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

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.