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Gentianine is a metabolite of gentiopicroside and swertiamarin. Several biological activities have been reported for gentianine, such as antiinflammatory and antidiabetic activity, and hypotensive effect. Gentiopicroside is found in 0.9–9.8% content in Gentian root or Gentian scabra root, and Swertiamarin is contained in Swertia herb in 2–10%. These natural products can be potential starting materials for the synthesis of gentianine. This study describes the β-glucosidase-catalyzed hydrolysis of gentiopicroside and swertiamarin in the presence of hydroxylamine to afford gentianine N-oxide, which can be a synthetic precursor of gentianine derivatives. Enzymatic hydrolysis of swertiamarin selectively afforded gentianine N-oxide in 81% yield, whereas gentiopicroside afforded gentianine N-oxide and gentianol N-oxide. Plausible reaction pathways leading to gentianine, gentianol, and their N-oxides were also investigated.

In this study, melanogenesis inhibition in B16 cells by eight compounds, namely, tokorogenin, tokoronin, yononin, gracillin, proto-yonogenin, proto-tokoronin, proto-yononin, and proto-gracillin, isolated from Dioscorea tokoro Makino ex Miyabe were evaluated. The results of the cytotoxicity and α-MSH-induced melanogenesis inhibition effects of the eight compounds revealed that tokoronin was the most effective in terms of low-cytotoxicity and melanogenesis inhibition. Tokoronin downregulated α-MSH-induced melanogenesis via suppression of the expression of the three types of melanogenesis-related enzymes [tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2] by the inhibition of phospho-microphthalmia-associated transcription factor (p-MITF) and cAMP response element binding protein (CREB) levels. p-MITF and CREB are regulated by various kinases [Akt, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK)]. As the results of measurement of the combined effects of tokoronin with inhibitors or promoters of these kinases, no change in the biological activity of tokoronin by Akt inhibitor (wortmannin) or p38 MAPK inhibitor (SB202190) was observed, however, the effect of tokoronin was reduced by the MEK/ERK inhibitor (U0126) and promoted by the MEK/ERK activator (FGF2). Therefore, it was deduced that tokoronin first inactivated ERK; then, it suppressed p-MITF and CREB levels; and finally, α-MSH-induced melanogenesis was suppressed.

Many natural products that inhibit melanogenesis, freckles, and hyperpigmentation have been selectively used in cosmetics because melanogenesis is linked to the multiple biogenesis cascades of melanin synthesis. However, some of these compounds have side effects that may result in their restriction in the future. We report here the isolation and structural elucidation of compounds extracted from Mansonia gagei and evaluate their activity on melanogenesis inhibition. We isolated five known compounds from M. gagei and identified them as mansonone E (1), mansorin I (2), populene F (3), mansonone G (4), and mansorin B (5). After evaluating the five compounds for cytotoxicity against B16 cells and inhibitory activity on α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis, we determined that the cytotoxicity and melanogenesis-inhibitory effect of 1 were relatively low and high, respectively. Next, the effect of 1 on the expression of melanogenesis-related proteins was assessed; it was confirmed that 1 dose-dependently inhibited the expression levels of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) which were increased after stimulation by α-MSH. Furthermore, the effects of 1 on the phosphorylation levels of intracellular signaling pathway-related proteins were evaluated, and it was found that 1 dose-dependently rescued the phosphorylation of Akt and p38 mitogen-activated protein kinases (MAPK), which were up- or down-regulated after stimulation by α-MSH. In contrast, treatment with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin enhanced melanogenesis inhibition by mansonone E. Cumulatively, the data suggest that 1 suppresses α-MSH-induced melanogenesis in B16 cells by inhibiting both phosphorylation in the PI3K/Akt pathway and the expression of melanogenesis-related proteins.

Inclusion compounds (ICs) have the potential to act as drug carriers. In this study, an IC consisting of acetaminophen incorporated into 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) was synthesized ([CLPOT-acetaminophen]). Elemental analysis, 1H NMR spectroscopy and thermogravimetry-differential thermal analysis (TG-DTA), of the IC confirmed that ~0.1 acetaminophen molecules were included as guest molecules per CLPOT unit cell. The inclusion of acetaminophen in the 1D nanochannels of CLPOT was further confirmed by the DTA results of [CLPOT-acetaminophen], which showed the endothermal peak at 157 °C indicating the desorption of acetaminophen confined in the CLPOT nanochannels. These results suggest that CLPOT could be used as a stable microscopic carrier of biomaterials.

