Frontiers in Pharmacology
·
2025
·
IF 4.8
Lingjie Meng,Huijing Lv,Anli Liu,Qian Cao,Xinyi Du,Chengjin Li,Qinggui Li,Qingqing Luo,Yi Xiao
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 Paeonia lactiflora 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 CCl4-induced liver fibrosis in mice. This was evidenced by improvements in liver and kidney function indexes, fibrosis indicators, and histopathological findings. In vitro 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 CCl4-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.
研究领域:
药理学
·
肝脏疾病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Qihui Deng,Shanru Chen,Die Pei,Jieyi Huang,Xuhong Li,Lixia Zhu,Yingfeng Zhang
Albiflorin (AF) is a natural monoterpene glycoside compound found in the traditional Chinese medicine Paeonia lactiflora , which has been found to have good antidepressant effects. To investigate its protective effect against corticosterone (CORT) -induced HT22 cell injury, CORT-injured HT22 cell model was established. The apoptosis rate of the cells was measured by flow cytometry, and the levels of NO, GABA, Glu, and HIAA in the cell supernatant were analyzed. An untargeted metabolomic study was conducted using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), combined with network analysis to identify the targets of AF's action in CORT-injured HT22 cells. The results showed that the apoptosis rate, Glu, and NO levels were significantly increased, while GABA and 5-HIAA levels were significantly decreased after CORT injury, and AF could significantly reverse the trend. Cell metabolomics results revealed that AF notably improved the metabolomic profile of CORT-injured HT22 cells. Major metabolic pathways involved glutathione metabolism, taurine and hypotaurine metabolism, nicotinic acid and nicotinamide metabolism. Network analysis indicated that GSR, GGT1, GPX6, GPX5, GPX2 may be key targets involved in the protection of CORT-injured HT22 cells. Molecular docking and molecular dynamics simulations showed that AF binds well to them. In conclusion, AF can protect CORT-injured HT22 cells, and its mechanism of action may be related to the regulation of glutathione metabolism, taurine and hypotaurine metabolism, nicotinic acid and nicotinamide metabolism.
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Musen Lin,Yue Wang,Yan Zhao,Xiaohan Zhai,Yan Hu,Qinrong Luan,Li Lv,Zhecheng Wang,Jihong Yao
Background Acetaminophen-induced hepatotoxicity remains a clinical challenge with limited targeted therapeutic options. While recent advances have identified blood‒biliary barrier disruption as a critical pathogenic mechanism, effective interventions preserving this barrier are notably lacking. Albiflorin, a key bioactive constituent of Paeonia lactiflora Pall ., exhibits unique bile acid modulation along with antioxidant and anti-inflammatory activities, suggesting its potential efficacy in preventing acetaminophen-induced liver injury. However, its specific role and underlying mechanisms in alleviating acetaminophen-induced hepatotoxicity remain unclear. Objective This study's objective was to examine the pharmacological effects and primary molecular mechanisms of albiflorin in alleviating acetaminophen-induced liver injury. Methods An acetaminophen-induced liver injury mouse model was created using a 300 mg/kg dose of acetaminophen. The hepatoprotective effects of albiflorin were assessed through histological and biochemical analyses. Blood‒biliary barrier integrity was evaluated via Evans blue dye tests, immunofluorescence, and bile acid assays. Transcriptomic analysis, gene overexpression and interference techniques, and ChIP‒qPCR were employed to explore the molecular mechanisms underlying the protective effects of albiflorin. Results Albiflorin significantly reduced acetaminophen-induced liver injury, as evidenced by improved biochemical profiles and hepatocyte morphology. It also prevented increases in blood‒biliary barrier permeability and bile acid levels. RNA sequencing identified 3,184 differentially expressed genes, revealing critical pathways involved in maintaining blood‒biliary barrier integrity. AF reversed the acetaminophen-induced changes in the expression of genes related to the blood‒biliary barrier, particularly occludin, claudin 5, ABCG5, and ABCG8. Albiflorin protected the blood‒biliary barrier and mitigated acetaminophen-induced liver injury by enhancing ATF3 protein stability, with ATF3 identified as a critical mediator of these protective effects. Conclusion This study provides pioneering evidence that albiflorin protects against acetaminophen-induced liver injury by interacting with ATF3 to regulate blood–biliary barrier proteins and maintain the integrity of the blood–biliary barrier. These findings deepen our understanding of the role of the blood‒biliary barrier in liver diseases and suggest a therapeutic strategy for drug overdose-induced liver injury.
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Haihua Zhang,Jing Wang,Wuying Lang,Hongli Liu,Zhiqiang Zhang,Tonglei Wu,Hongqiang Li,Liya Bai,Qiumei Shi
Methotrexate (MTX) treats various diseases but also damages intestinal barrier and leads to enteritis. Albiflorin (ALB) has a variety of pharmacological effects, including antioxidant, anti-inflammation and anti-apoptosis. In the present study, we evaluated the therapeutic effect of ALB on MTX-induced enteritis and investigated the possible mechanisms involved. Male SD rats were intraperitoneally injected with 7 mg/kg MTX for three consecutive days to establish the enteritis model. ALB (20 or 40 mg/kg/day) was intragastrically administrated since two days prior MTX treatment and lasted for six days. We found that ALB treatment increased body weight and intestinal weight of rats with MTX injection. The disease activity index (DAI) score was also decreased after ALB administration. In histological examination, ALB treatment attenuated inflammatory cells infiltration and promoted survival of goblet cells. In detection of inflammatory-associated factors, ALB treatment decreased CD68 + cells infiltration, inhibited myeloperoxidase activity, and suppressed intercellular cell adhesion molecule-1 and cyclooxygenase-2 expression. Additionally, ALB reduced malondialdehyde, glutathione levels, inhibited superoxide dismutase activity and suppressed reactive oxygen species production. Moreover, ALB treatment effectively inhibited NLRP3, as well as caspase 1 p20 and interleukin (IL)-1β and 18 expression. Finally, nuclear factor-κB (NF-κB) p65 phosphorylation and nuclear translocation were also demonstrated to be blocked upon ALB treatment. In conclusion, our findings indicated that ALB alleviated MTX-induced enteritis via inhibiting the NF-κB/NLRP3 pathway.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）