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Updated: May 9, 2026
A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice
Published on: June 22, 2022
Rhodiosin promotes cerebral angiogenesis in mice with ischemic stroke via PI3K/Akt pathway activation
Chaohui Wang1, Yuqing Zhang2, Linlin Li2
1Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, China; Key Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei 050000, China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei 050000, China; Key Research Laboratory for Screening and Transformation of Efficacious Substances in Traditional Chinese Medicine, Hebei Provincial Administration of Traditional Chinese Medicine, Shijiazhuang, Hebei 050000, China; Department of Neurology, Handan Central Hospital, 59 Congtaibei Road, Handan, Hebei 056000, China.
Background:
Ischemic stroke remains a lethal disease with high morbidity and disability, yet effective therapeutic options for chronic recovery are still limited. Angiogenesis facilitates post-stroke blood supply restoration by reconstructing vascular networks, which helps rescue the penumbra and recover neurological function. Rhodiosin is a bioactive compound derived from rhodiola crenulata, exhibiting multiple pharmacological activities. However, whether rhodiosin exerts protective effects by promoting angiogenesis after stroke, as well as the underlying mechanisms, remains unclear.
Purpose:
This study aimed to investigate whether rhodiosin promotes cerebral angiogenesis and neurological functional recovery after stroke, and to explore the underlying mechanisms.
Study Design And Methods:
Stroke was induced in mice by distal middle cerebral artery occlusion (dMCAO). Rhodiosin was administered intraperitoneally daily post-surgery. Therapeutic efficacy was assessed based on neurological deficits and infarct volume. Microvascular density and pericyte/astrocyte coverage were evaluated using immunofluorescence staining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Two-photon microscopy was employed to measure dynamic changes in cerebrovascular diameter and density. RNA sequencing was performed to identify rhodiosin-associated pathways. PI3K/Akt pathway factors were examined by Western blot and qRT-PCR. The human cerebral microvascular endothelial cells (hCMEC/D3) were utilized to explore the underlying mechanisms in vitro.
Results:
Rhodiosin enhanced neurological recovery and reduced infarct volume post-stroke. It improved CBF and increased vascular diameter and density in the penumbra. It also promoted angiogenesis by increasing BrdU⁺/CD31⁺ cells and enhancing pericyte/astrocyte coverage around microvessels. Moreover, rhodiosin facilitated endothelial cell migration and tube formation under OGD conditions. Rhodiosin upregulated PI3K/Akt phosphorylation and the expression of their downstream targets (HIF-1α, Ang1, VEGF). These effects were partially or fully reversed by PI3K/Akt inhibition (LY294002/MK-2206 in vivo, shRNA transfection in vitro). Integrating RNA-seq with experimental validation, we confirmed that activation of PI3K/Akt mediates rhodiosin's pro-angiogenic effect.
Conclusion:
Rhodiosin promotes neurological recovery post-stroke by enhancing cerebral angiogenesis via PI3K/Akt pathway activation, highlighting its potential as a therapeutic candidate for ischemic stroke during the subacute/chronic recovery phase.
