Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y

Objective: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-JianPi formula (BSJP) identified using network pharmacology analysis. Materials and methods: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. Results: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. Discussion: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. Conclusion: Evidence has been obtained showing that the core components: of What - - - icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.