2. Academic Validation
  3. Huperzine A protected against ferroptosis via activating PI3K/Akt signaling in lipopolysaccharide induced acute lung injury

Huperzine A protected against ferroptosis via activating PI3K/Akt signaling in lipopolysaccharide induced acute lung injury

  • Eur J Pharmacol. 2024 Nov 15:983:177004. doi: 10.1016/j.ejphar.2024.177004.
Jun Shi 1,  Wei Chen 2,  Jiajia Tang 1,  Chunyang Zhang 2,  Man Qi 2,  Xin Zheng 3,  Jiaxin Wang 3,  Qi Liu 3,  Lu Liu 1,  Xuxin Chen 4,  Zhihai Han 5
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 2 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100091, China.
  • 3 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
  • 4 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100091, China. Electronic address: 526416797@qq.com.
  • 5 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China; School of Medicine, South China University of Technology, Guangzhou, 510006, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100091, China. Electronic address: hanzhihai@301hospital.com.cn.
PMID: 39278310 DOI: 10.1016/j.ejphar.2024.177004
Abstract

Huperzine A (Hup A), an extract from Huperzia serrata, exerted its anti-inflammation and anti-oxidation effect to protect against neurodegenerative disorders and organ injury. Ferroptosis was indicated to involve in the development of acute lung injury (ALI) accompanying by lipid Reactive Oxygen Species (ROS) overexpressed. However, there is little research focused on the protective effect of Hup A on ALI, and the underlying molecular mechanism remains elusive. This study aims to determine the therapeutic effect of Hup A on ALI in vivo and in vitro. Hup A attenuated lung injury and cellular damage in lipopolysaccharide-induced ALI (LPS-ALI) models, both in vivo and in vitro, accompanied by the upregulation of ferroptosis-associated proteins (SLC7A11 and GPX4). Furthermore, the pretreatment with Hup A decreased the abundance of inflammation factors (IL-6, TNF-α), MDA, lipid ROS, and Fe2+ in the LPS-ALI model, while it also promoted the secretion of SOD and GSH to antagonize peroxidation. Mechanistically, RNA Sequencing and network pharmacological analysis synergistically revealed the PI3K/Akt signaling pathway as a potential target of Hup A. In vitro experiments demonstrated that Hup A effectively activated GPX4 through the PI3K/Akt signaling pathway, which was subsequently reversed by LY294002, an inhibitor of the PI3K/Akt signaling pathway. Consequently, our results revealed that Hup A inhibited Ferroptosis in LPS-ALI by activating the PI3K-Akt signaling pathway which indicated the potential therapeutical effect of Hup A and further emphasized the pivotal role of Ferroptosis in ALI.

Keywords

Acute lung injury; Ferroptosis; Huperzine A; Network pharmacology; PI3K/Akt signaling pathway.

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