In Vitro and In Vivo Neuroprotective Effects of Stellettin B Through Anti-Apoptosis and the Nrf2/HO-1 Pathway

Mar Drugs. 2019 May 29;17(6):315. doi: 10.3390/md17060315.

Abstract

Pharmaceutical agents for halting the progression of Parkinson's disease (PD) are lacking. The current available medications only relieve clinical symptoms and may cause severe side effects. Therefore, there is an urgent need for novel drug candidates for PD. In this study, we demonstrated the neuroprotective activity of stellettin B (SB), a compound isolated from marine sponges. We showed that SB could significantly protect SH-SY5Y cells against 6-OHDA-induced cellular damage by inhibiting cell apoptosis and oxidative stress through PI3K/Akt, MAPK, caspase cascade modulation and Nrf2/HO-1 cascade modulation, respectively. In addition, an in vivo study showed that SB reversed 6-OHDA-induced a locomotor deficit in a zebrafish model of PD. The potential for developing SB as a candidate drug for PD treatment is discussed.

Keywords: HO-1; Nrf2; Parkinson’s disease; apoptosis; oxidative stress; sponge-derived compound.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Aquatic Organisms / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Locomotion / drug effects
  • NF-E2-Related Factor 2 / metabolism*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects*
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy
  • Porifera / chemistry*
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Zebrafish

Substances

  • NF-E2-Related Factor 2
  • Neuroprotective Agents
  • Triterpenes
  • stellettin B
  • Oxidopamine
  • Heme Oxygenase-1