Gastroprotective effect of carnosic acid gamma-lactone derivatives.

Carnosic acid (1) has been shown to possess gastroprotective activity in vitro and in vivo. However, little is known of the gastroprotective effect or cytotoxicity of carnosic acid gamma-lactone (3). To determine structure-activity relationships, a series of 17 esters of 3 were prepared including aliphatic, aromatic, and heterocyclic derivatives.

Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol.

Gastroprotective and cytotoxic effect of semisynthetic ferruginol derivatives.

The gastroprotective abietane diterpene ferruginol has been shown to present high cytotoxicity. In order to obtain active compounds with less cytotoxicity, 18 semisynthetic ferruginol derivatives and totarol were assessed for their gastroprotective effects in the HCl/ethanol-induced gastric lesion model in mice, as well as for cytotoxicity in human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). At 20 mg kg(-1), the greatest gastroprotective effects were provided by abieta-8,11,13-triene (1), abieta-8,11,13-trien-12-yl-2-chloropropanoate (8), abieta-8,11,13-trien-12-yl propenoate (9), 12-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-abieta-8,11,13-triene (17) and 12-(beta-D-galactopyranosyloxy)-abieta-8,11,13-triene (18), all of which were as active as the reference drug lansoprazole at 20 mg kg(-1), reducing gastric lesions by 69, 76, 67, 72 and 61%, respectively.

Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: in vitro-in vivo relationships.

The triterpene oleanolic acid 1 and its semisynthetic derivatives 2-7 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E(2) content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 and AGS cells.

Gastroprotective activity of sesquiterpene derivatives from Fabiana imbricata.

An infusion or decoction of the aerial parts of Fabiana imbricata (Solanaceae) is used in traditional medicine in Chile and Argentina as a digestive and diuretic agent. The main sesquiterpene of the plant was identified as 11-hydroxy-4-amorphen-15-oic acid. At doses of 25, 50 and 100 mg/kg, the compound showed a dose-dependent gastroprotective effect in HCl/EtOH-induced gastric lesions in mice reducing the lesions by 68% at 100 mg/kg.

Gastroprotective and ulcer healing effect of ferruginol in mice and rats: assessment of its mechanism of action using in vitro models.

The gastroprotective activity of the diterpene ferruginol isolated from Prumnopitys andina wood and bark was determined on HCl/EtOH-induced gastric lesions in mice. The effect of the compound on the healing of subacute gastric lesions in rats was also studied. The mode of action of the diterpene was assessed using human gastric epithelial cells (AGS) and MRC-5 fibroblasts.

Gastroprotective effect and cytotoxicity of natural and semisynthetic labdane diterpenes from Araucaria araucana resin.

The resin of the tree Araucaria araucana (Araucariaceae) is used by the Mapuche Amerindians in southern Chile and Argentina to treat ulcers and has been shown to display a gastroprotective effect in animal models. A study was undertaken to isolate, identify and assess the gastroprotective effect of the resin constituents and its semisynthetic derivatives as well as to evaluate the cytotoxicity of the products in cell cultures. Eleven diterpenes (ten labdane and a pimarane) were isolated from a resin sample collected in Chile.

Gastroprotective and cytotoxic effect of dehydroabietic acid derivatives.

Dehydroabietic acid derivatives have been reported to display antisecretory and antipepsin effect in animal models. Some 19 dehydroabietic acid diterpenes were prepared and assessed for gastroprotective activity in the HCl/EtOH-induced gastric lesions in mice as well as for cytotoxicity in human lung fibroblasts (MRC-5) and human epithelial gastric (AGS) cells. At a single oral dose of 100 mg kg(-1), highest gastroprotective effect was provided by dehydroabietanol, its corresponding aldehyde, dehydroabietic acid (DHA) and its methyl ester, N-(m-nitrophenyl)-, N-(o-chlorophenyl)- and N-(p-iodophenyl)abieta-8,11,13-trien-18-amide (compounds 12-14), N-2-aminothiazolyl- and N-benzylabieta-8,11,13-trien-18-amide (compounds 18-19) being as active as lansoprazole at 20 mg kg(-1) and reducing the lesion index by at least 75%.

Gastroprotective effect of the Mapuche crude drug Araucaria araucana resin and its main constituents.

The resin from the tree Araucaria araucana (Araucariaceae) has been used since pre-columbian times by the Mapuche amerindians to treat ulcers. The gastroprotective effect of the resin was assessed in the ethanol-HCl-induced gastric ulcer in mice showing a dose-dependent gastroprotective activity at 100, 200 and 300 mg/kg per os. The main three diterpene constituents of the resin, namely imbricatolic acid, 15-hydroxyimbricatolal and 15-acetoxyimbricatolic acid were isolated and evaluated for gastroprotective effect at doses of 50, 100 and 200 mg/kg.

Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice.

The gastroprotective activity of the new semi-synthetic solidagenone derivative 15,16-epoxy8(9),13(16),14-labdatrien-7 beta-methoxy-6 beta-ol (ELMO) has been assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of action. The effect of ELMO on the prostaglandin E2 content, cellular reduced glutathione (GSH) and protection against damage induced by sodium taurocholate was assessed against AGS cells.