Andrographolide Promotes Post-Ischemic Endothelial Angiogenic Activity via IL-10-Mediated M2-Like Microglia-Endothelial Crosstalk Involving Endothelial VEGFR2 Upregulation.
- 1College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- 2School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
- 3Center for Paralysis Research, Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Abstract
Ischemic stroke remains a leading cause of disability worldwide, and angiogenesis is critical for functional recovery. Although andrographolide (ANP) has anti-inflammatory and neuroprotective properties, its role in post-stroke angiogenesis remains unclear. Here, we investigated whether ANP promotes post-ischemic angiogenesis by modulating microglia-endothelial crosstalk. Using a ferric chloride (FeCl₃)-induced carotid artery thrombosis model in male C57BL/6J mice, we found that ANP treatment (2.5 mg/kg) attenuated ischemic brain injury and neurological deficits, enhanced vascular stability, and improved cerebral blood perfusion. Mechanistically, ANP promoted a pro-reparative M2-like microglial state characterized by coordinated transcriptional changes, increased CD206 and IL-10, and reduced CD86 expression. ANP-treated microglia enhanced endothelial cell migration and tube formation while preserving tight-junction integrity through paracrine signaling. Co-immunoprecipitation and gain- and loss-of-function experiments further supported a microglial IL-10-dependent endothelial VEGFR2 upregulation. Together, these findings demonstrate that ANP promotes post-stroke reparative angiogenic activity through IL-10-mediated M2-like microglia-endothelial crosstalk involving endothelial VEGFR2 upregulation, linking its immunomodulatory effects to angiogenesis and highlighting microglia-endothelial crosstalk as a potential therapeutic target for ischemic stroke recovery.
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BibTeX
@article{li2026andrographolide,
title = {{Andrographolide Promotes Post-Ischemic Endothelial Angiogenic Activity via IL-10-Mediated M2-Like Microglia-Endothelial Crosstalk Involving Endothelial VEGFR2 Upregulation.}},
author = {Hongfei Li and Hairong Xiang and Xinyu Li and Jiazhen Xie and Linfeng Zhao and Lan Yang and Riyi Shi and Yong Wang and Liangqin Shi},
journal = {Biology},
year = {2026},
month = sep,
doi = {10.3390/biology15191715},
url = {https://europepmc.org/article/MED/42883388},
note = {CC BY},
}
RIS
TY - JOUR
TI - Andrographolide Promotes Post-Ischemic Endothelial Angiogenic Activity via IL-10-Mediated M2-Like Microglia-Endothelial Crosstalk Involving Endothelial VEGFR2 Upregulation.
AU - Hongfei Li
AU - Hairong Xiang
AU - Xinyu Li
AU - Jiazhen Xie
AU - Linfeng Zhao
AU - Lan Yang
AU - Riyi Shi
AU - Yong Wang
AU - Liangqin Shi
PY - 2026
DA - 2026/09/26
JO - Biology
DO - 10.3390/biology15191715
UR - https://europepmc.org/article/MED/42883388
AB - Ischemic stroke remains a leading cause of disability worldwide, and angiogenesis is critical for functional recovery. Although andrographolide (ANP) has anti-inflammatory and neuroprotective properties, its role in post-stroke angiogenesis remains unclear. Here, we investigated whether ANP promotes post-ischemic angiogenesis by modulating microglia-endothelial crosstalk. Using a ferric chloride (FeCl₃)-induced carotid artery thrombosis model in male C57BL/6J mice, we found that ANP treatment (2.5 mg/kg) attenuated ischemic brain injury and neurological deficits, enhanced vascular stability, and improved cerebral blood perfusion. Mechanistically, ANP promoted a pro-reparative M2-like microglial state characterized by coordinated transcriptional changes, increased CD206 and IL-10, and reduced CD86 expression. ANP-treated microglia enhanced endothelial cell migration and tube formation while preserving tight-junction integrity through paracrine signaling. Co-immunoprecipitation and gain- and loss-of-function experiments further supported a microglial IL-10-dependent endothelial VEGFR2 upregulation. Together, these findings demonstrate that ANP promotes post-stroke reparative angiogenic activity through IL-10-mediated M2-like microglia-endothelial crosstalk involving endothelial VEGFR2 upregulation, linking its immunomodulatory effects to angiogenesis and highlighting microglia-endothelial crosstalk as a potential therapeutic target for ischemic stroke recovery.
SN - 2079-7737
ER -