Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia

Xin-Yue Yang; Lina Geng; Ronghui Li; Ji-Xian Song; Cui-Ling Jia; Ji-Ren An; Meng-Fan Sun; Shan Xu; Ya-Jing Guo; Yashuo Zhao; En-Sheng Ji

doi:10.2147/IJN.S393346

Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia

Int J Nanomedicine. 2023 Feb 17:18:843-859. doi: 10.2147/IJN.S393346. eCollection 2023.

Authors

Xin-Yue Yang^#¹, Lina Geng^#², Ronghui Li², Ji-Xian Song¹, Cui-Ling Jia¹, Ji-Ren An^{1

3}, Meng-Fan Sun¹, Shan Xu¹, Ya-Jing Guo¹, Yashuo Zhao¹, En-Sheng Ji¹

Affiliations

¹ Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People's Republic of China.
² College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang, People's Republic of China.
³ The First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, People's Republic of China.

^# Contributed equally.

Abstract

Background: Chronic intermittent hypoxia (CIH) could cause neuronal damage, accelerating the progression of dementia. However, safe and effective therapeutic drugs and delivery are needed for successful CIH therapy.

Purpose: To investigate the neuroprotective effect of Huperzine A (HuA) packaged with nanoliposomes (HuA-LIP) on neuronal damage induced by CIH.

Methods: The stability and release of HuA-LIP in vitro were identified. Mice were randomly divided into the Control, CIH, HuA-LIP, and HuA groups. The mice in the HuA and HuA-LIP groups received HuA (0.1 mg/kg, i.p.), and HuA-LIP was administered during CIH exposure for 21 days. HuA-LIP contains the equivalent content of HuA.

Results: We prepared a novel formulation of HuA-LIP that had good stability and controlled release. First, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice. Second, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH. Furthermore, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression. In addition, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity. Most importantly, compared with HuA, HuA-LIP showed a superior performance against neuronal damage induced by CIH.

Conclusion: HuA-LIP has a good sustained-release effect and targeting ability and efficiently protects against neural injury caused by CIH.

Keywords: Iron; chronic intermittent hypoxia; huperzine A; nanoliposomes; neuronal damage.

MeSH terms

Alkaloids* / pharmacology
Animals
Hippocampus
Hypoxia / metabolism
Liposomes* / pharmacology
Mice
Oxidative Stress

Substances

huperzine A
Liposomes
Alkaloids

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number, 82004127], Natural Science Foundation of Hebei [grant number, C2019423117 and H2022423352] and Funded by Science and Technology Project of Hebei Education Department [grant number, ZD2022013].