Abstract：
Ischemic stroke is a serious cerebrovascular condition. Isobavachalcone (ISO) has been documented to exhibit an anti-inflammatory effect across a variety of diseases; however, its protective impact on ischemic stroke remains unexplored. In this study, we evaluated the influence of ISO in both transient middle cerebral artery occlusion/reperfusion (tMCAO/R) rat models and oxygen-glucose deprivation/reperfusion (OGD/R) cell models. We observed that pretreatment with 50 mg/kg ISO diminished the volume of brain infarction, reduced brain edema, and ameliorated neurological deficits in rats. A reduction in Nissl bodies was noted in the tMCAO/R group, which was reversed following treatment with 50 mg/kg ISO. TUNEL/NeuN double staining revealed a decrease in TUNEL-positive cells in tMCAO/R rats treated with ISO. Furthermore, ISO treatment suppressed the expression of cleaved caspase-3 and BAX, while elevating the expression of BCL-2 in tMCAO/R rats. The levels of CD86 and iNOS were elevated in tMCAO/R rats; conversely, ISO treatment enhanced the expression of CD206 and Arg-1. Additionally, the expression of TNF-α, IL-6, and IL-1β was elevated in tMCAO/R rats, whereas ISO treatment counteracted this effect. ISO treatment also increased the expression of TGF-β and IL-10 in the ischemic penumbra of tMCAO/R rats. It was found that ISO treatment hindered microglial M1 polarization and favored M2 polarization. Histone Deacetylase 1 (HDAC1) is the downstream target protein of ISO, with ISO treatment resulting in decreased HDAC1 expression in both tMCAO/R rats and OGD/R-induced cells. Overexpression of HDAC1 was shown to promote microglial M1 polarization and inhibit M2 polarization in OGD/R+ISO cells. Overall, ISO treatment mitigated brain damage following ischemic stroke by promoting M2 polarization and attenuated ischemic injury by repressing HDAC1 expression.
摘要：
缺血性中风是一种严重的脑血管疾病。Isobavachalcone（ISO）已被证明在各种疾病中表现出抗炎作用；然而，其对缺血性卒中的保护作用尚待探索.在这项研究中,我们评估了ISO在短暂性大脑中动脉阻塞/再灌注（tMCAO/R）大鼠模型和氧-葡萄糖剥夺/再灌注（OGD/R）细胞模型中的影响。我们观察到，用50mg/kgISO预处理减少了脑梗死的体积，减少脑水肿，并改善了大鼠的神经功能缺损。在tMCAO/R组中注意到Nissl体的减少，用50mg/kgISO治疗后逆转。TUNEL/NeuN双染色显示用ISO处理的tMCAO/R大鼠中TUNEL阳性细胞减少。此外，ISO处理抑制了裂解的caspase-3和BAX的表达，同时提高tMCAO/R大鼠BCL-2的表达。tMCAO/R大鼠的CD86和iNOS水平升高；相反，ISO处理增强了CD206和Arg-1的表达。此外,TNF-α的表达,IL-6和IL-1β在tMCAO/R大鼠中升高,而ISO处理抵消了这种影响。ISO治疗还增加了tMCAO/R大鼠缺血半暗带中TGF-β和IL-10的表达。发现ISO处理阻碍了小胶质细胞M1极化并有利于M2极化。组蛋白去乙酰化酶1(HDAC1)是ISO的下游靶蛋白,ISO处理导致tMCAO/R大鼠和OGD/R诱导的细胞中HDAC1表达降低。HDAC1的过表达显示在OGD/R+ISO细胞中促进小胶质M1极化和抑制M2极化。总的来说,ISO治疗通过促进M2极化减轻缺血性中风后的脑损伤，并通过抑制HDAC1表达减轻缺血性损伤。
