What question did this study set out to answer?

The study aims to assess esculetin's effects on preventing AKI-to-CKD transition in a mouse model of renal injury.

April 8, 2026Open Access

Esculetin Attenuates Inflammation and Fibrosis to Prevent AKI-to-CKD Transition in Adenine-Induced Renal Injury by Inhibiting the EGFR/SRC/PI3K/AKT/NF-κB Signaling Axis

Key Points

The study aims to assess esculetin's effects on preventing AKI-to-CKD transition in a mouse model of renal injury.
Developed an AKI-to-CKD mouse model using a 0.2% adenine diet.
Administered esculetin at doses of 30 and 60 mg/kg for 4 weeks.
Evaluated renal injury using serum creatinine, blood urea nitrogen, and renal histopathology.
Utilized network pharmacology and transcriptomics to identify targets and pathways.
Conducted Western blot analysis to confirm signaling pathway modulation.
Esculetin significantly reduced serum creatinine and blood urea nitrogen levels.
Alleviated renal tubular dilation and inflammatory infiltration.
Decreased levels of pro-inflammatory factors and enhanced antioxidant activity.
Inhibited collagen deposition and reversed EMT by affecting E-cadherin and α-SMA levels.
Inhibited phosphorylation of key signaling proteins in the EGFR/SRC/PI3K/AKT/NF-κB pathway.

Abstract

Background: Chronic kidney disease (CKD) is characterized by irreversible structural damage and functional deterioration of the kidneys. Esculetin (ES), with its anti-inflammatory, antioxidant, and immunomodulatory activities, shows potential in delaying renal function decline. This study aimed to investigate the protective effect of ES on adenine-induced CKD in mice and its underlying molecular mechanism, with a focus on its role in preventing the transition from acute kidney injury (AKI) to CKD. Methods: A AKI-to-CKD transition mice model was established by feeding mice a 0.2% adenine diet, and ES (30, 60 mg/kg) was co-administered for 4 weeks as a prophylactic intervention. Serum creatinine (SCr), blood urea nitrogen (BUN), and renal histopathology (HE, Masson, IHC) were evaluated to assess renal injury. Network pharmacology and transcriptomics were combined to screen the targets, and Western blot was used to verify the signaling pathways. Results: ES significantly reduced SCr and BUN levels in CKD mice and alleviated renal tubular dilation and inflammatory infiltration. ES decreased pro-inflammatory factors (IL-1β, IL-6, TNF-α) and MDA levels and enhanced SOD activity. Additionally, ES inhibited renal interstitial collagen deposition and reversed epithelial–mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA levels. Mechanism studies confirmed that ES significantly inhibited the phosphorylation levels of p-EGFR, p-SRC, p-PI3K, p-AKT, and p-p65 in renal tissues. Conclusions: ES effectively inhibits inflammation, oxidative stress, and fibrosis by modulating the EGFR/SRC/PI3K/AKT/NF-κB signaling axis, thereby preventing the AKI-to-CKD transition in the adenine-induced renal injury model and alleviating the progression of chronic renal damage.

Read Full Paperexternally

Mark Helpful

Bookmark

Relay

View Full Paper