Research Paper Volume 15, Issue 19 pp 10072—10088
Exploring anti-acute kidney injury mechanism of Dahuang-Gancao decoction by network pharmacology and experimental validation
- 1 Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430065, P.R. China
- 2 Department of Endocrinology, Second Affiliated Hospital of Wuhan University of Science and Technology, Wuhan 430065, P.R. China
- 3 Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, P.R. China
Received: April 12, 2023 Accepted: August 21, 2023 Published: September 18, 2023
https://doi.org/10.18632/aging.205033How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
This study aimed to investigate the pharmacological effects and molecular mechanisms of Dahuang-Gancao Decoction (DHGC) on acute kidney injury (AKI). Network pharmacology was utilized to analyze the key targets of DHGC against AKI. These targets were used to construct a protein-protein interaction (PPI) network, which was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict the mechanism of action. Based on the network pharmacological analysis, Sirtuin 3 (SIRT3) was identified as a key target, and apoptosis was suggested as a mechanism of DHGC for AKI treatment. Subsequently, an AKI mouse model was induced using lipopolysaccharide (LPS), and the study demonstrated that DHGC gradient intervention significantly reduced plasma urea and creatinine levels in AKI mice, ameliorated renal pathological changes, reduced apoptosis, and lowered serum inflammatory factors. The mechanism of DHGC’s anti-AKI effect may lie in the activation of the SIRT3/NRF2/HO-1 signaling pathway, which plays an antiapoptotic role in renal cells. In summary, DHGC improved LPS-induced AKI in mice by activating the SIRT3/NRF2/HO-1 signaling pathway. These findings shed light on the potential clinical application of DHGC for the treatment of nephropathy.
Abbreviations
DHGC: Dahuang-Gancao Decoction; AKI: Acute kidney injury; PPI: Protein-Protein interaction network; TCM: Traditional Chinese Medicine; LPS: lipopolysaccharide; H&E: hematoxylin and eosin; SIRT3: Sirtuin 3; NRF2: Nuclear Factor erythroid 2-Related Factor 2; HO-1: heme oxygenase 1; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; IL-1β: interleukin 1β; TNF-α: tumor necrosis factor-α; IL-6: interleukin 6; ROS: reactive oxygen species.