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  3. Jin-Gui-Shen-Qi Wan ameliorates diabetic retinopathy by inhibiting apoptosis of retinal ganglion cells through the Akt/HIF-1α pathway

Jin-Gui-Shen-Qi Wan ameliorates diabetic retinopathy by inhibiting apoptosis of retinal ganglion cells through the Akt/HIF-1α pathway

  • Chin Med. 2023 Oct 12;18(1):130. doi: 10.1186/s13020-023-00840-7.
Dan Liang # 1,  Yulin Qi # 2,  Lu Liu # 3,  Zhaoxia Chen 4,  Shiyun Tang 5,  Jianyuan Tang 6,  Nianzhi Chen 7
Affiliations

Affiliations

  • 1 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 2 Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 4 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
  • 5 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. [email protected].
  • 6 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. [email protected].
  • 7 State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China. [email protected].
  • # Contributed equally.
PMID: 37828620 DOI: 10.1186/s13020-023-00840-7
Abstract

Background: Jin-Gui-Shen-Qi Wan (JGSQ) has been used in China for thousands of years to treat various ailments, including frequent urination, blurred vision, and soreness in the waist and knees. It has traditional therapeutic advantages in improving eye diseases.

Aim of the study: Clinical studies have confirmed the therapeutic efficacy of JGSQ in improving diabetes and vision; however, its efficacy and pharmacological effects in treating diabetic retinopathy (DR) remain unclear. Therefore, the aim of this study was to investigate the specific pharmacological effects and potential mechanisms of JGSQ in improving DR through a db/db model.

Materials and methods: db/db mice were given three different doses of orally administered JGSQ and metformin for 8 weeks, and then PAS staining of the retinal vascular network patch, transmission electron microscopy, H&E staining, and TUNEL staining were performed to determine the potential role of JGSQ in improving DR-induced neuronal cell Apoptosis. Furthermore, network pharmacology analysis and molecular docking were carried out to identify the main potential targets of JGSQ, and the efficacy of JGSQ in improving DR was evaluated through western blotting and immunofluorescence staining, revealing its mechanism of action.

Results: According to the results from H&E, TUNEL, and PAS staining of the retinal vascular network patch and transmission electron microscopy, JGSQ does not have an advantage in improving the abnormal morphology of vascular endothelial cells, but it has a significant effect on protecting retinal ganglion cells from Apoptosis. Through network pharmacology and molecular docking, Akt, GAPDH, TNF, TP53, and IL-6 were identified as the main core targets of JGSQ. Subsequently, through western blot and immunofluorescence staining, it was found that JGSQ can inhibit HIF-1α, promote p-AKT expression, and inhibit TP53 expression. At the same time, inhibiting the release of inflammatory factors protects retinal ganglion cells and improves Apoptosis in DR.

Conclusion: These results indicated that in the db/db DR mouse model, JGSQ can inhibit the expression of inflammatory cytokines and protect retinal ganglion cells from Apoptosis, possibly by modulating the Akt/HIF-1α pathway.

Keywords

Akt/HIF-1α pathway; Diabetic retinopathy; JGSQ; Retinal ganglion cells.

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