Inhibition of trypsin and chymotrypsin by anti-inflammatory triterpenoids from Compositae flowers.

Taraxastane, oleanane, ursane, lupane, taraxane, cycloartane, dammarane and tirucallane triterpenoids isolated from flowers of Compositae plants have been previously reported to exhibit anti-inflammatory effects and are variously competitive and non-competitive inhibitors of the serine proteases trypsin and chymotrypsin. The general features of those triterpenoids found to be protease inhibitors are having a hydroxy group and an appropriate side chain in the region of the molecule distal to the 3-hydroxy group. However, fatty acid esterification of the triterpenoid 3-hydroxy group can have a marked effect on inhibitor effectiveness. This suggests a possible means of rapid alteration of the plant defensive complement in vivo and of the bioactivity of these anti-inflammatory compounds.

Anti-tumor promoting effects of multiflorane-type triterpenoids and cytotoxic activity of karounidiol against human cancer cell lines.

Forty-nine multiflorane-type triterpenoids consisting of 11 compounds isolated from the seeds of Trichosanthes kirilowii (Cucurbitaceae) and 38 of their derivatives have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in Raji cells as a primary screening test for anti-tumor promoters. All of the compounds tested showed an inhibitory effect against EBV-EA activation, and among which 43 were revealed to possess remarkable activity with potencies either comparable to or stronger than that of glycyrrhetic acid, a known natural anti-tumor promoter. Their structure-activity relationship is discussed. Evaluation of the cytotoxic activity of karounidiol (27) against human cancer cell lines exhibited cytotoxicity especially against a human renal cancer.

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.

Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase.

Fifty-five triterpenoids consisting of 19 tetracyclic, 32 pentacyclic, and 4 incompletely cyclized triterpenoids, and 2 sterols, mostly isolated from various plant and fungal materials, were examined for their inhibitory effects on a purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Twenty triterpenoids and one sterol showed inhibitory effects with 50% inhibition concentration (IC50) values less than 5.0 microM. Among these cycloartenol ferulate (IC50 = 2.2 microM), 24-methylenecycloartanol ferulate (1.9 microM), lupenone (2.1 microM), betulin diacetate (1.4 microM), and karounidiol 29-benzoate (2.2 microM) inhibited most effectively. Some of the triterpenoids and sterols may be potential new lead compounds to find still more potent HIV-1 reverse transcriptase inhibitors.

6S,8R-Stereochemistry of the C27- and C29-alkane-6,8-diols isolated from three compositae flowers.

The Deltadelta (deltaS-deltaR) values for the C-1 methyl 1H signals in the 1H-NMR spectroscopy of the bis-MTPA esters of four synthetic stereoisomers of alkane-6,8-diols, viz., bis-MTPA esters of (6S,8R)-C27- (1a) and C29- (3a) (Deltadelta = -0.05 ppm), (6R,8S)-C27- (2a) and C29- (4a) (Deltadelta = +0.05 ppm), (6S,8S)-C27- (5a) (Deltadelta = -0.01 ppm), and (6R,8R)-C27- (6a) (Deltadelta = +0.01 ppm) alkane-6,8-diols, made it possible to differentiate unequivocally among the four stereoisomers. This allowed the determination of the (6S,8R)-stereochemistry (Deltadelta = -0.05 ppm for the bis-MTPA esters) for the natural C27- and C29-alkane-6,8-diols isolated from the flowers of three Compositae plants, Carthamus tinctorius, Cynara cardanclus, and Taraxacum platycarpum.

Triterpene alcohol and sterol ferulates from rice bran and their anti-inflammatory effects.

Six novel feruloyl esters of triterpene alcohols and sterols, viz., two trans-ferulates, cycloeucalenol and 24-methylenecholesterol trans-ferulates, and four cis-ferulates, cycloartenol, 24-methyelenecycloartanol, 24-methylcholesterol, and sitosterol cis-ferulates, besides five known trans-ferulates, cycloartenol (CAR), 24-methylenecycloartanol (24-MCA), 24-methylcholesterol, sitosterol, and stigmastanol trans-ferulates, and one known cis-ferulate, stigmastanol cis-ferulate, were isolated from the methanol extract of edible rice bran. These and eight other synthetic trans- and cis-ferulates of triterpene alcohols and sterols, along with the corresponding free alcohols, were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg per ear) in mice. All of the ferulates showed marked inhibitory activity, and their 50% inhibitory dose (ID(50)) was 0. 1-0.8 mg per ear. On the other hand, whereas two free triterpene alcohols, CAR and 24-MCA, showed strong inhibition (ID(50) 0.2-0.3 mg/ear), eight free sterols examined showed weaker activity (ID(50) 0.7-2.7 mg/ear) than their corresponding ferulates.

Acyclic and incompletely cyclized triterpene alcohols in the seed oils of theaceae and gramineae.

The triterpene alcohol constituents of the non-saponifiable lipids of two Theaceae seed oils, sasanqua and camellia oils, and two Gramineae seed oils, wheat germ and rice bran oils, were investigated. This led to the isolation and characterization of one acyclic and eight incompletely cyclized triterpene alcohols. They are camelliol A, camelliol B, camelliol C, achilleol A, helianol, isohelianol, sasanquol, graminol A [(13R, 14R)-3,4-seco-25(10->9)abeo-8alpha,9beta,10al phapodioda-4,17,21 -trien-3-ol], and (2Z,6Z,10Z,14E,18E)-farnesyl-farnesol. Two other compounds isolated were characterized as (2Z,6Z,10E,14E)-geranylfarnesol, a sesterterpene alcohol, and phytol, a diterpene alcohol. Graminol A and (2Z,6Z,10E,14E)-geranylfarnesol are considered to be new natural products.

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).

[Development of electroforming apparatus for coronal restoration].

As dental technologies become highly developed, techniques have been more diversified. From as aspect of prosthodontic practice, both esthetic and functional requirements are emphasized for coronal restoration and consequently, these should be considered in the routine procedure. In fabrication of coronal restorations, metal, porcelain and resin are commonly used, and there exists the various disadvantages for metal cast method due to complicated processes by using different dental materials. Therefore, an electroforming apparatus was developed by us to replace the conventional procedure by a cathode rotary system. It was applied for coronal restorations to allow an electroforming directly on a working model. An experiment was successfully conducted to apply for a veneer crown on abutment tooth of upper central incisor on plaster model. The results were obtained as follows, 1. It was become possible to construct a metal framework by the electroforming. 2. Metal framework can be constructed on the same working model without a duplication of it. 3. The combined system for cathode rotation and liquid circulation could shorten the electroposition time, and allows a high current density extending to 50 A/dm2.