of CD8(+) cells in the spleens of SS rats was significantly higher than that in the spleens of HS rats (P < 0.05). In addition, splenic interferon-gamma secretion in the SE group, with or without conconavalin A stimulation, was significantly increased compared with the SS group (P < 0.05 and P < 0.01, respectively). 4. These results show that regular endurance exercise training with soybean supplementation ameliorates splenic T cell-mediated immunity.

Rubiae Radix suppresses the activation of mast cells through the inhibition of Syk kinase for anti-allergic activity.

The effect of extracts from various Oriental medicinal herbs on mast-cell-mediated allergic reactions was investigated in this study. Of these extracts, the medicinal herb Rubiae Radix exhibited the most potent activity in the cells, with an IC50 value (concentration necessary to obtain 50% inhibition of the response) of approximately 35 +/- 2.1 microg mL(-1), and its inhibition of compound-48/80-induced systemic anaphylaxis by 48.6 +/- 8.5% at 300 mg kg(-1) in mice. It also inhibited the expression of the pro-inflammatory mediator tumour necrosis factor-alpha (TNF-alpha). As for its mechanism of action, Rubiae Radix suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signalling processes, and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. These results suggest that Rubiae Radix suppresses the activation of mast cells through the inhibition of Syk for anti-allergic activity.

Induction of thioredoxin is required for nodule development to reduce reactive oxygen species levels in soybean roots.

Nodules are formed on legume roots as a result of signaling between symbiotic partners and in response to the activities of numerous genes. We cloned fragments of differentially expressed genes in spot-inoculated soybean (Glycine max) roots. Many of the induced clones were similar to known genes related to oxidative stress, such as thioredoxin and beta-carotene hydroxylase. The deduced amino acid sequences of full-length soybean cDNAs for thioredoxin and beta-carotene hydroxylase were similar to those in other species. In situ RNA hybridization revealed that the thioredoxin gene is expressed on the pericycle of 2-d-old nodules and in the infected cells of mature nodules, suggesting that thioredoxin is involved in nodule development. The thioredoxin promoter was found to contain a sequence resembling an antioxidant responsive element. When a thioredoxin mutant of yeast was transformed with the soybean thioredoxin gene it became hydrogen peroxide tolerant. These observations prompted us to measure reactive oxygen species levels. These were decreased by 3- to 5-fold in 7-d-old and 27-d-old nodules, coincident with increases in the expression of thioredoxin and beta-carotene hydroxylase genes. Hydrogen peroxide-producing regions identified with cerium chloride were found in uninoculated roots and 2-d-old nodules, but not in 7-d-old and 27-d-old nodules. RNA interference-mediated repression of the thioredoxin gene severely impaired nodule development. These data indicate that antioxidants such as thioredoxin are essential to lower reactive oxygen species levels during nodule development.

Inhibition of calmodulin-dependent protein kinase II by cyclic and linear peptide alkaloids from Zizyphus species.

The effects of sedative peptide alkaloids from Zizyphus species on calmodulin- dependent protein kinase II were investigated. Protein kinase II activity was assayed on the basis of its ability to activate tryptophan 5-monooxygenase as its substrate in the presence of calmodulin. All thirteen alkaloids tested were stronger inhibitors than chlorpromazine (IC50, 98 microM) on calmodulin-dependent protein kinase II. Among them, the most potent inhibitor was daechuine S27 (IC50 2.95 microM), which was stronger than pimozide (IC50, 15.0 microM).

Promoting effect and recovery activity from physical stress of the fruit of Morus alba.

We examined the effects of the fruit of M. alba extracts on the changes of the monoamine oxidase (MAO) activities during and after the physical exercise in rat. Each activity was measured by used serotonin(5-HT) and benzylamine as substrate. Lactate dehydrogenase(LDH) activity and the concentrations of lactate in blood which were clinical indexes of physical exercise were also determined to compare with the relation of MAO activities. Those activities during and after the physical exercise have different tendency in each other enzyme. MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise. All of these indexes were recovered to normal state by oral administration of extract of M. alba. These results of this study suggested M. alba may modulate the MAO activities during exercise and promote the capability of physical activities and show anti-stress effect. In general, MAO inhibitors have been used drugs for the purpose of treatment Parkinson's disease, dementia, depression. These results can apply to produce the health and functional foods that have modulating effects for these diseases.