Frontiers in Pharmacology
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2025
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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
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肝脏疾病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedicines
·
2025
·Vol. 13
·期 2
·486
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IF 3.9
Chunli Zhu,Yiheng Cheng,Lei Yang,Yifu Lyu,Jingjing Li,Pengbo Zhao,Ying Zhu,Xiaofei Xin,Lifang Yin
Background and Objectives: As a key mechanism of metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, inflammation triggered by chronic liver injury and immune cells with macrophages enables MASLD to progress to an advanced stage with irreversible processes such as fibrosis, cell necrosis, and cancer in the liver. The complexity of MASLD, including crosstalk between multiple organs and the liver, makes developing a new drug for MASLD challenging, especially in single-drug therapy. It was reported that upregulation of Notch1 is closely associated with the function of pro-inflammatory macrophages. To leverage this signaling pathway in treating MASLD, we developed a combination therapy.Materials and Methods: We chose Notch1 siRNA (siNotch1) to block the Notch pathway so that phenotypic regulation and functional recovery can be achieved in macrophages, combining with small molecule drug AMD3100. AMD3100 can cut off the migration of inflammatory cells to the liver to impede the development of inflammation and inhibit the CXCL12/CXCR4 biological axis in liver fibrosis to protect against the activation of HSCs. Then, we investigated the efficacy of the combination therapy on resolving inflammation and MASLD.Results: We demonstrated that in liver cells, siNotch1 combined with AMD3100 not only directly modulated macrophages by downregulating multiple pathways downstream of Notch, exerting anti-inflammatory, anti-migration, and switch of macrophage phenotype, but also modulated macrophage phenotypes through inhibiting NET release. The restored macrophages further regulate HSC and neutrophils. In in vivo pharmacodynamic studies, combination therapy exhibits a superior therapeutical effect over monotherapy in MASLD models.Conclusions: These results constitute an siRNA therapeutical approach combined with a small molecule drug against inflammation and liver injury in MASLD, offering a promising therapeutic intervention for MASLD.
研究领域:
医学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Lifeng Qin,Jinmei Qin,Xiumei Zhen,Qian Yang,Liyi Huang
The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis . Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis . Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin . The alleviation of liver fibrosis with curcumin treatment was associated with a reduction of CXCL12, CXCR4, α-SMA and RhoA. In addition, curcumin markedly inhibited the proliferation and migration of HSC-T6 cells. This study indicates that curcumin could protect against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
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2024
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IF 3.6
Gao Along,Lin Yuhua,Chai Yiwen,Han Jugan,Wu Liting,Ye Jianmin
Chemokines play crucial roles in the regulation of immune cell migration and development. The CXCL12/CXCR4 axis has been extensively studied in mammals, but its regulatory mechanism in teleost fish remains unclear. In this study, we used Nile tilapia (Oreochromis niloticus) as a teleost model to investigate the mediation of the CXCL12/CXCR4 axis in IgM+ B cells. Our findings demonstrate that the CXCL12/CXCR4 axis exhibits chemotactic activity on IgM+ B cells and promotes the phagocytosis of IgM+ B cells. Blocking CXCR4 severely impairs the chemotaxis and phagocytosis of IgM+ B cells in vitro and reduces the percentages and numbers of IgM+ B cells that migrate to peripheral blood after pathogen infection in vivo. This reduction in migration leads to a decrease in the inflammatory response, an increase in tissue bacterial load, and a decrease in survival rate. We also discovered that the evolutionarily conserved PI3K-AKT signaling pathway and Girdin are involved in the immune response during Streptococcus agalactiae infection. Inhibitors of the PI3K-AKT signaling pathway prevent the chemotaxis and phagocytosis of IgM+ B cells, impair the expression and phosphorylation levels of related proteins in vitro, and prevent IgM+ B cells chemotaxis into the peripheral blood after pathogen infection in vivo. Furthermore, CXCR4 blocking significantly downregulates the expression of AKT and Girdin. Overall, our study reveals the regulatory mechanism of the CXCL12/CXCR4 axis on IgM+ B cells via the PI3K-AKT signaling pathway in tilapia, suggesting that the functions of the CXCL12/CXCR4 axis in B cells may be conserved between mammals and teleost fish.
研究领域:
免疫学
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分子生物学
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鱼类生理学
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病理生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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