Protective effect of benzaldehyde combined with albendazole against brain injury induced by Angiostrongylus cantonensis infection in mice

Abstract

Angiostrongylus cantonensis, also known as rat lungworm, is an important food-borne zoonotic parasite that causes severe neuropathological damage and symptoms, including eosinophilic meningitis and eosinophilic meningoencephalitis, in humans. At present, the therapeutic strategy for cerebral angiostrongyliasis remains controversial. Benzaldehyde, an important bioactive constituent of Gastrodia elata (Tianma), reduces oxidative stress by inhibiting the production of reactive oxygen species. This study aimed to evaluate the therapeutic effect of benzaldehyde in combination with albendazole on angiostrongyliasis in animal models. First, the data from body weight monitoring and behavioural analyses demonstrated that benzaldehyde improved body weight and cognitive function changes after A. cantonensis infection. Next, blood‒brain barrier breakdown and pathological changes were reduced after benzaldehyde and albendazole treatment in BALB/c mice infected with A. cantonensis. Subsequently, four RNA-seq datasets were established from mouse brains that had undergone different treatments: normal, infection, infection + albendazole, and infection + albendazole + 3-hydroxybenzaldehyde groups. Ultimately, benzaldehyde was found to regulate cell apoptosis, oxidative stress and Sonic Hedgehog signalling in mouse brains infected with A. cantonensis. This study evaluated the therapeutic effect of benzaldehyde on angiostrongyliasis, and provided a potential therapeutic strategy for human angiostrongyliasis in the clinical setting. Moreover, the molecular mechanism of benzaldehyde in mouse brains infected with A. cantonensis was elucidated.

Keywords: Albendazole; Angiostrongylus cantonensis; Benzaldehyde; Cell apoptosis; Oxidative stress; Therapeutic strategy.