JOURNAL OF BIOLOGICAL CHEMISTRY
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2025
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IF 3.9
Yijun Yang,Nengyi Wang,Yuankun Chen,Tianpeng Ma,Minhua Weng,Haifeng Wu,Qiuping Wu,Yiqiang Xie,Chuanwu Zhu,Wenting Li
Nonalcoholic fatty liver disease (NAFLD) has posed a huge threat to public health globally, but there are currently no approved drugs available. Growing evidence has proved the close association between increased Th17 cells and NAFLD progression. Interleukin-4 induced protein 1 (IL4I1), an amino acid oxidase secreted by immune cells, was reported to regulate the Th17 cells, but its exact role in NAFLD progression has not been fully explained yet. We found that IL4I1 was highly expressed in the liver of C57BL/6J mice with NAFLD induced by an 8-weeks western diet. To explore the IL4I1’s effect, mice were injected with AAV8 encoding IL4I1 1 week before western diet administration. The results showed that IL4I1 overexpression inhibited the NAFLD progression, demonstrated by relieved liver damage and lipid accumulation. The underlying mechanism in which IL4I1 acts on NAFLD might be attributed to the inactivated AKT/forkhead box protein O1 (FOXO1) signaling pathway–mediated decrease of Th17 cells in liver tissues. Subsequently, by culturing naive CD4 + T cells isolated from the spleen of mice in Th17 cell-polarizing conditions, we determined that IL4I1 overexpression inhibited Th17 cell differentiation by inactivating the AKT/FOXO1 pathway, whereas its knockdown exhibited opposite effects. Further, the AKT activator SC79 reversed the effect of IL4I1 overexpression on Th17 cell differentiation. Collectively, our study supports that compensatory upregulation of IL4I1 protects against liver damage and lipid accumulation in NAFLD progression, partially by inhibiting the activated AKT/FOXO1 signaling pathway-induced Th17 cell differentiation.
研究领域:
免疫学
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肝病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Wenxuan Liu,Xiangka Hu,Xiaorui Han,Kexin Zeng,Xuedong Ren,Yining Chang,Chunmei Dai
Ethnopharmacology relevance Tangningtongluo Tablets (TNTL), a novel Miao ethnic medicine for treating type 2 diabetes mellitus (T2DM) and its complications. However, its potential bioactive components and the pharmacological mechanisms underlying its therapeutic effects remain unclear. Aim of the study This study aims to preliminarily explore the protective effects of TNTL and its active components on pancreatic cells via the PI3K/Akt/FoxO1 pathway and further investigate the underlying mechanisms. Materials and methods LC-MS was employed to identify components in serum, and network pharmacology was used to forecast active components and their mechanisms. The protective effects and mechanisms of TNTL and its active components on pancreatic β-cells in diabetic mice were investigated using HE staining, MTT assay, EdU assay, TUNEL staining, Western blot analysis, and qPCR analysis. Results A total of 29 active components of TNTL were detected in rat serum. Network pharmacology results indicated that luteolin, catechin, and chlorogenic acid are key compounds of TNTL in regulating the PI3K/Akt/FoxO1 pathway. Compared with the model group, TNTL and its active components reduced ROS and MDA levels, increased SOD levels, and reduced pro-apoptotic factor expression to alleviate pancreatic β-cells damage. They also activated PI3K/Akt/FoxO1 signaling and decreased apoptotic proteins. Conclusion This study demonstrates that TNTL mitigates oxidative stress and reduces pancreatic β-cell apoptosis in diabetic mice through modulation of the PI3K/Akt/FoxO1 pathway.
研究领域:
药理学
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民族药理学
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网络药理学
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糖尿病研究
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细胞生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2021
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IF 4.24
Feier Cheng,Xinhui Ge,Yao Zhang,Jia Li,Shaoqing Yan,Yunlong Li,Min Wang
The hypoglycemic effects and underlying molecular mechanisms of combining two dietary compounds, quercetin (Que) and d-chiro-inositol (DCI) on hepatic insulin resistance in C57BL/6J mice that were fed a high fat diet and saturated palmitic acid (PA)-treated hepatocytes were studied. Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) are important antioxidant enzymes . Insufficient secretion of these enzymes will inhibit the normal phosphorylation of insulin receptors in the liver, thereby limiting the transmission of insulin signals and producing insulin resistance. The results showed that QD (both Que and DCI) led to the recovery of the activity of CAT, SOD, GPx, suggesting that QD was helpful in preventing mice hepatic insulin resistance. In PA-induced human hepatoma cells (HepG2), QD improved the antioxidant level in cells. The fluoro-immunoassay showed that QD effectively reduced the translocation of protein kinase Cε to cell membranes in the HepG2. Western blotting results suggested that QD increased the signal transduction in the IRS-2/PI3K/Akt/FoxO1 pathway. Overall, these results showed that the combination of 5 μmol Que and 5 μmol DCI ameliorated high fat diet-induced hepatic insulin resistance.
研究领域:
药理学
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分子生物学
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内分泌学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
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