ABSTRACT
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.
Subject(s)
Alcohols/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Plants/chemistry , Alcohols/pharmacology , Alcohols/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Chromatography, High Pressure Liquid , Female , Inflammation/chemically induced , Inflammation/drug therapy , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred ICR , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
Ten dihydroxy- and trihydroxy triterpenes, viz., four taraxastanes: faradiol, heliantriol B0, heliantriol C and arnidiol; two lupanes: calenduladiol and heliantriol B2; two oleananes: maniladiol and longispinogenin; and two ursanes: brein and uvaol, isolated from the nonsaponifiable lipids of the flower extracts of Compositae plants were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. All the triterpenes were found to possess marked inhibitory activity. The 50% inhibitory dose of these compounds with respect to TPA-inflammation (1 microgram) was 0.03-0.2 mg/ear.
Subject(s)
Inflammation/chemically induced , Tetradecanoylphorbol Acetate/antagonists & inhibitors , Triterpenes/chemical synthesis , Animals , Mice , Plants , Tetradecanoylphorbol Acetate/pharmacology , Triterpenes/pharmacologyABSTRACT
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).
Subject(s)
Anticarcinogenic Agents/pharmacology , Carcinogens/toxicity , Skin Neoplasms/prevention & control , Sterols/pharmacology , Tetradecanoylphorbol Acetate/toxicity , Triterpenes/pharmacology , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Animals , Drugs, Chinese Herbal , Edema/chemically induced , Edema/prevention & control , Female , Inflammation , Mice , Mice, Inbred ICR , Skin Neoplasms/chemically induced , VegetablesABSTRACT
A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.
