Abstract

Objective: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi 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: 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.

*Contributed equally as co-first authors.

Author Details

Authors

• Wenli Yuan¹*
• Jiacheng Lin²*
• Jun Wang³
• Chenghui Wang³
• Yuetong Shan³
• Wei Jing³
• Zhimin Fei^{4, 5}
• Weidong Pan^{3, 5, 6}

Departments

• ¹ Department of Nephrology Diseases, Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,
• ² Central Laboratory, Science and Technology Laboratory Center,
• ³ Deparment of Neurology,
• ⁴ Department of Neurosurgery,
• ⁵ Encephalopathy Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, and
• ⁶ First Department of Encephalopathy, Anhui Provincial Hospital of Integrated Chinese and Western Medicine (The Third Affiliated Hospital of Anhui University of Chinese Medicine), Anhui, China

Address

Professor Zhimin Fei, MD
or
Professor Weidong Pan, MD, PhD
528, Pudong, New Areas
201203 Shanghai, China
Email: [email protected]; [email protected]

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