Gastroprotective and ulcer-healing effect of new solidagenone derivatives in human cell cultures.
The labdane diterpene solidagenone 1 and its semisynthetic and biotransformation derivatives 2-10 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), prostaglandin E(2) content, 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 fibroblasts and AGS cells. A significant reduction of cell damage after NaT incubation was observed when the AGS cells were pretreated with compounds 2 and 6. Treatment with compounds 4-6, 8 and 9 significantly stimulated the GSH content in AGS cell cultures. None of the studied compounds was active as a superoxide anion scavenger. In AGS cells treated with compounds 1-10, only compound 5 was able to increase prostaglandin content. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 2, 8, 9 on AGS cells and for 5, 7-9 on MRC-5 fibroblasts. Regarding cytotoxicity, solidagenone showed higher toxicity while compounds 4 and 7 were the less toxic. Our results showed that most of the studied compounds act in vitro as gastroprotectors increasing the cellular GSH content. Additionally, some derivatives exhibited in vitro ulcer-healing effect stimulating the cell proliferation.
Rodríguez
Jaime A
JA
Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile. jrodrig@utalca.cl
Theoduloz
Cristina
C
Sánchez
Marianela
M
Razmilic
Iván
I
Schmeda-Hirschmann
Guillermo
G
D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D000897:Anti-Ulcer Agents; D016166:Free Radical Scavengers; D005663:Furans; D009281:Naphthalenes; D013481:Superoxides; C406719:solidagenone; D005978:Glutathione; D015232:Dinoprostone