Gastroprotective activity of sesquiterpene derivatives fromFabiana imbricata

Abstract

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. Seven derivatives of the terpene were prepared and their gastroprotective effect was assessed in HCl/EtOH-induced gastric lesions in mice. The cytotoxicity of the products was evaluated in fibroblasts and AGS cells. At 100 mg/kg, 11-hydroxy-4-amorphen-15-p-toluidinamide presented the best gastroprotective effect reducing the gastric lesions by 80%, showing a similar effect to lansoprazole at 20 mg/kg. The compound, however, presented higher cytotoxicity than other derivatives with the IC50 ranging between 110 and 145 microm in AGS cells and fibroblasts, respectively. Most compounds proved to be non-toxic showing cytotoxicity values higher than 1000 microm. The spectroscopic data of six 11-hydroxy-4-amorphen-15-oic acid derivatives are presented here for the first time.

Gastroprotective activity and cytotoxic effect of cyperenoic acid derivatives

“…Most studies on the gastroprotective effect of sesquiterpenes have been focused on the sesquiterpene lactones (Giordano et al 1990;Lewis & Hanson 1991;Foglio et al 2002), 11-hydroxy-4-amorphen-15-oic acid derivatives (Reyes et al 2005) and polygodial and its derivatives (Matsuda et al 2002). Little is known about the mechanisms involved in the gastroprotective effect of plant sesquiterpenes.…”

Identification and characterization of a novel sesquiterpene synthase, 4-amorphen-11-ol synthase, from <i>Artemisia maritima</i>

“…Although 4-amorphen-11-ol has not been reported as a major sesquiterpenoid in Artemisia spp., it is one of the major natural compounds accumulated in Fabiana imbricata (Brown 1994a), a flowering plant in the family Solanaceae native to Southern Chile (Brown and Shill 1993). Several derivatives of this compound, either isolated from F. imbricata or chemically synthesized using 4-amorphen-11-ol as the starting material, have been reported (Brown 1994b;Reyes et al 2005;Schmeda-Hirschmann and Papastergiou 1994). Among these, 11-hydroxy-4-amorphen-15-oic acid and its derivatives are highly protective against gastric lesions and toxic to the human gastric adenocarcinoma cell line (AGS) (ATC C CRL-1739) (Reyes et al 2005).…”

“…Several derivatives of this compound, either isolated from F. imbricata or chemically synthesized using 4-amorphen-11-ol as the starting material, have been reported (Brown 1994b;Reyes et al 2005;Schmeda-Hirschmann and Papastergiou 1994). Among these, 11-hydroxy-4-amorphen-15-oic acid and its derivatives are highly protective against gastric lesions and toxic to the human gastric adenocarcinoma cell line (AGS) (ATC C CRL-1739) (Reyes et al 2005). In addition, 4-amorphen-11-ol can be converted to peroxofabianane via either chemical synthesis or autoxidation/rearrangement under the presence of singlet oxygen (Jung and Youn 1996;Ngo and Brown 1999a).…”

Natural Products as Gastroprotective and Antiulcer Agents: Recent Developments

“…The main sesquiterpene of Fabiana imbricata, 11hydroxy-4-amorphen-15-oic acid (9), at doses of 25, 50 and 100 mg/kg showed a dose-dependent gastroprotective effect in HCl/EtOH-induced gastric lesions in mice, reducing the lesions by 68% at 100 mg/kg [60]. Seven derivatives of this terpene were prepared and their gastroprotective effects were assessed in HCl/EtOH-induced gastric lesions in mice.…”