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Updated: May 23, 2025

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Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4-Mediated Ferritinophagy Associated with

Yin Chen1,2, Cheng Cheng1,2, Ao Li1,2

  • 1Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 7, 2025
PubMed

Insights

Pinoresinol diglucoside (PDG) may prevent cisplatin-induced hearing loss by inhibiting ferroptosis and ferritinophagy. This traditional Chinese medicine component downregulates SOCS1, offering a potential new clinical option for ototoxicity prevention.

Area of Science:

  • Ototoxicity research
  • Pharmacology
  • Traditional Chinese Medicine

Background:

  • Cisplatin chemotherapy can cause irreversible hearing loss (ototoxicity).
  • Effective preventive strategies for cisplatin-induced ototoxicity are lacking.
  • Traditional Chinese medicine offers potential therapeutic compounds.

Purpose of the Study:

  • To evaluate pinoresinol diglucoside (PDG) for preventing cisplatin-induced ototoxicity.
  • To elucidate the underlying molecular mechanisms of PDG's protective effects.
  • To explore PDG as a potential clinical intervention for hearing loss.

Main Methods:

  • In vitro studies using House Ear Institute-Organ of Corti 1 cells and basilar membranes.
  • Assessment of cell viability, reactive oxygen species (ROS) production, and ferroptosis.
  • Transcriptome sequencing to identify molecular targets.
  • Gene knockdown experiments (SOCS1) and protein interaction studies (Co-IP).
  • Transmission electron microscopy to observe cellular structures.

Main Results:

  • PDG significantly enhanced cell viability and reduced ROS production and ferroptosis in cisplatin-treated cells.
  • PDG partially ameliorated cisplatin-induced hearing loss.
  • Transcriptome analysis revealed Suppressor of Cytokine Signaling 1 (SOCS1) as a key target, elevated by cisplatin and reduced by PDG.
  • Knockdown of SOCS1 inhibited nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and reduced cisplatin-induced autophagic lysosomes.
  • SOCS1 was confirmed to interact with NCOA4.

Conclusions:

  • PDG protects against cisplatin-induced ototoxicity by downregulating SOCS1.
  • This mechanism involves the inhibition of NCOA4-mediated ferritinophagy.
  • PDG represents a promising therapeutic agent for preventing cisplatin-induced hearing loss.
Keywords:
Socs1cisplatinferritinophagyototoxicitypinoresinol diglucoside

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