Hepatoprotective and neuroprotective tocopherol analogues isolated from the peels of Citrus unshiu Marcovich.

Three tocopherol analogues methoxytocopherol (1), α-tocopherol (2) and γ-tocopherol (3) were isolated from the peels of Citrus unshiu Marcovich. The protective effects of the isolated compounds against tert-butyl hydroperoxide-induced hepatotoxicity in human liver-derived HepG2 cells and glutamate-induced oxidative stress in HT22-immortalised hippocampal cells were evaluated. Compounds 1-3 were significantly protective in HepG2 cells with EC50 values of 21.22 ± 2.01, 25.21 ± 2.11 and 25.25 ± 1.21 µM, respectively, and in HT22 cells, compounds 1-3 had EC50 values of 20.62 ± 1.36, 6.44 ± 1.65 and 9.52 ± 1.54 µM, respectively.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens.

Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS. Antibacterial activity of kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method. MIC of kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml. The bactericidal test showed that kuwanon G completely inactivated S. mutans at the concentration 20 microg/ml in 1 min. Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis. Transmission electron microscopy (TEM) of kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm.

The temporal alteration of GAD67/GAD65 ratio in the gerbil hippocampal complex following seizure.

In the present study, the distribution of glutamic acid decarboxylase (GAD) isoforms in the hippocampus of the Mongolian gerbil and its association with different sequelae of spontaneous seizure were investigated to identify the roles of balance of GAD isoforms in the epileptogenesis and the recovery mechanisms in these animals. The GAD67/GAD65 ratio in the hippocampus of pre-seizure seizure sensitive (SS) gerbil was approximately 3.5-fold higher as compared to seizure resistant (SR) gerbil. Following seizure, this ratio shifted to the level of SR gerbils up to 12 h postical. Therefore, the mismatched GAD67/GAD65 ratio (imbalance of GAD isoform expressions) in the hippocampus of SS gerbil implies that GABAergic neurons may be highly activated in order to regulate the increased neuronal excitability. In addition, the alteration in this ratio after seizure may be the compensatory response for reduction of epileptic activity in this animal.

In vitro anti-Helicobacter pylori activity of panaxytriol isolated from ginseng.

This study investigated the effect that some polyacetylenes and protopanaxatriol, which were isolated from heated ginseng (family Araliaceae), have on inhibiting Helicobacter pylori (HP) growth. Among the compounds tested, panaxytriol was quite effective in inhibiting HP growth with an MIC of 50 microg/ml. Ginsenoside Rh1 and protopanaxatriol weakly inhibited H+/K+-ATPase from a rat stomach.

Furanocoumarins from the root of Angelica dahurica.

Five furanocoumarins including a new one were isolated from the root of Angelica dahurica by repeated silica gel column chromatography. Their chemical structures were determined to be isoimperatorin (1), oxypeucedanin hydrate-3"-butyl ether (2), imperatorin (3), knidilin (4), and oxypeucedanin hydrate (5). This represents the first study in which the compound 2 has been isolated and identified. The long-range coupling (5J) in the 1H-NMR spectrum observed in the linear furanocoumarin skeleton was also investigated in detail.

Anticonvulsant compounds from the wood of Caesalpinia sappan L.

80% Aqueous MeOH extracts from the wood of Caesalpinia sappan, which showed remarkable anticonvulsant activity, were fractionated using EtOAc, n-BuOH, and H2O. Among them, the EtOAc fraction significantly inhibited the activities of two GABA degradative enzymes, succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR). Repeated column chromatographies for the fraction guided by activity test led to the isolation of the two active principal components. Their chemical structures were determined to be sappanchalcone and brazilin based on spectral data. The pure compounds, sappanchalcone (1) and brazilin (2), inactivated the SSAR activities in a dose dependent manner, whereas SSADH was inhibited partially by sappanchalcone and not by brazilin.

alpha-Glycosidase inhibitory activity of hexagalloylglucose from the galls of Quercus infectoria.

Hexagalloylglucose (3-O-digalloyl-1,2,4,6-tetra-O-galloyl-beta-D- glucose), which was isolated from the methanol extract of the galls of Quercus infectoria, significantly inhibited alpha-glycosidases such as sucrase, maltase and isomaltase. Its inhibitory activity was comparable to acarbose being used as a hypoglycemic agent, while the inhibitory activity on alpha-amylase was approximately 10 times lower than that of acarbose. The results indicate that, when compared to acarbose, hexagalloylglucose might reduce the side effects by reducing inhibition of alpha-amylase.

New cytotoxic butanolides from Lindera obtusiloba BLUME.

Three new butanolides, 2-(1-methoxy-11-dodecenyl)-penta-2,4-dien-4-olide (1), (2Z,3S,4S)-2-(11-dodecenylidene)-3-hydroxy-4-methylbutano lide (2) and (2E,3R,4R)-2-(11-dodecenylidene)-3-hydroxy-4-methoxy-4-methylbu tanolide (3), were isolated from the stems of Lindera obtusiloba BLUME. Their chemical structures were assigned by spectroscopic evidence. They exhibited cytotoxicity against cultured human tumor cell lines with their ED50 values ranging from 3.19 to 14.63 microg/ml.

Acyl-CoA: cholesterol acyltransferase inhibitory activity of ginseng sapogenins, produced from the ginseng saponins.

Ginseng sapogenins were produced from ginseng saponins, isolated from Korean ginseng roots. Ginseng saponins very mildly inhibited acyl-CoA:cholesterol acyltransferase (ACAT) in vitro, however, the sapogenins showed strong inhibitory activity on microsomal ACAT. Therefore, the sapogenins will be one of key ingredients of ginseng affected a lowering of the serum total cholesterol level.

