Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans.

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.

Four novel withanolide-type steroids from the leaves of Solanum cilistum.

Four novel withanolide-type steroids named cilistols p, pm, p1 and u (1-4, respectively), were isolated from the leaves of Solanum cilistum. The respective structures were characterized by spectroscopic means as follows: cilistol p (1) was (22R,24R,25R,26S)-1-oxo-22,26-epoxy-3alpha,5alpha-cycloergostane-6beta,17alpha, 24,25,26-pentaol 26-O-beta-D-glucopyranoside, cilistol pm (2) corresponded to the 6-O-methyl ether derivative of 1; cilistol p1 (3) was represented as the 24-O-methyl ether of 1, and cilistol u (4) was shown to be the epoxide between C-24 and -25, presumably bearing cilistols p, pm and p1 by ring-opening.

DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants.

A reactive oxygen species has been implicated in a range of human pathological diseases such as atherosclerosis and certain cancers. Flavonoids are reported to exhibit various biological activities, including antioxidative and free radical scavenging activities. Several flavonoids obtained from barley leaves, soybean and some medicinal plants, Silybum marianum, Sophorae Flos, Cinnamon, Ephedrae Herba and Scutellariae Radix, were tested for their DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity. The structure-activity relationships suggested that not only the numbers of hydroxy group but also the position of hydroxy group might be important for mediating potent activity.

Four new halimane-type diterpenes, vitetrifolins D-G, from the fruit of Vitex trifolia.

Four new halimane-type (rearranged labdane-type) diterpenes, vitetrifolins D-G were isolated from the fruit of Vitex trifolia L. (Verbenaceae). Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence.

Na+,K(+)-ATPase inhibiting activity of cardiac glycosides from Erysimum cheiranthoides.

We previously reported the isolation of eleven new cardiac glycosides called cheiranthosides I-XI together with two known ones (olitoriside and erysimoside) from the seeds of Erysimum cheiranthoides L. The glycosides were evaluated for their inhibitory activity against Na+,K(+)-ATPase by comparing with typical cardiac glycosides. Two of them, cheiranthoside III and VIII, showed high inhibiting activity which was equivalent to that of digitoxin. Cheiranthoside XI containing a rhamnopyranosyl digitoxopyranosyl moiety and a carboxyl group showed the lowest activity which was similar to that of the inactive aglycone, strophanthidin. Some characteristics in the structure-activity relationship are also discussed.

Metabolism of chiisanoside from Acanthopanax divaricatus var. albeofructus by human intestinal bacteria and its relation to some biological activities.

The metabolic pathway of chiisanoside isolated from leaves of Acanthopanax divaricatus var. albeofructus (Araliaceae) by human intestinal bacteria and by the protein fraction of leaves of this plant were investigated, and the cytotoxic and anti-rotaviral activities of chiisanoside and its metabolite, chiisanogenin, were assayed. Chiisanogenin was produced as a main metabolite, when chiisanoside were incubated for 15 h with human intestinal bacteria. This metabolic pathway proceeded more potently with the protein fraction than with human intestinal bacteria. The in vitro cytotoxicity of chiisanogenin was superior to that of chiisanoside. H+/K+ ATPase was more potently inhibited by chiisanogenin than by chiisanoside. However, the anti-rotaviral activity of chiisanoside was more potent than that of chiisanogenin.

Structure-antinociceptive activity studies of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis.

Incarvillateine (1), a new monoterpene alkaloid carrying a characteristic cyclobutane ring, has been found to show significant antinociceptive activity in a formalin-induced pain model in mice. To investigate the correlation between its structure and antinociceptive activity, and especially to study whether a cyclobutane ring is necessary or not for expression of activity, we evaluated the antinociceptive activity of two constructive units of incarvillateine, such as a monoterpene unit (incarvilline, 3) and a phenylpropanoid unit (ferulic acid, 2) in the formalin test, and compared activity of the units with that of incarvillateine. Furthermore, in order to obtain more information about the structure-activity relationships, monoterpene alkaloid derivatives, such as incarvine C (5, a precursor of incarvillateine), incarvine A (4, an ester compound comprised of two monoterpene alkaloids and a monoterpene) and 3,3'-demethoxy-4,4'-dehydroxyincarvillateine (6, a synthetic new compound), were examined. The antinociceptive effect of 3,3'-demethoxy-4,4'-dehydroxyincarvillateine was equal to that of incarvillateine. Meanwhile, the other compounds exhibited no or weak activity. These results suggested that the cyclobutane moiety of incarvillateine plays an important role in expression of antinociceptive action.

Interaction of phytoestrogens with estrogen receptors alpha and beta.

The human estrogen receptor (hER) exists as two subtypes, hER alpha and hER beta, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER alpha or hER beta protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER beta than to hER alpha. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 beta-estradiol. Equol induces transcription most strongly with hER alpha and hER beta. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half the activity of 17 beta-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.

Ten new labdane-type diterpenes from the fruit of Vitex rotundifolia.

Ten new labdane-type diterpenes were isolated from the fruit of Vitex rotundifolia L. (Verbenaceae), along with a known diterpene, vitexilactone. Their chemical structures were determined on the bases of spectroscopic data.

Two novel actinidine-type monoterpene alkaloids from Incarvillea delavayi.

Two new actinidine-type monoterpene alkaloids, delavayines B (1) and C (2), were isolated from the MeOH extract of the aerial parts of Incarvillea delavayi, a close species of which, I. sinensis, is used as an analgesic for rheumatic pain in China, and the structures have been elucidated on the basis of spectroscopic evidence.

