JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2026
·
IF 5.2
Qianqian Li,Yufang Ni,Zhaoyang Li,Yuanxia Zou,Huaiying Guo,Honglian Wang,Qiong Zhang,Li Wang,Jianchun Li
Chronic Kidney Disease (CKD) inevitably progresses to End-Stage Renal Disease (ESRD) via tubulointerstitial fibrosis, a process predominantly driven by the transforming growth factor-β (TGF-β)/SMAD family member 3 (Smad3) signaling pathway. Although curdione, a major sesquiterpenoid from Curcumae Rhizoma, exhibits anti-fibrotic activity, its specific mechanism in renal fibrosis remains undefined. Here, we investigated the protective effects of curdione using the Unilateral Ureteral Obstruction (UUO) mouse model and TGF-β1-stimulated renal tubular epithelial cells (TCMK1). We found that curdione (25 and 100 mg/kg) significantly mitigated UUO-induced renal injury and tubular necrosis, suppressed the injury marker kidney injury molecule-1 (KIM-1), and dose-dependently inhibited α-smooth muscle actin (α-SMA), fibronectin (FN), and Collagen I. Consistently, in TGF-β1-stimulated TCMK1 cells, curdione prevented fibrotic morphological changes and suppressed the upregulation of profibrotic markers. Mechanistically, curdione suppressed the expression of Filamin Binding LIM Protein 1 (Fblim1) and the phosphorylation of Smad2/3 in vivo and in vitro . Crucially, Fblim1 overexpression, achieved in vivo via ultrasound microbubble-mediated plasmid delivery and confirmed in vitro , significantly abrogated curdione’s anti-fibrotic effects and restored p-Smad3 levels. Furthermore, molecular docking predicted a strong binding affinity (-6.7 kcal/mol), while cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays physically validated that curdione directly binds to Fblim1, enhancing its molecular stability. In conclusion, this study provides convergent evidence at the tissue, cellular, and molecular levels that curdione exerts potent anti-fibrotic and renoprotective effects by directly targeting Fblim1, thereby functionally suppressing the TGF-β1/Smad3 signaling cascade. These findings establish curdione as a promising natural therapeutic candidate for CKD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 4.7
Jia-Yi Dou,Chen-Yu Wang,Sai-Hu Liu,Chong Gao,Shuang Zheng,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Pterostilbene (PTE) is a natural stilbene compound abundantly found in various small berries such as blueberry and grape, and exhibits multiple health promoting potentials and excellent pharmacological activities, especially antioxidant and anti-inflammatory activities. This study explored the protective effects of PTE on pulmonary fibrogenesis and inflammation and its underlying mechanisms. TGF-β-stimulated BEAS-2B or primary lung fibroblasts (LFs) were cultured with PTE or pirfenidone (PFD). Mice were received intratracheal instillation of bleomycin (BLM) and administered PTE or PFD. IL-23/ATP6V 0 D 2 -deficient BEAS-2B were treated with TGF-β or PTE. Primary LFs were stimulated with conditioned medium from TGF-β-primed RLE-6TN (CM) and treated with PTE. In vitro , PTE inhibited TGF-β-induced BEAS-2B cell migration, extracellular matrix (ECM) deposition, epithelial-mesenchymal transition (EMT) and inflammation. In BLM-induced mice, PTE reduced lung index and IL-1β levels in BALF, and improved histopathological changes. PTE inhibited BLM-induced fibrogenesis, EMT, inflammation and immune cell infiltration through blocking IL-23 and activating ATP6V 0 D 2 . In TGF-β-induced BEAS-2B, PTE decreased IL-23, increased ATP6V 0 D 2 and ATP levels, and disrupted the interaction between IL-23 and ATP6V 0 D 2 . In IL-23-deficient BEAS-2B, PTE further elevated ATP6V 0 D 2 and decreased α-SMA, Vimentin and IL-1β expressions. ATP6V 0 D 2 deficiency attenuated the anti-fibrotic and anti-inflammatory effects of PTE in TGF-β-induced BEAS-2B. PTE also inhibited fibrogenesis, EMT, and inflammation in activated-primary LFs and blocked CM-triggered primary LFs activation by regulating IL-23-ATP6V 0 D 2 axis. In conclusion, PTE ameliorated pulmonary fibrosis targeting IL-23/ATP6V 0 D 2 pathway, especially remodeling the local microenvironment of alveolar epithelial cells and fibroblasts, which might be a novel therapeutic strategy against pulmonary fibrosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2026
·
IF 5.3
Chenfeng Hua,Chaojie Qu,Liu Yang,Wenfei Zhao,Junwei Zhao,Yongliang Jia,Chengjie Ma,Pingping Shang,Xiang Li,Fuwei Xie,Cong Nie
