2. Academic Validation
  3. Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome

Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome

  • Ecotoxicol Environ Saf. 2025 Sep 1:302:118711. doi: 10.1016/j.ecoenv.2025.118711.
Leisheng Wang 1,  Yifei Fu 2,  Shiwei Xu 2,  Enhong Chen 3,  Shuo Zhang 3,  Dongjie Yang 3,  Youzhao He 3,  Yuanlong Gu 3,  Yong Mao 4,  Fenglai Yuan 5,  Hao Hu 6
Affiliations

Affiliations

  • 1 Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China; Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
  • 2 Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China.
  • 3 Affiliated Hospital of Jiangnan University, Wuxi 214122, China.
  • 4 Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China. Electronic address: 9812015252@jiangnan.edu.cn.
  • 5 Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China. Electronic address: bjjq88@jiangnan.edu.cn.
  • 6 Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China. Electronic address: 9862019012@jiangnan.edu.cn.
PMID: 40712551 DOI: 10.1016/j.ecoenv.2025.118711
Abstract

6PPD-quinone (6PPDQ), a derivative of the antioxidant 6PPD used in the rubber industry, has been implicated in environmental and public health risks. To explore its impact on metabolic and cognitive functions, we orally administered 6PPDQ to mice and assessed its effects. Our results show that 6PPDQ induces a dose-dependent increase in body weight, elevated fasting blood glucose, Insulin resistance, and Other hallmarks of metabolic syndrome. Furthermore, cognitive tests revealed significant impairments in learning and memory in 6PPDQ-treated mice. Transcriptomic and Western blot analyses suggest that 6PPDQ disrupts Insulin signaling through inhibition of the PI3K-AKT pathway, leading to metabolic and cognitive dysfunction. Notably, treatment with the PI3K-AKT agonist SC79 partially alleviated these effects. These findings highlight the health risks of 6PPDQ exposure and suggest potential avenues for preventive and therapeutic strategies.

Keywords

6PPD-quinone; Cognitive impairment; Metabolic syndrome.

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