Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling

  • Pharm Biol. 2022 Dec;60(1):1646-1655. doi: 10.1080/13880209.2022.2110599.
Yong Fan  1 ,  Yongkun Li  2 ,  Yongkai Yang  3 ,  Kunzhe Lin  3 ,  Qingqiang Lin  4 ,  Shenghui Luo  5 ,  Xiaohui Zhou  3 ,  Qun Lin  6 ,  Fan Zhang  7
Affiliations
  • 1. Central Laboratory, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China.
  • 2. Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
  • 3. Department of Neurosurgery, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China.
  • 4. College of Life Sciences, Fujian Normal University, Fuzhou, China.
  • 5. Department of Neurology, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China.
  • 6. Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
  • 7. Department of Neurosurgery, Affiliated Fuzhou Second Hospital of Xiamen University, Fuzhou, China.
PMID: 35981220 DOI: 10.1080/13880209.2022.2110599
Abstract

Context: Chlorogenic acid (CGA) has good antioxidant effects, but its explicit mechanism in cerebral ischaemia-reperfusion injury is still uncertain.

Objective: We studied the effect of CGA in human brain microvascular endothelial cells (HBMECs) under OGD/R damage.

Materials and methods: HBMECs in 4 groups were treated with oxygen-glucose deprivation/re-oxygenation (OGD/R) (4 + 24 h), normal no CGA treatment and different concentrations (20, 40 or 80 μM) of CGA. Male C57BL/6J mice were classified as sham, middle cerebral artery occlusion (MCAO), and MCAO + CGA (30 mg/kg/day) groups. Mice in the sham group were not subjected to MCAO. Cell viability, Apoptosis, angiogenesis and related protein levels were investigated by CCK-8, flow cytometry, TUNEL staining, tube formation and western blot assays. Infarct volume of brain tissues was analyzed by TTC staining.

Results: CGA curbed Apoptosis (from 32.87% to 13.12% in flow cytometry; from 34.46% to 17.8% in TUNEL assay) but accelerated cell angiogenesis of HBMECs with OGD/R treatment. Moreover, CGA augmented activation of the PI3K-Akt signalling (p-PI3K/PI3K level, from 0.39 to 0.49; p-Akt/Akt level, from 0.52 to 0.81), and the effect of CGA on Apoptosis and angiogenesis was abolished by an inhibitor of PI3K-Akt signalling. Furthermore, CGA attenuated infarct (from 41.26% to 22.21%) and Apoptosis and promoted angiogenesis and activation of the PI3K/Akt signalling in MCAO-induced mice.

Conclusions: CGA effectively repressed Apoptosis and promoted angiogenesis in OGD/R-treated HBMECs and MCAO-treated mice by modulating PI3K-Akt signalling. Our research provides a theoretical basis for the use of CGA in the treatment of ischaemic stroke.

Keywords
Ischaemic stroke; cerebral infarction; neuronal damage.
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