Constituents of compositae plants. 2. Triterpene diols, triols, and their 3-o-fatty acid esters from edible chrysanthemum flower extract and their anti-inflammatory effects.

The n-hexane soluble and the nonsaponifiable lipid fractions of the edible flower extract of chrysanthemum (Chrysanthemum morifolium) were investigated for triterpene diol and triol constituents. These triterpenes occur as the 3-O-fatty acid esters in the n-hexane soluble fraction from which 26 new and 6 known fatty acid esters were isolated and characterized. From the nonsaponifiable lipid fraction, 24 triterpene diols and triols were isolated, of which 3 were new compounds: (24S)-25-methoxycycloartane-3beta,24-diol (11), (24S)-25-methoxycycloartane-3beta,24,28-triol (22), and 22alpha-methoxyfaradiol (23). Faradiol (9) and heliantriol C (19), present in the nonsaponifiable lipid fraction and as the 3-O-palmitoyl esters in the n-hexane soluble fraction, were the most predominant triterpene diol and triol constituents. Fourteen triterpene diols and triols and 9 fatty acid esters were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. All of the triterpenes examined showed marked inhibitory activity, with a 50% inhibitory dose (ID50) of 0.03-1.0 mg/ear, which was more inhibitive than quercetin (ID50 = 1.6 mg/ear), a known inhibitor of TPA-induced inflammation in mice.

Antiallergic agent from natural sources. 2. Structures and leukotriene release-inhibitory effect of torososide B and torosachrysone 8-O-6"-malonyl beta-gentiobioside from Cassia torosa Cav.

Two new anti-allergic compounds, torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were isolated from the seeds of Cassia torosa Cav., and their structures were established as physcion 8-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl- (1-->3)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and torosachrysone 8-O-beta-D-glucopyranosyl-(1-->6)-6-malonyl beta-D-glucopyranoside on the basis of spectral and chemical evidence. Torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were found to inhibit the release of leucotrienes from rat peritoneal mast cells induced by calcium ionophore A 23187.

Limonoids from fruit of Melia toosendan and their cytotoxic activity.

Two new limonoids, toosendanal and 12-O-methylvolkensin, were isolated from the fruits of Melia toosendan Sieb. et Zucc. along with three known limonoids, meliatoxin B1, trichillin H, and toosendanin. The structures of the new limonoids were established by spectroscopic methods, with toosendanal having C-1/C-29 and C-19/C-29 acetal bridges. Both meliatoxin B1 and toosendanin exhibit cytotoxic activity against KB cells.

Antiallergic agent from natural sources. Structures and inhibitory effect of histamine release of naphthopyrone glycosides from seeds of Cassia obtusifolia L.

Two new naphthopyrones, cassiasides B2 (1) and C2 (2), were isolated from the seeds (Cassiae Semen) of Cassia obtusifolia L. The structures of the two new compounds 1 and 2 were established as rubrofusarin 6-O-beta-D- glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl-(1-->3)-O-beta-D- glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside and toralactone 9-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl- (1-->3)-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside, respectively, on the basis of spectral and chemical evidence. Compound 2 was found to inhibit the histamine release from rat peritoneal exudate mast cells induced by antigen-antibody reaction.

Inhibitory effect of cycloartenol ferulate, a component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin.

Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice was observed in the methanol extract of rice bran and gamma-oryzanol. The active components of rice bran, sitosterol ferulate, 24-methylcholesterol ferulate, cycloartenol ferulate and 24-methylenecycloartanol ferulate inhibited markedly the TPA-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.2-0.3 mg/ear. Furthermore, cycloartenol ferulate markedly inhibited the tumor-promoting effect of TPA in 7,12-dimethylbenz[a]anthracene-initiated mice.

3 beta-p-hydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effect.

The structure of a new triterpene derivative isolated from Poria cocos was determined to be 3 beta-p-hydroxybenzoyldehydrotumulosic acid by spectral and chemical methods. 3 beta-p-hydroxybenzoyldehydrotumulosic acid showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)- and arachidonic acid (AA)-induced ear inflammation in mice. The 50% inhibitory doses of 3 beta-p-hydroxybenzoyldehydrotumulosic acid were 0.27 and 1.25 mg per ear on TPA- and AA-induced inflammation, respectively.