Based on NOE experiments, the structure of naphthodipyranodione from Gentianaceae plants was revised to 1,2-dihydro-4H,6H,8H-naphto[1,2-d:4,5- c'd']dipyrano-4,8-dione. Naphthodipyranodione was assumed to be formed by the degradation of gentiopicroside by enzymatic hydrolysis at low water -concentration. The degradation pathway was a unique domino-reaction triggered by enzymatic hydrolysis. Naphthodipyranodione may become an index compound for the drying and/or fermenting procedure of Gentian root.

Obesity is directly associated with cancer, cardiovascular injury, hypertension, and type 2 diabetes. To date, Yamamoto identified that hot water extracts of edible Chrysanthemum (EC) induced cell size reduction, up-regulation of adiponectin expression, and glucose absorption inhibition in 3T3-L1 cells during adipocyte differentiation. Furthermore, EC showed antidiabetic effects such as improvement in insulin resistance and the down-regulation of the blood glucose level and liver lipid content in type 2 diabetes model mice. In this study, we attempted to identify the antidiabetic components in EC. The methanol fraction from EC that showed relatively strong biological activity was purified by chromatography to obtain acacetin-7-O-glucoside, apigenin-7-O-glucoside, kaempferol-7-O-glucoside, and naringenin-7-O-glucoside. Among the isolated compounds and their aglycones, naringenin (NA) and naringenin-7-O-glucoside (NAG) up-regulated the intracellular accumulation of lipid and adiponectin-secretion and down-regulated the diameter of 3T3-L1 cells during adipocyte differentiation. Because the PPARγ antagonist BADGE and PI3K/Akt inhibitors wortmannin and LY29004 inhibited the intracellular lipid accumulation by NA and NAG associated with adipogenesis, it was considered that NA and NAG showed the above-mentioned activities via the activation of PPARγ as well as phosphorylation of the PI3K/Akt pathway.

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from Myanmar, induced adipogenesis similar to rosiglitazone (ROS), which is a TZD, in 3T3-L1 preadipocytes. In the present study, we attempted to isolate from V. trifolia those compounds that showed ROS-like effects. Among the extracts of hexane, ethyl acetate, and methanol obtained from V. trifolia, the ethyl acetate extract with the strongest ROS-like effects was purified by various chromatographic methods to obtain three known compounds: vitexilactone (1), vitexicarpin (2) and oleanolic acid (3). Among the isolated compounds, the ROS-like action of 1 was the strongest. The effects of 1 on 3T3-L1 cells during adipogenesis were compared with those of ROS. Both 1 and ROS increased lipid accumulation, the expression of adiponectin and GLUT4 in the cell membrane and decreased both the size of adipocytes and the phosphorylation of IRS-1, ERK1/2 and JNK in 3T3-L1 cells. In contrast, unlike ROS, the induction of proteins involved in lipogenesis was partial. ROS-like effects of 1 in 3T3-L1 cells were suppressed by the addition of bisphenol A diglycidyl ether (BADGE), one of a peroxisome proliferator-activated receptor γ (PPARγ) antagonists, suggesting that the action of 1 on adipocytes is mediated by PPARγ. From the results of the present study, it can be concluded that 1 is a novel insulin sensitizer candidate.

Five novel phenolic glycosides, adenophorasides A (1), B (2), C (3), D (4), and E (5), were isolated from commercial Adenophora roots, together with vanilloloside (6), 3,4-dimethoxybenzyl alcohol 7-O-beta-D: -glucopyranoside (7), and lobetyolin (8). The structures of the new compounds (1-5) were characterized as 4-hydroxy-3-methoxyphenylacetonitrile 4-O-beta-D: -glucopyranoside (1), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-beta-D: -glucopyranosyl-(1--6)-beta-D: -glucopyranoside (2), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-alpha-L: -rhamnopyranosyl-(1--6)-beta-D: -glucopyranoside (3), 4-hydroxyphenylacetonitrile 4-O-beta-D: -glucopyranosyl-(1--6)-beta-D: -glucopyranoside (4), and 4-hydroxy-3-methoxybenzyl alcohol 4-O-beta-D: -glucopyranosyl-(1--6)-beta-D: -glucopyranoside (5), respectively, by means of spectroscopic and chemical analyses.

