Suntamide A, a neuroprotective cyclic peptide from Cicadidae Periostracum

Bioorg Chem. 2021 Jan:106:104493. doi: 10.1016/j.bioorg.2020.104493. Epub 2020 Nov 19.

Abstract

Suntamide A (1), a new cyclic peptide, was isolated from Cicadidae Periostracum. The gross structure of 1 was elucidated by detailed analysis of HRMS and 1D/2D NMR spectra, and the absolute configuration was established by C3 Marfey's method. We extended our study to examine biological activity of 1, and found that 1 protected SH-SY5Y cells against rotenone-induced neurotoxicity. This effect of 1 seemed to be attributed to antioxidant induction and protection of mitochondria from rotenone-caused injury. Along with augmentation of the antioxidant system by 1, there was an evident activation of Nrf2, a transcription factor involved in the activation of the antioxidant system. These results indicate that 1 rescued the cells from rotenone-mediated neurotoxicity by enhancing antioxidant capacity via induction of Nrf2, suggesting that the compound could be used as a therapeutic intervention in neurodegenerative diseases such as Parkinson's disease.

Keywords: Antioxidative capacity; Cicadidae Periostracum; Cyclic peptide; Mitochondria; Neurotoxicity; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hemiptera / chemistry*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Structure
  • NF-E2-Related Factor 2 / metabolism*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Rotenone / antagonists & inhibitors
  • Rotenone / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neuroprotective Agents
  • Peptides, Cyclic
  • Reactive Oxygen Species
  • Rotenone