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Updated: Aug 12, 2026
High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
Moschus exerted protective activity against H2O2-induced cell injury in PC12 cells through regulating Nrf-2/ARE
Danni Xie1, Ting Deng2, Zhenwei Zhai3
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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.
Insights
Moschus, a traditional Chinese medicine, demonstrated neuroprotective effects against oxidative stress in Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
- Oxidative Stress Research
Background:
- Alzheimer's disease (AD) is characterized by irreversible memory loss and cognitive decline, with oxidative stress implicated in its pathogenesis.
- Chinese herbal medicines, including Moschus, are explored for their potential therapeutic benefits in neurodegenerative diseases.
- Moschus, a valuable animal-derived medicine, exhibits known antioxidant and antiapoptotic properties relevant to brain health.
Purpose of the Study:
- To investigate the neuroprotective potential of Moschus against hydrogen peroxide (H₂O₂)-induced cellular injury in PC12 cells.
- To elucidate the underlying mechanisms, particularly the involvement of the Nrf-2/ARE signaling pathway.
Main Methods:
- Gas chromatography-mass spectrometry (GC-MS) was used to analyze the chemical constituents of Moschus.
- PC12 cells were pretreated with Moschus and then exposed to H₂O₂ to induce oxidative stress.
- Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), oxidative stress markers (e.g., MDA), and apoptotic proteins (e.g., BAX, Caspase-3) were assessed.
Main Results:
- GC-MS identified nineteen active compounds in Moschus.
- Moschus pretreatment significantly improved cell viability, reduced lactate dehydrogenase release, and preserved MMP in H₂O₂-treated cells.
- Moschus downregulated ROS and MDA levels, decreased the expression of pro-apoptotic proteins (BAX, Caspase-3), and upregulated antioxidant proteins (HO-1, Nrf-2, NQO1), suggesting activation of the Nrf-2/ARE pathway.
Conclusions:
- Moschus exhibits significant neuroprotective activity against H₂O₂-induced cellular damage in vitro.
- The protective mechanism is likely mediated by the regulation of the Nrf-2/ARE signaling pathway, highlighting Moschus as a potential therapeutic agent for AD.
- Further research in AD animal models is warranted to explore Moschus's therapeutic potential and identify new therapeutic targets.
