Safety evaluation and protective effects of ethanolic extract from maca (Lepidium meyenii Walp.) against corticosterone and H2O2 induced neurotoxicity

Regul Toxicol Pharmacol. 2020 Mar:111:104570. doi: 10.1016/j.yrtph.2019.104570. Epub 2019 Dec 26.

Abstract

Maca has been traditionally used to enhance sexual behavior and fertility. Recently, maca's neuroprotective effects have been reported. The purpose of this study was to investigate whether the ethanol extract of maca (EEM) (100 mg/kg/bw, 200 mg/kg/bw, 400 mg/kg/bw, p.o.) exerted neuroprotective effects in corticosterone (CORT)-induced (40 mg/kg/bw, s.c.) rats, to determine the neuroprotective effects of EEM (12.5, 25, 50 μg/ml) and macamides in H2O2-induced (50 μM) PC12 cells. The acute toxicity (2000 mg/kg/bw, p.o.) and subacute toxicity (200 mg/kg/bw, 500 mg/kg/bw, 1000 mg/kg/bw, p.o.) of EEM were evaluated by mouse models. EEM reversed CORT-induced abnormal behaviors, reduced the contents of TNF-α, IL-6 in hippocampi, and increased the positive cells of doublecortin (DCX), bromodeoxyuridine (BrdU) and DCX + BrdU in the hippocampus of rats. Moreover, EEM and 4 macamides remarkably increased the cell viability in H2O2-induced PC12 cells. EEM promoted the phosphorylation of IκBα and p65, suppressed the NF-κB activation, and inhibited the levels of pro-inflammatory cytokines such as TNF-α, IL-6 and their mRNA levels in H2O2-induced PC12 cells. In conclusion, EEM could exert neuroprotective effects in CORT-induced rats and in H2O2-induced PC12 cells. Moreover, EEM did not present relevant toxicity after exposure to single and repeated doses.

Keywords: Corticosterone; Ethanolic extract from maca; Macamides; Neuroprotective effects; Pro-inflammatory cytokines; Safety evaluation.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Corticosterone / administration & dosage
  • Corticosterone / antagonists & inhibitors*
  • Corticosterone / toxicity*
  • Dose-Response Relationship, Drug
  • Doublecortin Protein
  • Ethanol / chemistry*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydrogen Peroxide / administration & dosage
  • Hydrogen Peroxide / antagonists & inhibitors*
  • Hydrogen Peroxide / toxicity*
  • Lepidium / chemistry*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Toxicity Tests, Acute

Substances

  • Dcx protein, mouse
  • Dcx protein, rat
  • Doublecortin Protein
  • Neuroprotective Agents
  • Plant Extracts
  • Ethanol
  • Hydrogen Peroxide
  • Corticosterone