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Forsythia fruit (Forsythia suspensa Vahl (Oleaceae)) is a common component of Kampo medicines for treating the common cold, influenza, and allergies. The main polyphenolic compounds in the leaves of F. suspensa are pinoresinol β-d-glucoside, phillyrin and forsythiaside, and their levels are higher in the leaves of the plant than in the fruit. It is known that polyphenolic compounds stimulate lipid catabolism in the liver and suppress dyslipidemia, thereby attenuating diet-induced obesity and polyphenolic anti-oxidants might attenuate obesity in animals consuming high-fat diets. Recently, phillyrin was reported as a novel cyclic AMP phosphodiesterase 4 (PDE4) inhibitor derived from forsythia fruit. It was expected that the leaves of F. suspensa might display anti-obesity effects and serve as a health food material. In this review, we summarized our studies on the biological effects of forsythia leaves containing phillyrin and other polyphenolic compounds, particularly against obesity, atopic dermatitis, and influenza A virus infection, and its potential as a phytoestrogen.

Red yeast rice has been used to produce alcoholic beverages and various fermented foods in China and Korea since ancient times; it has also been used to produce tofuyo (Okinawan-style fermented tofu) in Japan since the 18th century. Recently, monacolin K (lovastatin) which has cholesterol-lowering effects, was found in some strains of Monascus fungi. Since statins have been used world-wide as a cholesterol-lowering agent, processed foods containing natural statins are drawing attention as materials for primary prevention of life-style related diseases. In recent years, large-scale commercial production of red yeast rice using traditional solid-state fermentation has become possible, and various useful materials, including a variety of monascus pigments (polyketides) that spread as natural pigments, in addition to statins, are produced in the fermentation process. Red yeast rice has a lot of potential as a medicinal food. In this paper, we describe the history of red yeast rice as food, especially in Japan and East Asia, its production methods, use, and the ingredients with pharmacological activity. We then review evidence of the beneficial effects of red yeast rice in improving lipid metabolism and the circulatory system and its safety as a functional food.

Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine. We investigated the effect of ELE on the development of atherosclerosis and changes in peritoneal macrophage function in apolipoprotein E knockout (ApoE-/- ) mice. At 8 weeks of age, ApoE-/- mice were randomly divided into three groups that were fed a high-fat diet blended with 0% (control), 5% or 10% ELE for a period of 7 weeks. The 10% ELE dose caused an approximately 36% reduction in atherosclerotic lesions, as estimated by oil red O staining. Real-time PCR analysis showed that the 1-week treatment with ELE reduced mRNA levels of Tnf-alpha, Il-1, and Mif in peritoneal macrophages isolated from the ApoE-/- mice. Furthermore, a 1-week treatment with the 10% ELE diet significantly reduced migration and adhesion functions in peritoneal macrophages. These results suggest that a 10% ELE diet reduces atherosclerotic lesions and modulates macrophage function by reducing cytokine expression. PRACTICAL APPLICATION: Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine that reduces atherosclerotic lesions and suppresses inflammatory cytokines expression.

Geniposidic acid (GEA), the main ingredient of several medicinal herbs, has pharmacological effects on hypertension, inflammation, diabetes, atherosclerosis, and cancer. The current study evaluated the mechanism underlying the hypotensive effects of a single oral administration of 100 mg GEA/kg in male spontaneously hypertensive rats. Blood pressure was significantly reduced at 6 h post GEA treatment, as compared with control rats. Plasma levels of atrial natriuretic peptide (ANP) were also upregulated by GEA, indicating that its anti-hypertensive activity involved enhanced ANP secretion from cardiomyocytes. This could reflect GEA-mediated activation of glucagon-like peptide-1 (GLP-1) receptors on atrial cardiomyocytes. Plasma GLP-1 levels were not significantly altered by GEA. This study is the first to report that orally administered GEA produces beneficial effects on heart tissue by increasing plasma ANP levels, although GEA is a known GLP-1 receptor agonist. These effects could underlie the broad physiological effects of medicinal herbs containing GEA.

The highly abundant and widely dispersed plant Plantago lanceolata L. (narrow leaf or English plantain) has been used for culinary and medicinal purposes since ancient times. Here, we investigated the anti-obesity effects of P. lanceolata leaf powder (shortly PL) when fed to male C57BL/6 J mice. Addition of PL to a high-fat diet did not affect food intake but significantly reduced food efficiency, suppressed body weight gain and visceral fat accumulation, and reduced serum free-fatty acid and glucose levels. PL-fed mice exhibited marked increases in HSL, Adrd3 and Cpt2 mRNA levels, and significant decreases in Fas transcripts in epididymal white adipose tissue (WAT). These findings suggest that dietary PL exerts anti-obesity effects by stimulating metabolism throughout visceral fat tissue by activating lipolysis, accelerating fatty acid β-oxidation and suppressing fatty acid synthase in WAT. To our knowledge, this is the first demonstration of anti-obesity substances derived from a Plantago species.

