3-Hydroxybenzaldehyde and 4-Hydroxybenzaldehyde enhance survival of mouse astrocytes treated with Angiostrongylus cantonensis young adults excretory/secretory products

Background: Human cerebral angiostrongyliasis, induced by Angiostrongylus cantonensis, is an emerging disease in many parts of the world. A. cantonensis is also an important causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. 3-Hydroxybenzaldehyde (3-HBA) and 4-Hydroxybenzaldehyde (4-HBA) have been shown to increase intracellular antioxidant activity, vasculoprotective potency, wound healing, and cell migration. However, the function of 3-HBA and 4-HBA in mouse astrocytes in response to A. cantonensis young adults excretory-secretory products (ESPs) treatment remains unclear. Methods: Here, we examined the effect of 3-HBA and 4-HBA by real-time qPCR, western blotting, and cell viability assay in astrocytes after A. cantonensis young adults ESPs treatment. The real-time qPCR, western blotting were employed to detect the expression of apoptosis- and Shh pathway-related molecule. The percentage of cell viability was monitored by CCK-8 assay. Results: We demonstrated that expression of apoptosis-related molecules was increased in response to A. cantonensis young adults ESPs treatment. However, the cell viability of astrocytes was elevated by treatment with 3-HBA and 4-HBA. Further investigation found that 3-HBA and 4-HBA activate the Shh signaling pathway and inhibit apoptosis-related molecule expression. Conclusions: These findings were confirmed using A. cantonensis young adults ESPs to activate apoptosis-related pathways in astrocytes. Moreover, 3-HBA and 4-HBA induced a protective phenotype through regulation of apoptosis in response to A. cantonensis young adults ESPs treatment. Hence, 3-HBA and 4-HBA represent potential therapeutic drugs for the treatment of human angiostrongyliasis.