Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (w/w) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy.

译文

氧化应激和炎症反应是脑缺血再灌注损伤的重要机制。木犀草素 (Lu) 是经典藏方的主要活性成分之一,自公元前700年以来一直用于治疗心血管疾病,具有潜在的IR损伤治疗潜力。它的疏水性阻碍了它的进一步应用。在这项研究中,我们首先通过薄膜水合方法与两亲共聚物自组装制备了Lu胶束 (M-Lu),以改善Lu在水中的分散性。获得的M-Lu为约30 nm,具有窄的粒度分布,并且Lu的5% (w/w)。在体外和体内进一步评估了胶束的生物利用度。与游离Lu相比,M-Lu具有更好的穿透效率,增强了其在IR损伤修复中的治疗效果。M-Lu通过核因子-κ 基因结合 κ (NF-κ B) 和丝裂原活化蛋白激酶 (MAPK) 途径进一步加强对神经细胞的保护,并通过调节b细胞淋巴瘤-2 (Bcl-2) 和Bcl-2相关X蛋白的表达来抑制细胞凋亡 (Bax) 在氧化应激损伤的情况下。M-Lu诱导干细胞分化为神经元样细胞,促进神经元的修复和再生。Lu对大脑中动脉模型闭塞的体内药效学结果进一步表明,M-Lu通过下调炎性细胞因子,包括肿瘤坏死因子 (TNF)-α,白细胞介素 (IL)-1β 和IL-6,更好地抑制炎症和氧化应激反应,以及抗氧化激酶 (超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-px)) 活性的上调,进一步改善了IR的损伤程度。M-Lu可能是IR损伤治疗的新策略。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录