Eucommia bark (Eucommia ulmoidesOliver) has been used as an herbal medicine, and more recently, the plant's leaves have been widely used to prepare tea which may have anti-obesity properties. We used a metabolic syndrome-like rat model, produced by feeding a 35 % high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of Eucommia leaf as an extract or green leaf powder. Eighty rats were studied for 3 months in ten groups. Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion. Increases in plasma levels of TAG and NEFA, and insulin resistance secondary to HFD were lessened by both forms of Eucommia leaf. Concomitantly, an increase in plasma adiponectin levels and suppression of plasma resistin and TNF-α levels were confirmed. Real-time PCR studies showed that both forms of Eucommia leaf enhanced metabolic function across several organs, including diminishing ATP production (white adipose tissue), accelerating β-oxidation (liver) and increasing the use of ketone bodies/glucose (skeletal muscle), all of which may exert anti-obesity effects under HFD conditions. These findings suggest that chronic administration of either form of Eucommia leaves stimulates the metabolic function in rats across several organs. The anti-obesity and anti-metabolic syndrome activity in this rat model may be maintained through secretion and regulation of adipocytokines that depend on the accumulation of visceral fat to improve insulin resistance or hyperlipaemia.

Twenty-four plant lignans were analyzed by high-performance liquid chromatography-tandem mass spectrometry in bran extracts of 16 cereal species, in four nut species, and in two oilseed species (sesame seeds and linseeds). Eighteen of these were lignans previously unidentified in these species, and of these, 16 were identified in the analyzed samples. Four different extraction methods were applied as follows: alkaline extraction, mild acid extraction, a combination of alkaline and mild acid extraction, or accelerated solvent extraction. The extraction method was of great importance for the lignan yield. 7-Hydroxymatairesinol, which has not previously been detected in cereals because of destructive extraction methods, was the dominant lignan in wheat, triticale, oat, barley, millet, corn bran, and amaranth whole grain. Syringaresinol was the other dominant cereal lignan. Wheat and rye bran had the highest lignan content of all cereals; however, linseeds and sesame seeds were by far the most lignan-rich of the studied species.

The vascular effects of three extract preparations from Eucommia ulmoides Oliv., which is historically an active ingredient commonly used in antihypertensive herbal prescriptions in China, were investigated with isometric contraction using isolated rat aortic and dog carotid rings. Both aqueous extracts isolated from Eucommia leaf (L) and bark (B) concentration dependently caused endothelium-dependent relaxation in vessels precontracted with 1 μM phenylephrine (PE), but the methanol extract of the leaf (M) had no effect. Vessels precontracted with KCl and de-endothelialized vessels pre-contracted with PE were not affected by B or L. The endothelium-dependent relaxation evoked by B and L was either abolished or substantially inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB), indicating the involvement of the nitric oxide (NO) synthase pathway in the vasorelaxant action of B and L. The relaxation to the aqueous extract of Eucommia bark was not inhibited with 1 μM atropine, but was inhibited by 3-5 mM tetraethylammonium (TEA) and 3 mM 4-aminopyridine. This suggests that the endothelium-dependent, NO-mediated relaxation evoked by the aqueous Eucommia extracts was not mediated via the activation of endothelium muscarinic receptors and may involve the activation of K+ -channels. In smaller muscular artery, like rat mesenteric artery, the action of Eucommia extract also involves endothelium derived hyperpolarizing factor in addition to NO. Endothelium-dependent relaxation elicited by Eucommia extract also occur in dog carotid artery. This vasodilatory action of E. ulmoides Oliv. provides a pharmacological basis for its well-documented antihypertensive action.

The antihypertensive effects of the Eucommia ulmoides leaf extract (ELE) and its methanol-eluted fraction (MeOH ext, Eucommia leaf (EL) glycoside) and water-eluted fraction (H2O ext), fractionated using a Diaion HP-20 column, were studied in spontaneously hypertensive rats (SHR) by intravenous (i.v.) administration. Additionally, to clarify the oral antihypertensive effect, a single oral (p.o.) administration of ELE, MeOH ext, and H2O ext as well as geniposidic acid (GA) and chlorogenic acid (CA)—the major component of the ELE and MeOH ext—were performed in SHR. The i.v. administration of the ELE and MeOH ext showed significant transient antihypertensive effects, which were attenuated with atropine pretreatment in SHR, implying that the effect was mediated via an agonistic action on the muscarinic acetylcholine receptors. In a similar manner, p.o. administration of both ELE and MeOH ext showed significant antihypertensive effects. Although both the components also showed antihypertensive effects, the effect of GA was more potent than that of CA. On the other hand, the H2O ext showed a persistent antihypertensive effect with i.v. administration, which remained unaffected on atropine pretreatment, although such an effect was not observed with p.o. administration. The findings mentioned above imply that the MeOH ext (EL glycoside) contributes to the ELE-induced antihypertensive effect, with GA contributing more to the effect than CA.

