International Journal of Medical Sciences
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2020
·
IF 2.523
Zhao Qu,Yushan Lin,Daniel Kam-Wah Mok,Qingya Bian,William Chi-Shing Tai,Sibao Chen
Triple-Negative Breast Cancer (TNBC) is a most dangerous breast cancer subtype. The naturally occurring sesquiterpene lactone, arnicolide D (AD), has proven effective against a variety of tumors, however, the inhibitory effects of AD against TNBC and the underlying mechanisms remain unclear. In the present study, two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and an MDA-MB-231 xenograft mouse model were employed to investigate the anti-TNBC effects of AD in vitro and in vivo . Cell viability was assessed by MTT assay. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by immunoblotting. In vitro studies demonstrated that AD significantly decreased cell viability, and induced G2/M cell cycle arrest and apoptosis. In vivo assays showed that oral administration of 25 or 50 mg/kg AD for 22 days led to a reduction of tumor weights by 24.7% or 41.0%, without appreciable side effects. Mechanistically, AD inhibited the activation of Akt/mTOR and STAT3 signaling pathways. Based on our findings, AD is a promising candidate for development as an adjunctive therapeutic drug for TNBC.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yichong Wang,Danyan Li,Luqing Zhao,Jixiang Liu,Dan Dou,Nian Liu,Yudi Zhuo,Shengsheng Zhang
Ethnopharmacological relevance Yinxu Weitong Capsule (YXWTC) is a Chinese patent medicine used to treat chronic gastritis. However, its efficacy and mechanisms of action in treating precancerous lesions of gastric cancer (PLGC) remain unclear. Aim of the study To evaluate the effects of YXWTC on PLGC and explore the underlying mechanisms. Materials and methods YXWTC components were identified using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole-exactive orbitrap mass spectrometry. A PLGC animal model was established and the protective effects of YXWTC on the gastric mucosa in PLGC rats were evaluated using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff and Alcian blue-high iron diamine staining, and transmission electron microscopy (TEM). The vital organs of the rats were examined using H&E staining to evaluate biosafety. Network pharmacology identified potential targets and pathways of YXWTC in PLGC treatment, followed by molecular docking validation. Various techniques, including enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, Western blotting, immunohistochemistry, apoptosis detection, and reactive oxygen species fluorescence staining were employed to elucidate the underlying mechanisms. Results In total, 340 YXWTC components were identified. YXWTC effectively improves gastric mucosal pathology in rats with PLGC. Network pharmacology identified 403 targets common to PLGC and YXWTC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified 2,323 biological processes and 206 signaling pathways, respectively. Molecular docking revealed that the primary target proteins and major drug molecules exhibited strong binding affinities. Animal studies demonstrated that YXWTC inhibited the IL-6/STAT3 pathway, promoted mitochondrial apoptosis, and induced ROS release. Conclusions We verified the pharmacodynamic effects of YXWTC in PLGC. In summary, the effects are mediated by inhibition of the IL-6/STAT3 pathway, promotion of mitochondrial apoptosis, and induction of ROS release.
研究领域:
药理学
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肿瘤学
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分子生物学
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Antioxidants
·
2025
·Vol. 14
·期 11
·1296
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IF 6.6
Kang Cheng,Guangbo He,Xiaxia Li,Yuqian Li,Xiaolin Cui,Xuefei Wu,Jau-Shyong Hong,Jie Zhao,Sheng Li,Yanjie Guo
Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders.
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IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2025
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IF 3
Song Peng,Yang-yang Sun,Qiangqiang Chu,Hua-dong Meng,Ming-wei Hao,Yan-bei Zhang
Background Leonurine (Leo) has antioxidant and anti-inflammatory activities. In this study, we investigated the effect of Leo in a rat model of lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD).Methods Rats with COPD were administered Leo, and the pulmonary function parameters, pathological changes, and inflammatory mediators in tissues were evaluated. The expression of IκBa, p65, JAK2, STAT3, p-IκBa, p-p65, p-JAK2 and p-STAT3 was measured using western blotting.Results Leo effectively improved the clinical manifestations of COPD by decreasing the pulmonary function parameters including peak expiratory flow and expiratory flow at 50% tidal volume, and improving pathological changes. Leo reduced lung inflammation and oxidative stress by reducing CD68+ cell infiltration, regulating Treg/Th17 cell differentiation, attenuating the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-17, increasing IL-10 secretion, and regulating malondialdehyde and glutathione peroxidase levels. In vitro experiments revealed that Leo exhibits similar inhibitory effects on Th17 cell differentiation and macrophage activation. Furthermore, Leo effectively protected against LPS-induced damage to bronchial airway epithelial cells by reducing reactive oxygen species production. Mechanistic investigations revealed Leo inhibits NF-κB transcriptional activity, downregulates the levels of p-p65, p-JAK2, and p-STAT3 without affecting their total protein levels.Conclusion Our results suggest that Leo exerts therapeutic effect against COPD. Leo inhibited tissue inflammation and oxidative stress in COPD rat models via inhibition of the NF-κB and JAK2/STAT3 signaling pathways.