Inhibitory effect of heliantriol C; a component of edible Chrysanthemum, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two hydroxy taraxastane-type triterpenes, faradiol and heliantriol C, have been isolated from the ligulate flowers of Chrysanthemum morifolium Ramat. var. sinense Makino fa. esculentum Makino, the edible Chrysanthemum. These compounds showed strong inhibitory activity against 12-O-tetradecanoyl-phorbol-13-aetate (TPA)-induced inflammation in mice. At 0.2 µmol/mouse, these compounds markedly inhibited the promoting effect of TPA (1 µg/mouse) on skin tumor formation followed by 7,12-dimethylbenz[a]anthracene (50 µg/mouse).

Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects.

Eleven tabular and nine ligulate flowers from 15 species of Compositae plants were investigated for their triterpene alcohol constituents. This led to the isolation and identification of 11 triterpene alcohols as follows: heliaol, taraxasterol, psi-taraxasterol, alpha-amyrin, beta-amyrin, lupeol, taraxerol, cycloartenol, 24-methyl-enecycloartanol, tirucalla-7,24-dienol and dammaradienol. The tabular flowers of Calendula officinalis, Carthamus tinctorius, Cosmos bipinnatus, Chrysanthemum morifolium, Helianthus annuus and Matricaria matricarioides showed a characteristic feature by containing helianol as the most predominant component (29-86%) in the triterpene alcohol fractions. The triterpene alcohols from Compositae flowers were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation (1 microgram per ear) in mice. All of these showed marked inhibitory activity, and their 50% inhibitory dose was 0.1-0.8 mg per ear.

Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Pachymic acid, 3-O-acetyl-16 alpha-hydroxytrametenolic acid, and poricoic acid B had been isolated from the sclerotium of Poria cocos Wolf. These compounds showed a strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. At 0.2 mumol/mouse, these compounds markedly inhibited the promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse).

Inhibitory effect of taraxastane-type triterpenes on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two taraxastane-type hydroxy triterpenes, taraxasterol and faradiol, isolated from the flowers of Compositae plants Cynara scolymus (artichoke) and Chrysanthemum morifilolium (chrysanthemum), respectively, showed strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. At 2.0 mumol/mouse, these compounds inhibited markedly the tumor-promoting effect of TPA (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[alpha]anthracene (50 micrograms/mouse).

Inhibitory effect of oral administration of Monascus pigment on tumor promotion in two-stage carcinogenesis in mouse skin.

Monascus pigment was extracted from red malted rice, Monascus anka. It has been used as coloring matter for foodstuffs in Japan and certain Asian countries. Oral administration of Monascus pigment suppressed the tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in mice following initiation by 7,12-dimethylbenz[a]anthracene.

Cytotoxic cardenolides from woods of Euonymus alata.

Three cytotoxic cardenolides, acovenosigenin A 3-O-alpha-L-ramnopyranoside (1), euonymoside A (2) and euonymusoside A (3), were isolated from the woods of Euonymus alata (Celastraceae). The chemical structure of a new cardenolide, euonymusoside A (3) has been elucidated on the basis of extensive spectral analysis and enzymic hydrolysis to be acovenosigenin A (1 beta, 3 beta, 14 beta-trihydroxy-5 beta-cardenolide) 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranoside. All three showed potent cytotoxic activity against some neoplastic cell lines.

Inhibitory effect of rikkunshi-to, a traditional Chinese herbal prescription, on tumor promotion in two-stage carcinogenesis in mouse skin.

We report the inhibitory effect of topical application of extracts of a traditional Chinese herbal prescription on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Methanol and water extracts obtained from 22 traditional Chinese herbal prescriptions were assayed and their inhibition ratios calculated. In general, the methanol extracts produced more effective inhibition than the water extracts. Of the various traditional Chinese herbal prescriptions, the methanol extract of Rikkunshi-to was more effective than other prescriptions as far as inhibition of TPA-induced inflammation was concerned. Hoelen, Glycyrrhizae Radix, Atractylodis Rhizoma, components of Rikkunshi-to markedly inhibited the inflammatory activity involved by TPA in mice. Furthermore, topical application of the methanol extract of Rikkunshi-to markedly inhibited TPA-induced tumor promotion in two-stage carcinogenesis in mouse skin.

Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

We have found that several lupane-type triterpenes, including lupeol, its acetate, betulin and betulinic acid, inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, and that betulinic acid inhibits tumor promotion in two-stage carcinogenesis in mice. Among seven lupane-type triterpenes assayed, these compounds inhibited the inflammatory activity induced by TPA in mice. The 50 % inhibitory dose of these compounds for TPA-induced inflammation was 0.4-4.0 µmol. Furthermore, topical application of lupeol, lupeol 3-acetate and betulin markedly suppressed the tumor-promoting effect of TPA (1 µg/mouse) in mouse skin initiated with 7,12-dimethyl-benz[a]anthracene (50 µg/mouse), at a grade corresponding to that of betulinic acid.

Bitetrahydroanthracenes from flowers of Cassia torosa Cav.

A new bitetrahydroanthracene derivative, torosaol-III, was isolated from the flowers of Cassia torosa Cav. along with physcion, 5,7'-physcionanthrone-physcion, 5,7'-biphyscion, torosanin-9,10-quinone, 5,7-dihydroxy-chromone, naringenin, and chrysoeriol. The structure of torosaol-III was established as 3,3'-4,4'-tetrahydro-3,3'8,8'9,9'-hexahydroxy-6,6'-dimethoxy-3,3'- dimethyl-1(2H),1'(2H)-5,7'-bianthracenone on the basis of spectral and chemical evidence. Dimeric tetrahydroanthracenes exhibited cytotoxic activity against KB cells in the tissue culture.

Five D:C-friedo-oleanane triterpenes from the seeds of Trichosanthes kirilowii Maxim. and their anti-inflammatory effects.

Five triterpenes with a D:C-friedo-oleanane skeleton, D:C-friedo-oleana-7,9(11)-diene-3 beta,29-diol (3-epikarounidiol), 7-oxo-D:C-friedo-olean-8-en-3 beta-ol (7-oxoisomultiflorenol), 7-oxo-8 beta-D:C-friedo-olean-9(11)-ene-3 alpha,29-diol, D:C-friedo-olean-8-ene-3 alpha,29-diol (3-epibryonolol), and D:C-friedo-olean-8-ene-3 beta,29-diol (bryonolol), the first four of which are new naturally occurring compounds, were isolated from the seeds of Trichosanthes kirilowii Maxim. The structures were determined by spectral and chemical methods. 3-Epikarounidiol, 7-oxoisomultiflorenol, and 3-epibryonolol showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 microgram) was 0.2-0.6 mg/ear.

Atractylodis Rhizoma extract and its component, atractylon, inhibit tumor promotion in mouse skin two-stage carcinogenesis.

The methanol extract of Atractylodis Rhizoma, a traditional Chinese medicine, was found to have antitumor-promoting activity in two-stage carcinogenesis. From the active fraction of the extract, atractylon was isolated. The isolated compound showed inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. Furthermore, atractylon markedly inhibited tumor promotion by TPA following 7,12-dimethylbenz[a]anthracene initiation in mice.

Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED50 of these compounds for TPA-induced inflammation was 1.4-4.4 mumol. Gomisin A, with an ED50 of 1.4 mumol, showed the strongest inhibitory effect. Furthermore, at 5 mumol/mouse, it markedly suppressed the promotion effect of TPA (2.5 micrograms/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.

Potential inhibitors of platelet aggregation from plant sources, V. Anthraquinones from seeds of Cassia obtusifolia and related compounds.

Three anthraquinone glycosides, gluco-obtusifolin [11], gluco-chryso-obtusin [15], and gluco-aurantioobtusin [13], were found to be platelet anti-aggregatory constituents of seeds of Cassia obtusifolia. Various other anthraquinone analogues were also tested, and their structure-activity relationships are discussed.