To clarify the mechanisms underlying the antihypertensive effect of Luobuma (Apocynum venetum L. (Apocynaceae)) leaf extract (LLE), we investigated the vasodilator effect of LLE in the rat mesenteric vascular bed, which plays an important role in changes in peripheral resistance and thus the regulation of blood pressure. In the perfused mesenteric vascular bed with active tone and intact endothelium, perfusion of LLE (0.1 ng to 100 mg/ml for 15 min) caused dose-dependent vasodilation, which was abolished by chemical removal of the endothelial layer with perfusion of sodium deoxycholate, but not by N(G)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of nitric oxide (NO), which instead increased the effect. The LLE-induced vasodilation was partially inhibited by high K(+)-containing Krebs solution and tetraethylammonium (a K(+) channel blocker) and completely by the combination of L-NAME and high K(+)-Krebs solution. However, atropine (a muscarinic acetylcholine receptor antagonist) did not affect the vasodilation. These results suggest that the vasodilation induced by LLE is endothelium-dependent and mediated by endothelium-derived hyperpolarizing factor, which involves the activation of K(+)-channels. The higher concentrations of LLE may enhance NO production/release to cause vasodilation.

The vascular effects of three extract preparations from the Chinese medicinal herb, Eucommia ulmoides Oliv., which is historically an active ingredient commonly used in antihypertensive herbal prescriptions in China, were investigated with isometric contraction using isolated rat aortic and dog carotid rings. Both aqueous extracts isolated from eucommia leaf (L) and bark (B) concentration dependently caused endothelium-dependent relaxation in vessels precontracted with 1 microM phenylephrine (PE), but the methanol extract of the leaf (M) had no effect. Vessels precontracted with KCl and de-endothelialized vessels precontracted with PE were not affected by B or L. The endothelium-dependent relaxation evoked by B and L was either abolished or substantially inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB), indicating the involvement of the nitric oxide (NO) synthase pathway in the vasorelaxant action of B and L. The relaxation to the aqueous extract of eucommia bark was not inhibited with 1 microM atropine, but was inhibited by 3-5 mM tetraethylammonium (TEA) and 3 mM 4-aminopyridine. This suggests that the endothelium-dependent, NO-mediated relaxation evoked by the aqueous eucommia extracts was not mediated via the activation of endothelium muscarinic receptors and may involve the activation of K+ -channels. Results in this study have provided the first evidence on the in vitro vasorelaxant action of E. ulmoides Oliv. that forms the pharmacological basis for its well-documented antihypertensive action.

Wines have been studied a lot and several different groups of phenolic compounds have been analysed in wine samples, but lignans in wines have been only preliminary studied. In this study, we analysed 10 different wines of which eight were red wines and two white wines. Samples were selected among the most consumed wines in Finland in year 1999. Eight different lignans were analysed with HPLC using coulometric electrode array detector. The amount of lignans in red wines ranged from 0.812 to 1.406 mg/l. The main lignan in all studied wines was isolariciresinol and percentage amount of mammalian lignan precursors varied from 34 to 43% in the red wines. The amount of lignans was much lower in the studied white wines compared with the red wines.

The caulis (stem and leaf) of Trachelospermum jasminoides (Lindl.) Lem. (Apocynaceae) is listed as the plant origin of Luoshiteng in the Chinese Pharmacopeia. However, preparations from the caulis of Ficus pumila L. (Moraceae) or Psychotria serpens L. (Rubiaceae) are distributed on the Chinese market. The fruit of Forsythia suspensa Vahl (Oleaceae) is listed as the plant origin of Forsythia Fruit in the Chinese Pharmacopeia, although the fruits of two Forsythia species, F. suspensa and F. viridissima Lindley, are listed as the plant origins in the Japanese Pharmacopeia, and fruits of three Forsythia species, F. viridissima, F. koreana Nakai, and F. suspensa, are listed in the Korean Pharmacopeia. The whole plant of Plantago asiatica L. (Plantaginaceae) is listed as the plant origin of Plantago Herb in the Japanese Phamacopeia, but the whole plants of two Plantago species, P. asiatica and P. depressa Wild, are listed as the plant origins in the Chinese Pharmacopeia. The leaves of two Plantago species, P. lanceolata L. and P. major L., are distributed as Plantain on the European market. Each of these herbal medicines is reviewed based on the differences in plant origins and their quality evaluation from the viewpoints of the morphological properties, chemical components, and biological activities, respectively.

