Study on the mechanism of Shenkang injection in the treatment of chronic renal failure based on the strategy of "Network pharmacology-Molecular docking-Key target validation"

PLoS One. 2023 Oct 5;18(10):e0291621. doi: 10.1371/journal.pone.0291621. eCollection 2023.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Emodin*
  • Kidney Failure, Chronic* / drug therapy
  • Molecular Docking Simulation
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Renal Insufficiency, Chronic* / drug therapy

Substances

  • astragaloside A
  • hydroxysafflor yellow A
  • tanshinol
  • shenkang
  • Emodin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Drugs, Chinese Herbal

Grants and funding

This research was supported by the National Natural Science Foundation of China [82104515], the Key Scientific Research Project of Colleges and Universities in Henan Province [23A360018; 23A320050], and the Science and Technology Project of Henan Province [202102310487] in the form of grants to LZ, and the Medical Science and Technology Project of Henan Province [LHGJ20220496; LHGJ20210283] in the form of grants to PD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.