Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy.

Abstract

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

• Authors: Ping Zhou, Weijie Xie, Xiangbao Meng, Yadong Zhai, Xi Dong, Xuelian Zhang, Guibo Sun, Xiaobo Sun
• Journal: Cells (Cells) Vol. 8 Issue 3 (03 02 2019) ISSN: 2073-4409 [Print] Switzerland
• PMID: 30832367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• Ginsenosides
• Nerve Growth Factors
• Serpins
• Vascular Endothelial Growth Factor A
• pigment epithelium-derived factor
• Protein Kinases
• PTEN-induced putative kinase
• Glucose
• notoginsenoside R1

Topics

• Animals
• Cell Death (drug effects)
• Diabetic Retinopathy (drug therapy, enzymology, pathology)
• Ependymoglial Cells (drug effects, ultrastructure)
• Eye Proteins (metabolism)
• Ginsenosides (pharmacology, therapeutic use)
• Glucose (toxicity)
• Inflammation (pathology)
• Mice
• Mitochondria (drug effects, metabolism, ultrastructure)
• Mitophagy (drug effects)
• Nerve Growth Factors (metabolism)
• Oxidative Stress (drug effects)
• Protein Kinases (metabolism)
• Rats
• Serpins (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)