RETRACTED ARTICLE: Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling

Abstract

Context Sepsis is a systemic inflammatory disease; pristimerin exhibits strong antibacterial, anti-inflammatory and antioxidant properties. Objectives We explored whether pristimerin protected against cognitive dysfunction and neuroinflammation in C57BL/6 J mice with sepsis-induced brain injuries. Materials and methods Sepsis was induced by intraperitoneal administration of 2 mg/kg lipopolysaccharide (LPS). C57BL/6 J mice were separated into four groups ( n = 10 per group): positive control, negative control, pristimerin 10 mg/kg and pristimerin 100 mg/kg. Pristimerin was administered orally for 28 days prior to LPS administration and for six days thereafter. Behavioural changes were assessed one day after LPS administration using the Morris water maze and via neurological dysfunction scoring. Molecular pathogenesis was explored by measurement of malondialdehyde, superoxide dismutase, reactive oxygen species and inflammatory cytokine levels in mouse brains. Neuronal apoptosis was evaluated using the TUNEL assay. The levels of p-Akt/Akt, p-PI3K/PI3K, mTOR, Bax, Bcl-2 and caspase-3 proteins were determined via Western blotting. Results Pristimerin improved cognitive function and reduces the neurological score to 1.15 ± 0.03. Pristimerin significantly reduced all cytokine levels: TNF-α by 18 ± 0.6 pg/mg, IL-1β by 43 ± 1.3 pg/mg and IL-6 by 34 ± 1.12 pg/mg. There was significant ( p < 0.01) improvement in PI3K/Akt signalling and histopathological changes in the brain tissue of sepsis induced brain injured rats. Conclusions Pristimerin ameliorated neuronal injury by regulating PI3K/Akt signalling in mice with sepsis-induced brain injuries. Pristimerin may merit further development for clinical applications.

The neuroprotective mechanism of lithium after ischaemic stroke

“…Meanwhile, after injuries, Neuronal apoptosis induced by ischaemia-reperfusion is associated with the neuroinflammation 45 , while oxidative stress induced by the injuries could stimulate the neuroinflammatory cascades, including activations of NLRP3 inflammasome and secretion of inflammatory cytokines, IL-1β, IL-18, TNF-α and IL-6 46 . Pro-inflammatory cytokines may further exacerbate neuronal apoptosis resulting in behavioural deficits 47 , 48 .…”

Identification of biomarkers and therapeutic targets related to Sepsis-associated encephalopathy in rats by quantitative proteomics

“…However, some studies have suggested that activation of PI3K/AKT signaling could mediate neuronal survival during sepsis. Various biomolecules and pharmaceuticals, such as Chromogranin A-derived peptide CGA47-66, Ghrelin, Pristimerin, and Dexmedetomidine, could attenuate blood-brain barrier (BBB) destruction [ 24 ], brain edema [ 25 ], neuroinflammation [ 25 ], synaptic injury [ 26 ], neuronal apoptosis [ 27 , 28 ]. Thus, PI3K/AKT signaling could represent potential diagnosis markers, therapeutic targets, and prognosis indicators in neural dysfunction during sepsis.…”

Traditional Chinese Medicine: A promising strategy to regulate inflammation, intestinal disorders and impaired immune function due to sepsis

“…Pristimerin can ameliorate neuronal injury in septic brain injury mice, mainly by regulating PI3K/Akt signaling pathway (Xue et al, 2021). Tanshinone IIA has a neuroprotective effect on sepsis mice, and in addition to its anti-inflammatory effects, its mechanism may be related to inhibiting the activation of astrocytes and microglia (Xiong et al, 2019).…”