Lycium barbarum polysaccharides attenuates N-methy-N-nitrosourea-induced photoreceptor cell apoptosis in rats through regulation of poly (ADP-ribose) polymerase and caspase expression

J Ethnopharmacol. 2016 Sep 15:191:125-134. doi: 10.1016/j.jep.2016.05.037. Epub 2016 May 18.

Abstract

Ethnopharmacological relevance: Lycium barbarum L., popularly known as "Goji berry", a classic of Traditional Chinese Medicine has long been used to treat ocular diseases and cardiovascular diseases. Recently, the photoreceptor cell protection of Lycium barbarum polysaccharides (LBP), a water extract from Lycium barbarum L. has received more attention. The present study was designed to investigate the effect of LBP on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis, and the involvement of the poly (ADP-ribose) polymerase (PARP) and caspase.

Materials and methods: Photoreceptor cell injury was induced in male Sprague-Dawley rats by an intraperitoneal injection of MNU 60mg/kg. Seven days prior to MNU injection, LBP were intragastrical administered daily, rats were sacrificed at 24h and 7 days after MNU injection. Retinal morphologies, photoreceptor cells apoptosis, and protein expression were evaluated at 24h and 7 days after MNU injection.

Results: Morphologically, the outer nuclear layer was well preserved in the LBP-treated rat retinas throughout the experimental period. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) assays showed that LBP could significantly suppress the loss of photoreceptor cells, as determined by the photoreceptor cell ratio at the central retina 24h and 7 days after MNU administration. Western-blot analysis demonstrated the expression levels of procaspase-9, -7, -3 and cleaved caspase-9, -7, -3 were upregulated, and PARP were downregulated both 24h and 7 days after MNU injection. LBP treatment significantly decreased protein levels of procaspase and cleaved caspase, increased the level of PARP and cleaved PARP on 24h and 7 days.

Conclusions: LBP inhibits MNU-induced rat photoreceptor cell apoptosis and protects retinal structure via the regulation of the expressions of PARP and caspase.

Keywords: Apoptosis; Caspase; DAPI (PubChem CID:2954); Dithiothreitol (PubChem CID: 446094); Eosin (PubChem CID: 11048); Formalin (PubChem CID: 712); Hematoxylin (PubChem CID: 442514); Lycium barbarum polysaccharide; N,N'-Methylenebisacrylamide (PubChem CID: 8041); N-Methyl-N-nitrosourea (PubChem CID: 12699); N-methyl-N-nitrosourea; PMSF (PubChem CID: 4784); Photoreceptor cell; Poly (ADP-Ribose) polymerase; Rat; SDS (PubChem CID:3423265); Tris base (PubChem CID:6503).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspases / metabolism*
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Enzyme Activation
  • Lycium / chemistry*
  • Male
  • Methylnitrosourea*
  • Photoreceptor Cells, Vertebrate / drug effects*
  • Photoreceptor Cells, Vertebrate / enzymology
  • Photoreceptor Cells, Vertebrate / pathology
  • Phytotherapy
  • Plants, Medicinal
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Rats, Sprague-Dawley
  • Retinal Degeneration / chemically induced
  • Retinal Degeneration / enzymology
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control*
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Drugs, Chinese Herbal
  • Protective Agents
  • lycium barbarum polysaccharide
  • Methylnitrosourea
  • Poly(ADP-ribose) Polymerases
  • Caspases