Shabyar Ameliorates High Glucose Induced Retinal Pigment Epithelium Injury Through Suppressing Aldose Reductase and AMPK/mTOR/ULK1 Autophagy Pathway

Xiao Yan Liu; Jun Peng; Fei He; Xirali Tursun; Shu Ping Li; Xue Lei Xin; Haji Akber Aisa

doi:10.3389/fphar.2022.852945

Shabyar Ameliorates High Glucose Induced Retinal Pigment Epithelium Injury Through Suppressing Aldose Reductase and AMPK/mTOR/ULK1 Autophagy Pathway

Front Pharmacol. 2022 May 10:13:852945. doi: 10.3389/fphar.2022.852945. eCollection 2022.

Authors

Xiao Yan Liu^{1

2

3}, Jun Peng^{1

2}, Fei He¹, Xirali Tursun⁴, Shu Ping Li¹, Xue Lei Xin¹, Haji Akber Aisa¹

Affiliations

¹ The State Key Laboratory Basis Xinjiang Indigenous Medicinal Plant Resource, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Xinjiang Institute of Materia Medica, Urumqi, China.
⁴ Institute of Xinjiang Traditional Uyghur Medicine, Urumqi, China.

Abstract

Shabyar (SBA) is a traditional medicine formula for relieving vision loss caused by factors including diabetic retinopathy (DR) in clinics. However, the mechanism of it on retina protective effect still unclear. The present study aimed to investigate whether its protective effect was related to aldose reductase (AR) inhibition and retinal pigment epithelial cell injury mediated by autophagy or not. Human retinal pigment epithelial cells (ARPE-19) induced by high glucose was used as a model in vitro, with Epalrestat (EPL, AR inhibitor) and Difrarel (DFR, DR therapeutic drug) as positive controls. Western blotting and Polyol pathway products assay showed that SBA reduced the expression of AR protein and the content of ROS, and sorbitol, increased the level of Na⁺-K⁺-ATPase and alleviated cell edema. Western blotting and DCFH-DA probe assay showed that SBA decreased pAMPK/AMPK and pULK1/ULK1 which associated with autophagy initiation, down-regulated Beclin-1, Atg3, Atg5, Atg7, LC3 II and Bax/Bcl2 ratio, and up-regulated pmTOR/mTOR, SQSTM1/p62 and mitochondrial membrane potential (MMP), reduces intracellular autophagosomes. Real-Time PCR assay showed that SBA had no significant effect on mRNA expression of AR and mTOR. These data demonstrated that SBA treatment inhibits the autophagy of ARPE-19 through the AMPK/mTOR/ULK1 signaling pathway, and reduced early-stage apoptosis occurred by high glucose. These findings reveal the protective role and mechanism of SBA on retinal pigment epithelium, and provide experimental basis for the clinical application of SBA in the treatment of DR.

Keywords: aldose reductase; autophagy; retinal pigment epithelium; shabyar; traditional medicine formula.