Extract Protects Glutamate-Induced Nerve Cell Damage by Inhibiting Receptor Activation.

Neurocytotoxicity elicited by receptors (NMDAR) is a substantial contributor to neurodegenerative diseases. Our current study expands on the previous findings in which (L.) extract (PAS840) was shown to protect PC12 cells from hydrogen peroxide-induced injury. In this investigation, we performed LC-MS/MS and peptidomics analyses on the constituents of PAS840. Considering Alzheimer's disease (AD) as the primary focus, we utilized network pharmacology and molecular-docking techniques to predict PAS840's influence on AD targets. We established a glutamate (Glu)-induced PC12 cell injury model to conduct a comprehensive examination of PAS840's effects on pivotal cellular parameters, including intracellular Ca levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, reactive oxygen species (ROS) levels, cell apoptosis rate, mitochondrial membrane potential (MMP) levels, and the expression of key proteins such as NMDAR1, cytochrome c (Cytc), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). The results suggest that PAS840 manifests multi-target actions, robustly attenuating NMDAR activity. It efficaciously suppresses excessive NMDAR1 activation, restricts Ca influx, alleviates oxidative stress, and mitigates inflammation, thereby ameliorating neuronal cell damage. Consequently, it establishes a solid scientific foundation for further exploration of PAS840's potential in addressing neurological diseases.