2. Academic Validation
  3. Emodin facilitates the transformation of A1/A2 reactive astrocytes through the 11β-HSD1/AKT signaling pathway in the context of cerebral ischemia

Emodin facilitates the transformation of A1/A2 reactive astrocytes through the 11β-HSD1/AKT signaling pathway in the context of cerebral ischemia

  • Int Immunopharmacol. 2025 Sep 27:166:115628. doi: 10.1016/j.intimp.2025.115628.
Wenfang Lai 1,  Huiling Wu 1,  Yuting Jiang 2,  Xuerui Zheng 1,  Jingquan Chen 1,  Zehao Huang 1,  Haimian Hong 3,  Yingzheng Wang 4,  Wen Xu 5,  Guizhu Hong 6,  Ya Lin 7
Affiliations

Affiliations

  • 1 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China.
  • 2 Training department, Fujian North Health College, No.1088 New Village, Tongyou Road, Jianyang, Nanping 354200, China.
  • 3 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China; Department of Pharmacy, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, No. 602, 817 Middle Road, Fuzhou 350004, China.
  • 4 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: wangyingzheng@live.com.
  • 5 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: 13559102126@163.com.
  • 6 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: guizhuhong@fjtcm.edu.cn.
  • 7 College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: 80979984@qq.com.
PMID: 41016200 DOI: 10.1016/j.intimp.2025.115628
Abstract

Emodin is the main active ingredient of Rhei Radix et Rhizoma, a herb widely used for ischemic stroke treatment. This study demonstrates for the first time that emodin exerts neuroprotective effects against ischemic stroke by regulating astrocyte phenotypic transformation via the 11β-HSD1/Akt signaling pathway. In rat MCAO and astrocyte/neuron OGD/R models, emodin improved neurological function, reduced infarction volume, and shifted astrocytes from detrimental A1 to beneficial A2 phenotypes. Mechanistically, emodin activated Akt phosphorylation while suppressing the NF-κB pathway (reducing p-IκBα/IκBα and p-p65/p65 ratios). These effects-along with functional improvements-were reversed by Akt Inhibitor LY294002. Furthermore, 11β-HSD1 siRNA mimicked emodin's actions in vitro, and supernatants from both emodin- and siRNA-treated astrocytes enhanced neuronal MAP2 expression. These findings identify astrocyte phenotypic modulation via 11β-HSD1/Akt as a key therapeutic mechanism of emodin.

Keywords

11β-HSD1; Astrocytes; Cerebral ischemia; Emodin; Neuroprotection; Phenotype.

Figures
Products