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[Daidzein attenuates high glucose-induced inflammatory injury in macrophages by regulating NLRP3 inflammasome signaling pathway].
Liu, Yu-Hui; Chang, Shi-Yao; Zhu, Hong-Yang; Li, Yu-Ting; You, Yu.
Afiliação
  • Liu YH; Jiangxi University of Chinese Medicine Nanchang 330004, China.
  • Chang SY; Jiangxi University of Chinese Medicine Nanchang 330004, China.
  • Zhu HY; Jiangxi University of Chinese Medicine Nanchang 330004, China.
  • Li YT; Jiangxi University of Chinese Medicine Nanchang 330004, China.
  • You Y; Department of Gastroenterology, the First Affiliated Hospital of Nanchang University Nanchang 330006, China.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4734-4743, 2024 Sep.
Article em Zh | MEDLINE | ID: mdl-39307808
ABSTRACT
This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1ß secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1ß, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 µmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Inflamassomos / Proteína 3 que Contém Domínio de Pirina da Família NLR / Glucose / Isoflavonas / Macrófagos Limite: Animals Idioma: Zh Revista: Zhongguo Zhong Yao Za Zhi Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Inflamassomos / Proteína 3 que Contém Domínio de Pirina da Família NLR / Glucose / Isoflavonas / Macrófagos Limite: Animals Idioma: Zh Revista: Zhongguo Zhong Yao Za Zhi Ano de publicação: 2024 Tipo de documento: Article