2. Academic Validation
  3. Rhein-Emodin Combination Activates UQCRC1 to Attenuate MPP+-Induced Ferroptosis in Dopaminergic Neurons

Rhein-Emodin Combination Activates UQCRC1 to Attenuate MPP+-Induced Ferroptosis in Dopaminergic Neurons

  • Chem Biodivers. 2026 Mar;23(3):e02053. doi: 10.1002/cbdv.202502053.
Ayiguzhali Yusun 1 2,  Hongmei Wan 1,  Shuang Li 3,  Yanping Liu 1,  Huaxian Chen 1,  Mo Sun 4,  Xudong Ding 1,  Chenning Zhang 1
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, Postgraduate Union Training Base of Xiangyang No.1 People's Hospital, School of Medicine, Wuhan University of Science and Technology, Xiangyang, Hubei, China.
  • 2 Department of Rehabilitation Medicine, The 947th Army Hospital of the Chinese PLA, Kashgar, China.
  • 3 Department of Child Health Care, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
  • 4 School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
PMID: 41838561 DOI: 10.1002/cbdv.202502053
Abstract

Ferroptosis plays a critical role in Parkinson's disease (PD). This study investigates the neuroprotective effect of a combination of two natural Anthraquinones, rhein and emodin, against Ferroptosis, focusing on the mitochondrial complex III subunit UQCRC1. Using network pharmacology and experimental validation in erastin/MPP+-induced PC12 cells, we found that the optimal rhein-emodin combination potently inhibited ferroptotic cell death. This effect was associated with restored mitochondrial function, reduced lipid peroxidation, and the coordinated regulation of ferroptosis-related proteins, including the upregulation of GPX4 and FTH and downregulation of ACSL4. Crucially, the co-treatment markedly activated UQCRC1 expression. Furthermore, UQCRC1 knockdown abolished these anti-ferroptotic effects, establishing it as an essential mediator. Our findings demonstrate that the rhein-emodin combination attenuates Ferroptosis primarily through UQCRC1 activation, highlighting its therapeutic promise and identifying UQCRC1 as a novel regulatory node for PD intervention.

Keywords

Parkinson's disease; UQCRC1; ferroptosis; network pharmacology; rhein–emodin.

Figures
Products