Neuroprotective effect of He-Ying-Qing-Re formula on retinal ganglion cell in diabetic retinopathy

Cheng Zhang, Yu Xu, Hor Yue Tan, Sha Li, Ning Wang, Yinjian Zhang*, Yibin Feng*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

32 Citations (Scopus)


Ethnopharmacology relevance: He-Ying-Qing-Re Formula (HF) was empirically modified from Si-Miao-Yong-An Decoction (SD), which was recorded in the literature of Divine Doctor's Secret Transmission, and has been utilized for centuries to treat vasculopathy through clearing heat and accelerating bloodstream. HF has been used as an effective holistic treatment of diabetic retinopathy (DR) for decades and experimentally reported to ameliorate retinal condition in diabetic mice.

Aim of the study: Our study aims to investigate the effect of HF in preventing sustained hyperglycemia and hyperlipidemia-associated retinal ganglion cell (RGC) cell death and its possible mechanism.

Materials and methods: Chromatographic fingerprint of HF was obtained upon the UPLC-based analytic system; Diabetic retinopathy was established in streptozotocin (STZ) injection-induced hyperglycemic mice; Alterations of retinal structure was assayed by H&E staining. Expression of PSD-95 and CHOP in retinae was assessed by immunofluorescence; RGC cell line (mRGC) was used for in vitro study. Cell death was analyzed by flow cytometry; Intracellular reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescin diacetate (DCFDA); Apoptosis-related proteins and signaling were monitored with immunoblotting and colorimetric assay.

Results: Chlorogenic acid, ferulic acid, and rutin were identified in HF. HF attenuates the loss of RGCs, thinning of inner retinal layers in diabetic mice. Furthermore, expressions of Brn3a and PSD-95 were restored while CHOP level was downregulated upon HF treatment. In vitro study, HF alleviates H2O2-induced apoptosis of mRGCs and loss of postsynaptic protein via scavenging ROS and suppressing ATF4/CHOP-mediated endoplasmic reticulum stress and mitochondria-related pro-apoptotic factors, probably as cleaved-caspase-3, and phospho-p38 mitogen-activated protein kinase (MARK). Meanwhile, both pro-survival protein levels like Bcl-2/Bcl-xL and postsynaptic protein of PSD-95 were upregulated upon HF treatment.

Conclusion: HF administration was a valid therapeutic approach for DR treatment, oriented at the blockade of endoplasmic reticulum- and mitochondria-dependent oxidative stress-induced retinal neurodegeneration including RGC apoptosis.

Original languageEnglish
Pages (from-to)179-189
Number of pages11
JournalJournal of Ethnopharmacology
Publication statusPublished - 25 Mar 2018

Scopus Subject Areas

  • Pharmacology
  • Drug Discovery

User-Defined Keywords

  • Diabetic retinopathy
  • Endoplasmic reticulum stress
  • He-Ying-Qing-Re formula
  • Retinal degeneration
  • RGC apoptosis


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