Ginsenoside Rk3 modulates glutamine metabolism and inhibits Th17 cell differentiation via gut microbiota regulation...

Dysbiosis of the gut microbiota has been demonstrated to trigger immune responses that may heighten psoriasis susceptibility. However, conventional therapies for psoriasis are often limited by significant side effects. Ginsenoside Rk3 (Rk3), a bioactive triterpenoid glycoside compound derived from natural ginseng, has shown promise as a potent immunomodulator and gut regulator. Therefore, this study aims to investigate the potential protective effect of Rk3 against psoriasis, with a focus on the gut microbiota modulation and immune response regulation. Network pharmacology was first employed to predict potential targets for the action of Rk3 on psoriasis and an imiquimod (IMQ)-induced psoriasis mice model was used to investigate the palliative effect of Rk3 on psoriasis. Our results reveal that Rk3 restores gut microbiota homeostasis, especially modulating the abundance of Akkermansia muciniphila and Parabacteroides distasonis, and effectively alleviates IMQ-induced psoriasis through gut microbiota-dependent mechanisms. Furthermore, Rk3 exerts a regulatory effect on aberrant amino acid metabolism, suppressing glutamine catabolism while enhancing short-chain fatty acids (SCFAs) biosynthesis. Rk3-mediated regulation of glutamine metabolism exerts an inhibition effect on the conversion of glutamine to glutamate, suppresses Th17 cell differentiation and alleviates psoriasis via the IL-6/JAK1-STAT3 signaling axis. Overall, our research elucidates Rk3's mechanism of action in ameliorating psoriasis and highlights its potential as a gut microbiota modulator for psoriasis treatment.