2. Academic Validation
  3. Baicalin attenuates neuronal damage associated with SDH activation and PDK2-PDH axis dysfunction in early reperfusion

Baicalin attenuates neuronal damage associated with SDH activation and PDK2-PDH axis dysfunction in early reperfusion

  • Phytomedicine. 2024 Mar 28:129:155570. doi: 10.1016/j.phymed.2024.155570.
Kaili Liu 1,  Ying Zhou 1,  Xianrui Song 2,  Jiahan Zeng 1,  Zhuqi Wang 1,  Ziqing Wang 1,  Honglei Zhang 1,  Jiaxing Xu 1,  Wenting Li 1,  Zixuan Gong 1,  Min Wang 1,  Baolin Liu 1,  Na Xiao 3,  Kang Liu 4
Affiliations

Affiliations

  • 1 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
  • 2 Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
  • 3 College of Agronomy, Shandong Agriculture University, Tai'an, Shandong 271018, PR China. Electronic address: [email protected].
  • 4 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China. Electronic address: [email protected].
PMID: 38579645 DOI: 10.1016/j.phymed.2024.155570
Abstract

Background: Energy deficiency and oxidative stress are interconnected during ischemia/reperfusion (I/R) and serve as potential targets for the treatment of cerebral ischemic stroke. Baicalin is a neuroprotective antioxidant, but the underlying mechanisms are not fully revealed.

Purpose: This study explored whether and how baicalin rescued neurons against ischemia/reperfusion (I/R) attack by focusing on the regulation of neuronal pyruvate dehydrogenase kinase 2 (PDK2)-pyruvate dehydrogenase (PDH) axis implicated with succinate dehydrogenase (SDH)-mediated oxidative stress.

Study design: The effect of the tested drug was explored in vitro and in vivo with the model of oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R), respectively.

Methods: Neuronal damage was evaluated according to cell viability, infarct area, and Nissl staining. Protein levels were measured by western blotting and immunofluorescence. Gene expression was investigated by RT-qPCR. Mitochondrial status was also estimated by fluorescence probe labeling.

Results: SDH activation-induced excessive production of Reactive Oxygen Species (ROS) changed the protein expression of Lon protease 1 (LonP1) and hypoxia-inducible factor-1ɑ (HIF-1ɑ) in the early stage of I/R, leading to an upregulation of PDK2 and a decrease in PDH activity in neurons and cerebral cortices. Treatment with baicalin prevented these alterations and ameliorated neuronal ATP production and survival.

Conclusion: Baicalin improves the function of the neuronal PDK2-PDH axis via suppression of SDH-mediated oxidative stress, revealing a new signaling pathway as a promising target under I/R conditions and the potential role of baicalin in the treatment of acute ischemic stroke.

Keywords

Baicalin; Hypoxia-inducible factor-1 ɑ; Lon protease 1; Pyruvate dehydrogenase kinase 2; Reactive oxygen species; Succinate dehydrogenase.

Figures
Products