Scholarlink

<p>Puerarin has demonstrated protective effects against Alzheimer's disease (AD) and diabetes. This study aimed to explore the therapeutic potential and mechanistic basis of puerarin against high-fat high-sugar (HFHS) diet-induced AD-like pathology and insulin resistance, with a specific focus on p35/cyclin-dependent kinase 5 (CDK5) signaling. SH-SY5Y cells were cultured under high glucose (HG) conditions to induce AD-like pathology, and mice were fed with an HFHS diet to establish an AD model. Both models were treated with various concentrations of puerarin. The expression and activity of p35/CDK5 were examined by Western blot and kinase assays. Rescue experiments were conducted by transfecting SH-SY5Y cells with p35 overexpression plasmids. The protein levels of amyloid-beta (Aβ)42, amyloid precursor protein (APP), and phosphorylated-Tau were assessed by immunofluorescence. The protein levels in the insulin signal-related signaling pathway were examined. Mitochondrial dysfunction mediated by CDK5/dynamin-related protein 1 (DRP1) was determined. Additionally, cognitive function in mice was evaluated using behavioral tests, including the open field test, novel object recognition test, and Morris water maze. Insulin resistance in mice was assessed using biochemical assays. Puerarin inhibited HG-induced p35/CDK5 activation in SH-SY5Y cells. It also decreased the HG-induced upregulation of Aβ42, APP, and p-Tau in SH-SY5Y cells. Moreover, puerarin ameliorated HG-induced insulin resistance and mitochondrial dysfunction in SH-SY5Y cells, as evidenced by improved insulin signaling and restored mitochondrial ultrastructure. However, p35 overexpression abrogated these protective effects. In vivo, puerarin alleviated HFHS diet-induced cognitive impairment, Aβ deposition, and Tau phosphorylation in mice. Furthermore, puerarin ameliorated HFHS diet-induced insulin resistance and mitochondrial dysfunction in mice. Puerarin ameliorated HFHS diet-induced cognitive impairment, insulin resistance, and mitochondrial dysfunction by inhibiting p35/CDK5 activity. Our findings highlight the therapeutic potential of puerarin in the management of diet-induced AD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Puerarin Alleviates High-fat High-sugar Diet-induced Alzheimer's Disease-like Pathology and Insulin Resistance in Mice by Inhibiting p35/CDK5-mediated Mitochondrial Fission

  • 期刊论文

  • 发表日期：

    2025年11月7日

查看全文
  • Hailing Lv,
  • Ni Mao,
  • Aiju Liu,
  • Xiumin Zhao,
  • Baike Zhu

摘要

Puerarin has demonstrated protective effects against Alzheimer's disease (AD) and diabetes. This study aimed to explore the therapeutic potential and mechanistic basis of puerarin against high-fat high-sugar (HFHS) diet-induced AD-like pathology and insulin resistance, with a specific focus on p35/cyclin-dependent kinase 5 (CDK5) signaling. SH-SY5Y cells were cultured under high glucose (HG) conditions to induce AD-like pathology, and mice were fed with an HFHS diet to establish an AD model. Both models were treated with various concentrations of puerarin. The expression and activity of p35/CDK5 were examined by Western blot and kinase assays. Rescue experiments were conducted by transfecting SH-SY5Y cells with p35 overexpression plasmids. The protein levels of amyloid-beta (Aβ)42, amyloid precursor protein (APP), and phosphorylated-Tau were assessed by immunofluorescence. The protein levels in the insulin signal-related signaling pathway were examined. Mitochondrial dysfunction mediated by CDK5/dynamin-related protein 1 (DRP1) was determined. Additionally, cognitive function in mice was evaluated using behavioral tests, including the open field test, novel object recognition test, and Morris water maze. Insulin resistance in mice was assessed using biochemical assays. Puerarin inhibited HG-induced p35/CDK5 activation in SH-SY5Y cells. It also decreased the HG-induced upregulation of Aβ42, APP, and p-Tau in SH-SY5Y cells. Moreover, puerarin ameliorated HG-induced insulin resistance and mitochondrial dysfunction in SH-SY5Y cells, as evidenced by improved insulin signaling and restored mitochondrial ultrastructure. However, p35 overexpression abrogated these protective effects. In vivo, puerarin alleviated HFHS diet-induced cognitive impairment, Aβ deposition, and Tau phosphorylation in mice. Furthermore, puerarin ameliorated HFHS diet-induced insulin resistance and mitochondrial dysfunction in mice. Puerarin ameliorated HFHS diet-induced cognitive impairment, insulin resistance, and mitochondrial dysfunction by inhibiting p35/CDK5 activity. Our findings highlight the therapeutic potential of puerarin in the management of diet-induced AD.