In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 27, No. 12 ( 2023-06), p. 1653-1663
Kurzfassung:
High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL‐1β, TNF‐α, IL‐6 and IFN‐γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl‐2 protein levels, while suppressing Bax and Cleaved Caspase‐3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF‐κB and attenuated nuclear transfer of nuclear factor kappa B (NF‐κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF‐κB inflammatory network.
Materialart:
Online-Ressource
ISSN:
1582-1838
,
1582-4934
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2023
ZDB Id:
2076114-4