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白花芍药苷通过靶向小鼠体内的CXCL12/CXCR4轴抑制炎症以改善肝纤维化。

Albiflorin inhibits inflammation to improve liver fibrosis by targeting the CXCL12/CXCR4 axis in mice.

作者信息

Meng Lingjie, Lv Huijing, Liu Anli, Cao Qian, Du Xinyi, Li Chengjin, Li Qinggui, Luo Qingqing, Xiao Yi

机构信息

Institute of life sciences, Zunyi Medical University, Zunyi, Guizhou, China.

College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou, China.

出版信息

Front Pharmacol. 2025 Apr 30;16:1577201. doi: 10.3389/fphar.2025.1577201. eCollection 2025.

Abstract

Liver fibrosis is a common pathological feature of chronic hepatic injury that currently lacks effective therapeutic interventions. Albiflorin (ALB), a pinane-type monoterpene derived from Pall, has notable anti-inflammatory and hepatoprotective effects. However, the potential role of ALB against liver fibrosis is largely unknown. In this study, we discovered that ALB significantly inhibited CCl-induced liver fibrosis in mice. This was evidenced by improvements in liver and kidney function indexes, fibrosis indicators, and histopathological findings. studies also showed that ALB inhibited TGF-β1-induced LX-2 cell activation and reduced the expression of α-SMA and collagen I. Additionally, we found that ALB mitigates inflammation and ameliorates liver fibrosis by targeting the CXCL12/CXCR4 axis, as confirmed using the CXCR4 inhibitor AMD3100 in CCl-treated mice. Notably, combining ALB with metformin (MET) enhanced the inhibition of liver fibrosis progression. These findings highlight that ALB exerts anti-liver fibrosis effects by targeting the CXCL12/CXCR4 axis, underscoring its potential as a standalone treatment or as an adjuvant therapy.

摘要

肝纤维化是慢性肝损伤的常见病理特征,目前缺乏有效的治疗干预措施。白花芍药苷(ALB)是一种从芍药中提取的蒎烷型单萜,具有显著的抗炎和肝保护作用。然而,ALB对肝纤维化的潜在作用在很大程度上尚不清楚。在本研究中,我们发现ALB能显著抑制小鼠四氯化碳诱导的肝纤维化。肝功能和肾功能指标、纤维化指标及组织病理学结果的改善证明了这一点。研究还表明,ALB抑制转化生长因子-β1(TGF-β1)诱导的肝星状细胞系LX-2细胞活化,并降低α-平滑肌肌动蛋白(α-SMA)和I型胶原蛋白的表达。此外,我们发现ALB通过靶向CXC趋化因子配体12(CXCL12)/CXC趋化因子受体4(CXCR4)轴减轻炎症并改善肝纤维化,这在四氯化碳处理的小鼠中使用CXCR4抑制剂AMD3100得到证实。值得注意的是,将ALB与二甲双胍(MET)联合使用可增强对肝纤维化进展的抑制作用。这些发现突出表明,ALB通过靶向CXCL12/CXCR4轴发挥抗肝纤维化作用,强调了其作为单一治疗或辅助治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2545/12074940/c5463697355c/fphar-16-1577201-g001.jpg

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