The plantain is used in herbal medicines and for pasturage. Two cultivars of plantain (Plantago lanceolata L.), Grasslands Lancelot and Ceres Tonic, were sown in spring. Changes in catalpol, aucubin, and acteoside concentrations in the leaves during the growing season and by drying after harvesting were quantitatively determined by high-performance liquid chromatography. The concentration of catalpol was relatively low, fluctuating between 1 and 2% of dry matter during the growing season, and there was no clear-cut seasonal change. From spring to midfall, the aucubin concentration increased from 2.1 to 4.8% in Grasslands Lancelot and from 1.0 to 2.7% in Ceres Tonic. These increases were gradual over the season, except for during midsummer, when aucubin concentrations were relatively constant. The acteoside concentration increased from 3.4 to 7.1% in Grasslands Lancelot and from 1.5 to 4.1% in Ceres Tonic over the course of the growing season, although in the summer it declined steadily to lows of 2.5% in Grasslands Lancelot and 1.9% in Ceres Tonic. Our data suggested that midfall was the appropriate time for harvesting plantain for medicinal use. The concentrations of the bioactive compounds steadily decreased in the initial stages of drying both under natural climatic conditions and at 60 degrees C. The development of processing methods to minimize the loss of bioactive compounds is imperative.

An extract of the leaves of Apocynum venetum L. (Apocynaceae) markedly shortened the immobility time of male rats in a forced swimming test (FST) in a dose range of 30-125 mg/kg, indicating a possible antidepressant activity. This effect was comparable to that of the tricyclic antidepressant imipramine (20 mg/kg). Neither imipramine (20 mg/kg) nor the Apocynum extract in various doses (30, 60, 125 mg/kg) produced any overt behavioural change or motor dysfunction in the open field test. This result confirms the assumption that the antidepressant effect of an Apocynum extract in the FST is specific. Further, it can be speculated that this effect might be related to hyperoside and isoquercitrin which are major flavonoids in the extract.

Chemopreventive effects of arctiin, a lignan isolated from Arctium lappa (burdock) seeds, on the initiation or post initiation period of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced mammary carcinogenesis in female rats and on 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-associated hepatocarcinogenesis in male rats were examined. In experiment 1, female Sprague-Dawley (SD) rats were given intragastric doses of 100 mg/kg body wt of PhIP once a week for 8 weeks as initiation. Groups of 20 rats each were treated with 0.2 or 0.02% arctiin during or after PhIP initiation. Control rats were fed 0.2 or 0.02% arctiin, or basal diet alone during the experimental period. Animals were killed at the end of week 48. Although the incidence of mammary carcinomas did not significantly differ among the PhIP-treated groups, multiplicity was significantly decreased in rats given 0.2 (0.7+/-0.7, P

1. Chemistry Eucommia ulmoides Oliver is a single species of the genus Eucommia which is the only genus in the family Eucommiaceae. The bark has been traditionally used in analgesics, tonics, and hypotensives in China. Moreover, the Chinese medical book “Bencao gangmu” describes fresh Eucommia leaf (EL) as being “consumed as a vegetable.” The product “Tochu-cha,” which is available in the Japanese markets and used in beverages, is roasted EL containing the iridoid glycosides: geniposidic acid and asperuloside, and a caffeic acid derivative: chlorogenic acid as its major ingredients. Eight iridoids, together with 14 known compounds were isolated from Eucommia leaf extract (ELE). The detailed investigation of the constituents of Eucommia green leaf powder (EGLP) led to the isolation of six iridoids, five flavonoids, and chlorogenic acid. Three additional new iridoids were obtained, two of which (eucomoside B and eucomoside C) were isolated by the condensation of geniposidic acid and amino acids (phenylalanine and tryptophan, respectively), whereas the third (eucomoside A) was determined to be an acetal compound with a linkage from C-3 of the iridoid to C-2 of the glucose unit, each being the first such natural compound described. 2. Bioactivities Spontaneously hypertensive rats fed ELE exhibited a dose-dependent antihypertensive effect. Moreover, follow-up studies have confirmed that ELE decreases systolic blood pressure in humans after long-term intake. These antihypertensive effects are presumed to be due to the activity of a so-called EL glycoside, which contains geniposidic acid as a major component. The extract from ELs containing EL glycoside is used as the food supplement in the food for specified health uses (FOSHU). Metabolic syndrome (MS)-like rats fed ELE or EGLP exhibited dose-dependent antiobesity and anti-MS effects. Both forms of ELs minimized increases in body weight and visceral fat in a dose-dependent manner. Concomitantly, an increase in plasma adiponectin levels and a suppression of plasma resistin and tumor necrosis factor α levels were demonstrated. The chronic administration of asperuloside isolated from ELs suppressed increases in body weight, white adipose tissue (WAT) weight, plasma triglyceride levels, and free fatty acid levels in a mouse model. Further, the chronic administration of asperuloside enhanced the basal metabolic rate in rats fed a high-fat diet (HFD) and significantly decreased respiratory quotientsmore than that in the HFD control group, suggesting an acceleration of lipid metabolism. Real-time PCR studies showed that ELE and asperuloside enhanced metabolic function in several organs, including the diminution of adenosine 5′-triphosphate production in WAT, the acceleration of β-oxidation in the liver, and an increase in the use of ketone bodies/glucose in skeletal muscle, all of which may exert antiobesity effects under HFD conditions due to novel mechanisms. To our knowledge, this is the first study showing the antiobesity effects of iridoid asperuloside. These findings are expected to result in new health applications of EL and the development of EL as a FOSHU.

