Rhubarb attenuates intracerebral hemorrhage injury by upregulating Snord17 to inhibit PANoptosis.

BACKGROUND

Intracerebral hemorrhage (ICH) is the most severe subtype of stroke and currently lacks effective therapies. PANoptosis, a novel programmed cell death mode, plays an important role in ICH. Rhubarb has shown neuroprotective potential in ICH, but its mechanisms remain unclear.

PURPOSE: To investigate whether rhubarb attenuates PANoptosis in microglia after ICH by regulating small nucleolar RNA (snoRNA).

METHODS

ICH was induced in mice by collagenase VII injection and treated with rhubarb (0.6, 1.2, 2.4 g/kg, gavage). Neurological function, histopathology, and blood-brain barrier integrity were evaluated. snoRNA sequencing and RT-qPCR were used to identify differentially expressed snoRNAs. Inflammatory cytokines and PANoptosis-related proteins were assessed by ELISA and Western blot. BV2 microglia were treated with rhubarb-containing serum, and Snord17 was knocked down to explore functional mechanisms.

RESULTS

Rhubarb significantly improved neurological scores, reduced neuronal damage and blood-brain barrier disruption, and inhibited IL-1β, TNF-α, and IL-6 expression. ICH markedly decreased Snord17 expression, while rhubarb reversed this change. Rhubarb also suppressed PANoptosis markers (ZBP-1, RIPK3, NLRP3, Caspase-3). In vitro, rhubarb reduced oxidative stress and inflammation in BV2 cells. Snord17 knockdown activated the p53 signaling pathway and promoted PANoptosis.

CONCLUSION

Rhubarb ameliorates neurological deficits and neuroinflammation after ICH by upregulating Snord17, thereby suppressing PANoptosis.