First of all, this research demonstrated that university students have changed their understanding about older adults' competence for the better. The recent studies, incorporating the perspectives of life—span development, revealed that at least some part of intelligence continues to develop and maintain its capacity even after middle age. Aging does not necessarily deteriorate older adults' competence in all areas of life. The present study also cited the example of older adults, editing a “local community magazine” by gathering materials and rediscovering their community in Katsushika Ward in Tokyo. This example indicated that learning directly correlates with social participation, and such activities potentially create a situation in which this social participation provides further learning opportunities for the elderly. In order to transform negative notions about the elderly, we need the actual proof of social participation activities that demonstrate that older adults continue to play a significant role in supporting society. The author also emphasized the importance of a learning that includes the perspectives of human rights study, that aims at every generation to overcome ageism, and that enables communities to acquire a new understanding of older adults' capabilities.

Achyranthoside H methyl ester (AH-Me) is an oleanolic acid saponin derivative isolated from the roots of Achyranthes fauriei through diazomethane treatment. AH-Me exhibited significant cytotoxicity against human breast cancer MCF-7 and MDA-MB-453 cells, with respective ID(50) values of 4.0 and 6.5 muM: in the MTT assay. AH-Me is a unique saponin containing three methoxycarbonyl groups in the sugar moiety linked to the C-3 position of oleanolic acid. The demethylation of these methoxycarbonyl groups by alkaline hydrolysis caused a marked reduction of the cytotoxicity of AH-Me, suggesting that the methoxycarbonyl groups of AH-Me are key groups for the acquisition of cytotoxicity against human cancer cells. The staining of cancer cells with 4',6'-diamidino-2-phenylindole (DAPI) showed that the population of cells with altered nuclear morphology, for example chromatin condensation and fragmentation, increased markedly after AH-Me treatment. Exposure of MCF-7 and MDA-MB-453 cells to AH-Me resulted in a dose-dependent and time-dependent increase in the sub-G1 population, and in the cleavage of poly-ADP-ribose polymerase (PARP) followed by the formation of an 89 kD peptide. Pretreatment of the cells with the pan-caspase inhibitor z-VAD-fmk abolished the cleavage of PARP by AH-Me treatment and suppressed the antiproliferative effect of AH-Me on tumor cell growth. These results together led to the suggestion that AH-Me induces apoptosis via the caspase activation pathway in human breast cancer cells, and apoptosis is the major mode of the cytotoxic effect triggered by AH-Me.

Two oleanolic acid saponins named achyranthosides G (1) and H (2) were newly isolated from Achyranthes fauriei root as methyl esters in addition to methyl esters of achyranthosides A - F and five oleanolic acid glucuronides (chikusetsusaponins IVa, V, 28-deglucosyl chikusetsusaponin V, pseudoginsenoside RT(1), and oleanolic acid 3-O-beta-D-glucuronopyranoside) as well as oleanolic acid 28-O-beta-D-glucopyranoside, beta-ecdysterone, and polypodine B. Their structures were characterized as follows on the basis of the chemical and spectroscopic evidences.

We isolated and characterized 23 compounds, including a new iridoid named gentiolutelin and its dimethyl acetal, and a new lignan named gentioluteol from fresh roots (including small amounts of rhizome) of Gentiana lutea cultivated in Japan (Hokkaido). The structures of gentiolutelin and gentioluteol were determined as (1S,2R,3S,5R)-3-hydroxy-2-methyl-5-(2-oxoethyl)-cyclopentanecarboxylic acid methyl ester and (7R,8S,8′S)-4,4′,8,9-tetrahydroxy-3,3′,5-trimethoxy-7,9′-epoxylignan, respectively, on the basis of chemical and spectroscopic evidence. It was noteworthy that gentiopicroside, known to be a major secoiridoid glycoside in Gentian root, was not detected from the fresh roots of 3-year-old G. lutea.

rac-Hept-1-en-3-ol 4 was subjected to an enantioselective esterification in the presence of Novozyme 435 and vinyl crotonate as the acyl donor to give (3S)-oct-1-en-3-yl crotonate 7 in >99% ee and (3R)-alcohol 4 in 99% ee. The E-value of this enzymatic reaction was found to be >1000. The (S)-crotonic ester 7 was converted by ring-closing metathesis (RCM) using Grubbs’ catalyst to give (S)-oct-2-en-4-olide 1 in 96% yield while keeping the high enantiomeric excess.

