Panax notoginseng glycosides with astragaloside IV improve cerebral ischemic injury through autophagy-NLRP3 inflammasome pathway

Abstract

Autophagy-NLRP3 pathway participates in cerebral ischemia injury. However, whether Panax notoginsenoside (PN) combined with astragaloside IV (A-IV) plays an anti-inflammatory role in cerebral ischemia injury remains unclear. SD rats were in this study divided into sham operation group, model group, combination drug low-dose group (PN 40 mg/kg+ A-IV 14 mg/kg), medium dose group (80 mg/kg+ 28 mg/kg), high dose group (160 mg/kg+ 56 mg/kg), control group (propofol 4–6 mg/kg) followed by analysis of cerebral ischemia injury and PINK1/Parkin signaling. The model group presented increased infarct volume and NLRP3 level compared to drug and sham operation group. However, the higher the dose, the smaller was the infarct volume and lower NLRP3 expression (P < 0.05). LC3-II/LC3-I ratio increased with ischemia injury, while the ratios of P62, COX4 II and TomM20 were contrary. P62 presented declined level in treatment group compared to model group (P < 0.05). P62, COX4 II and TOMM20 levels were lower in the high-dose group and higher in the P62 group (P < 0.01). After 3-MA and mdivi-1 intervention, NLRP3-related pathway, LC3-II/LC3-I and P62 abundance in mitochondria were highest in the model group with downregulated COX4 II and TOMM20. The neurological deficit score and infarct volume were highest in the model group and improved in medium dose group. The cerebral infarction volume and neurological deficit score were elevated in the drug group combined with 3-MA and MIDIV-1 (P < 0.05). The higher the dose was, the lower were the expressions of PINK and Parkin (P < 0.01). In conclusion, Panax notoginsenoside combined with astragaloside IV effectively alleviated cerebral ischemia injury in rats and improved mitochondrial autophagy by inhibiting inflammasome activation.