Hyperoside alleviates epilepsy-induced neuronal damage by enhancing antioxidant levels and reducing autophagy
Hyperoside alleviates epilepsy-induced neuronal damage by enhancing antioxidant levels and reducing autophagy
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DOI：
10.1016/j.jep.2020.112884
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发表时间：
2020-07-15
影响因子：
5.4
通讯作者：
Yan, Bing Chun
中科院分区：
文献类型：
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作者：
Cao, Jianwen;Tang, Cheng;Yan, Bing Chun
民族药理学相关性：贯叶连翘（Hypericum perforatum L.，连翘属，连翘科）是一种传统中药中常用的植物，据信其茎叶煎剂具有多种功效，包括退烧、解毒、镇静和止痛。金丝桃苷（Hyperoside， HYP）是一种从贯叶连翘（Hypericum perforatum L.）中提取的天然化合物，具有抗氧化、抗炎、抗细胞凋亡等多种生物活性。在本研究中，我们研究了HYP对小鼠癫痫性神经元损伤的影响及其相关的调节因子。研究目的：本研究考察了HYP对小鼠癫痫模型神经元损伤的潜在治疗作用，并探讨了HYP预处理与抗氧化水平和自噬的潜在神经保护作用的关系。材料与方法：将ICR小鼠随机分为6组：sham组、sham- hyp组、KA组、KA- hyp组、KA- hypp - ddc组和KA- cq组。采用免疫组织化学染色评估海马CA3区NeuN、IBA-1和GFAP表达的变化。免疫荧光染色观察HYP对海马CA3区神经元自噬体数量的影响。Western blot检测SOD1、SOD2、LC3I/II、Beclin1、PI3K/AKT、MAPK信号相关蛋白的表达水平。结果：预处理50 mg/kg HYP对癫痫诱导的海马CA3区神经元损伤有保护作用。此外，HYP通过PI3K/AKT和MAPK途径增强抗氧化水平，降低自噬相关蛋白水平。结论：HYP通过提高抗氧化水平和减少自噬来保护海马CA3区免受癫痫诱导的神经元损伤。其作用机制可能与通过PI3K/Akt和MAPK途径维持抗氧化水平和抑制自噬有关。
Ethnopharmacological relevance: Hypericum perforatum L. (genus Hypericum, family Hypericaceae), a plant commonly used in traditional Chinese medicine, is believed to confer a wide range of benefits, including fever reduction, detoxification, calming, and pain relief via decoctions of its stems and leaves. Hyperoside (HYP), a natural compound extracted from Hypericum perforatum L., has been shown to demonstrate a wide array of bioactivities including antioxidative, anti-inflammatory, and anti-apoptotic effects. In this study, we investigated the effects of HYP on epilepsy-induced neuronal damage in mice and the associated regulatory factors.Aim of the study: This study examined the potential therapeutic use of HYP for the treatment of neuronal damage in a mouse model of epilepsy and explored the relationships of the potential neuroprotective effects of HYP pretreatment with antioxidant levels and autophagy.Materials and methods: ICR mice were randomly divided into six groups: sham group, sham-HYP group, KA group, KA-HYP group, KA-HYP-DDC group and KA-CQ group. Immunohistochemical staining was used to assess changes in NeuN, IBA-1, and GFAP expression in the CA3 region of the hippocampus. Immunofluorescence staining was used to assess the effects of HYP on the number of autophagosomes that accumulated in neurons in the hippocampal CA3 region. The levels of SOD1, SOD2, LC3I/II, Beclin1, and PI3K/AKT and MAPK signaling-related proteins were detected by Western blot.Results: Pretreatment with 50 mg/kg HYP protected against epilepsy-induced neuronal damage in the hippocampal CA3 region. Additionally, HYP enhanced antioxidant levels and reduced the levels of autophagy-related proteins via the PI3K/AKT and MAPK pathways.Conclusion: HYP protected the hippocampal CA3 region against epilepsy-induced neuronal damage via enhancing antioxidant levels and reducing autophagy. The mechanism of action may be related to the maintenance of antioxidant levels and the suppression of autophagy via the PI3K/Akt and MAPK pathways.