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Publications

Journal Article Epublish

PubMed: 40172584 DOI: 10.1007/s11011-025-01581-2

Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop.

Metab Brain Dis 40(4):161

Authors: Lijuan Song, Yige Wu, Lijun Yin, Yanzhe Duan, Jianlin Hua, Mengwei Rong, Kexin Liu, Junjun Yin, Dong Ma, Ce Zhang, Baoguo Xiao, Cungen Ma

Affiliations

  • Department of Physiology, Shanxi Medical University, Taiyuan, China.
  • The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong, China.
  • Department of Neurosurgery, Sinopharm Tongmei General Hospital, Datong, China.
  • Department of Physiology, Shanxi Medical University, Taiyuan, China.
  • Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
  • The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong, China. Department of Neurosurgery, Sinopharm Tongmei General Hospital, Datong, China.

Abstract

Lipocalin-2 (LCN2), an acute phase protein mainly expressed in astrocytes (Ast), is closely related to the production of inflammatory cytokines following ischemic stroke. During the pathophysiological process of ischemic stroke, the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is activated. Despite evidence suggesting some link between the two, the relationship between the JAK2/STAT3 signaling pathway and the LCN2 expression in Ast following brain ischemia is incompletely understood. Hydroxysafflower yellow A (HSYA), an active ingredient found in Carthamus tinctorius L flowers, has been demonstrated to effectively mitigate cerebral ischemia via its anti-inflammatory effect. However, whether HSYA mitigates the neuroinflammatory damage after ischemic stroke by disrupting the interaction between the JAK2/STAT3 signaling pathway and LCN2 in Ast is unknown. Focusing on these two scientific questions, we established an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and in vitro primary astrocyte oxygen glucose deprivation/reperfusion (OGD/R) model. In vivo results showed that HSYA treatment alleviated nerve damage and inhibited the expression of LCN2 and inflammatory factors in Ast. In vitro results showed after OGD/R the expression of LCN2 and inflammatory cytokines increased and the JAK2/STAT3 was activated in Ast. Meanwhile, after OGD/R the JAK2/STAT3 activation in Ast increased LCN2 expression, and the inhibition of LCN2 expression by HSYA decreased the JAK2/STAT3 activation in Ast. These findings suggest that there is an interaction between the LCN2 and JAK2/STAT3 in Ast after ischemic stroke, which can enhance the inflammatory factors and exacerbate neuroinflammatory injury. Therefore, we conclude that HSYA may inhibit the LCN2/STAT3 loop in Ast, thereby mitigating neuroinflammation after cerebral ischemia.

MeSH

Cytokines, Feedback, Astrocytes, Ischemic Stroke, Stroke, Reperfusion, Ischemia