Ferulago angulata Methanolic Extract Protects PC12 Cells Against Beta-amyloid-induced Toxicity

INTRODUCTION: Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid (Aβ)-induced neurotoxicity has a pivotal role in AD pathogenesis; therefore, the modulation of Aβ toxicity is the promising therapeutic approach to control the disease progression. Medicinal plants because of their multiple active ingredients are effective in complex diseases, such as AD. Therefore, several studies have studied medicinal plants to find an effective treatment for AD. Ferulago angulata is a medicinal plant with antioxidant and neuroprotective activity. The present study was done to assess the protective effect of the methanolic extract of Ferulago angulate on Aβ-induced toxicity and oxidative stress in PC12 cells. METHODS: The methanolic extract of aerial parts of the plant was prepared by the maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aβ alone, and Aβ in combination with various concentrations of the F. angulata extract. Cell viability was determined by the methyl thiazole tetrazolium (MTT) assay. Also, reactive oxygen species (ROS) production and the activity of acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. RESULTS: The extract dose-dependently protected PC12 cells against Aβ-induced cell death. Also, Aβ increased ROS production, AChE, and caspase-3 activity, and decreased the GPx activity, which all were ameliorated by F. angulata extract. CONCLUSION: F. angulata extract protects against Aβ-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended to assess F. angulata extract as an anti-AD agent. HIGHLIGHTS: Ferulago angulata extract dose-dependently ameliorates Aβ-induced cytotoxicity in PC12 cells. Aβ induced oxidative stress in PC12 cells, which was attenuated by the F. angulata extract. Aβ increased acetylcholinesterase activity in PC12 cells, which was prevented by the F. angulata extract. PLAIN LANGUAGE SUMMARY: Alzheimer’s disease (AD) is a common form of dementia in the elderly with a complex pathophysiology. Beta-amyloid (Aβ)- induced neurotoxicity plays a pivotal role in AD progression. So far, there is no cure for AD. Medicinal plants contain various pharmacologically active compounds that make them suitable for the treatment of complex diseases. In this study, the anti-AD effect of F. angulata extract was investigated by assessing its protective effect against Aβ-induced toxicity in PC12 cells F. angulata extract improved Aβ-induced toxicity by diminishing oxidative stress and apoptosis. Therefore, F. angulata extract merits further studies for use in the treatment of AD.