背景：K.C. Ting ex H.T. Chang-related, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. 方法：Notopterygium incisum代谢物及其潜在靶点从公共数据库中提取。我们在Genecards, OMIM，PharmGkb, TTD 和 DrugBank数据库中搜索OSAS相关基因。使用Cytoscape 3.9.0构建药物-靶点-疾病网络并筛选核心基因。人支气管上皮细胞在缺氧和慢性间断性低氧（CIH）培养基中培养24小时。使用酶联免疫吸附分析（ELISA）定量检测白细胞介素-6（IL-6），肿瘤坏死因子-α（TNF-α）和前列腺素E2（PGE2）。使用RT-qPCR检测前列腺素内过氧化物合酶2（PTGS2）mRNA, 用Western blot分析鉴定PTGS2和核因子-κB（NF-κB）蛋白。利用共免疫沉淀（CoIP）和Western blot法评价HBE细胞中PTGS2的泛素化水平。 结果：从Notopterygium incisum中分离的Pterostilbene和notopterol具有治疗OSAS的潜在疗效。PTGS2和雌激素受体α（ESR1）核心基因与OSAS相关。通路富集分析集中在NF-κB、凋亡和HIF-1A通路上。对CIH的响应中，pterostilbene和notopterol降低了IL-6、TNF-α和PGE2水平。通过增加PTGS2水平激活了NF-κB通路。Pterostilbene促进了PTGS2蛋白经蛋白酶体介导的泛素化，降低了PTGS2水平，抑制了NF-κB通路。 结论：本研究揭示了Notopterygium incisum的活性代谢物和与治疗OSAS相关的核心基因，为该植物药物的后续开发和开发提供了基础。版权所有 © 2023年 刘、唐、赵、周和胡。

Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum, had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.Copyright © 2023 Liu, Tang, Zhao, Zhou and Hu.