Glaucocalyxin A alleviates ulcerative colitis by inhibiting PI3K/AKT/mTOR signaling

Abstract

Isodon japonicus (Burm.f.) Hara var. glaucocalyx (Maxim.) Hara is a herbaceous perennial plant. Historically, it has often been used to treat dysentery and other diseases, indicating its potential efficacy in the treatment of inflammatory conditions affecting the intestines. Glaucocalyxin A (GLA) is a diterpenoid isolated from I. japonicus; recent studies have revealed that it exhibits a range of biological activities, including neuroprotective, anticancer, anti-inflammatory, hepatoprotective, and anti-fibrotic effects. However, previous studies have not specifically explored the mechanism whereby GLA alleviates ulcerative colitis (UC). Therefore, in the present study, we generated a DSS-induced UC mouse model and lipopolysaccharide-induced RAW264.7 inflammation model and performed network pharmacology analysis and peripheral blood analysis of patients with acute UC to investigate the mechanisms underlying the positive effects of GLA on UC. This study demonstrated the anti-inflammatory effects of GLA in a mouse model of DSS-induced UC. Network pharmacology analysis revealed that AKT is a common target of GLA and inflammatory bowel disease (IBD). The changes in LPS-induced RAW264.7 cell inflammation further verified that GLA reduced the expression of inflammatory cytokines by inhibiting PI3K/AKT/mTOR signaling. Finally, in vitro magnetic bead sorting experiments showed that GLA could be used in the treatment of UC patients.