Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (19): 4044-4051.doi: 10.12307/2025.057

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Inhibitory effect of hydroxy safflower yellow A on neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment

Wang Zeqian1, Duan Yanzhe1, Wu Yige1, Ma Dong2, Huang Jianjun2, Yan Yuqing1, 3, Song Lijuan1, 4   

  1. 1The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; 2Department of Neurosurgery/The Key Laboratory of Prevention and Treatment of Neurological Disease of Shanxi Provincial Health Commission, Sinopharm Tongmei General Hospital, Datong 037003, Shanxi Province, China; 3Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China; 4The Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2024-02-01 Accepted:2024-04-03 Online:2025-07-08 Published:2024-09-13
  • Contact: Song Lijuan, MD, Associate professor, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; The Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China. Co-corresponding author: Yan Yuqing, MD, Professor, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • About author:Wang Zeqian, Master candidate, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China
  • Supported by:
    National Natural Science Foundation of China, 82004028 (to SLJ); China Postdoctoral Science Foundation (General Program), No. 2020M680912 (to SLJ); “Zhang Zhongjing Inheritance and Innovation Special Project” of National Administration of Traditional Chinese Medicine, No. GDY-KJS-2022-048-1 (to SLJ); Shanxi Science and Technology Innovation Talent Youth Team Project, No. 202204051001028 (to SLJ); 2022 Annual Science and Technology Innovation Team Project of Shanxi University of Chinese Medicine, No. 2022TD2010 (to SLJ); Medical Science and Technology Leading Team Project of Shanxi Provincial Health Commission, No. 2020TD05 (to MCG [executer: SLJ]); Cardiovascular Special Fund Project of National Regional TCM Medical Center, Affiliated Hospital of Shanxi University of Chinese Medicine, No. XGZX202115 (to SLJ); Young Scientist Training Project of Shanxi University of Chinese Medicine, No. 2021PY-QN-09 (to SLJ); Discipline Construction Fund of Shanxi University of Chinese Medicine, No. 2023XKJS-02 (to MCG [executer: SLJ])

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Abstract: BACKGROUND: Hydroxy safflower yellow A has anti-ischemia, anti-oxidation, anti-thrombotic and anti-inflammatory effects. Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear.
OBJECTIVE: To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. 
METHODS: HT22 cells in logarithmic growth phase were randomly divided into five groups: normal group, model group, hydroxy safflower yellow A group, colivelin group, and colivelin+hydroxy safflower yellow A group. HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model, and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A. JC-1 probe was employed to assess changes in mitochondrial membrane potential. Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells. GSDMD/TUNEL staining was conducted to observe cell pyroptosis. Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression. RT-PCR was utilized for assessing mRNA expression levels of STAT3, NLRP3, and Caspase-1. Western blot assay was utilized to measure the protein expression levels of p-STAT3, NLRP3, GSDMD, Cleaved-caspase-1, and interleukin-1β. 
RESULTS AND CONCLUSION: (1) Compared with the normal group, the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3, NLRP3, Cleaved-caspase-1, GSDMD, and interleukin-1β. Compared with the model group, the number of pyroptotic cells reduced, and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group. (2) In comparison with the model group, pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3, NLRP3, and Caspase-1, as well as increased protein expression levels of p-STAT3, NLRP3, GSDMD, Cleaved-caspase-1, and interleukin-1β. Compared with the Colivelin group, above indexes were improved in the colivelin+hydroxy safflower yellow A group. These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Key words: HT22 cell, pyroptosis, hydroxy safflower yellow A, neuron, glucose-oxygen deprivation, reglucose-reoxygenation

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