A new guaiacylgycerol ether, threo and erythro guaiacylglycerol-8′-vanillic acid ethers were identified from fruits of Boreava orientalis. Structural elucidation was carried out on the basis of UV, mass, 1H and 13C NMR spectral data, including 2D shift correlation.

The structure of a new acylated flavonol glycoside from the leaf extract of Euphorbiamaculata was characterized as quercetin 3-O-(2″,3″-di-O-galloyl)-β-D-glucopyranoside. Four new hydrolyzable tannins together with twelve known tannins were also isolated and their structures were established by spectral and chemical means as 1,2,6-tri-O-galloyl-α-D-glucose, 1-O-galloyl-2,4;3,6-di-O-chebuloyl-β-D-glucose (eumaculin E), and dimers (eumaculins B and D) having a tergalloyl and a macaranoyl group as the linking unit of monomers, respectively. Keywords: Euphorbiamaculata, Euphorbiaceae, tannin, eumaculin B, eumaculin E.

Examination was made by the effects of antioxidative activity of phenolic compounds isolated from Boreava orientalis fruit (Cruciferae) and related compounds on free radical-oxidation of methyl linolate in solution. Based on methyl linolate hydroperoxide production using 2, 2'-azobis (2, 4-dimethyl valeronitrile) (AMVN) as the radical initiator. Dihydroxybenzoic acids and phenylpropanoids, particularly cinnamic acid derivatives, were shown to be strong antioxidatnts.

Acteoside (verbascoside) was isolated as an analgesic principle from Cedron (leaves and stem of Lippia triphylla (L'HER) O. KUNTZE; Verbenaceae), a Peruvian medicinal plant, by activity-guided separation. The compound exhibited analgesia on acetic acid-induced writhing and on tail pressure pain in mice by the oral administration of 300 mg/kg and 100 mg/kg, respectively. Acteoside also caused weak sedation by its effect on the prolongation of pentobarbital-induced anesthesia and on the depression of locomotion enhanced by methamphetamine. An intravenous injection of acteoside reduced the effective dose to 2 mg/kg by the writhing method. Thirteen related compounds were tested for the activity by intravenous and oral administration to obtain information on the active structure.

Two new dihydrobenzofuran lignanamides and three known dihydrobenzofuran lignans have been isolated from fruits of Boreava orientalis. The structures of the two new compounds were established as cis- and trans- (2 R ,3 S )-2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxybenzofuran-5-propen-1-ic(1,5-dimethyl)glutamate amide on the bases of chemical and spectral evidence, including NOE, 2D shift-correlation and HMBC NMR experiments.

Bioactive phenolic compounds in traditional medicines were investigated. Arctigenin, matairesinol, trachelogenin and nortrachelogenin from Caulis Trachelospermi, mauritianin from Herba Catharanthi, plantamajoside, acteoside and plantaginin from Plantago Herb, suspensaside, forsythiaside and (+)-pinoresin01 0-p-D-glucoside from Forsythia Fruit, and (+)- syringaresinol di-0-p-D-glucoside from Eleutherococcus, were respectively isolated and subjected to assays for their biological activities.

