Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-β-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/β-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/β-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

中文翻译：

---

金丝桃苷通过上调 SIRT1 活性 Wnt/β-Catenin 和 Sonic Hedgehog 通路减轻 HT22 细胞的炎症

神经炎症在神经发育改变、感觉神经性听力损失和某些神经退行性疾病的发病机制和进展中起重要作用。Hyperoside (quercetin-3-O- β -D-galactoside) 是一种从金丝桃属植物中分离出来的活性化合物。在这项研究中，我们研究金丝桃苷对神经炎症的保护作用及其可能的分子机制。脂多糖（LPS）和金丝桃苷用于治疗HT22细胞。通过MTT法测量细胞活力。通过流式细胞仪测定细胞凋亡率。白细胞介素1β（IL- 1β）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、肿瘤坏死因子-α（TNF -α ）的mRNA表达水平) 通过定量逆转录聚合酶链反应测定。通过试剂盒测量氧化应激指标超氧化物歧化酶（SOD）、活性氧（ROS）、过氧化氢酶（CAT）、谷胱甘肽（GSH）和丙二醛（MDA）的水平。Western blotting检测神经营养因子的表达及其与金丝桃苷、沉默交配型信息调节2同源物1（SIRT1）和Wnt/ β -catenin、Sonic Hedgehog的关系。在LPS诱导的HT22细胞中，金丝桃苷促进细胞存活；减轻IL- 1β、IL-6、IL-8、TNF- α的水平、ROS、MDA、Bax 和 caspase-3；并增加 CAT、SOD、GSH、Bcl-2、BDNF、TrkB 和 NGF 的表达。此外，金丝桃苷上调了 SIRT1 的表达。进一步的机制研究表明，金丝桃苷通过上调 SIRT1 激活 Wnt/ β -catenin 和 sonic Hedgehog 通路来减轻 LPS 诱导的炎症、氧化应激和细胞凋亡。总之，我们的数据表明金丝桃苷在神经炎症中起到保护作用。