Ginsenoside Rc Targets ROCK2 to Inhibit NF-κB Activation and Alleviate Cognitive Dysfunction in Septic Encephalopathy in vitro and in vivo.

Septic encephalopathy (SE), a severe complication of systemic inflammatory response syndrome, continues to lack effective therapeutic options due to its complex pathophysiology. Ginsenoside Rc (GRc), a principal bioactive component in several medicinal herbs, has demonstrated neuroprotective and anti-tumor properties. However, its potential role in the pathogenesis of SE and the identification of its molecular targets remain unclear. Rho-associated kinase (ROCK) has been implicated in the onset and progression of sepsis, although its precise mechanism of action is not fully understood. In this study, we demonstrated that GRc significantly alleviated cognitive impairment in a murine model of SE, as assessed by the Morris water maze and open-field tests. To explore the ROCK-mediated mechanisms underlying SE and the anti-septic effects of GRc, we examined changes in ROCK2 protein expression in LPS-induced SE mice and identified NF-κBp65 as a downstream phosphorylation target. GRc treatment effectively reduced ROCK2 expression and suppressed the secretion of inflammatory cytokines. These findings elucidate the pathological role of the ROCK2/NF-κBp65 signaling axis in SE and provide compelling evidence that GRc mitigates SE, at least in part, by directly binding to ROCK2 and inhibiting NF-κBp65 phosphorylation.