2. Academic Validation
  3. Anemarrhena asphodeloides-derived small extracellular vesicle ameliorate diabetes-induced muscle atrophy via activating Pink1-mediated mitophagy

Anemarrhena asphodeloides-derived small extracellular vesicle ameliorate diabetes-induced muscle atrophy via activating Pink1-mediated mitophagy

  • Phytomedicine. 2025 Dec:149:157573. doi: 10.1016/j.phymed.2025.157573.
Pingcui Xu 1,  Yuzhen Xia 1,  Leqian Wang 2,  Lisha Zhao 1,  Chao Feng 3,  Mingli Ye 4,  Kai Huang 1,  Nani Wang 5
Affiliations

Affiliations

  • 1 Tongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, China.
  • 2 College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
  • 3 Hangzhou Kanglun Chinese Medicine Pieces Co. Ltd., Hangzhou, Zhejiang, 311100, China.
  • 4 College of Biological and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, China.
  • 5 Tongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310007, China; College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Hangzhou 310007, China. Electronic address: [email protected].
PMID: 41308393 DOI: 10.1016/j.phymed.2025.157573
Abstract

Background: Diabetes-induced muscle atrophy, characterized by progressive loss of skeletal muscle mass and function, poses a major challenge in diabetes management. To address this, we developed a phyto-exosomal formulation derived from Anemarrhena asphodeloides small extracellular vesicle (AA-sEV) and evaluated its therapeutic potential against diabetic muscle atrophy.

Methods: AA-sEV were isolated by ultracentrifugation and characterized for exosomal morphology. The therapeutic efficacy of AA-sEV was assessed through in vivo studies in diabetic db/db mice and in vitro assays using C2C12 myoblasts exposed to high glucose conditions.

Results: Fluorescently labeled AA-sEV efficiently accumulated in skeletal muscle tissue and myoblasts. Oral administration of AA-sEV enhanced muscle performance, as indicated by increased grip strength and hanging endurance, restoration of myofiber cross-sectional area, and upregulation of FNDC5 expression. Transcriptomic analysis revealed that Mitophagy served as the central mechanism mediating AA-sEV's therapeutic effects. Specifically, AA-sEV activated the Pink1/Parkin-dependent Mitophagy pathway, reducing mitochondrial Reactive Oxygen Species accumulation. This restoration of mitochondrial quality control promoted the MyoG/MyoD1-driven anabolic program while suppressing the MuRF1/MAFbx-mediated catabolic response. Treatment with the Mitophagy inhibitor 3-methyladenine abolished the anabolic and catabolic regulatory effects of AA-sEV under hyperglycemic conditions.

Conclusions: Our findings demonstrate that AA-sEV mitigate diabetes-induced muscle atrophy by restoring protein anabolic-catabolic balance via Pink1-mediated Mitophagy. These results highlight a novel extracellular vesicle-based therapeutic strategy for managing diabetic myopathy and related complications.

Keywords

Anemarrhena asphodeloides; Diabetes; Mitophagy; Muscle atrophy; Small extracellular vesicle.

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