Background Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with limited therapeutic options. Existing hiPSC-derived lung organoid models are largely restricted to single epithelial lineages and cannot endogenously integrate multiple pulmonary cell types, limiting mechanistic studies and drug screening. Methods We established a staged directed differentiation protocol to sequentially differentiate hiPSCs into definitive endoderm, anterior foregut endoderm, and lung progenitor cells, ultimately generating a multi-lineage lung model on Transwell inserts. The model was characterized by bright-field microscopy, hematoxylin-eosin (H&E) staining, scanning and transmission electron microscopy, immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and single-cell RNA sequencing. Fibrosis-like phenotypes were induced by transforming growth factor-beta 1 (TGF-β1) stimulation. Transcriptomic similarity to human IPF was assessed by RNA sequencing (RNA-seq) combined with bidirectional gene set enrichment analysis (GSEA), and drug responsiveness was validated with pirfenidone. Results Without genetic editing or exogenous cell supplementation, the model endogenously generated proximal duct-like epithelium, distal alveolar epithelium, fibroblasts, endothelial cells, and CD68 + macrophage-like cells confirmed by immunofluorescence. Single-cell sequencing identified 13 transcriptional subclusters and revealed epithelial-mesenchymal co-development. TGF-β1 stimulation induced epithelial barrier disruption, ferroptosis-like mitochondrial ultrastructural alterations, extracellular matrix (ECM) remodeling, and aberrant secretion of multiple IPF-associated biomarkers. Transcriptomic analysis showed that upregulated genes in the fibrosis model group were significantly enriched in ECM organization, cell adhesion, and the PI3K-Akt pathway. Protein-protein interaction (PPI) network analysis identified COL1A1 , FN1 , and integrin family members as central hubs. Bidirectional GSEA validation confirmed that the transcriptomic signature of the model was highly similar to human IPF, with differentially expressed genes significantly enriched in three independent IPF cohorts. Pirfenidone reversed TGF-β1-induced ECM deposition and myofibroblast activation, and partially restored type II alveolar epithelial (AT2) cell marker expression. Conclusion We successfully established a humanized multi-lineage lung model that captures epithelial-mesenchymal co-development in vitro . Its responsiveness to TGF-β1 stimulation and sensitivity to pirfenidone highlight its potential for antifibrotic drug screening. This platform offers a humanized tool with the potential to be standardized for investigating cell fate determination during early lung development and the pathogenesis of IPF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Yonghu Chen,Linying Hu,Qiang Fu,Hongzhen Chen,Zhe Jiang,Xuezheng Li
Ethnopharmacological relevance Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by alveolar epithelial injury, inflammation, and excessive extracellular matrix deposition, yet current therapeutic options remain limited. Panax ginseng C.A. Meyer, a renowned qi-tonifying herb in traditional Chinese medicine, has long been used to enhance spleen and lung function by replenishing qi. However, the mechanism of action of its primary active component, ginseng stem and leaf saponins (GSLS), in pulmonary fibrosis remains incompletely understood. Aim of the study : This study aims to elucidate the protective role of GSLS against pulmonary fibrosis by investigating how GSLS regulates mitochondrial transcription factor A (TFAM)–mtDNA homeostasis and suppresses PANoptosis in alveolar epithelial cells. Materials and methods The major constituents of GSLS were identified using UHPLC–Q Exactive HFX. A BLM-induced mouse model of pulmonary fibrosis and an MLE-12–primary fibroblast co-culture system were established to evaluate the therapeutic effects of GSLS. Surface plasmon resonance (SPR) and cell thermal shift assays (CETSA) were performed to assess the direct interaction and thermal stability between GSLS and TFAM. Co-immunoprecipitation (Co-IP), RT-qPCR, and immunofluorescence were used to evaluate PANoptosome assembly, cytosolic double-stranded DNA (dsDNA) leakage, and fibrotic marker expression. Results GSLS was found to contain multiple active ginsenosides, including Rk2, CK, Rk3, and Rf. In vivo , GSLS markedly alleviated BLM-induced lung pathological injury, reduced collagen deposition, and decreased oxidative stress. In vitro , GSLS