Eucommialeaves (Eucommia ulmoidesOliver) contain chlorogenic acid (a caffeic acid derivative) and geniposidic acid and asperuloside (ASP), iridoid glucosides used in beverages. We used a metabolic syndrome rat model, produced by feeding a 35 % high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of ASP. These effects were compared withEucommialeaf extract (ELE), the positive control, which exhibits anti-obesity effects. A total of six rats were studied for 3 months in five groups. ASP suppressed body weight, visceral fat weight, food intake and circulating levels of glucose, insulin and lipids, and increased the plasma adiponectin level in rats on a HFD. These effects are similar to those of ELE, except for the influence on the plasma glucose level. RT–PCR studies showed that ASP (like ELE with known anti-obesity effects) diminished isocitrate dehydrogenase 3α, NADH dehydrogenase flavoprotein 1 (Comp I) mRNA and fatty acid synthase levels (white adipose tissue), increased carnitine palmitoyltransferase 1α and acyl-CoA dehydrogenase, very-long-chain mRNA levels (liver), and increased Glut4, citrate synthase, isocitrate dehydrogenase 3α, succinyl CoA synthase, peroxisomal 3-ketoacyl-CoA thiolase, dihydrolipoamide succinyl transferase and succinate dehydrogenase mRNA levels (skeletal muscle) under HFD conditions. Interestingly, ASP administration resulted in significantly increased mRNA levels of uncoupling protein 1 (UCP1) in the brown adipose tissue of HFD-fed rats; ELE did not affect the expression of UCP1. The increased expression of UCP1 may be negated by many ingredients other than ASP in the ELE. These findings suggest that chronic administration of ASP stimulates anti-obesity and anti-metabolic syndrome activity in HFD-fed rats across several organs, similar to ELE administration; thus, ASP may be an important ingredient of ELE.

Ethnopharmacological relevance Apocynum venetum Linn. (Apocynaceae family), also called Luobuma, is a shrub which grows widely in the Xinjiang Autonomous Region of China. Its leaves are used in herbal tea for the treatment of hypertension, anxiety and depression. Animal studies have also shown that Apocynum venetum leaf extract (AVLE) also exerts anti-depressant and anti-anxiety activities. The effects of AVLE on neuronal tissues in vitro are not fully understood. Materials and methods Using the whole-cell voltage-clamp method, we studied the effects of AVLE on ion channels in cultured mouse neuroblastoma N2A cells. Results AVLE inhibited voltage-gated inward Na+ current in a reversible and concentration-dependent manner (half-inhibitory concentration was 18 μg/ml and maximum inhibition at 100 μg/ml). AVLE specifically promoted steady-state inactivation of Na+ channels but did not affect voltage-dependence of activation. The inhibitory effect was not use-dependent and was not affected by 300 μM L-NAME, suggesting that NO was not involved in the action of AVLE in neuronal cells. AVLE also had a mild inhibitory effect on voltage-gated K+ channels, but did not affect ATP-sensitive K+ channels. Conclusions Since voltage-gated Na+ and K+ channels are associated with neuronal excitability and therefore affect neurotransmission, the modulation of neuronal ion channels by AVLE may exert neuropharmacological effects. In particular, the inhibition of voltage-gated Na+ currents by AVLE may in part account for the psychopharmacological effects of this herbal remedy.

A new nonglycosidic secoiridoid, ligstral, and two new secoiridoid diglucosides, angustifolioside A [6″- O -(β- d -glucopyranosyl)-oleuropein] and angustifolioside B [6″- O -(β- d -glucopyranosyl)-ligstroside], were isolated from the methanolic extract of the leaves of Fraxinus angustifolia along with the two known secoiridoid glucosides, ligstroside and oleuropein. The chemical structures of the isolated compounds were established by chemical and spectral evidence.

Serum concentrations of arctiin, tracheloside, and their metabolites formed in the gastrointestinal tract were investigated in the rat. Arctiin or tracheloside was not detected in the serum after oral administration (200 mg/kg). In regard to their metabolites, each metabolite 1 (AM1, TM1), their genuine genins, appeared in the serum, and the serum concentration of arctiin metabolite 1 (AM1) reached its peak at 4 h and that of tracheloside metabolite 1 (TM1) reached its peak at 8 h. On the other hand, both metabolites 2 (AM2, TM2), which each possess a catechol moiety as reported previously, were not found in the serum. Now, we have studied the detection of their metabolites in the rat large intestinal contents after oral administration. It was revealed that all metabolites reported previously were certainly formed in rat gastrointestinal tract in vivo. Thus, we presumed a possibility that metabolite 2 was converted into metabolite 1 through C-3" methylation by catechol-O-methyltransferase (COMT) in rat liver. Each metabolite 2 was incubated with rat liver cytosol in the presence of S-adenosyl-L-methionine. It was proved that metabolite 2 was rapidly converted into metabolite 1 within 3 min. We suggest that arctiin or tracheloside was transformed to at least two metabolites in the gastrointestinal tract, and after absorption from the intestine, metabolite 2 was converted into metabolite 1 through methylation by COMT in the liver, and arctiin and tracheloside existed as metabolite 1, the genuine genin, in the blood stream.

Two new polyphenolic compounds, melitric acids A (2) and B (5), were isolated from the aboveground part of Melissa officinalis (Labiatae) and their structures, consisting of three caffeic acid units, were determined from chemical rections and spectral data. Rosmarinic acid (1) was also isolated.

