Lycium barbarum L. and Salvia miltiorrhiza Bunge extract ameliorates retinitis pigmentosa in rd10 mice by affecting endoplasmic reticulum stress

J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118971. doi: 10.1016/j.jep.2024.118971. Epub 2024 Oct 19.

Abstract

Ethnopharmacological relevance: Lycium barbarum L. and Salvia miltiorrhiza Bunge (Gouqi and Danshen, LS) have led to their inclusion in the pharmacopoeia and healthcare systems of numerous countries globally. Traditional herbs known as LS are used in China to treat retinitis pigmentosa (RP). However, the mechanism is not clear.

Aim of the study: This study is to investigate the mechanism by which LS improves RP using rd10 mice as a model.

Materials and methods: LS extract was used to treat the rd10 mice for four weeks. Fundus photographs, optical coherence tomography, electroretinography, histopathological examination, TUNEL apoptosis assay, digital PCR analysis, western blotting, and immunofluorescence double staining were performed.

Results: The outer nuclear layer (ONL) thickness of the retina was significantly increased by the LS extract, improving atrophy, and both the ONL and the retinal pigment epithelium (RPE) layer were visible. Following treatment with LS extract, there was a notable increase in the magnitudes of ERG a- and b-waves in the retina, along with a significant reduction in the quantity of TUNEL-positive cells. Additionally, LS extract significantly reduced the levels of ER stress-related factors in rd10 mice. The results of immunofluorescence double staining further confirm that LS extract inhibits the GRP78/PERK/ATF4/CHOP pathway.

Conclusion: In this study, the protective effects of LS extract on the retina were uncovered, suggesting that its mechanism could involve decreasing retinal cell apoptosis through the inhibition of the ER stress pathway.

Keywords: Endoplasmic reticulum stress; Lycium barbarum L.; Retinitis pigmentosa; Salvia miltiorrhiza bunge; rd10 mice.

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Activating Transcription Factor 4 / metabolism
  • Animals
  • Apoptosis* / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Electroretinography
  • Endoplasmic Reticulum Chaperone BiP*
  • Endoplasmic Reticulum Stress* / drug effects
  • Lycium* / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology
  • Retina* / drug effects
  • Retina* / metabolism
  • Retina* / pathology
  • Retinitis Pigmentosa* / drug therapy
  • Retinitis Pigmentosa* / metabolism
  • Retinitis Pigmentosa* / pathology
  • Salvia miltiorrhiza* / chemistry
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • Hspa5 protein, mouse
  • Drugs, Chinese Herbal
  • Plant Extracts
  • Activating Transcription Factor 4
  • Transcription Factor CHOP