directly bound to TFAM and enhanced its thermal stability. RT-qPCR and immunofluorescence analyses further demonstrated that GSLS effectively suppressed abnormal cytosolic dsDNA leakage, reduced MLE-12 cell death, and ameliorated mitochondrial dysfunction. Moreover, GSLS inhibited the assembly of the PANoptosome complex, suppressed epithelial PANoptosis, and decreased the expression of fibrosis-related proteins. Conclusion GSLS mitigates BLM-induced pulmonary fibrosis by stabilizing TFAM, maintaining mtDNA homeostasis, and suppressing PANoptosis. This clarifies the potential mechanism of GSLS therapy for PF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Wang Qin,Zhao Yun,Mao Yuanhu,Zhang Xiaobo,Huang Lei,Tang Lei,Chen Yi,Gong Zipeng,Peng Jianqing
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease marked by relentless deterioration of pulmonary function. Clinically, oral pharmacotherapy for IPF is hampered by two major limitations: inefficient drug delivery to the lung parenchyma and systemic exposure leading to unavoidable off-target side effects. In this study, we developed an inhalable tanshinone IIA (TA) formulation based on lipid nanocrystals to address these challenges. Leveraging the high drug loading capacity and structural stability of lipid nanocrystals, this platform overcomes the intrinsic hydrophobicity of TA, thereby markedly improving its aqueous dispersibility, aerosolization performance, and regional deposition in the deep lung. In vitro, TA lipid nanocrystals significantly enhanced cellular uptake in both pulmonary epithelial cells and lung fibroblasts. In vivo, they achieved substantially high and sustained pulmonary drug exposure. In a bleomycin-induced mouse model of IPF, inhaled TA lipid nanocrystals attenuated histopathological fibrosis, preserved lung function, and suppressed chronic inflammation via modulating the PI3K-Akt signaling pathway and the coagulation-fibrinolysis system. Collectively, this study establishes TA as a promising inhaled therapeutic agent for IPF and introduces lipid nanocrystals as a versatile, scalable, and clinically translatable platform for targeted pulmonary delivery in fibrotic and other chronic respiratory diseases. Graphical Inhalable TA lipid nanocrystals for IPF treatments
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 9
·1374
·
IF 5.7
Qinxiu Zhang,Shouwei Sun,Miaomiao Lu,Runxin Qin,Junxuan Ren,Lianjie Yao,Dianlong Jia,Jinjie Chang,Xiaohong Chu,Rui Wang,Fang Liu,Jun Li
Background:Pulmonary fibrosis (PF) is a progressive lung disease with limited therapies. Oral Pirfenidone (PFD), an approved anti-fibrotic, shows poor lung bioavailability and significant toxicity. S-Allylmercapto-N-acetylcysteine (ASSNAC) has been demonstrated to possess significant anti-inflammatory and antioxidant properties.Methods:In this study, dry powder inhaler formulations (DPIs) co-encapsulating ASSNAC and PFD in liposomes are reported. The formulation was prepared via spray freeze-drying (SFD) using L-leucine as both a cryoprotectant and a surface morphology modifier. The interfacial enrichment of L-leucine during atomization and freezing created a hydrophobic, corrugated surface that lowered particle surface energy, prevented liquid/solid bridge formation, and reduced hygroscopicity.Results:The resulting liposomal powders exhibited optimal aerosol performance: fine particle fraction (FPF) of 61.08% ± 2.45% and mass median aerodynamic diameter (MMAD) of 2.22 ± 0.11 µm. Cellular studies demonstrated that dual-loaded liposomes were efficiently taken up by Beas-2B and HFL-1 cells, with no cytotoxicity (cell viability > 90%) and negligible hemolysis. In the TGF-β1-induced in vitro fibrosis model, the combined treatment exerted prominent therapeutic effects. This regimen preserved normal epithelial morphology, accelerated wound repair, suppressed fibroblast invasiveness, and lowered the expression levels of Collagen I, Collagen III, and α-SMA. In bleomycin-induced pulmonary fibrosis rats, inhaled ASSNAC + PFD liposomal powder markedly relieved lung tissue injury and collagen accumulation. It restored redox balance and lowered pulmonary TGF-β1, hydroxyproline and collagen III levels. The formulation blocked TGF-β1 signaling and fibrotic gene expression.Conclusions:Pulmonary administration avoids oral pirfenidone-induced liver and stomach toxicity. Collectively, the ASSNAC + PFD co-encapsulated liposomal dry powder produced by SFD represents a safe and efficacious therapeutic strategy for PF.