Three known saponins, chiisanoside, 11-deoxyisochiisanoside, and isochiisanoside, and one novel saponin, 3,4-seco-4(23),20(29)-lupadiene-3,28-dioic acid 28-O-alpha-l-rhamnopyranosyl (1-->4)-beta-d-glucopyranosyl (1-->6)-beta-d-glucopyranoside, referred to as sessiloside, were isolated from a hot water extract of Acanthopanax sessiliflorus leaves. All of these saponins were lupane-type triterpene triglycosides, and their concentrations were 4.1, 1.0, 0.5, and 0.4% (w/w) of the total extract, respectively. Sessiloside and chiisanoside inhibited pancreatic lipase activity in vitro, and addition of the saponin-rich fraction to a high-fat diet suppressed the body weight gain of mice. The possibility of application of the lupane-type saponins from A. sessiliflorus leaves to the treatment of obesity is discussed.

Gentianae Radix, the dried root and rhizoma of Gentiana lutea L. (Gentianaceae), has long been used as a remedy for liver and stomach inflammation, eye troubles, etc. In this paper, the gastroprotective effects of the methanol extract of Gentian root (GM) were studied using different gastric lesion models. In pylorus-ligated rats, administration of GM in the duodenum suppressed gastric juice secretion and total acid output in a dose-dependent manner. Oral or duodenum administration of GM showed significant protection against acute gastric ulcer induced by aspirin plus pylorus ligation, water-immersion restraint stress-induced ulcers, and gastric mucosal injury induced by ethanol. Furthermore, four secoiridoid glycosides, amarogentin (A1), gentiopicroside (A2), amaroswerin (A3), and swertiamarin (A4), were obtained from Gentian root or Swertia herb, and their protective effects against stress-induced ulcers and ethanol-induced gastric mucosal injury were evaluated. The doses required for 50% inhibition (ID50) of A1, A3, and A4 on stress-induced ulcers were calculated to be 5.76, 2.58, and 167 mg/kg respectively. The protective effect of A2 at 250 mg/kg was 26.5%. On ethanol-induced gastritis, 5.0 mg/kg of A1 and A3 showed remarkable suppressive effects (33.7 and 45.4%, respectively), and 20 mg/kg of A4 exhibited a suppressive effect (30.8%). The effects of A1, A3, and A4 on ethanol-induced gastric lesions were canceled by 5.0 mg/kg indomethacin pretreatment. These results suggest that the therapeutic effects of Gentian root on gastric lesions are associated with enhanced mucosal defensive factors via the prostaglandin pathway in the cell membrane, and that secoiridoid glycosides contribute to this activity.

Five sulfonated compounds, namely 4-gingesulfonic acid and shogasulfonic acids A, B, C and D, were isolated together with seven known compounds including 6-gingesulfonic acid from Zingiberis rhizome (Japanese name: Shokyo) made out of ginger. Their structures were characterized by means of spectroscopic analysis.

Screening using a reporter under the control of the hypoxia-response element (HRE) identified several flavonoids and homoisoflavonoids that inhibit the activation of HRE under hypoxic conditions. Among various compounds, isorhamnetin, luteolin, quercetin, and methyl ophiopogonanone B (MOB) were effective at 3 to 9 microg/ml in inhibiting the reporter activity. The expression of vascular endothelial growth factor (VEGF) mRNA during hypoxia was also inhibited by MOB in HepG2 cells, but the effective doses were 10 to 20 microg/ml. MOB caused destabilization of hypoxia-inducible factor (HIF)-1alpha, as revealed by Western blotting, that was dependent on proteasome activity and the tumor suppressor, p53. The tubular formation and migration of human umbilical vein endothelial cells was also inhibited by MOB. MOB is expected to act as an inhibitor of angiogenesis.

Based on NOE experiments, the structure of naphthodipyranodione from Gentianaceae plants was revised to 1,2-dihydro-4 H,6 H,8 H-naphto[1,2-d:4,5-c'd']dipyrano-4,8-dione. Naphthodipyranodione was assumed to be formed by the degradation of gentiopicroside by enzymatic hydrolysis at low water concentration. The degradation pathway was a unique domino-reaction triggered by enzymatic hydrolysis. Naphthodipyranodione may become an index compound for the drying and/or fermenting procedure of Gentian root.

