China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, PR China.
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, PR China.
J Ethnopharmacol. 2022 Jun 28;292:115241. doi: 10.1016/j.jep.2022.115241. Epub 2022 Mar 26.
Zhibai Dihuang Granule (ZDG) is known as traditional Chinese patent medicine with the functions of "Ziyin decrease internal heat" in Traditional Chinses medicine. In clinical, it is also used to treat various kidney diseases.
We aimed to provide a basis for the curative effect of ZDG on acute kidney injury induced by cisplatin (CIAKI).
The active compounds and protein targets of ZDG, as well as the potential targets of the CIAKI were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. Enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of ZDG on the prevention and treatment of CIAKI was experimentally validated in vivo and in vitro.
From the database, we screened 22 active compounds of ZDG and 226 related targets. We obtained 498 gene targets related to CIAKI, among which 40 genes overlapped with ZDG-related targets. Go enrichment and KEGG analysis got 339 terms and 64 pathways, respectively. Based on the above study, we speculated that ZDG has the potential effect on treatment CIAKI, and the mechanism may be related to cell apoptosis and inflammation. The results in vitro experiments showed that ZDG reduced the cytotoxicity of cisplatin to HK-2 and 293T cells, but did not affect the antitumor effect of cisplatin. Moreover, in vivo experiments further proved that ZDG effectively controlled kidney damage caused by cisplatin in SD rats. The results showed that ZDG could regulate the expression of CASP3, p65 and MAPK pathway related proteins, suggesting that ZDG's prevention of CIAKI may be related to apoptosis and inflammatory response.
Our study showed that ZDG could prevent and treat CIAKI by inhibiting cell apoptosis and inflammation, which provided a new efficacy and clinical application for ZDG.
知柏地黄丸（ZDG）是一种传统的中药方剂，具有中医“滋阴降火”的功能。在临床上，它也被用于治疗各种肾脏疾病。
本研究旨在为 ZDG 治疗顺铂（CIAKI）诱导的急性肾损伤的疗效提供依据。
从数据库中搜索 ZDG 的活性化合物和蛋白质靶标，以及 CIAKI 的潜在靶标。构建蛋白质-蛋白质相互作用（PPI）网络图和药物-化合物-靶标-疾病网络。通过基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）进行富集分析。随后，在体内和体外实验中验证了 ZDG 对 CIAKI 的防治作用。
从数据库中筛选出 22 种 ZDG 的活性化合物和 226 个相关靶点，获得与 CIAKI 相关的 498 个基因靶点，其中 40 个基因与 ZDG 相关靶点重叠。GO 富集和 KEGG 分析分别得到 339 个和 64 个通路。基于上述研究，我们推测 ZDG 具有治疗 CIAKI 的潜力，其机制可能与细胞凋亡和炎症有关。体外实验结果表明，ZDG 降低了顺铂对 HK-2 和 293T 细胞的细胞毒性，但不影响顺铂的抗肿瘤作用。此外，体内实验进一步证明 ZDG 能有效控制 SD 大鼠顺铂引起的肾损伤。结果表明，ZDG 能调节 CASP3、p65 和 MAPK 通路相关蛋白的表达，提示 ZDG 防治 CIAKI 可能与细胞凋亡和炎症反应有关。
本研究表明，ZDG 可通过抑制细胞凋亡和炎症反应来预防和治疗 CIAKI，为 ZDG 的新疗效和临床应用提供了依据。
