凤醒脑液通过SIRT1 /核因子-红细胞2相关因子2 (Nrf2)/血红素加氧酶1 （HO-1）通路改善脑卒中后认知障碍

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2025-01-01 DOI:10.1016/S1875-5364(25)60808-9

Yang Wenqin , Wen Wen , Chen Hao , Zhang Haijun , Lu Yun , Wang Ping , Xu Shijun

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引用次数: 0

摘要

sirtuin1 (SIRT1)/核因子-红细胞2相关因子2 (Nrf2)/血红素加氧酶1 （HO-1）途径的激活已被证明可以通过降低活性氧（ROS）水平来减轻氧化应激诱导的细胞凋亡和线粒体损伤。临床试验表明，中风醒脑液可改善脑卒中后认知功能障碍（PSCI）。然而，其潜在的机制，特别是是否涉及通过SIRT1/Nrf2/HO-1途径保护线粒体和抑制细胞凋亡，尚不清楚。本研究采用SH-SY5Y细胞建立氧糖剥夺（OGD）细胞模型，并通过改良双侧颈动脉结扎（2VO）诱导大鼠PSCI。在体内和体外评估ZFXN对学习记忆、神经保护活性、线粒体功能、氧化应激和SIRT1/Nrf2/HO-1通路的影响。结果表明，ZFXN显著增加b细胞淋巴瘤2 (Bcl2)/Bcl2相关X （Bax）比值，降低末端脱氧核苷酸转移酶介导的dUTP镍端标记(TUNEL)+细胞，显著改善海马和皮质的认知、突触可塑性和神经元功能。此外，ZFXN表现出较强的抗氧化活性，表现为ROS和丙二醛（MDA）含量降低，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）水平升高。ZFXN还显示出线粒体膜电位（MMP）、Tom20荧光强度、三磷酸腺苷（ATP）和能量电荷（EC）水平以及线粒体复合体I和III活性的显著增强，从而抑制线粒体损伤。此外，ZFXN显著增加SIRT1活性，升高SIRT1、核Nrf2和HO-1水平。值得注意的是，在体外，当抑制剂EX-527抑制SIRT1时，这些作用基本上被抵消了。综上所述，ZFXN通过激活SIRT1/Nrf2/HO-1通路和防止线粒体损伤来减轻PSCI。

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Zhongfeng Xingnao Liquid ameliorates post-stroke cognitive impairment through sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway

The activation of the sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species (ROS) levels. Clinical trials have demonstrated that Zhongfeng Xingnao Liquid (ZFXN) ameliorates post-stroke cognitive impairment (PSCI). However, the underlying mechanism, particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway, remains unclear. This study employed an oxygen-glucose deprivation (OGD) cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation (2VO). The effects of ZFXN on learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro. Results indicated that ZFXN significantly increased the B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax) ratio, reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)⁺ cells, and markedly improved cognition, synaptic plasticity, and neuronal function in the hippocampus and cortex. Furthermore, ZFXN exhibited potent antioxidant activity, evidenced by decreased ROS and malondialdehyde (MDA) content and increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels. ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential (MMP), Tom20 fluorescence intensity, adenosine triphosphate (ATP) and energy charge (EC) levels, and mitochondrial complex I and III activity, thereby inhibiting mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity and elevated SIRT1, nuclear Nrf2, and HO-1 levels. Notably, these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro. In conclusion, ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.