1. Academic Validation
  2. Ginsenoside Rd ameliorates high glucose-induced retinal endothelial injury through AMPK-STRT1 interdependence

Ginsenoside Rd ameliorates high glucose-induced retinal endothelial injury through AMPK-STRT1 interdependence

  • Pharmacol Res. 2022 May;179:106123. doi: 10.1016/j.phrs.2022.106123.
Kai Tang 1 Weiwei Qin 1 Rongyun Wei 1 Yeying Jiang 1 Lingling Fan 1 Zhen Wang 2 Ninghua Tan 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
  • 2 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: drwang@cpu.edu.cn.
  • 3 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: nhtan@cpu.edu.cn.
Abstract

Diabetic retinopathy (DR) manifests as a complicated and blinding complication in diabetes mellitus. First-line treatments for advanced DR have shown ocular side-effects in some patients. Ginsenoside Rd (Rd), an active ingredient isolated from Panax notoginseng and P. ginseng, has demonstrated diverse and powerful activities on neuroprotection, Anticancer and anti-inflammation, but its vascular protective effects have rarely been reported. Herein, this study aims to investigate the protective effects of Rd on retinal endothelial injury with emphasis on AMPK/SIRT1 interaction. The results indicated that Rd promoted AMPK activation and SIRT1 expression. Besides, Rd strengthened the interaction between AMPK and SIRT1 by increasing NAD+/NADH levels and LKB1 deacetylation in endothelial cells. Moreover, Rd reversed high glucose-induced activation of NOX2, oxidative stress, mitochondrial dysfunction, and endothelial Apoptosis in an AMPK/SIRT1-interdependent manner. Hyperglycemia induced loss of endothelial cells and other retinal damage, which was restored by Rd via activating AMPK and SIRT1 in vivo. The enhancement of AMPK/SIRT1 interaction by Rd beneficially modulated oxidative stress and Apoptosis, and ameliorated diabetes-driven vascular damage. These data also supported the evidence for Rd clinical development of pharmacological interventions and provided a novel potential vascular protective drug for early DR.

Keywords

AICA-Riboside (PubChem CID: 17513); AMPK; Compound C (PubChem CID: 11524144); D-(+)-Glucose (PubChem CID: 107526); Diabetic Retinopathy; Diphenyleneiodonium chloride (PubChem CID: 2733504); Endothelial Injury; Ginsenoside Rd; Ginsenoside Rd (PubChem CID: 24721561); N-Acetyl-L-cysteine (PubChem CID: 12035); Nicotinamide (PubChem CID: 936); Resveratrol (PubChem CID: 445154); SIRT1; Streptozocin (PubChem CID: 29327).

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