Bioactive phenolic compounds in traditional medicines were investigated. Arctigenin, matairesinol, trachelogenin and nortrachelogenin from Caulis Trachelospermi, mauritianin from Herba Catharanthi, plantamajoside, acteoside and plantaginin from Plantago Herb, suspensaside, forsythiaside and (+)-pinoresin01 0-p-D-glucoside from Forsythia Fruit, and (+)- syringaresinol di-0-p-D-glucoside from Eleutherococcus, were respectively isolated and subjected to assays for their biological activities.

Two new phenylethanoid glycosides, ferruginoside A (3, 4-dihydroxy-β-phenylethoxy-O-β-D-glucopyranosyl-(1→6)-2-O-caffeoyl-β-D-glucopyranoside) and ferruginoside (3, 4-dihydroxy-β-phenylethoxy-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside) were isolated, along with the known compounds lugrandoside and trans-ferulic acid, from the aerial parts of D. ferruginea subsp. ferruginea. For structural elucidation of the isolates, chemical transformation (acetylation, methylation, alkaline hydrolysis), one and two dimensional (COSY, HMQC, HMBC, ROESY) NMR techniques and FAB-MS were used.

The caulis (stem and leaf) of Trachelospermum jasminoides (Lindl.) Lem. (Apocynaceae) is listed as the plant origin of Luoshiteng in the Chinese Pharmacopeia. However, preparations from the caulis of Ficus pumila L. (Moraceae) or Psychotria serpens L. (Rubiaceae) are distributed on the Chinese market. The fruit of Forsythia suspensa Vahl (Oleaceae) is listed as the plant origin of Forsythia Fruit in the Chinese Pharmacopeia, although the fruits of two Forsythia species, F. suspensa and F. viridissima Lindley, are listed as the plant origins in the Japanese Pharmacopeia, and fruits of three Forsythia species, F. viridissima, F. koreana Nakai, and F. suspensa, are listed in the Korean Pharmacopeia. The whole plant of Plantago asiatica L. (Plantaginaceae) is listed as the plant origin of Plantago Herb in the Japanese Phamacopeia, but the whole plants of two Plantago species, P. asiatica and P. depressa Wild, are listed as the plant origins in the Chinese Pharmacopeia. The leaves of two Plantago species, P. lanceolata L. and P. major L., are distributed as Plantain on the European market. Each of these herbal medicines is reviewed based on the differences in plant origins and their quality evaluation from the viewpoints of the morphological properties, chemical components, and biological activities, respectively.

Structural transformation of arctiin and tracheloside, major components of seeds of Arctium lappa and Carthamus tinctorius, were investigated using rat gastric juice (pH 1.2-1.5) and rat large intestinal flora in vitro. Quantitative analysis of lignans and their metabolites was carried out by high performance liquid chromatography. Both lignans were stable in rat gastric juice and arctiin was rapidly transformed to arctigenin in rat large intestinal flora, followed by conversion to the major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-butyrolactone. On the other hand, tracheloside also decreased dependently with time and was converted to trachelogenin and its major metabolite, 2-(3",4"-dihydroxybenzyl)-3-(3',4'-dimethoxybenzyl)-2-hydroxybutyrola ctone. These experiments suggest that in the course of metabolism of lignans, firstly a cleavage of the glycosidic bond occurred and then demethylation of the phenolic methoxy group in the alimentary tract followed.

The four known phenolic compounds, 3,4-dihydroxyphenethyl alcohol-6- O -caffeoyl-β- d -glucoside, acteoside (verbascoside), plantaginin and plantamajoside, and a new phenylpropanoid glycoside, hellicoside, were isolated from the aerial parts of Plantago asiatica , which is used in oriental medicine ‘Plantaginis Herba’. The structure of hellicoside was deduced from chemical and spectral evidence to be 3,4,7-trihydroxy-β-phenethyl- O -β- d -glucopyranosyl-(1 → 3)-4- O -caffeoyl-β- d -glucopyranoside. Plantamajoside and hellicoside showed high inhibition of cyclic AMP phosphodiesterase and 5-lipoxygenase. Acteoside showed high inhibition of lens aldose reductase.