Five new triterpenoid saponins, nipponosides A-E (1, 3-6), were isolated from Acanthopanax nipponicus leaves, along with a known saponin, kalopanaxsaponin G (2). Nipponosides A-E were characterized as the 28-O-alpha-L-rhamnopyranosyl(1--4)-beta-D-glucopyranosyl(1--6)-beta -D-glucopyranosyl ester of 3-oxohederagenin, oleanolic acid 3-O-beta-D-glucopyranoside, gypsogenin 3-O-beta-D-glucopyranoside, 3beta,23,29-trihydroxyolean-12-en-28-oic acid, and 3beta,20alpha, 23-trihydroxy-30-nor-olean-12-en-28-oic acid, respectively. The structures of these new compounds were based on chemical and spectral methods.

Our previous report stated that kikyo-to, a Japanese herbal medicine, consisting of the roots of Platycodon grandiflorum and Glycyrrhiza sp., stimulates the pancreatic exocrine secretion of conscious rats. The present study focused on the effective components of kikyo-to and the mechanism of stimuli to pancreatic secretion of rats. When 10 to 100 mg of platycodin D, a saponin from the root of Platycodon grandiflorum, was intragastrically administered, the pancreatic secretion of rats was stimulated. At the same time, the plasma CCK concentration increased. On the other hand, the stimulative effects of glycyrrhizin, a saponin from the root of Glycyrrhiza sp. were weak compared to platycodin D. The effects of 10 mg/kg of platycodin D on pancreatic secretion were inhibited by loxiglumide (50 mg/kg, i.g.), a CCK receptor antagonist. In contrast, the suppressive effect of atropine (300 micrograms/kg/h, i.v.) on pancreatic secretion was reduced by administering 10 mg/kg of platycodin D. In addition, up to 1 mM of platycodin D did not inhibit the trypsin activities in vitro. In conclusion, kikyo-to serves to stimulate pancreatic exocrine secretion mainly because platycodin D causes gastrointestinal hormones, particularly, CCK to be released from the duodenum.

Further investigation of the leaves of Acanthopanax divaricatus gave two analogues of chiisanoside, which is a lupane triterpenoid oligoglycosyl ester. The structures were established as 28- O -α- l -rhamnopyranosyl(1 → 4)-β- d -glucopyranosyl(1 → 6)β- d -glucopyranosyl esters of 1β,11α-dihydroxy-3-oxo-lup-20(29)-en-28-oic acid and 1( R ),11α,22α-trihydroxy-3,4-seco-lupa-4(23),20(29)-diene-3,28-dioic acid 3,11α-lactone based on chemical and spectroscopic evidence. in biosynthetic terms, one is the precursor of chiisanoside and the other is an oxygenated derivative chiisanoside.

In a continuation of phytochemical studies on the underground organs of Liriope spicata var. prolifera, four new steroidal glycosides, lirioproliosides A-D, along with two known compounds, 25(S)-ruscogenin 1-O-[alpha-L-rhamnopyranosyl(1-->2)[beta-D-xylopyranosyl (1-->3)]-beta-D-fucopyranoside and ophiopogonin A, were identified. The structures of lirioproliosides A-D were established by a combination of spectroscopic and chemical methods as 25(S)-ruscogenin 1-O-[alpha-L-rhamnopyranosyl(1-->2)][beta-D-xylopyranosyl (1-->3)]-beta-D-fucopyranoside-3-O-alpha-L-rhamnopyranoside, 25(S)-ruscogenin 1-O-[3-O-acetyl-alpha-L-rhamnopyranosyl(1-->2)]-beta-D-fucopyranoside, 25(S)-ruscogenin (1-O-[2-O-acetyl-alpha-L-rhamnopyranosyl (1-->2)]-beta-D-fucopyranoside and ruscogenin (1-O-[2-O-acetyl-alpha-L-rhamnopyranosyl(1-->2)]-beta-D-fucopyranoside, respectively. Among these steroidal glycosides, ophiopogonin A and lirioprolioside B, and lirioproliosides C and D, were isolated as epimeric pairs.

