Taohong Siwu Decoction switches the detrimental/reparative phenotypes of astrocytes via RhoA/ROCK2/Profilin-1 axis to bolster oligodendrogenesis and remyelination after ischemic stroke.

J Ethnopharmacol 2026

Feng X, Tang L, Chen H, Wu J, Wei L et al.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Promoting remyelination is crucial for recovery after ischemic stroke and astrocyte polarization toward detrimental A1 or reparative A2 phenotypes shapes the post-stroke microenvironment. Taohong Siwu Decoction (THSWD) has neuroprotective effects, but its impact on remyelination and astrocyte polarization remains unclear. RhoA/ROCK2/Profilin-1 (PFN1) signals may be key regulators. AIM OF THE STUDY: This research investigated whether THSWD promoted post-stroke remyelination by modulating astrocytic A1/A2 polarization via RhoA/ROCK2/PFN1 axis. MATERIALS AND METHODS: In vivo, the middle cerebral artery occlusion/reperfusion (MCAo/R) model was conducted to rats which were received THSWD treatment for 14 days, then mNSS, TTC staining, histopathology, SEM, immunofluorescence and Western blot were assessed. In vitro, astrocytes induced to A1/A2 polarization were treated with THSWD-containing serum. Phenotypic markers and signaling proteins were examined with ELISA, Western blot and immunofluorescence. Transwell co-culture system assessed oligodendrocyte precursor cell (OPC) proliferation and differentiation affected by astrocytes. RhoA knockdown (RhoA-siRNA) validated the mechanism. RESULTS: THSWD improved neurological recovery, infarction and remyelination in MCAo/R rats. THSWD suppressed A1 markers (GFAP/C3, TNF-α, iNOS) and promoted A2 markers (GFAP/S100A10, IL-10, TGF-β), besides, it increased proliferating OPCs (NG2 CONCLUSION: THSWD promoted post-stroke functional recovery and remyelination. Its core mechanism involved switching astrocyte phenotypes via RhoA/ROCK2/PFN1 axis, thereby creating a microenvironment conducive to oligodendrogenesis and cerebral repair.

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