Related Experiment Video
Updated: May 22, 2026
Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research
Published on: November 3, 2023
Integrating network pharmacology, molecular docking, machine learning, and experimental validation: puerarin improves
Shangping Fang1,2, Jiameng Liu2, Wanning Li2
1Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China.
Abstract:
Acute kidney injury (AKI) associated with sepsis has a high clinical mortality rate, and there is a lack of effective therapeutic targets; uncontrolled oxidative stress and inflammatory responses are central pathological mechanisms. The Sirt1-Nrf2-HO-1 pathway plays a key role in renal antioxidant and anti-inflammatory protection. Although puerarin possesses anti-inflammatory and antioxidant activity, its specific molecular mechanisms for improving sepsis-induced AKI have not yet been fully elucidated. The aim of this study was to determine whether puerarin protects against sepsis-induced AKI by activating the Sirt1-Nrf2-HO-1 pathway and to establish a theoretical foundation for its clinical application. Using network pharmacology, we identified Sirt1, Nrf2, and HO-1 as key targets linked to oxidative stress and inflammation. Molecular docking suggested that puerarin binds well to all three proteins. In both cell and animal studies, we found that puerarin activates the Sirt1-Nrf2-HO-1 pathway, which in turn improves kidney function, reduces tissue damage, and lowers oxidative stress and inflammation. Our findings suggest that puerarin protects against sepsis-induced AKI by triggering the Sirt1-Nrf2-HO-1 pathway, pointing to this signaling axis as a possible target for treatment.
Insights
Puerarin protects against sepsis-induced acute kidney injury (AKI) by activating the Sirt1-Nrf2-HO-1 pathway. This mechanism reduces oxidative stress and inflammation, offering a potential therapeutic target for sepsis-associated AKI.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Sepsis-induced acute kidney injury (AKI) presents a high mortality rate with limited therapeutic options.
- Oxidative stress and inflammation are key pathological drivers in sepsis-associated AKI.
- The Sirt1-Nrf2-HO-1 pathway is crucial for renal antioxidant and anti-inflammatory defense.
Purpose of the Study:
- To investigate if puerarin ameliorates sepsis-induced AKI by activating the Sirt1-Nrf2-HO-1 pathway.
- To elucidate the molecular mechanisms underlying puerarin's protective effects in sepsis-induced AKI.
- To provide a theoretical basis for the clinical use of puerarin in treating sepsis-associated kidney injury.
Main Methods:
- Network pharmacology identified Sirt1, Nrf2, and HO-1 as critical targets.
- Molecular docking simulations assessed puerarin's binding affinity to target proteins.
- In vitro and in vivo studies evaluated puerarin's effects on kidney function, tissue damage, oxidative stress, and inflammation.
Main Results:
- Puerarin demonstrated favorable binding to Sirt1, Nrf2, and HO-1.
- Puerarin treatment activated the Sirt1-Nrf2-HO-1 signaling pathway in cellular and animal models.
- Administration of puerarin improved renal function, attenuated kidney tissue damage, and reduced oxidative stress and inflammation.
Conclusions:
- Puerarin exerts protective effects against sepsis-induced AKI through the activation of the Sirt1-Nrf2-HO-1 pathway.
- The Sirt1-Nrf2-HO-1 pathway represents a promising therapeutic target for managing sepsis-associated kidney injury.
- Puerarin holds potential as a therapeutic agent for clinical application in sepsis-induced AKI.
