Mechanistic investigation of the ameliorative effect of crocin on arsenic trioxide-induced HT22 nerve cells injury based on network pharmacology and in vitro validation.
Li Chen, Xian Mengqi, Liu Jiaze, An Yahui, Di Xiaoxia, Yin Jintuo, Zuo Yalan, Chu Xi, Wang Hefei, Han Xue
Abstract
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 ATO-induced 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 ([Ca2⁺]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 [Ca2⁺]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.
Key Findings
- Crocin exhibits neuroprotective effects against arsenic trioxide-induced damage in HT22 nerve cells.
- Crocin reduces intracellular calcium ion concentration, oxidative stress, cell apoptosis, ROS production, and inflammatory factor levels in damaged nerve cells.
- The neuroprotective mechanism of crocin involves activation of the Nrf2/HO-1 signaling pathway, leading to anti-oxidative stress, anti-apoptotic, and anti-inflammatory effects.
Clinical Significance
Crocin may serve as a potential therapeutic agent to mitigate neurotoxicity caused by arsenic trioxide exposure by targeting oxidative stress and inflammation through the Nrf2/HO-1 pathway.
Citation
Li Chen, Xian Mengqi, Liu Jiazeet al.. Mechanistic investigation of the ameliorative effect of crocin on arsenic trioxide-induced HT22 nerve cells injury based on network pharmacology and in vitro validation. Neuroscience. 2026-Aug-17.