ReferenceID 6032
Polydatin attenuates orbital oxidative stress in Graves' orbitopathy through the NRF2 pathway
Chem Biol Interact
Graves' orbitopathy (GO) is a sight-threatening ocular disease that occurs in patients with hyperthyroidism and is especially associated with oxidative stress. Polydatin (PD) is a major active component of Polygonum cusp
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- Reference Id
- 6032
- Evidence Id
- 22622
- Core Evidence Id
- 22622
- Source Reference Id
- 5327
- Herb2 Reference Id
- HBREF006124
- Subject Paper Key
- HBIN040403_31705858
- Pubmed Id
- 31705858
- Doi
- 10.1016/j.cbi.2019.108894
- Paper Title
- Polydatin attenuates orbital oxidative stress in Graves' orbitopathy through the NRF2 pathway
- Paper Abstract
- Graves' orbitopathy (GO) is a sight-threatening ocular disease that occurs in patients with hyperthyroidism and is especially associated with oxidative stress. Polydatin (PD) is a major active component of Polygonum cuspidatum Sieb. et Zucc. It has various therapeutic effects including anti-inflammatory and antioxidant properties. In the present study, we investigated the effects of PD on H2O2-induced oxidative stress in orbital fibroblasts in vitro and in a GO mouse model of orbital oxidative stress in vivo. The mechanisms responsible for these effects were investigated using standard molecular techniques. Our initial findings in GO mice were that PD attenuated orbital muscle adipose tissue expansion and lipid droplet accumulation through a nuclear factor E2-related factor 2 (NRF2)-mediated oxidative stress response involving the Keap1/Nrf2/ARE pathway. The results demonstrated that PD could reverse the accumulation of lipid droplets and production of reactive oxygen species (ROS) induced by H2O2 and increase the expression of antioxidant genes such as NAD(P)H dehydrogenase, quinone 1 (NQO1). NQO1 levels were the lowest in the GO mouse model. In addition, PD enhanced NRF2 nuclear translocation in cultured orbital fibroblasts. We also found that silencing NRF2, using RNA interference, reduced the protective effects of PD against H2O2-induced oxidative stress in orbital fibroblasts in vitro. Taken together, our results indicate that PD can reduce the production of ROS and inhibit adipogenesis in orbital fibroblasts in vitro and in vivo.
- Journal
- Chem Biol Interact
- Publish Year
- 2020
- Experiment Subject
- mouse; patient; cultured orbital fibroblasts
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hyperthyroidism; Graves' Orbitopathy; Sight-threatening Ocular Disease
- Paper Title Cn
- Paper Title En
- Polydatin attenuates orbital oxidative stress in Graves' orbitopathy through the NRF2 pathway
- Bilingual Status
- semi_complete