Background <p>Renal ischemia-reperfusion injury (IRI) is a common clinical condition that triggers a complex cascade of biological responses, including inflammation, oxidative stress, and apoptosis. These responses can lead to impaired renal function and acute kidney injury (AKI). Despite advancements in therapeutic agents, there is still a need for safe and effective drugs. In this study, we investigated the therapeutic effects and mechanisms of Gancao Xiexin Decoction (GCXXD), an herbal compound known for its anti-inflammatory, antioxidant, and immunomodulatory properties, in treating renal IRI.</p> Methods <p>We utilized network pharmacology to identify the intersection targets of the active ingredients in GCXXD and AKI. Cytoscape software was used to obtain core targets, and the String database was used to map the interaction network of these targets. GO and KEGG enrichment analyses were conducted to assess the biological functions and potential pathways involved. Molecular docking simulations were performed to examine the binding of the main active components of GCXXD to the key pathways. Validation experiments were conducted using an IRI mouse model and a hypoxia-reoxygenation-mediated HK2 injury model.</p> Results <p>A total of 11 core targets of GCXXD for the treatment of AKI were identified. GO and KEGG analyses revealed enrichment in biological functions related to oxidative stress, apoptosis, and the PI3K/AKT signaling pathway. Molecular docking results indicated strong binding affinity between the key active components (baicalein, ginsenoside Rh2, quercetin, and wogonin) of GCXXD and the PI3K/AKT pathway. In both in vivo and ex vivo experiments, GCXXD activated the PI3K/AKT pathway and ameliorated renal IRI.</p> Conclusion <p>This study demonstrated that GCXXD effectively improved ischemia-reperfusion-induced renal injury primarily via activating the PI3K/AKT pathway. These findings provided a scientific basis for the clinical application of GCXXD and paved the way for the development of new drugs and therapeutic strategies.</p>

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Therapeutic effects of Gancao Xiexin Decoction on renal ischemia-reperfusion injury based on network pharmacology and experimental validation

  • Hongfeng Jin,
  • Hao Zhang,
  • Xiaokang Zheng,
  • Xuejia Yang,
  • Binbin Li

摘要

Background

Renal ischemia-reperfusion injury (IRI) is a common clinical condition that triggers a complex cascade of biological responses, including inflammation, oxidative stress, and apoptosis. These responses can lead to impaired renal function and acute kidney injury (AKI). Despite advancements in therapeutic agents, there is still a need for safe and effective drugs. In this study, we investigated the therapeutic effects and mechanisms of Gancao Xiexin Decoction (GCXXD), an herbal compound known for its anti-inflammatory, antioxidant, and immunomodulatory properties, in treating renal IRI.

Methods

We utilized network pharmacology to identify the intersection targets of the active ingredients in GCXXD and AKI. Cytoscape software was used to obtain core targets, and the String database was used to map the interaction network of these targets. GO and KEGG enrichment analyses were conducted to assess the biological functions and potential pathways involved. Molecular docking simulations were performed to examine the binding of the main active components of GCXXD to the key pathways. Validation experiments were conducted using an IRI mouse model and a hypoxia-reoxygenation-mediated HK2 injury model.

Results

A total of 11 core targets of GCXXD for the treatment of AKI were identified. GO and KEGG analyses revealed enrichment in biological functions related to oxidative stress, apoptosis, and the PI3K/AKT signaling pathway. Molecular docking results indicated strong binding affinity between the key active components (baicalein, ginsenoside Rh2, quercetin, and wogonin) of GCXXD and the PI3K/AKT pathway. In both in vivo and ex vivo experiments, GCXXD activated the PI3K/AKT pathway and ameliorated renal IRI.

Conclusion

This study demonstrated that GCXXD effectively improved ischemia-reperfusion-induced renal injury primarily via activating the PI3K/AKT pathway. These findings provided a scientific basis for the clinical application of GCXXD and paved the way for the development of new drugs and therapeutic strategies.