Anti-inflammatory activity of α-tomatine <i>via</i> inhibition of the MAPK and NF-κB signaling pathway <i>in vitro</i> and <i>ex vivo</i>

α-Tomatine is a steroidal glycoalkaloid found in immature tomatoes that has been shown to have multiple beneficial effects on health. However, its anti-inflammatory properties have been little investigated thus far. The aim of this study was to evaluate its potential anti-inflammatory properties and underlying molecular mechanisms in rat splenocytes <i>in vitro</i> and <i>ex vivo</i>. We measured the lipopolysaccharide (LPS)-stimulated secretion of inflammatory molecules by splenocytes to assess the anti-inflammatory effects of α-tomatine. The underlying mechanism was investigated <i>via</i> western blotting. Next, we verified the anti-inflammatory potential of α-tomatine in rat splenocytes <i>ex vivo</i>. Rats were subcutaneously injected with one of two dosages of α-tomatine for seven days. We then collected their splenocytes and used them to further investigate anti-inflammatory responses <i>ex vivo</i>. α-Tomatine reduced LPS-evoked TNF-α, IL-1β, and NO secretion in a dose-dependent manner in the splenocytes. It also suppressed the expression of phosphorylated p38, ERK, and NF-κB <i>in vitro</i>. Notably, in the <i>ex vivo</i> experimental model, α-tomatine strongly inhibited parts of the MAPK and NF-κB signaling pathways, resulting in reduced secretion of inflammatory molecules. These results revealed that α-tomatine exerted strong anti-inflammatory activities both <i>in vitro</i> and <i>ex vivo</i>. Further, its underlying mechanisms may be related to suppressing parts of the MAPK and NF-κB signaling pathways. We thus expect α-tomatine to be developed as a novel therapeutic candidate for the treatment of inflammation-related diseases.