Zhang Shuang, Wang Yu, Lu Fang, Mohammed Shadi A D, Liu Hanxing, Ding Song, Liu Shu-Min
Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.
Front Pharmacol. 2022 Apr 5;13:745074. doi: 10.3389/fphar.2022.745074. eCollection 2022.
Shenerjiangzhi formulation (SEJZ) is a new traditional Chinese medicine formulation (patent number: CN110680850A). SEJZ contains ( and ), (Araliaceae; radix and rhizome), Thunb (Caprifoliaceae; branch, stem), Bunge (Rosaceae; Crataegus pinnatifida fruit), and . SEJZ has been designed to treat hyperlipidemia. Despite the therapeutic benefits of SEJZ, its underlying mechanism of action is not known. We explored the efficacy of SEJZ against hyperlipidemia by integrating network pharmacology and 16S rRNA gene sequencing and elucidated its mechanism of action. First, SEJZ targets were found through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and from the literature. Hyperlipidemia-related therapeutic targets were obtained from GeneCards, Online Mendelian Inheritance in Man, and DrugBank databases. Then, Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were applied for the analyses and construction of a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes database was employed to identify signaling pathways that were enriched. Second, the therapeutic effects of SEJZ against hyperlipidemia induced by consumption of a high-fat diet in rats were evaluated by measuring body weight changes and biochemical tests. SEJZ treatment was found to alleviate obesity and hyperlipidemia in rats. Finally, 16S rRNA gene sequencing showed that SEJZ could significantly increase the abundance of short-chain fatty acid-producing bacteria, restore the intestinal barrier, and maintain intestinal-flora homeostasis. Using PICRUSt2, six metabolic pathways were found to be consistent with the results of network pharmacology: "African trypanosomiasis", "amoebiasis", "arginine and proline metabolism", "calcium signaling pathway", "NOD-like receptor signaling pathway", and "tryptophan metabolism". These pathways might represent how SEJZ works against hyperlipidemia. Moreover, the "African trypanosomiasis pathway" had the highest association with core genes. These results aid understanding of how SEJZ works against dyslipidemia and provide a reference for further studies.
申尔降旨方（SEJZ）是一种新型中药制剂（专利号：CN110680850A）。SEJZ含有（此处原文缺失具体成分信息）、人参（五加科；根及根茎）、忍冬（忍冬科；枝、茎）、山楂（蔷薇科；山里红果实）以及（此处原文缺失具体成分信息）。SEJZ旨在治疗高脂血症。尽管SEJZ具有治疗益处，但其潜在作用机制尚不清楚。我们通过整合网络药理学和16S rRNA基因测序来探究SEJZ抗高脂血症的疗效，并阐明其作用机制。首先，通过中药系统药理学数据库及分析平台并从文献中查找SEJZ的靶点。从GeneCards、人类孟德尔遗传在线数据库和DrugBank数据库中获取高脂血症相关治疗靶点。然后，应用检索相互作用基因/蛋白质的搜索工具及Cytoscape进行分析并构建蛋白质-蛋白质相互作用（PPI）网络。利用京都基因与基因组百科全书数据库来识别富集的信号通路。其次，通过测量体重变化和生化检测来评估SEJZ对大鼠高脂饮食诱导的高脂血症的治疗效果。发现SEJZ治疗可减轻大鼠的肥胖和高脂血症。最后，16S rRNA基因测序表明，SEJZ可显著增加短链脂肪酸产生菌的丰度，恢复肠道屏障，并维持肠道菌群稳态。使用PICRUSt2发现，有六个代谢途径与网络药理学结果一致：“非洲锥虫病”“阿米巴病”“精氨酸和脯氨酸代谢”“钙信号通路”“NOD样受体信号通路”和“色氨酸代谢”。这些途径可能代表了SEJZ抗高脂血症的作用方式。此外，“非洲锥虫病途径”与核心基因的关联度最高。这些结果有助于理解SEJZ如何对抗血脂异常，并为进一步研究提供参考。
