Moschus exerted protective activity against H2O2-induced cell injury in PC12 cells through regulating Nrf-2/ARE signaling pathways

Biomed Pharmacother. 2023 Mar:159:114290. doi: 10.1016/j.biopha.2023.114290. Epub 2023 Jan 26.

Abstract

The pivotal characteristics of Alzheimer's disease (AD) are irreversible memory loss and progressive cognitive decline, eventually causing death from brain failure. In the various proposed hypotheses of AD, oxidative stress is also regarded as a symbolic pathophysiologic cascade contributing to brain diseases. Using Chinese herbal medicine may be beneficial for treating and preventing AD. As a rare and valuable animal medicine, Moschus possesses antioxidant and antiapoptotic efficacy and is extensively applied for treating unconsciousness, stroke, coma, and cerebrovascular diseases. We aim to evaluate whether Moschus protects PC12 cells from hydrogen peroxide (H2O2)-induced cellular injury. The chemical constituents of Moschus are analyzed by GC-MS assay. The cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) levels, oxidative stress-related indicators, and apoptotic proteins are determined. Through GC-MS analysis, nineteen active contents were identified. The cell viability loss, lactate dehydrogenase releases, MMP levels, ROS productions, and Malondialdehyde (MDA) activities decreased, and BAX, Caspase-3, and Kelch-like ECH-associated protein 1 expression also significantly down-regulated and heme oxygenase 1, nuclear factor erythroid-2-related factor 2 (Nrf-2), and quinine oxidoreductase 1 expression upregulated after pretreatment of Moschus. The result indicated Moschus has neuroprotective activity in relieving H2O2-induced cellular damage, and the potential mechanism might be associated with regulating the Nrf-2/ARE signaling pathway. A more in-depth and comprehensive understanding of Moschus in the pathogenesis of AD will provide a fundamental basis for in vivo AD animal model research, which may be able to provide further insights and new targets for AD therapy.

Keywords: Alzheimer's disease; Apoptosis; Moschus; Nrf-2/ARE signaling pathway; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Survival
  • Hydrogen Peroxide* / toxicity
  • NF-E2-Related Factor 2 / metabolism
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Neuroprotective Agents
  • NF-E2-Related Factor 2