Kidney Week

Abstract: SA-PO0244

AMP-Activated Protein Kinase-Dependent Restoration of Autophagic Flux by Ginsenoside Rg3 Protects Against Ischemic AKI

Session Information

• AKI: Mechanisms - Cell Signaling
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Park, Hyerim, Chungnam National University School of Medicine, Daejeon, Korea (the Republic of)

Hyerim Park

• Jeong, Seongyeop, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Seongyeop Jeong

• Jang, Soyoung, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Soyoung Jang, MD

• Yoon, Suyeon, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Suyeon Yoon, MD

• Park, Heewon, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)

Heewon Park, PhD

• Choi, Hyunsu, The Catholic University of Korea Daejeon St Mary's Hospital, Daejeon, Korea (the Republic of)

Hyunsu Choi

• Chang, Yoon-Kyung, The Catholic University of Korea College of Medicine, Seoul, Korea (the Republic of)

Yoon-Kyung Chang, MD, PhD

• Choi, Dae Eun, Chungnam National University School of Medicine, Daejeon, Korea (the Republic of)

Dae Eun Choi, MD, PhD

Background

Ischemic acute kidney injury (AKI) lacks targeted pharmacotherapy. Tubular epithelial cells respond to ischemia–reperfusion (I/R) with oxidative stress, inflammation, and programmed cell death; autophagy is a protective adaptation, but I/R commonly disrupts late-stage autophagic flux. We tested whether ginsenoside Rg3, a Panax ginseng saponin, restores autophagic flux through AMP-activated protein kinase (AMPK) and thereby mitigates ischemic AKI.

Methods

C57BL/6 mice (10 weeks) underwent bilateral renal pedicle clamping for 35 minutes after intraperitoneal Rg3 pretreatment (10 mg/kg) 1 hour before ischemia. Functional, histological, and molecular endpoints were assessed at 6, 24, and 72 hours of reperfusion. Mechanistic specificity was probed by co-administering autophagy inhibitors (bafilomycin A1 or chloroquine) in vivo. HK-2 proximal tubular cells were exposed to hypoxia/reoxygenation (H/R), and AMPK dependence was tested with compound C.

Results

Rg3 lowered serum creatinine and blood urea nitrogen and attenuated tubular necrosis and leukocyte infiltration at all reperfusion time points. The injured cortex showed up-regulated antioxidant defenses (SOD1, catalase, glutathione peroxidase) with parallel suppression of MCP-1 and osteopontin. Rg3 raised phospho-AMPK and LC3-II while lowering p62, consistent with re-engagement of late-stage autophagic flux. Bafilomycin A1 or chloroquine abolished the functional, histological, and antioxidant benefits of Rg3, indicating autophagy is required for—not merely associated with—renoprotection. In HK-2 cells, Rg3 restored viability and reduced apoptosis under H/R; these effects were lost when autophagy was blocked or AMPK was inhibited by compound C, placing AMPK upstream of the protective autophagy response.

Conclusion

Ginsenoside Rg3 attenuates ischemic AKI by reactivating impaired autophagic flux through AMPK, with downstream suppression of oxidative stress, inflammation, and tubular cell death. The AMPK–autophagy axis is a tractable mechanism, and Rg3 warrants further translational evaluation as a renoprotective candidate.

Funding

• Government Support – Non-U.S.