Two monoterpene glycosides, tentatively named OJV-I (1) and OJV-II (2), and eight steroidal glycosides, tentatively named OJV-III (3), OJV-IV (4), OJV-V (5), OJV-VI (6), OJV-VII (7), OJV-VIII (8), OJV-IX (9) and OJV-X (10), were isolated from the butanol-soluble fraction of the fresh subterranean part of Ophiopogon japonicus KER-GAWLER cv. Nanus. Among these compounds, 1, 2, 3, 4, 5, 6 and 7 were identified as l-borneo1 O-beta-D-glucopyranoside, l-borneo1 O-beta-D-apiofuranosyl (1-->6)-beta-D-glucopyranoside, ophiopogonin B, glycoside C, ophiopogonin D, Ls-10, and ruscogenin 1-O-sulfate, respectively. The structures of compounds 8, 9, and 10 were established to be (23S,24S,25S)-23,24-dihydroxyruscogenin 1-O-[ alpha-L-rhamnopyranosyl(1-->2)] [beta-D-xylopyranosyl(1-->3)]-alpha-L-arabinopyranoside 24-O-beta-D-fucopyranoside, (23S,24S,25S)-23,24-dihydroxyruscogenin I-O-[alpha-L-2,3,4-tri-O-acetylrhamnopyranosyl(1-->2)][beta-D-xylo pyranosyl(1-->3)]-alpha-L-arabinopyranoside 24-O-beta-D-fucopyranoside, and (23S,24S,25S)-23,24-dihydroxyruscogenin 1-O-[alpha-L-2,3,4-tri-O-acetylrhamnopyranosyl(1-->2)] [beta-D-xylopyranosyl(1-->3)]=alpha-L-arabinopyranoside 24-O-beta-D-fucopyranoside, respectively.

Two novel triterpene glycosides, achyranthosides E and F, were isolated as methyl esters from the root of Achyranthes fauriei, an antiinflammatory medicinal plant. Their structures were characterized as oleanolic acid glucuronides having unique substituents composed of C6H9O5 and C9H15O7, respectively, at the C-3 position of glucuronic acid. These compounds are active components which can inhibit the excess recruiting of neutrophiles to injured tissues 1,000 times more potently than sialyl Lewis X.

Methylophiopogonanone B, a constituent of Ophiopogonis tuber, found to be a potent inhibitor of hypoxia induced factor-1α (HIF-1α) activity, was synthesized from 2,4,6-trihydroxy-3,5-dimethylacetophenone in 57% yield. The synthetic methylophiopogonanone B inhibited the reporter activity at 3 to 10 μg/mL.

The anxiolytic effects of four Kampo formulations (Japanese traditional herbal medicines): Tokishakuyakusan, Kamishoyosan, Keishi-bukuryogan, and Unkeito, were investigated. These Kampo formulations ware used to treat menopausal syndromes in women. Although the herbal ingredients of each Kampo formula are similar, clinical uses of these Kampo formulations are different. Therefore we investigate the differences of them from the basic pharmacological and chemical studies.

Steroid sponins and flavonoids of leavs of Phoenix rupicola T. ANDERSON, P. loureirii KUNTH, P. reclinate N. J. JACQUIN, and Arecastrum romanzoffianum BECCARI have been investigated. Tricin 7-O, β-D-glucopyranoside (I), vitexin (II), methyl proto-Pb (VII), methyl proto-taccaoside (26- O, β-D-glucopyranosyl (25R)-22-O-methyl-furost-5-en-3β, 26-diol 3-O-[α-L-rhamnopyranosyl-(1→2)][α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranoside, VI), and methyl proto-rupicolaside (26-O, β-D-glucopyranosyl (25R)-22-O-methy-furost-5-en-3β, 26-diol 3-O-[β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)][α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, VIII) from P. rupicola, II, glucoluteolin (III), orientin (IV), isoorientin (V), VII, VIII, and methyl proto-loureiroside (26-O-β-D-glucopyranosyl (25R)-22-O-methyl-furost-5-en-3β, 26-diol 3-O-[β-D-glucopyranosyl-(1→5)-α-L-arabinofu-ranosyl-(1→4)][α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside, IX) from P.loureirii, VII, VIII and methyl proto-reclinatoside (26-O-β-D-glucopyranosyl (25R)-22-O-methyl-furost-5-en-3β, 26-diol 3-O-[α-L-rhamnopyranosyl-(1→5)-α-L-arabinofuranosyl-(1→4)][α-L-rhamnopyranosyl(1→2)]-β-D-glucopyranoside, X) from P. reclinata, III and VII from A. romanzoffianum were isolated are identified. VI, VIII, IX and X were the first isolated and characterized from natural sources.