研究领域:
呼吸医学
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药理学
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分子生物学
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炎症研究
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信号转导
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FOOD RESEARCH INTERNATIONAL
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2026
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IF 8
Kaili Wang,Xu Zhao,Tong Zhang,Sijia Yang,Sufang Duan,Aili Li,Lu Li
Food allergy (FA) is characterized by an imbalance in T helper cell responses, specifically a dysregulation of the Th17 and Treg cells. While bovine milk exosomes (BMEs) are known to possess immunomodulatory properties, their role in modulating Th17/Treg balance in FA remains unclear. This study aimed to investigate whether BMEs could alleviate FA by restoring Th17/Treg balance and to identify the key miRNA mediators involved, particularly focusing on the STAT signaling pathway. An OVA-sensitized mouse model of FA was established. Mice were treated with varying doses of BMEs. Symptoms, immune parameters, cytokine levels, and relevant signaling pathways were assessed. High-throughput sequencing and bioinformatics were used to identify miRNA candidates. Functional validation was performed using gain- and loss-of-function experiments in splenic lymphocytes. The results showed that BMEs administration significantly alleviated FA symptoms in a dose-dependent manner, restored Th17/Treg balance, and suppressed STAT3/p-STAT3/RORγt activation. High-throughput sequencing revealed miR-320a as a key BME-derived miRNA that targets the STAT pathway. Functional experiments demonstrated that miR-320a overexpression in OVA-sensitized lymphocytes significantly reduced specific antibody production, promoted Treg cell differentiation, and downregulated the STAT3/p-STAT3/RORγt pathway. Conversely, miR-320a knockdown yielded opposing effects, exacerbating the allergic response. BMEs alleviate FA by delivering miR-320a, which targets the STAT3/RORγt axis and corrects Th17/Treg imbalance. These findings reveal a novel cross-species regulatory mechanism of BMEs and support their potential as a natural intervention strategy for FA.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Fuyu Xiong,Yuxin Bai,Shifei Wu,Yulu Wang,Xinjie Dai,Yang Yang,Jiyu Gong,Gaole Zhang,Tianzhu Zhang
Ethnopharmacological relevance Yupingfeng San (YPFS), a classic tonic formula in Traditional Chinese Medicine (TCM), has been extensively applied clinically for centuries. Originating from Jiuyuan Fang , its earliest extant record is Danxi Xinfa . YPFS is composed of Huangqi ( Astragalus membranaceus Bunge), Baizhu ( Atractylodes rubra Dekker), and Fangfeng ( Saposhnikovia divaricata (Turcz.) Schischk). Due to its traditional efficacy of " replenishing qi and consolidating the exterior," YPFS is commonly prescribed for allergic rhinitis, nephrotic syndrome, and chronic nephritis. Recent studies have confirmed that YPFS protects renal function and alleviates renal fibrosis in mice with diabetic nephropathy, while simultaneously improving lung function and reducing pulmonary fibrosis in bleomycin-induced rats. Taken together, these results suggest YPFS possesses substantial potential for mitigating organ fibrosis. Purpose This study investigated the renoprotective efficacy and underlying mechanism of YPFS extract in a cisplatin-induced mouse model of renal interstitial fibrosis. Using an integrated in vivo and in vitro approach, we sought to validate the therapeutic potential of this traditional formula against chemotherapy-induced nephrotoxicity. Methods The chemical components of YPFS extract were analyzed using UPLC-Q-TOF -MS. For the in vivo study, male BALB/c mice received YPFS extract (1, 1.95, or 3 g/kg) by oral administration once daily for 7 days after a single injection of cisplatin (20 mg/kg, i.p.). Renal function was assessed by measuring serum creatinine, plasma BUN, fasting blood glucose, and the urine protein-to-creatinine ratio. Kidney tissues were examined using H&E and Masson's trichrome staining for histopathological analysis, and the expression of fibrosis markers (α-SMA, collagen I, fibronectin) was