Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Rhubarb attenuates intracerebral hemorrhage injury by upregulating Snord17 to inhibit PANoptosis.
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Lai ZiLi, Zhang Xindi, Li Jiao, Fan Li, Hu En, Li Teng, Yang Yujie, Luo Jiekun, Wang Yang, Tang Tao, Yang Xueping
Аннотация
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.
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.