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Polygalasaponin F ameliorates middle cerebral artery occlusion-induced focal ischemia / reperfusion injury in rats through inhibiting TXNIP/NLRP3 signaling pathway.
Chen, Yao; Li, Hanzhou; Yang, Yan; Feng, Lei; Yang, Ling; Zhao, Jie; Xin, Xiaochi; Lv, Shuquan; Fang, Xixing; Wen, Weibo; Cui, Youxiang; Cui, Huantian.
Afiliação
  • Chen Y; Nanjing University of Chinese Medicine, Nanjing 210000, China; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Li H; Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China.
  • Yang Y; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Feng L; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Yang L; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Zhao J; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Xin X; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China.
  • Lv S; Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province, Cangzhou 061001, China.
  • Fang X; College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, China.
  • Wen W; Nanjing University of Chinese Medicine, Nanjing 210000, China; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China. Electronic address: wenweibo2020@163.com.
  • Cui Y; College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, China. Electronic address: heartwing1985@163.com.
  • Cui H; Yunnan University of Traditional Chinese Medicine, Kunming 650000, China; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266000, China. Electronic address: 1762316411@qq.com.
J Neuroimmunol ; 387: 578281, 2024 02 15.
Article em En | MEDLINE | ID: mdl-38198981
ABSTRACT

BACKGROUND:

Polygalasaponin F (PGSF), an oleanane triterpenoid saponin extracted from Polygala japonica, has been demonstrated with neuroprotective effect. However, the therapeutic effects and mechanisms of PGSF on focal ischemia remain unknown;

METHODS:

In this study, male Sprague Dawley (SD) rats aged 6-8 weeks were initially selected to establish a rat model of middle cerebral artery occlusion (MCAO) to evaluate the therapeutic effect of PGSF intervention and to investigate the impact of PGSF on the thioredoxin-interacting protein/NOD-, LRR-, and pyrin domain-containing protein 3 (TXNIP/NLRP3) inflammatory pathway. Secondly, brain neuron cells were isolated, and the cells received oxygen-glucose deprivation/reoxygenation (OGD/R) culture to establish the cell injury model in vitro. The mechanism of PGSF on the TXNIP/NLRP3 pathway was further validated;

RESULTS:

Our results showed that PGSF treatment reduced neurological scores, brain tissue water content and infarct volume and ameliorated the pathological changes in cerebral cortex in MCAO-induced focal ischemia rats. The TNF-α, IL-1ß and IL-6 levels decreased in MCAO-induced focal ischemia rats after PGSF treatment. Moreover, PGSF down-regulated the protein expressions of TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18 in MCAO-induced focal ischemia rats. Meanwhile, PGSF treatment inhibited apoptosis, and reduced the levels of ROS, inflammatory cytokine and TXNIP/NLRP3 pathway-related proteins (TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18) in OGD/R-induced neuronal injury cells. Finally, PGSF treatment also disrupted the interaction between NLRP3 and TXNIP in vitro;

CONCLUSIONS:

Our study demonstrated the therapeutic effects of PGSF on MCAO-induced focal ischemia rats. Moreover, the neuroprotective mechanism of PGSF on focal ischemia was associated with the inhibition of TXNIP/NLRP3 signaling pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saponinas / Triterpenos / Traumatismo por Reperfusão / Isquemia Encefálica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neuroimmunol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saponinas / Triterpenos / Traumatismo por Reperfusão / Isquemia Encefálica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neuroimmunol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China