2. Academic Validation
  3. Wogonin, a bioactive flavonoid from Scutellaria baicalensis, alleviates alcoholic pancreatitis via AMPK-mediated TFEB activation

Wogonin, a bioactive flavonoid from Scutellaria baicalensis, alleviates alcoholic pancreatitis via AMPK-mediated TFEB activation

  • J Adv Res. 2025 Nov 10:S2090-1232(25)00879-3. doi: 10.1016/j.jare.2025.11.006.
Zhen Qin 1,  Xiaohong Sun 2,  Jingmin Zeng 3,  Guorong Li 1,  Haixia Wang 1,  Shujun Chen 3,  Shiyun Tan 3,  Lin An 1,  Caiyan Wang 1,  Liming Wang 4,  Jinping Wang 5,  Xiaowen Ma 6,  Zhongxiang Zhao 1,  Xiaojuan Chao 7,  Zhongqiu Liu 8,  Shaogui Wang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 2 Department of Pharmacy, Shenzhen Children's Hospital, Shenzhen, China.
  • 3 State Key Laboratory of Traditional Chinese Medicine Syndrome, Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Key Laboratory of Chinese Medicinal Resource from Lingnan (Guangzhou University of Chinese Medicine), Ministry of Education, Guangzhou, China.
  • 4 School of Biomedical Science, Hunan University, Changsha, Hunan, China.
  • 5 Department of Pharmacy, Shenzhen Second People's Hospital, Shenzhen, China.
  • 6 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
  • 7 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 8 State Key Laboratory of Traditional Chinese Medicine Syndrome, Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Key Laboratory of Chinese Medicinal Resource from Lingnan (Guangzhou University of Chinese Medicine), Ministry of Education, Guangzhou, China. Electronic address: [email protected].
  • 9 State Key Laboratory of Traditional Chinese Medicine Syndrome, Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Key Laboratory of Chinese Medicinal Resource from Lingnan (Guangzhou University of Chinese Medicine), Ministry of Education, Guangzhou, China. Electronic address: [email protected].
PMID: 41223988 DOI: 10.1016/j.jare.2025.11.006
Abstract

Introduction: Transcription factor EB (TFEB) deficiency contributes to insufficient autophagic degradation, resulting in zymogen granule (ZG) accumulation and subsequent premature activation, which underlies the pathogenesis of alcoholic pancreatitis (AP). Despite this mechanistic insight, pharmacological activation of TFEB via plant-derived agents remains an underdeveloped therapeutic avenue.

Objectives: This study aims to investigate Wogonin's role as a key Scutellaria baicalensis (Huangqin, HQ) component in protecting against AP, with specific focus on TFEB-mediated Autophagy activation.

Methods: Using TFEB-AcGFP and mRFP-GFP-LC3 reporter systems, we assessed Wogonin-enriched HQ extracts on TFEB nuclear translocation and autophagic flux. Pharmacological and genetic approaches were combined to established HQ/Wogonin's effects on alcohol-induced pancreatic injury through TFEB-mediated autophagic restoration. Structure-based virtual screening and molecular docking techniques were employed to predict the binding activity of Wogonin with upstream kinases regulating TFEB. Prioritized interactions underwent biophysical validation via surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and cellular thermal shift assay (CETSA) assays.

Results: HQ/Wogonin enhanced TFEB nuclear translocation and transcriptional activity, thereby restoring autophagic degradation to exert protection against alcohol-induced ZG accumulation and pancreatic injuries. Acinar TFEB knockout abolished HQ's protective effects against AP. Mechanistic studies revealed Wogonin directly bound with AMPK (AMP-activated protein kinase) to promote its protein stability, leading to improved TFEB activation.

Conclusion: This study establishes Wogonin as the pivotal bioactive driver behind HQ's therapeutic efficacy, orchestrating AMPK-TFEB-autophagy coordination to mitigate AP. Atomic-level resolution of Wogonin's adenine-mimetic binding to AMPK provides novel therapeutic strategies for developing kinase-stabilizing botanicals targeting TFEB activation to treat pancreatitis.

Keywords

Alcoholic pancreatitis; Autophagy; TFEB; Zymogen granule.

Figures
Products