β-asarone inhibits autophagic neuron death by downregulating reactive astrocytes-derived SPARC expression in LPS-induced SH-SY5Y cells

Abstract β-asarone, the main active component ofAcori tatarinowiirhizoma (ATR), exhibits several pharmacological properties, including anti-inflammatory, anti-aging, and neuroprotective effects. In recent years, a large number of studies have shown that β-asarone exerts a positive effect on improving the cognitive level of individuals with Alzheimer’s disease (AD). However, the effects of β-asarone on autophagy in neuroinflammation-induced AD and the potential underlying mechanisms remain unclear. In the present study, we found that β-asarone inhibited LPS-induced activation of NHA cells and significantly decreased the expression of inflammatory factors andsparc. Exposure to exogenous SPARC promoted apoptosis and autophagy in neuronal cells. Further, we co-cultured LPS-induced reactive human astrocytes [NHA (normal human astrocytes)] with human neuronal cells (SH-SY5Y cell line) to establish a neurocyte inflammatory microenvironment to mimic the neuroinflammatory model of ADin vitro. Based on the above co-culture system, we observed that after SPARC overexpression in NHA, the behavior of the neuronal cells resembled that after exogenous SPARC treatment. However, β-asarone treatment reversed these effects and protected the cells against neuronal damage. These findings suggested that the matrix protein SPARC plays an important role in neuronal damage in AD model mice, and β-asarone intervention can be utilized as a potential therapeutic strategy for AD.