2. Academic Validation
  3. Apigenin regulates CCR5/JAK1/STAT1/MMPs signaling to alleviate secondary brain injury after intracerebral hemorrhage and its enhanced delivery via targeted nanoparticles

Apigenin regulates CCR5/JAK1/STAT1/MMPs signaling to alleviate secondary brain injury after intracerebral hemorrhage and its enhanced delivery via targeted nanoparticles

  • J Nanobiotechnology. 2025 Nov 3;23(1):696. doi: 10.1186/s12951-025-03748-6.
Jia-Wei Wu # 1,  Yi-Ting Zhou # 2,  Bing-Xin Wang # 3,  Li-Ping Shen 1,  Xu-Qi Zhang 3,  Zhi-Yong Du 3,  Peng Wang 4,  Xiao-Jie Lu 5,  Zeng-Li Miao 6,  Xu-Dong Zhao 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Jiangnan University Medical Center, 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, Jiangsu Province, China.
  • 2 Department of Intervention Therapy, The Affiliated Hospital of Jiangnan University, Wuxi, 214005, China.
  • 3 Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
  • 4 Department of Neurosurgery, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi No, 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, Jiangsu Province, China.
  • 5 Department of Neurosurgery, Jiangnan University Medical Center, 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, Jiangsu Province, China. [email protected].
  • 6 Department of Neurosurgery, Jiangnan University Medical Center, 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, Jiangsu Province, China. [email protected].
  • 7 Department of Neurosurgery, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi No, 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, Jiangsu Province, China. [email protected].
  • # Contributed equally.
PMID: 41177867 DOI: 10.1186/s12951-025-03748-6
Abstract

Intracerebral hemorrhage (ICH), a severe cerebrovascular disorder with high mortality, leads to secondary brain injury (SBI) primarily through neuroinflammation and blood-brain barrier (BBB) disruption. Among the pathological cascades, excessive activation of macrophages and the CCR5/JAK1/STAT1/MMPs signaling pathway play pivotal roles in amplifying neuronal damage. Apigenin (API), a natural flavonoid with anti-inflammatory and neuroprotective properties, has emerged as a promising therapeutic candidate to counteract these processes. In this study, we developed apigenin-loaded PLGA nanoparticles functionalized with DSPE-PEG2000-RVG29 and DSPE-PEG2000-folic acid (RVG/FA-NPs@API) to achieve targeted delivery to inflammatory macrophages and investigated their therapeutic effects against SBI after ICH. In a murine ICH model, API administration significantly improved neurological outcomes, reduced cerebral edema, suppressed neuronal Apoptosis, and preserved BBB integrity. Mechanistically, API bound covalently to JAK1 at Cys1052, inhibiting its phosphorylation and subsequently downregulating the CCR5/JAK1/STAT1/MMPs cascade. Furthermore, RVG/FA-NPs@API demonstrated excellent stability, efficient brain-targeting, and superior biocompatibility, achieving enhanced therapeutic efficacy compared with free API. These findings highlight a novel strategy for targeted immunomodulation and provide translational insights into nanoparticle-assisted delivery of natural compounds for the treatment of ICH-induced SBI.

Keywords

Apigenin; Intracerebral hemorrhage; Molecular dynamics simulation; Network pharmacology; Neuroprotection; PLGA nanoparticles.

Figures
Products
Inhibitors & Agonists
Other Products