School of Minerals Processing and Bioengineering, Central South University, Changsha, China.
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
PLoS One. 2023 Oct 5;18(10):e0291621. doi: 10.1371/journal.pone.0291621. eCollection 2023.
To explore the potential mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure based on network pharmacology and molecular docking technology, and to verify the core targets and key pathways by using the renal failure model.
The active components and targets of Shenkang injection were retrieved by TCMSP database, and the disease related targets were obtained by OMIM, GeneCards and other databases. Then, the intersection was obtained, and were imported into String database for PPI analysis. After further screening of core targets, GO and KEGG analysis were performed. Autodock software was used to predict the molecular docking and binding ability of the selected active ingredients and core targets. Chronic renal failure (CRF) model was established by adenine induction in rats, and the pathological observation of renal tissues was conducted. Meanwhile, the effects of Shenkang injection and its active components on core targets and pathways of renal tissues were verified.
The results of network pharmacology showed that the main components of Shenkang injection might be hydroxysafflor yellow A (HSYA)、tanshinol、rheum emodin、Astragaloside IV. Through enrichment analysis of core targets, it was found that Shenkang injection may play an anti-chronic renal failure effect through PI3K-Akt signaling pathway. Molecular docking results showed that the above pharmacodynamic components had strong binding ability with the target proteins PI3K and Akt. The results of animal experiments showed that renal function indexes of Shenkang injection group and pharmacodynamic component group were significantly improved compared with model group. HE staining results showed that the pathological status of the kidney was significantly improved in SKI and pharmacodynamic component treatment groups. Immunohistochemical results showed that the renal fibrosis status was significantly reduced in SKI and pharmacodynamic component treatment groups. q-RTPCR and WB results showed that the expression levels of PI3K and Akt were significantly decreased in the treatment groups (P< 0.05).
Shenkang injection may inhibit PI3K-Akt signaling pathway to play an anti-chronic renal failure role through the pharmacodynamic component hydroxysafflor yellow A (HSYA), tanshinol, rheum emodin, Astragaloside IV.
基于网络药理学和分子对接技术，探讨肾康注射液（SKI）治疗慢性肾衰竭的潜在机制，并通过肾衰竭模型验证核心靶点和关键途径。
通过 TCMSP 数据库检索肾康注射液的活性成分和靶点，通过 OMIM、GeneCards 等数据库获得疾病相关靶点。然后，进行交集获取，并将其导入 String 数据库进行 PPI 分析。进一步筛选核心靶点后，进行 GO 和 KEGG 分析。使用 Autodock 软件预测所选活性成分和核心靶点的分子对接和结合能力。通过腺嘌呤诱导大鼠建立慢性肾衰竭（CRF）模型，对肾组织进行病理观察。同时，验证肾康注射液及其活性成分对肾组织核心靶点和途径的影响。
网络药理学结果表明，肾康注射液的主要成分可能是羟基红花黄色素 A（HSYA）、丹参醇、大黄素、黄芪 IV。通过核心靶点的富集分析，发现肾康注射液可能通过 PI3K-Akt 信号通路发挥抗慢性肾衰竭作用。分子对接结果表明，上述药效成分与靶蛋白 PI3K 和 Akt 具有较强的结合能力。动物实验结果表明，与模型组相比，肾康注射液组和药效成分组的肾功能指标均有明显改善。HE 染色结果表明，SKI 及药效成分治疗组肾脏病理状态明显改善。免疫组化结果表明，SKI 及药效成分治疗组肾纤维化状态明显减轻。q-RTPCR 和 WB 结果表明，治疗组 PI3K 和 Akt 的表达水平均明显降低（P<0.05）。
肾康注射液可能通过药效成分羟基红花黄色素 A（HSYA）、丹参醇、大黄素、黄芪 IV 抑制 PI3K-Akt 信号通路发挥抗慢性肾衰竭作用。
