Ligustilide provides neuroprotection by promoting angiogenesis after cerebral ischemia

ABSTRACT

Objectives

Following stroke, angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. Ligustilide (LGSL) is known to have neuroprotection against ischemic stroke-induced injury. But the effect of LGSL on promoting angiogenesis after ischemic stroke is unknown. The purpose of this study was to determine the effects of LGSL on neuroprotection and angiogenesis after stroke.

Methods

BrdU cell proliferation assay, transwell, wound healing, and tube-formation experiments were performed to evaluate the effects of LGSL on mouse microvascular endothelial cells (bEnd.3). Male adult C57/BL6 mice were subjected to focal transient cerebral ischemia followed by intragastric LGSL administration. Immunostaining was performed to assess angiogenesis. VEGF level was assayed by ELISA. eNOS expression was performed by Western blot.

Results

LGSL significantly improved neurological function. LGSL promoted angiogenesis in vitro and in vivo. Neurological improvement conferred by LGSL correlated with increased cerebral vessels number. We also found an increase of VEGF and eNOS activation in mice ischemic hemisphere following LGSL administration.

Conclusion

LGSL promoted focal angiogenesis and attenuated ischemia-induced brain injury, suggesting that LGSL is a potential agent that improves angiogenesis and promotes recovery from ischemic stroke.

KEYWORDS:

• Ischemic stroke
• angiogenesis
• ligustilide
• VEGF/eNOS

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant No. 81573867, 81971114, 81473591, 81801313), Beijing Municipal Administration of Hospitals’ Youth Program (No. QML 20180801), the National Key R&D Program of China (2017YFC1308402).