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<p>Diabetic encephalopathy is a severe consequence of diabetes mellitus characterised by cognitive deterioration. Neuroinflammation is pivotal in the pathophysiology of this illness. This study examined the efficacy of 5,7,4′-trimethoxyflavone (TMF) in modulating neuroinflammation to mitigate cognitive deficits in streptozotocin (STZ)-induced diabetic mice. Diabetes was induced in male mice through STZ administration before treatment with TMF. Cognitive function was evaluated using the Morris water maze and Y-maze tests. Brain tissue was examined for indicators of oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). The expression levels of critical neuroinflammatory components – including the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its apoptosis-associated Speck-like protein containing a CARD (ASC) – together with the downstream cytokines interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), were assessed. In addition, the concentrations of brain-derived neurotrophic factor (BDNF), cleaved caspase-1, glial fibrillary acidic protein (GFAP), and neuron-specific nuclear protein (NeuN) were measured. TMF treatment markedly boosted cognitive function in diabetic mice, as reflected by improved spatial learning and memory in the Morris water maze and superior working memory performance in the Y-maze. Moreover, TMF treatment diminished oxidative stress, as evidenced by elevated SOD and CAT activity and decreased MDA levels. TMF markedly inhibited the activation of the NLRP3 inflammasome by diminishing the expression of NLRP3 and ASC, thereby reducing the levels of IL-1β and IL-18. Furthermore, TMF therapy elevated BDNF levels and decreased cleaved caspase-1 expression, indicating neuroprotective properties. Immunohistochemistry demonstrated that TMF reduced GFAP expression and elevated NeuN expression in the hippocampus. The results collectively indicate that TMF provides neuroprotection and mitigates cognitive deficits in STZ-induced diabetic mice, effectively suppressing neuroinflammation and oxidative stress pathways in a dose-dependent manner. Consequently, TMF holds potential as a treatment for diabetic encephalopathy.</p>

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5,7,4′-Trimethoxyflavone Attenuates Cognitive Impairment in Diabetic Mice via Inhibition of NLRP3 Inflammasome Activation

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Maryam N. ALNasser,
  • Peramaiyan Rajendran

摘要

Diabetic encephalopathy is a severe consequence of diabetes mellitus characterised by cognitive deterioration. Neuroinflammation is pivotal in the pathophysiology of this illness. This study examined the efficacy of 5,7,4′-trimethoxyflavone (TMF) in modulating neuroinflammation to mitigate cognitive deficits in streptozotocin (STZ)-induced diabetic mice. Diabetes was induced in male mice through STZ administration before treatment with TMF. Cognitive function was evaluated using the Morris water maze and Y-maze tests. Brain tissue was examined for indicators of oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). The expression levels of critical neuroinflammatory components – including the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its apoptosis-associated Speck-like protein containing a CARD (ASC) – together with the downstream cytokines interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), were assessed. In addition, the concentrations of brain-derived neurotrophic factor (BDNF), cleaved caspase-1, glial fibrillary acidic protein (GFAP), and neuron-specific nuclear protein (NeuN) were measured. TMF treatment markedly boosted cognitive function in diabetic mice, as reflected by improved spatial learning and memory in the Morris water maze and superior working memory performance in the Y-maze. Moreover, TMF treatment diminished oxidative stress, as evidenced by elevated SOD and CAT activity and decreased MDA levels. TMF markedly inhibited the activation of the NLRP3 inflammasome by diminishing the expression of NLRP3 and ASC, thereby reducing the levels of IL-1β and IL-18. Furthermore, TMF therapy elevated BDNF levels and decreased cleaved caspase-1 expression, indicating neuroprotective properties. Immunohistochemistry demonstrated that TMF reduced GFAP expression and elevated NeuN expression in the hippocampus. The results collectively indicate that TMF provides neuroprotection and mitigates cognitive deficits in STZ-induced diabetic mice, effectively suppressing neuroinflammation and oxidative stress pathways in a dose-dependent manner. Consequently, TMF holds potential as a treatment for diabetic encephalopathy.