Seven steroidal glycosides, tentatively named glycosides Ls-1, Ls-2 (1), Ls-3 (2), Ls-4 (3), Ls-5 (4), Ls-6 (5) and Ls-7 (6) were isolated from the subterranean part of Liriope spicata (THUMB.) LOUR. var. prolifera Y. J. MA (Liliaceae) and three steroidal glycosides, tentatively named glycosides Lm-1, Lm-2 (7), Lm-3 (8) were isoalted from L. muscari (DECN.) BAILEY (Liliaceae). Glycosides Ls-1 and Lm-1 were identified as so-called β-sitosterol β-D-glucopyranoside. The structures of eight glycosides (1-8) were established as (25S)-ruscogenin 1-O-β-D-fucopyranosido-3-O-α-L-rhamnopyranoside (1)(=glycoside B from L. platyphylla WANG. et TANG.), (25S)-ruscogenin 1-O-β-D-xylopyranosido-3-O-α-L-rhamnopyranoside (2), (25S)-ruscogenin 1-O-α-L-rhamnopyranosyl(1→2)-β-D-xylopyranoside (3), (25S)-ruscogenin 1-O-[(2-O-acetyl)-α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-fucopyranoside (4), (25S)-ruscogenin 1-O-[(3-O-acetyl)-α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-fucopyranoside (5), yamogenin 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-glucopyranoside (6), ruscogenin 1-O-β-D-glucopyranosyl(1→2)-β-D-fucopyranoside (7) and ruscogenin 1-O-[β-D-glucopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-fucopyranoside (8), respectively.

Kamishoyosan (KSS), a Kampo formula used to treat menopausal psychotic syndromes in women, consists of ten crude herbal drugs. The anxiolytic effect of KSS was investigated by the social interaction (SI) test using mice, and whether the effect of KSS was due to the stimulating and/or sedating effects was examined by the open field locomotion test. Furthermore, the present study examined the effect of individual crude drugs in KSS by the SI test to clarify its active components. Oral administration of KSS increased the total SI time in a dose-dependent manner (50--200 mg/kg), but this effect was not observed over a dose of 300 mg/kg. On the other hand, there were no significant changes observed for the open field locomotion test. These results suggest that the appearance of KSS-induced SI behavior is due to an anxiolytic effect. The unaltered results of the open field test indicated that KSS was neither a stimulant nor sedative. To identify the essential herbs in KSS, the effects of "the component herbs in KSS" and "KSS minus one component herb" using the SI test were examined. An increase in the SI time was observed for hot water extracts of Menthae herba and Gardeniae Fructus, the same as for the KSS treatment. On the other hand the effect of KSS on the SI time was reduced to the control level for KSS minus Gardeniae Fructus, KSS minus Paeoniae Radix, KSS minus Glycyrrhizae Radix and KSS minus Hoelen. Oral administration of Gardeniae Fructus-extract or its common constituent, geniposide increased the SI time in a dose-dependent manner. These results indicate that Gardeniae Fructus and geniposide play a role in the anxiolytic effect of KSS.

Chinese medicines have been applied to a variety of diseases producing various favorable effects, possibly due to the interactions between individual components. Establishment of an evaluation method for such interactions may facilitate the production of new natural medicines. We investigated here the interaction of the hot water extract of Aconiti Tuber (one of the most prominent Chinese medicines) and that of Scutellariae Radix, Coptidis Rhizoma, Glycyrrhizae Radix, Atractylodesi, Lanceae Rhizoma or Poria, by measuring the superoxide anion (O2-), hydroxyl radical (OH) and nitric oxide (NO) scavenging activity, using ESR spectroscopy. We found that a 1:1 mixture of the hot water extract of one herb and that of another herb (referred to as a combined formula) showed a higher radical scavenging activity and cytotoxic activity than the hot water extract of a 1:1 mixture of two herbs (referred to as a blended formula). Both formulae showed higher cytotoxic activity against human oral tumor cell lines than against normal cells. These data further confirm the medicinal usefulness of combinations of empirical Chinese medicines.

The whole structure of platycodin D is found to be essential to stimulate the volumetric increase in the pancreatic exocrine secretion, while the prosapogenins prepared from platycodin D increased only protein output of pancreatic juice.

Eight new triterpenoid saponins, platyconic acids B (1), C (2), D (3), E (4), platycodins J (5), K (6), L (7) and platycosaponin A (8), were isolated from Platycodon Root, together with twelve known compounds, and they were characterized on the basis of their spectroscopic and chemical data.

Methylophiopogonanone B, a constituent of Ophiopogonis tuber, found to be a potent inhibitor of hypoxia induced factor-1α (HIF-1α) activity, was synthesized from 2,4,6-trihydroxy-3,5-dimethylacetophenone in 57% yield. The synthetic methylophiopogonanone B inhibited the reporter activity at 3 to 10 μg/mL.

