Mechanistic investigation of the ameliorative effect of crocin on arsenic trioxide-induced HT22 nerve cells injury based on network pharmacology and in vitro validation

Background: This study aims to explore the protective effect of crocin on arsenic trioxide (ATO)-induced HT22 nerve cell damage and its molecular mechanism.Preliminary predictions from network pharmacology indicate that the neuroprotective effect of crocin involves a wide range of areas, including the regulation of oxidative stress, inhibition of inflammation, and intervention in apoptosis.Methods: Pharmacology methods were used to systematically explore the potential targets and core molecular mechanisms of crocin's neuroprotective effect; An ATOinduced neuronal damage model was established in HT22 nerve cells;In in vitro cell experiments, the inhibitory effect of crocin on cellular endoplasmic reticulum stress was detected; The correlation between the neuroprotective effect of crocin and the activation of the Nrf2/HO-1 pathway was verified;The detection indicators included: intracellular calcium ion concentration ([Ca] i ), oxidative stress level, cell apoptosis rate, reactive oxygen species (ROS) production, inflammatory factor expression level, and the expression levels of Nrf2/HO-1 pathway-related proteins.Results: Pharmacology analysis confirmed that crocin has multi-dimensional neuroprotective potential against ATO-induced neurotoxicity, with its effects covering key pathological processes such as oxidative stress, inflammatory response, and cell apoptosis;After crocin intervention, the [Ca] i level, oxidative stress degree, cell apoptosis rate, ROS production, and inflammatory factor levels in HT22 nerve cells were significantly reduced;Crocin treatment could effectively regulate the expression levels of Nrf2/HO-1 pathway-related proteins.Conclusion: Crocin has a significant neuroprotective effect on ATO-induced HT22 nerve cell damage.Its mechanism may involve anti-oxidative stress, anti-cell apoptosis, and inhibition of inflammatory response, and this protective effect is likely achieved by activating the Nrf2/HO-1 signaling pathway.