Effects of triterpenoids from Pueraria lobata on immunohemolysis: beta-D-glucuronic acid plays an active role in anticomplementary activity in vitro.

The anticomplementary properties of kaikasaponin III (4) and soyasaponin I (8) from Pueraria lobata and their hydrolytic analogs were investigated in vitro. Diglycosidic saponins [kaikasaponin I (3), soyasaponin III (7)] showed most potent anticomplementary activities, followed by monoglycosidic saponins [soyasapogenol B monoglucuronide (6), sophoradiol monoglucuronide (2)] and triglycosidic saponins [soyasaponin I (8), kaikasaponin III (4)], whereas sophoradiol (1) and soyasapogenol B (5) showed enhancement of hemolysis under the presence of serum on the classical pathway of complement system. But all of them showed very weak or no anticomplementary activities on the alternative pathway of complement system. The anticomplementary activity of the saponins was influenced by the nature of glucuronic acid, where the free acid forms (-COOH) showed much more potent activity than the sodium salt forms (-COO-Na+) or methyl ester forms (-COOCH3), and the reduced forms (-CH2OH) decreased the activity significantly.

Benzophenone C-glucosides from Polygala telephioides.

Three novel benzophenone C-glucosides, 3'-C-beta-D-glucopyranosyl-2',4',6',3-tetrahydroxy-4-methoxybenzophen one, 3'-C-beta-D-glucopyranosyl-2',4',6'-trihydroxy-3,4-dimethoxybenzophen one and 4'-C-beta-D-glucopyranosyl-2',3',5',6',3-pentahydroxybenzophenone, named telephenones A, B, and C were isolated from the whole plant of Polygala telephioides WILLD and their structures determined by analysis of spectroscopic data.

Three oligosaccharide esters, telephioses A-C, from Polygala telephioides.

Three new oligosaccharide esters named telephioses A-C, were isolated from Polygala telephioides WILLD. and their structures were characterized by spectroscopic data.

Four new triterpene glycosides from Thalictrum squarrosum.

Four new triterpene glycosides were isolated from the dried aerial parts of Thalictrum squarrosum (Ranunculaceae). They were designated as squarroside I, being a cycloartane-type glycoside, and squarrosides II, III and IV, being oleanene-type glycosides. Their structures were established by using two dimensional (2D) NMR techniques.

Eudesmane derivatives from Tessaria integrifolia.

Five eudesmane-type sesquiterpenoids were isolated from the methanol extract of the aerial part of Tessaria integrifolia Ruiz. et Pavon (Compositae). Their structures were elucidated on the basis of spectroscopic analysis is well as chemical evidence.

A new oleanene glucuronide obtained from the aerial parts of Melilotus officinalis.

A new oleanene glucuronide called melilotus-saponin O2 (1) was isolated together with three known ones (soyasaponin I, astragaloside VIII, wistariasaponin D) from the aerial parts of Melilotus officinalis (L.) Pallas (Leguminosae). The structure of 1 was determined to be 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl- (1-->2)-beta-D-glucuronopyranosyl melilotigenin by spectroscopic and chemical methods.

Cardiac glycosides from Erysimum cheiranthoides.

Two new cardiac glycosides called cheiranthosides VI (2) and VII (3) were isolated together with a known one, glucoerysimoside (1) from the seeds of Erysimum cheiranthoides. Based on spectroscopic data, the structures of 2 and 3 were characterized as periplogenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-fucopyranoside and periplogenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-antiaropyranoside, respectively.

Anti-herpes virus activity of Solanum steroidal glycosides.

Since some Solanum-genus plants have traditionally been used for anti-cancer and anti-herpes agents from olden times, we examined anti-herpes simplex virus type 1 (HSV-1) activity of typical steroidal glycosides with the frameworks of spirostane (including nuatigenin glycoside), furostane, solasodane, tomatidane and ergostane (including dimer) obtained from Solanum plants. Among these steroidal glycosides, the spirostanol glycosides were most effective. An inclination was observed for the potency of activity to decrease in the order of spirostane, tomatidane, ergostane, solasodane, nuatigenin type, dimer of ergostane and furostane. It was also suggested that the activity depends on the kind of oligosacchride moiety.

Antinociceptive substances from Incarvillea delavayi.

Antinociceptive activities of an Incarvillea delavayi extract, as well as its constituents, 8-epideoxyloganic acid and delavayine A, were evaluated in the acetic acid induced writhing test in mice. An oral administration of the delavayi extract weakly decreased the number of writhings and stretchings in this test, in a dose-dependent manner. Furthermore, orally administered 8-epideoxyloganic acid showed weak antinociceptive activity, whereas administration by subcutaneous injection did not. However, subcutaneous injection of delavayine A, a novel monoterpene alkaloid, showed a more significant level of antinociceptive activity.

New 3,4-seco-lupane-type triterpene glycosides from Acanthopanax senticosus forma inermis.

Four new 3,4-seco-lupane-type triterpene glycosides (1-4) were isolated from the leaves of Acanthopanax senticosus forma inermis. The structures of 1-4 were established as 11alpha-hydroxy-3, 4-seco-lup-4(23),20(30)-dien-3-oic acid methyl ester 28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-be ta-D-glucopyranoside, designated as inermoside (1); 1-deoxychiisanoside (2); 24-hydroxychiisanoside (3); and 11-deoxyisochiisanoside (4) by (1)H-(1)H COSY and (1)H-(13)C COSY(HMBC, HMQC) methods and FABMS.