2. Academic Validation
  3. Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway

Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway

  • Front Pharmacol. 2021 Apr 28:12:609693. doi: 10.3389/fphar.2021.609693.
Lina Zhao 1,  Huanming Li 2,  Qian Gao 3,  Jin Xu 1,  Yongjie Zhu 4,  Meili Zhai 5,  Peijun Zhang 5,  Na Shen 6,  Yanbo Di 6,  Jinhui Wang 7,  Tie Chen 7,  Meina Huang 8,  Jinglai Sun 9,  Chong Liu 6 7
Affiliations

Affiliations

  • 1 Department of Anaesthesiology, Tianjin Hospital, Tianjin, China.
  • 2 Department of Cardiology, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin, China.
  • 3 Department of Emergency Medicine, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.
  • 4 Department of Pathology, First People's Hospital of Aksu, Xinjiang, China.
  • 5 Department of Anaesthesiology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin, China.
  • 6 Department of Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.
  • 7 Department of Anaesthesiology, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin, China.
  • 8 Department of Anaesthesiology, Wuqing People's Hospital, Tianjin, China.
  • 9 Department of Biomedical Engineering, Tianjin Key Laboratory of Biomedical Detecting Techniques and Instruments, Tianjin University, Tianjin, China.
PMID: 33995012 DOI: 10.3389/fphar.2021.609693
Abstract

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and Apoptosis induced by CIRI in rats (p < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced Apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment (p < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal Apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK Inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK Inhibitor partially reversed the ability of BBR to inhibit apoptotic protein (p < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal Apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.

Keywords

CNPY2; apoptosis; berberine; cerebral ischemia-reperfusion injury; pathway.

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