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
  • 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: [email protected].
  • 5. College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: [email protected].
  • 6. College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: [email protected].
  • 7. College of Pharmacology, Fujian University of Traditional Chinese Medicine, No.1, Qiu Yang Road, Min Hou Shang Jie, Fuzhou 350122, China. Electronic address: [email protected].
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.
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