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Keywords = TLR4/NF-κB/HIF-1α axis

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26 pages, 21699 KB  
Article
A Nasal Taxifolin Hydrogel Targets the TLR4/NF-κB/HIF-1α Axis to Suppress Ferroptosis in Alzheimer’s Disease
by Miao Zhang, Liangliang Zhu, Yusu Wang, Weijia Chen and Zhongmei He
Antioxidants 2026, 15(3), 316; https://doi.org/10.3390/antiox15030316 - 3 Mar 2026
Viewed by 823
Abstract
In order to further explore new therapeutic targets for Alzheimer’s disease (AD), this study, under the guidance of network pharmacology and molecular docking analysis, focused on the TLR4/NF-κB/HIF-1α signal axis and ferroptosis and verified the mechanism of a nasal taxifolin thermosensitive hydrogel (TF-Gel). [...] Read more.
In order to further explore new therapeutic targets for Alzheimer’s disease (AD), this study, under the guidance of network pharmacology and molecular docking analysis, focused on the TLR4/NF-κB/HIF-1α signal axis and ferroptosis and verified the mechanism of a nasal taxifolin thermosensitive hydrogel (TF-Gel). In the Okada acid (OA)-induced AD mouse model, intranasal administration of TF-Gel significantly improved cognitive dysfunction and reduced neuroinflammation and oxidative stress. Mechanism studies have shown that TF-Gel effectively reduces the accumulation of reactive oxygen species in the hippocampus, enhances mitochondrial membrane potential, and improves mitochondrial ultrastructure by specifically inhibiting the TLR4/NF-κB/HIF-1α pathway, thereby effectively inhibiting neuronal ferroptosis. Western blot analysis confirmed the regulation of ferroptosis, synaptic function, and apoptosis-related proteins by TF-Gel. Of particular importance, the therapeutic benefits of TF-Gel were completely abolished by co-administration of the ferroptosis inducer Erastin, directly confirming that ferroptosis inhibition is the core link in its neuroprotective effect. This study reveals for the first time that TF-Gel exerts a multi-target neuroprotective effect by precisely regulating the TLR4/NF-κB/HIF-1α axis ferroptosis pathway, providing a new perspective for research into the mechanism and treatment of AD. Full article
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18 pages, 3039 KB  
Article
L-Theanine Mitigates Acute Alcoholic Intestinal Injury by Activating the HIF-1 Signaling Pathway to Regulate the TLR4/NF-κB/HIF-1α Axis in Mice
by Simin Tan, Jiayou Gu, Jiahao Yang, Xuhui Dang, Kehong Liu, Zhihua Gong and Wenjun Xiao
Nutrients 2025, 17(4), 720; https://doi.org/10.3390/nu17040720 - 18 Feb 2025
Cited by 8 | Viewed by 3188
Abstract
Background/Objectives: Acute alcohol consumption can cause intestinal dysfunction, whereas L-theanine (LTA) has shown the potential to support intestinal health. We explored L-theanine’s ability to protect against acute alcohol-induced injury. Methods: Male C57BL/6 mice were administered LTA for 28 d and then underwent acute [...] Read more.
Background/Objectives: Acute alcohol consumption can cause intestinal dysfunction, whereas L-theanine (LTA) has shown the potential to support intestinal health. We explored L-theanine’s ability to protect against acute alcohol-induced injury. Methods: Male C57BL/6 mice were administered LTA for 28 d and then underwent acute alcohol intestinal injury modeling for 8 days. Results: The results revealed that LTA ameliorated alcohol-induced pathological damage in the duodenum and gut permeability, improved secretory immunoglobulin A (SIgA) content, and reduced oxidative stress, inflammatory markers, and serum lipopolysaccharide (LPS) content in mice. Furthermore, LTA restored the composition of the intestinal flora, increasing the abundance of Alloprevotella, Candidatus_Saccharimonas, Muribaculum, and Prevotellaceae_UCG-001. Additionally, LTA increased beneficial metabolites, such as oxyglutaric acid and L-ascorbic acid, in the HIF-1 pathway within the enrichment pathway. Further investigation into the HIF-1 signaling pathway identified up-regulation of claudin-1, HIF-1α, occludin, and ZO-1, and down-regulation of TLR4, PHD2, p65 NF-κB, TNF-α, and IFN-γ mRNA and protein levels. Conclusions: These results suggest that LTA may enhance the intestinal barrier by activating the HIF-1 signaling pathway to regulate the TLR4/NF-κB/HIF-1α axis, thereby reducing acute alcoholic intestinal injury. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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