INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Han Zhou,Pianpian Chen,Chuanyong Zhao,Siyuan Zou,Hao Wu,Chenhao Huang,Hongwei Hu,Qianmo Wu,ChunWu Zhang,Weidong Weng
Osteoporosis is characterized by increased osteoclast activity, which is strongly associated with increased levels of reactive oxygen species (ROS). Fraxin, a natural coumarin glycoside, has shown anti-inflammatory and antioxidant properties, but its effects on bone homeostasis are obscure. The effects of fraxin on osteoclast formation and activation were measured via an in vitro osteoclastogenesis assay. Mitochondrial and total ROS production were evaluated with the aid of MitoSOX Red and DCFH-DA, respectively. Osteoclast-related gene expression analysis was performed via qPCR. Key proteins related to osteoclast formation, ROS scavenging, and ROS-regulated signaling, such as mitogen-activated protein kinases (MAPKs), NF-κB pathways, and nuclear factor of activated T cells 1 (NFATc1) signaling, were detected via western blotting. An ovariectomized mouse model was used to evaluate the therapeutic effects of fraxin in vivo. Fraxin inhibited osteoclastogenesis and osteoclast-related gene expression. Mechanistically, fraxin restored the levels of ROS-scavenging enzymes to inhibit ROS accumulation, eventually downregulating ROS-regulated signaling. The measurement of Micro-CT and histological analyses revealed that fraxin treatment significantly reduced OVX-induced bone loss by decreasing the number of osteoclasts. Fraxin shows promise as a novel therapeutic agent for osteoclast-related bone diseases, especially osteoporosis.
研究领域:
医学
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细胞生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Hao Li,Youyang Shi,Wenjing Zhang,Qingping Li,Yan Feng,Rongzhou Wu
Fraxin alleviates MI-induced cardiac dysfunction, oxidative stress, inflammation, and apoptosis. • Fraxin promotes HXK2 binding to VDAC, enhances its mitochondrial localization, and reduces ROS production, improving anti-MI effects. • Fraxin protects against MI via PI3K/AKT-mediated HXK2 upregulation, reducing ROS, inflammation, and apoptosis. Acute myocardial infarction (AMI) is a persistent ischaemic and anoxic necrosis of the myocardium that triggers oxidative stress and ultimately leads to remodelling and heart failure. Fraxin is a traditional Chinese medicine that is commonly used in clinical practice. In this study, Fraxin improved cardiac function, reduced the area of myocardial infarction, and reduced cardiac damage such as myocardial inflammation and fibrosis. Fraxin reduced myocardial oxidative stress injury, myocardial inflammation index and myocardial apoptosis level. Network pharmacology analysis identified hexokinase II (HXK2) as the key target protein and the phosphatidylinositol-3-kinase (PI3K)/AKT pathway as the key signalling pathway. Molecular docking revealed strong binding affinity between Fraxin and HXK2. Fraxin was found to reduce oxidative stress damage, inflammation and apoptosis by enhancing HXK2's mitochondrial localization and its interaction with voltage-dependent anion channels (VDAC) via HXK2 inhibitors and HXK2-VDAC binding domain peptides. Furthermore, inhibition of the PI3K/AKT signalling pathway abolished the regulatory effects of Fraxin on HXK2 during myocardial infarction. Taken together, Fraxin exerts a cardioprotective effect by regulating HXK2 through PI3K/AKT signaling pathway to reduce reactive oxygen species (ROS) levels, inflammation and myocardial apoptosis. This study provides a scientific basis for the therapeutic potential of the traditional Chinese medicine Fraxin in AMI.
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DOI
高影响因子
EXPERIMENTAL ANIMALS
·
2026
·
IF 2
Yang LI,Xinchang FENG,Lingpeng ZHENG
Insulin resistance (IR) and hepatic steatosis are key pathological features of type 2 diabetes mellitus (T2DM). Fraxin, a natural flavonoid with potential metabolic regulatory properties, has been proposed to modulate metabolic disorders. This study aimed to investigate whether fraxin protects against IR and steatosis via Sirt1/AMPK/mTOR-mediated autophagy activation. A T2DM rat model was established using high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. Rats were treated with fraxin (25 or 50 mg/kg) for 4 weeks, followed by assessment of fasting blood glucose (FBG), insulin (FINS), HOMA-IR index, serum lipid profiles and liver function. Histopathological examination (H&E and Oil Red O staining) evaluated hepatic steatosis. BRL 3A cells exposed to palmitic acid (PA) were treated with fraxin (40 or 80 μM), and glucose uptake, lipid accumulation, and protein expression (IRS-1 phosphorylation, GLUT-2 translocation, autophagy markers and Sirt1/AMPK/mTOR pathway components) were analyzed. The specific autophagy inhibitor chloroquine (CQ) was used to verify whether the regulatory effects of fraxin were dependent on autophagy activation. Fraxin significantly reduced FBG, FINS, HOMA-IR, and dyslipidemia in diabetic rats. In PA-treated BRL 3A cells, fraxin enhanced glucose uptake, reduced lipid droplets, and restored IRS-1 phosphorylation and GLUT-2 membrane localization. Mechanistically, fraxin activated autophagy and modulated the Sirt1/AMPK/mTOR pathway, which were abolished by the Sirt1 inhibitor EX527. In conclusion, fraxin alleviates IR and hepatic steatosis in HFD/STZ-induced diabetic rats by activating autophagy through Sirt1/AMPK/mTOR pathway, suggesting its potential as a therapeutic agent for diabetes-associated metabolic disorders.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li
The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.
研究领域:
放射生物学
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药理学
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分子生物学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
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