✓ 已验证
产品关联
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Xiaohua Xie,Xiaofeng Wu,Dongsheng Zhao,Ying Liu,Qiyue Du,Yitian Li,Yaping Xu,Yuhang Li,Yan Qiu,Yungang Yang
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 11
·1394
·
IF 5.215
Tingting Li,Dong Han,Zhongxian Li,Mengqi Qiu,Yuting Zhu,Kai Li,Jiawei Xiang,Huizhen Sun,Yahong Shi,Tun Yan,Xiaoli Shi,Qiang Zhang
Idiopathic pulmonary fibrosis is a fatal interstitial disease characterized by fibroblast proliferation and differentiation and abnormal accumulation of extracellular matrix, with high mortality and an increasing annual incidence. Since few drugs are available for the treatment of pulmonary fibrosis, there is an urgent need for high-efficiency therapeutic drugs and treatment methods to reduce the mortality associated with pulmonary fibrosis. The interstitium, a highly efficient transportation system that pervades the body, plays an important role in the occurrence and development of disease, and can be used as a new route for disease diagnosis and treatment. In this study, we evaluated the administration of hydroxysafflor yellow A phytosomes via intervaginal space injection (ISI) as an anti-pulmonary fibrosis treatment. Our results show that this therapeutic strategy blocked the activation of p38 protein in the MAPK-p38 signaling pathway and inhibited the expression of Smad3 protein in the TGF-β/Smad signaling pathway, thereby reducing secretion of related inflammatory factors, deposition of collagen in the lungs of mice, and destruction of the alveolar structure. Use of ISI in the treatment of pulmonary fibrosis provides a potential novel therapeutic modality for the disease.Keywords:intervaginal space injection;pulmonary fibrosis;hydroxysafflor yellow A;phytosome;interstitial treatment
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2022
·Vol. 381
·期 3
·257-265
·
IF 4.402
Jian-Li Qiu,Guo-Feng Zhang,Yu-Na Chai,Xiao-Yan Han,Hai-Tao Zheng,Xiang-Feng Li,Fei Duan,Ling-Yan Chen
To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-β (TGF-β) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-β/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-β1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-β/smads pathway–related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-β/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-β/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Qi Fang,Shaoyu Liu,Jiangyu Cui,Ruiyue Zhao,Qian Han,Peng Hou,Youcai Li,Jie Lv,Xiaoyao Zhang,Qun Luo,Xinlu Wang
Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung in vivo can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI in vivo were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Yin Zhang,Ranran Yu,Cheng Zhao,Jiawei Liang,Yixuan Zhang,Haochen Su,Jing Zhao,Hao Wu,Shijin Xu,Ziying Zhang,Lei Wang,Xiaoping Zou,Yun Zhu,Shu Zhang,Ying Lv
BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several BET inhibitors (BETi) have entered clinical trials, demonstrating potential in inducing cancer cell apoptosis and tumor regression. However, resistance to BETi is common in solid tumors. In pancreatic cancer, it is found that cancer-associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Moreover, CAFs play a crucial role in the formation of a dense stromal barrier. Therefore, targeting CAFs in the tumor microenvironment of pancreatic cancer not only enhances cancer cells sensitivity to JQ1 but also increases drug perfusion and improves oxygen supply, thus reducing glycolysis and limiting energy supply. To address this challenge, a homologous targeting mechanism utilizing activated fibroblast membrane-coated liposomes is proposed for specific drug precise target to CAFs-rich pancreatic cancer. Additionally, TAT peptides enable liposomes penetration, delivering PFD for targeted anti-fibrotic therapy, reducing extracellular matrix generation and glycolysis, and enhancing JQ1 delivery and sensitivity. In conclusion, the findings indicate the tremendous potential of this CAFs-targeting liposomal delivery system in pancreatic cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-15
·
IF 16.6
Huang Ting,Lin Ruyi,Su Yuanqin,Sun Hao,Zheng Xixi,Zhang Jinsong,Lu Xiaoyan,Zhao Baiqin,Jiang Xinchi,Huang Lingling,Li Ni,Shi Jing,Fan Xiaohui,Xu Donghang,Zhang Tianyuan,Gao Jianqing
The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.
✓ 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）