Isolation and identification of succinic semialdehyde dehydrogenase inhibitory compound from the rhizome of Gastrodia elata Blume.

In our search for the anticonvulsant constituent of Gastrodia elata repeated column chromatographies guided by activity assay led to isolation of an active compound, which was identified as gastrodin on the basis of spectral data. Brain succinic semialdehyde dehydrogenase (SSADH) was inactivated by preincubation with gastrodin in a time-dependent manner and the reaction was monitored by absorption and fluorescence spectroscopic methods. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of 1.2 x 10(3) M-1min-1. The time course of the reaction was significantly affected by the coenzyme NAD+, which affected complete protection against the loss of the catalytic activity, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme. It is postulated that the gastrodin is able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on one of the GABA degradative enzymes, SSADH.

Noncariogenic intense natural sweeteners.

There is a definite relationship between the dietary consumption of sucrose and the incidence of dental caries. Noncaloric sucrose substitutes for use in the sweetening of foods, beverages, and medicines may be either synthetic compounds or natural products. In the United States, four potently sweet artificial sweeteners are approved, namely, saccharin, aspartame, acesulfame potassium, and sucralose. Highly sweet plant constituents are used in Japan and some other countries, including the diterpene glycoside stevioside and the protein thaumatin. Recent progress in a research project oriented towards the discovery and evaluation of novel potentially noncariogenic sweeteners from plants has focused on substances in the sesquiterpenoid, diterpenoid, triterpenoid, steroidal saponin, and proanthocyanidin structural classes. The feasibility of using Mongolian gerbil electrophysiological and behavioral assays to monitor the sweetness of plant extracts, chromatographic fractions, and pure isolates has been investigated. An in vivo cariogenicity study on the commercially available natural sweeteners stevioside and rebaudioside A has been carried out.

Four new cytotoxic germacranolides from Carpesium divaricatum.

In a bioassay-guided search for cytotoxic compounds from higher plants of South Korea, four new sesquiterpenes of the germacranolide type, named cardivins A (1), B (2), C (3), and D (4), have been isolated from the aerial parts of Carpesium divaricatum. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds 1, 2, 3, and 4 showed cytotoxicity to the human tumor cells, A-549 (nonsmall cell lung), SK-OV-3 (ovary), SK-MEL-2 (skin), XF-498 (central nervous system), and HCT-15 (colon).

Anticomplementary activity of ergosterol peroxide fromNaematoloma fasciculare and reassignment of NMR data.

A very high content (at least 0.23%) of ergosterol peroxide was isolated fromNaematoloma fasciculare Karst. Not only ergosterol peroxide but also ergosterol showed very strong anticomplementary activity on the classical pathway, the IC(50) values being 5.0 muM and 1.0 muM, respectively. The(1)H and(13)C NMR data of ergosterol peroxide were revised and completely assigned by DEPT,(1)H-(1)H COSY, HMQC and HMBC correlations.

Ginsenoside Rs(3), a genuine dammarane-glycoside from Korean red ginseng.

A genuine dammarane-glycoside, named as ginsenoside Rs(3), was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6''-O-acetyl-beta-D-glucopyranosyl (1-->2)-beta-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.

Indonesian medicinal plants. XIX. 1) Chemical structures of four additional resin-glycosides, mammosides A, B, H1, and H2, from the tuber of Merremia mammosa (Convolvulaceae).

Four new resin-glycosides, named mammosides A (10), B (11), H1 (12), and H2 (13), were isolated from the tuber of Merremia mammosa (Convolvulaceae), a Jamu raw material. Their chemical structures have been elucidated on the bases of chemical and physicochemical evidence, including synthesis of a glycosidic acid designated as mammoside I.

Synthesis of ginsenoside Rg3, a minor constituent of Ginseng radix.

Glycosylation of 12beta-acetoxy-dammar-24-en-3beta,20(S)-diol (4), with hepta-O-acetyl-alpha-sophorosyl bromide (5) under catalysis by Ag2CO3 or Ag2O afforded a chromatographically unseparated mixture of the alpha- and beta-linked octaacetates 6 and 7 in an approximately 2.5:1 ratio. After deprotection and chromatographic purification, the free alpha- (8) and beta-glycosides (9) were obtained. Sophoroside 9 was identical in all respects with ginsenoside Rg3, the minor component of Ginseng Radix rubra. All compounds were fully characterized by 1H and 13C NMR spectroscopy.

Indonesian medicinal plants. XV. Chemical structures of five new resin-glycosides, merremosides a, b, c, d, and e, from the tuber of Merremia mammosa (Convolvulaceae).

Five new resin-glycosides, named merremosides a (1), b (2), c (3), d (4), and e (5), were isolated from the tuber of Merremia mammosa (LOUR.) HALLIER f. (Convolvulaceae), an Indonesian medicinal plant. The structures of 1, 2, 3, 4, and 5 have been elucidated on the basis of chemical and physiochemical evidence, including syntheses of (11S)-(+)- and (11R)-(--)-jalapinolic acid (16b and 18b) and the glycosidic acid designated as merremoside i (6).

Indonesian medicinal plants. XVI. Chemical structures of four new resin-glycosides, merremosides f, g, h1, and h2, from the tuber of Merremia mammosa (Convolvulaceae).

Four new resin-glycosides named merremosides f (6), g (7), h1 (8), and h2 (9) were isolated from the tuber of Merremia mammosa (Lour.) Hallier f. (Convolvulaceae), an Indonesian medicinal plant. Their chemical structures have been elucidated on the bases of their chemical and physicochemical properties.