Zhi Tang , Ting Sha , Yuanshang Wang , Yan Xiao , Yuanting Ding , Ruiqing Ni , Xiaolan Qi
{"title":"异尿酸原在链脲霉素诱导的阿尔茨海默病小鼠模型中减轻认知障碍、大脑tau磷酸化和氧化应激","authors":"Zhi Tang , Ting Sha , Yuanshang Wang , Yan Xiao , Yuanting Ding , Ruiqing Ni , Xiaolan Qi","doi":"10.1016/j.lfs.2025.123759","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>Isoliquiritigenin is a natural flavonoid extracted from the root of the medicinal herb liquorice. Isoliquiritigenin has various biological effects, including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic activities, and improved mitochondrial function in earlier studies. Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer's disease (AD). Here, we assessed the neuroprotective effects of isoliquiritigenin on a streptozotocin-injected mouse model.</div></div><div><h3>Materials</h3><div>Molecular docking analysis of isoliquiritigenin with mammalian target of rapamycin (mTOR) and ERK2. The mice (<em>n</em> = 27, male) were intracerebroventricularly injected with streptozotocin, treated with isoliquiritigenin (intraperitoneal, 2 days) and assessed using the Morris water maze. Oxidative stress, tau phosphorylation, mitochondrial dysfunction and synaptic impairment were evaluated in the cortex and hippocampal tissues of the mice by using biochemical assays and immunostaining.</div></div><div><h3>Results</h3><div>Isoliquiritigenin treatment mitigated the spatial memory capacity of streptozotocin-injected mice and alleviated tau phosphorylation at Ser396 and Thr231, the production of reactive oxygen species, the intracellular ATP level, the mitochondrial proteins p-DRP1 (S616), Mfn1 and Mfn2, neuronal loss, and synaptic impairment (PSD95, SNAP25). Isoliquiritigenin treatment reduced the levels of mTOR Ser2448 and ERK2 Thr202/Tyr204 and upregulated the level of GSK-3β Ser9 in the cortex and hippocampus of streptozotocin-injected mice.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings suggest that isoliquiritigenin ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, oxidative stress, mitochondrial dysfunction and synaptic impairment by decreasing mTOR and ERK activity and increasing GSK-3β activity.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123759"},"PeriodicalIF":5.2000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimer's disease\",\"authors\":\"Zhi Tang , Ting Sha , Yuanshang Wang , Yan Xiao , Yuanting Ding , Ruiqing Ni , Xiaolan Qi\",\"doi\":\"10.1016/j.lfs.2025.123759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>Isoliquiritigenin is a natural flavonoid extracted from the root of the medicinal herb liquorice. Isoliquiritigenin has various biological effects, including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic activities, and improved mitochondrial function in earlier studies. Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer's disease (AD). Here, we assessed the neuroprotective effects of isoliquiritigenin on a streptozotocin-injected mouse model.</div></div><div><h3>Materials</h3><div>Molecular docking analysis of isoliquiritigenin with mammalian target of rapamycin (mTOR) and ERK2. The mice (<em>n</em> = 27, male) were intracerebroventricularly injected with streptozotocin, treated with isoliquiritigenin (intraperitoneal, 2 days) and assessed using the Morris water maze. Oxidative stress, tau phosphorylation, mitochondrial dysfunction and synaptic impairment were evaluated in the cortex and hippocampal tissues of the mice by using biochemical assays and immunostaining.</div></div><div><h3>Results</h3><div>Isoliquiritigenin treatment mitigated the spatial memory capacity of streptozotocin-injected mice and alleviated tau phosphorylation at Ser396 and Thr231, the production of reactive oxygen species, the intracellular ATP level, the mitochondrial proteins p-DRP1 (S616), Mfn1 and Mfn2, neuronal loss, and synaptic impairment (PSD95, SNAP25). Isoliquiritigenin treatment reduced the levels of mTOR Ser2448 and ERK2 Thr202/Tyr204 and upregulated the level of GSK-3β Ser9 in the cortex and hippocampus of streptozotocin-injected mice.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings suggest that isoliquiritigenin ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, oxidative stress, mitochondrial dysfunction and synaptic impairment by decreasing mTOR and ERK activity and increasing GSK-3β activity.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"376 \",\"pages\":\"Article 123759\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320525003947\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525003947","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimer's disease
Aims
Isoliquiritigenin is a natural flavonoid extracted from the root of the medicinal herb liquorice. Isoliquiritigenin has various biological effects, including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic activities, and improved mitochondrial function in earlier studies. Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer's disease (AD). Here, we assessed the neuroprotective effects of isoliquiritigenin on a streptozotocin-injected mouse model.
Materials
Molecular docking analysis of isoliquiritigenin with mammalian target of rapamycin (mTOR) and ERK2. The mice (n = 27, male) were intracerebroventricularly injected with streptozotocin, treated with isoliquiritigenin (intraperitoneal, 2 days) and assessed using the Morris water maze. Oxidative stress, tau phosphorylation, mitochondrial dysfunction and synaptic impairment were evaluated in the cortex and hippocampal tissues of the mice by using biochemical assays and immunostaining.
Results
Isoliquiritigenin treatment mitigated the spatial memory capacity of streptozotocin-injected mice and alleviated tau phosphorylation at Ser396 and Thr231, the production of reactive oxygen species, the intracellular ATP level, the mitochondrial proteins p-DRP1 (S616), Mfn1 and Mfn2, neuronal loss, and synaptic impairment (PSD95, SNAP25). Isoliquiritigenin treatment reduced the levels of mTOR Ser2448 and ERK2 Thr202/Tyr204 and upregulated the level of GSK-3β Ser9 in the cortex and hippocampus of streptozotocin-injected mice.
Conclusion
In conclusion, our findings suggest that isoliquiritigenin ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, oxidative stress, mitochondrial dysfunction and synaptic impairment by decreasing mTOR and ERK activity and increasing GSK-3β activity.
期刊介绍:
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