Recent epidemiological studies have demonstrated that consumption of certain natural products can lower cancer risk in humans. For example, plant-derived lignans have been shown to exert chemopreventive effects against cancer in vitro and in vivo. In the present study, the effects of three such lignans, termed arctiin, arctigenin, and nordihydroguaiaretic acid (NDGA), on the proliferation of Helicobacter pylori and the prevention of H. pylori-associated gastric cancer were investigated in Mongolian gerbils. To examine the effects of arctigenin and NDGA on stomach carcinogenesis, specific pathogen-free male, 5-week-old gerbils were infected with H. pylori, administered 10 p.p.m. N-methyl-N-nitrosourea in their drinking water and fed diets containing various concentrations of lignans until they were killed after 52 weeks. At a dietary level of 0.25%, NDGA significantly decreased the incidence of gastric adenocarcinomas. Arctigenin, in contrast, failed to attenuate neoplasia at a level of 0.1%. Both NDGA and arctigenin significantly reduced serum 8-hydroxy-2'-deoxyguanosine levels at doses of 0.25 and 0.05% (NDGA), and 0.1% (arctigenin). Administration of 0.25% NDGA significantly suppressed the formation of intestinal metaplasia both in the antrum and the corpus. Although all three lignans dose-dependently inhibited the in vitro proliferation of H. pylori, there were no differences in the titers of anti-H. pylori antibodies or the amount of the H. pylori-specific urease A gene among all H. pylori-infected groups. These results suggest that NDGA might be effective for prevention of gastric carcinogenesis. The possible mechanisms appear to be related to inhibitory effects on progression of gastritis and antioxidative activity rather than direct antimicrobial influence.

Many Phenylethanoid glycosides were isolated from Cistanche Herb, produced from Cistanche deserticola, C. salsa, and other Cistanche plants, C. tubulosa, C. sinensis and C. phelypaea (Orobanchaceae). Cistanoside A-I and tubuloside A-E were isolated from C. deserticola and C. tubulosa, respectively, together with known phenylethanoid glycosides; echinacoside, acteoside and isoacteoside. They possessed rhamnosyl (1 → 3)glucosyl group. Suspensaside and forsythiaside, possessed rhamnosyl (1 → 6)glucosyl group, were isolated as main components from Forsythia suspensa (Oleaceae), not from F. viridissima. On the other hand, acteoside and β-hydroxyacteoside were isolated from F. viridissima as main components, not from F. suspensa. Plantamajoside, isoplantamajoside and hellicoside, possessed glucosyl (1 → 3)glucosyl group, were isolated from Plantago asiatica (Plantaginaceae) together with acteoside, β-oxoacteoside, β-hydroxyacteoside, and campenoside. Several phenylethanoid glycosides, forsythiaside, suspensaside, acteoside, β-hydroxyacteoside and plantamajoside, showed an antibiotic activity against Staphylococcus aureus. Forsythiaside, suspensa-side, plantamajoside and iso-plantamajoside showed a strong inhibitory activity against cAMP phosphodiesterase, whereas acteoside and β-hydroxyacteoside showed a weak activity. Plantamajo-side, hellicoside exhibited a strong inhibitory activity on arachidonic acid-induced mouse ear edema. Acteoside and isoacteoside showed a weak activity. Suspensaside showed a continuous hypotensive activity on spontaneously hypertensive rat (SHR).

SUMMARY 1. In the present study, a novel in vitro vascular relaxant effect of Apocynum venetum leaf extract (AVLE; also called ‘Luobuma’), obtained from a traditional Chinese medicinal herb with known antihypertensive effects, is reported in isometric contraction studies of rat aorta and superior mesenteric artery. At low concentrations (0.3–10 µg/mL), AVLE had no effect on the resting tension of either blood vessel and caused relaxation in agonist-precontracted vessels with functionally intact endothelium. 2. We demonstrated pharmacologically that the AVLE-induced vasorelaxation was mediated selectively by the endothelial cells in both blood vessels. Using NG-nitro-l-arginine methyl ester (l-NAME) and a low concentration of KCl (15 mmol/L), we also demonstrated that AVLE acted by releasing endothelium-derived relaxation factors; nitric oxide (NO) in the rat aorta and NO plus endothelium-derived hyperpolarizing factor in the rat mesenteric artery. 3. The vascular relaxation following brief exposure to AVLE appeared to persist even after subsequent prolonged washout; this was manifested as an attenuated contraction to subsequent application of phenylephrine (PE) compared with the PE-induced contraction after exposure to carbachol (CCh) and subsequent similar washout. The addition of l-NAME at this point in the absence of AVLE totally restored the contraction to PE, suggesting that enzymatic generation of endothelial NO persisted even after brief exposure to AVLE. 4. Unlike the endothelium-dependent NO-mediated relaxation induced by CCh, which is mediated by endothelial muscarinic receptors (and inhibited by atropine), the relaxation induced by AVLE was not inhibited by atropine and, thus, was not mediated by muscarinic receptors. However, similar to CCh-induced relaxation, AVLE-induced relaxation was associated with the activation of K+ channels. 5. These results provide a strong scientific basis for the folk use of AVLE decoction for antihypertensive therapy in traditional Chinese medicine.