2. Academic Validation
  3. Neohesperidin alleviates the inhibitory effect of bisphenol A on the myogenic differentiation of umbilical cord mesenchymal stem cells via the IGF1R/AKT1/RHOA signaling pathway

Neohesperidin alleviates the inhibitory effect of bisphenol A on the myogenic differentiation of umbilical cord mesenchymal stem cells via the IGF1R/AKT1/RHOA signaling pathway

  • Ecotoxicol Environ Saf. 2024 Jul 30:283:116804. doi: 10.1016/j.ecoenv.2024.116804.
Jie Yang 1,  Sen Qin 2,  Nannan Sun 1,  Yang Cai 3,  Junling Li 3,  Zhuhui Zhai 3,  Jie An 1,  Hejie Wang 3,  Rong Du 3,  Jian Qin 4
Affiliations

Affiliations

  • 1 College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
  • 2 School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.
  • 3 College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
  • 4 College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China; College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Center of Experiment Teaching, Shanxi Agricultural University, Taigu, Shanxi 030801, China. Electronic address: qinjian969@163.com.
PMID: 39083871 DOI: 10.1016/j.ecoenv.2024.116804
Abstract

Bisphenol A (BPA), a typical environmental endocrine disruptor, has raised concerns among researchers due to its toxicological effects. Whether neohesperidin (NEO) can intervene in the toxic effects of BPA remains unknown. This study aims to investigate the effects and mechanisms of NEO on the myogenic differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) exposed to BPA. Sheep UC-MSCs were isolated, characterized, and induced to myogenic differentiation. BPA decreased cell viability, cell migration, and the expressions of myogenic marker genes, leading to myogenic differentiation inhibition, which were reversed by NEO. Network pharmacology suggested the IGF1R/Akt1/RHOA pathway as potential targets of BPA and NEO regulating muscle development. Western blot results showed that NEO could reverse the down-regulation of the pathway proteins induced by BPA, and counteract the effects of picropodophyllin (PPP) or MK-2206 dihydrochloride (MK-2206) in the myogenic differentiation of sheep UC-MSCs. Additionally, the expression levels of (p-) IGF1R, Akt1, and RHOA were positively correlated. Taken together, the mechanisms of NEO resistance to BPA involved the IGF1R/Akt1/RHOA signaling pathway. These findings provide a scientific basis for alleviating BPA toxicity, preventing and treating muscular dysplasia, and promoting muscle damage repair.

Keywords

Bisphenol A; IGF1R/AKT1/RHOA pathway; Mesenchymal stem cells; Myogenic differentiation; Neohesperidin.

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