Journal of Functional Foods
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2026
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IF 3.9
Lu Wang,Kejian Wei,Jiahua Yan,Kun Wang,Siqi Liu,Fei Fang,Yu Jiang
As a major citrus flavonoid, hesperidin (HP) shows bone-protective potential, yet its role in calcium–phosphorus homeostasis and antioxidant mechanisms remains unclear. This study investigated the anti-osteoporotic effects of HP in retinoic acid (RA)-induced osteoporotic mice and primary bone marrow mesenchymal stem cells (BMSCs). HP promoted BMSC proliferation, migration, and osteogenic differentiation, with increased alkaline phosphatase (ALP) activity and mineralization. Network pharmacology identified antioxidant PI3K/AKT/FOXO1 pathways as key targets, with fibroblast growth factor 23 (FGF23) as a pivotal effector. In osteoporotic mice, HP normalized serum calcium, phosphorus, and 25-hydroxyvitamin D, increased bone formation and decreased resorption markers, alleviating bone loss and preserving trabecular microarchitecture and enhancing biomechanical properties. Mechanistically, PI3K/AKT/FOXO1-mediated FGF23 suppression was essential for osteoprotection, as confirmed using a PI3K inhibitor. Collectively, these findings suggest that HP ameliorates RA-induced osteoporosis by restoring calcium–phosphorus homeostasis via PI3K/AKT/FOXO1-dependent FGF23 inhibition, underscoring its potential as a functional food ingredient.
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高影响因子
Pharmacognosy Magazine
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2023
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IF 0.7
Jiang-Long Shi,Li-Yun Liu,Yu-Ting Dong,Tao Shen
BackgroundSeveral studies have demonstrated the anti-inflammatory properties of gastrodin. However, its specific role and mechanism in the context of osteoarthritis (OA) remain unclear.ObjectivesThe objective of this study was to explore the function and mechanism of gastrodin in both in vivo and in vitro OA models.Materials and MethodsIn this study, the targets of gastrodin against osteoarthritis were analyzed using bioinformatics methods. The effect of gastrodin on neutrophil infiltration and inflammatory cytokines in OA synovial tissue was evaluated using H&E staining. The levels of inflammatory cytokines were determined using ELISA and Q-PCR. The extracellular matrix degradation-related proteins and PI3K/AKT/FoxO1 signaling pathway were tested using western blotting.ResultsBioinformatics analysis predicted that the target of gastrodin against OA might act on the FoxO pathway. The use of gastrodin resulted in a significant reduction in the infiltration of neutrophils in the synovial tissue of rats, as observed through H&E staining. Additionally, gastrodin was found to attenuate IL-1β-induced inhibition of chondrocyte viability, pro-inflammatory cytokine production, and extracellular matrix degradation. This effect can be attributed to the suppression of PI3K/AKT/FoxO1 by gastrodin.ConclusionThese findings indicate that gastrodin is a treatment for OA.
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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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PubMed
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eLife
·
2024
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IF 6.4
Lu Yang,Zijin Lin,Ruijing Mu,Wenhan Wu,Hao Zhi,Xiaodong Liu,Hanyu Yang,Li Liu
Blood–brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs’ BBB permeability.
研究领域:
神经科学
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细胞生物学
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药理学
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PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 7
·e13771
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IF 2.72
Chao Xin,Mengya Zhao,Jiahui Wang,Zhenyu Wang
Hawthorn berry has been proved hypoglycemic effect due to the presence of some α-glucosidase inhibitors. Herein, screening and identifying of α-glucosidase inhibitors from hawthorn berry were conducted, and the results showed polyphenols mainly containing quercetin (74.58%) and hyperioside (9.58%) were responsible for its bioactivity. In order to enhance the hypoglycemic effect, the combined glucose-lowering complex (DEH) consisting of hawthorn polyphenols, D-chiro-inositol (DCI), and epigallocatechin gallate (EGCG) was prepared, where three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. In STZ/HFD-induced mice, DEH effectively improved insulin resistance, reduced fasting blood glucose (FBG) and hepatic gluconeogenesis, and increased hepatic glycogen synthesis and storage via down-regulation of PI3K/Akt/FOXO1-mediated PEPCK and G6Pase and up-regulation of PI3K/Akt/GSK3-mediated GS activation in the liver. In summary, these findings indicate that DEH is a potential novel strategy for the treatment of type 2 diabetes. Practical applications Glucose-lowering complex (DEH) with superior hypoglycemic effect, can effectively improve the insulin resistance, reduce the fasting blood glucose, hepatic gluconeogenesis and increase the hepatic glycogen synthesis and storage in mice, which represents a potential novel strategy for the treatment of type 2 diabetes.
研究领域:
药理学
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糖尿病研究
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分子生物学
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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
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