Five monoterpene glycosides were isolated from Zingiberis rhizome (Japanese name: Shokyo). They were characterized to be (+)-angelicoidenol 2-O-β-D-glucopyranoside (1), (+)-angelicoidenol 2-O-β-D-glucopyranosido-5-O-β-D-glucopyranoside (2), (+)-angelicoidenol 2-O-β-D-apiofuranosyl(1→6)-β-D-glucopyranoside (3), (+)-angelicoidenol 2-O-[6'-O-S-3-hydroxy-3-methylglutaryl]-β-D-glucopyranoside (4) and its methyl ester (5), respectively, by means of spectroscopic and chemical methods. Of them, the new glycosides (2, 3 and 4) were named zingiberosides A, B and C, respectively.

Five steroidal compounds were isolated from the dried underground part of Aspidistra elatior BLUME (Liliaceae), and four of them were elucidated to be aspidistrin (diosgenin 3-O-β-lycotetraoside), proto-aspidistrin, methyl proto-aspidistrin, and 1β, 2β, 3β, 4β, 5β-pentahydroxyspirost-25 (27)-ene (Δ25 (27)-pentologenin or Δ25 (27)-neopentologenin), on the basis of physical and chemical investigations. The remaining steroidal compound is suggested to be a new spirostanol compound.

The constituents of the leaves, stems and underground parts of Chamaerops humilis L. and Trachycarpus wagnerianus BECC. (Palmae) have been investigated. We isolated and identified methyl proto-dioscin and methyl proto-Pb from the stems, dioscin, Pb, methyl proto-dioscin, methyl proto-Pb and methyl proto-rhapissaponin from the underground parts, and tricin 7-O-rutinoside and methyl proto-Pb from the leaves of C. humilis L. On the other hand, we isolated and identified methyl proto-dioscin and pseudoproto-dioscin from the stems, Pb, Tg, methyl proto-Pb and pseudoproto-Pb from the underground parts, and glucoluteolin, scolymoside, methyl proto-Pb and pseudoproto-Pb from the leaves of T. wagnerianus BECC. This is the first report of the isolation of tricin 7-O-β-rutinoside, Tg and pseudodiosgenin oligosides from Palmae plants, and also the first discovery of pseudosteroidal saponin from natural sources.

The constituents of the leaves, stems and underground parts of Trachycarpus fortunei (HOOK.) H. WENDL. (Palmae) have been investigated. Glucoluteolin (3), luteolin 7-O-rutinoside (=scolymoside, 4) and methyl proto-Pb (6) from the leaves, dioscin (1), Pb (2), methyl protodioscin (5) and methyl proto-Pb (6) from the stems, and dioscin (1) and methyl proto-Pb (6) from the underground parts were isolated and identified. This is the first report of the isolation of steroidal saponins from Palmae plants and these results are interesting from the standpoint of chemotaxonomy.

Isolement et identification des glycoides steroides et des flavonoides extraits des feuilles. Interet chimiosystematique

Further studies have been done on the constituents of the stems, underground parts and leaves of two Palmae plants, Rhapis exelsa HENRY and R. humilis BL. We isolated and identified dioscin, Pb, deltonin, methyl proto-dioscin, methyl proto-Pb and methyl proto-deltonin from the stems, dioscin, methyl proto-dioscin and methyl proto-Pb from the underground parts, and saponaretin (=isovitexin), methyl proto-dioscin, methyl proto-Pb and methyl proto-rhapissaponin from the leaves of R. exelsa. On the other hand, we isolated and identified prosapogenin A of dioscin, dioscin, deltonin, methyl proto-prosapogenin A of dioscin, methyl proto-dioscin and methyl protodeltonin from the stems, dioscin, methyl proto-prosapogenin A of dioscin, methyl proto-dioscin and methyl proto-Pb from the underground parts, and saponaretin, vitexin, isoorientin, methyl proto-prosapogenin A of dioscin, methyl proto-dioscin and methyl proto-Pb from the leaves of R. humilis. Methyl proto-rhapissaponin is a new furostanol saponin and its structure has been established to be 26-O-β-D-glucopyranosyl 22-O-methyl-25(R)-furost-5-en-3β, 22, 26-triol 3-O-[β-D-glucopyranosyl(1→4)-α-L-rhamnopyranosyl(1→4)]-[α-L-rhamnopyranosyl(1→2)]-β-D-glucopyranoside. This is the second report of the isolation of steroidal saponins from Palmae plants, and the results are interesting from the standpoint of chemotaxonomy.