ETHNOPHARMACOLOGICAL RELEVANCE Thistles species (Family: Compositae) are traditionally used in the Mediterranean area, particularly in Sardinia. They are usually gathered from the wild and used for both food and therapeutic purposes, including gastrointestinal disorders. AIM OF THE STUDY This work aims to evaluate the anti-inflammatory activity of eight wild thistles from Sardinia, in an in vitro model of gastric inflammation, and to identify the major active compounds in the extracts. MATERIALS AND METHODS The hydro-alcoholic extract of the aerial part of each species was prepared. After the induction of inflammation by the addition of tumor necrosis factor-α (TNFα) (10ng/mL), AGS cells were treated with extracts/pure compounds under study. The inhibition of interleukin-8 (IL-8) release, IL-8 and NF-κB promoter activities and NF-κB nuclear translocation were evaluated. Extracts main components were identified by HPLC-PDA-MS/MS. RESULTS Only Onopordum horridum Viv. and Onopordum illyricum L. hydro-alcoholic extracts reduced, in a concentration-dependent fashion, the IL-8 release and promoter activity in human gastric epithelial cells AGS. The effect was partially due to the NF-κB pathway impairment. Onopordum hydro-alcoholic extracts were also chemically profiled, and caffeoylquinic acid derivatives were the main compounds identified in the extract. Further investigations showed that 3,5 dicaffeoylquinic acid highly inhibited IL-8 secretion in AGS cells (IC50 0.65μM), thus suggesting that this compound contributed, at least in part, to the anti-inflammatory activity elicited by O. illyricum extracts. CONCLUSIONS Our results suggest that Onopordum species may exert beneficial effects against gastric inflammatory diseases. Thus, these wild plants deserve further investigations as preventive or co-adjuvant agents in gastric diseases.