measured by immunohistochemistry and western blotting. For the in vitro study, MPC-5 podocytes were treated with high glucose (25 mM) for 48 h to induce injury, and then intervened with YPFS extract at concentrations of 20, 40, or 80 μg/mL, along with JAK2 inhibitor AG490 and STAT3 agonist Colivelin for mechanism verification. Cell viability was measured by MTT assay, apoptosis was assessed by Hoechst 33342 staining, the expression of α-SMA was measured by cellular immunofluorescence, and mitochondrial morphology was observed using MitoTracker Red staining and TEM. Mitochondrial function was evaluated by Na + /K + -ATPase and Complex I activities, and oxidative stress levels were determined by T-SOD, GSH, and MDA assays. RNA-seq was conducted to identify DEGs in MPC-5 cells, and Western blotting was used to verify key protein expression in both cells and tissues. Results UPLC-Q-TOF-MS analysis identified 57 compounds in YPFS extract, predominantly flavonoids (40.35%) and saponins (21.05%). In cisplatin-treated mice, the extract dose-dependently reduced serum creatinine, blood urea nitrogen, Urine protein-to-creatinine ratio, and fasting blood glucose. It also decreased collagen deposition and α-SMA overexpression in kidney tissues. In MPC-5 cells, the extract restored cell viability, reduced apoptosis and α-SMA overexpression, improved mitochondrial membrane potential and redox balance, and restored mitochondrial fusion-fission balance by increasing Mfn1/2 and decreasing Drp1 expression. Transcriptomic analysis revealed that the extract reversed the high glucose-induced activation of gene pathways related to IL-6/JAK/STAT3 signaling, oxidative phosphorylation, and apoptosis, with findings confirmed at the protein level. Mechanistic investigations using the JAK2 inhibitor AG490 and STAT3 agonist Colivelin confirmed that the cytoprotective and anti-fibrotic effects of YPFS were primarily dependent on the IL-6/JAK/STAT3 signaling pathway. Conclusion YPFS extract ameliorates cisplatin-induced renal interstitial fibrosis by suppressing IL-6/JAK/STAT3 signaling and restoring mitochondrial homeostasis. These findings provide a pharmacological basis for the traditional use of this formula and highlight its potential as an adjunct therapy for reducing chemotherapy-related kidney injury.
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Pharmaceutics
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2025
·Vol. 17
·期 10
·1307
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IF 5.5
Ruoqing Guan,Xiangjun He,Yuxing Dai,Guangye Huang,Zhaoyun Xue,Jianwen Chen,Peiqing Liu
Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive loss of lung function and poor prognosis. Cryptotanshinone (CTS), a small-molecule compound extracted from Salvia miltiorrhiza, possesses diverse pharmacological activities but suffers from poor oral bioavailability, which restricts its clinical development, particularly in pulmonary fibrosis. DST-3, a newly synthesized derivative of CTS, was designed to overcome these limitations.Methods: The antifibrotic effects of DST-3 were investigated in a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice through lung function assessment, histopathological evaluation, hydroxyproline quantification, and cytokine profiling. In vitro, TGF-β1-stimulated MRC5 fibroblasts were employed to explore the mechanism of action, focusing on STAT3/Smad signaling via Western blotting and molecular binding assays. Furthermore, a validated HPLC–MS/MS method was developed for DST-3, and its pharmacokinetic profile was characterized in Sprague–Dawley rats and compared with that of CTS.Results: DST-3 markedly attenuated pulmonary fibrosis in vivo, as evidenced by improved lung function, reduced collagen deposition, and decreased proinflammatory cytokine levels. In vitro, DST-3 inhibited TGF-β1-induced fibroblast activation by directly binding to STAT3 and suppressing STAT3/Smad signaling. Pharmacokinetic analysis demonstrated that, compared with CTS, DST-3 exhibited more rapid absorption, a higher peak plasma concentration, a greater area under the curve (AUC), improved hepatic metabolic stability, and enhanced lung tissue exposure.Conclusions: Our study demonstrates that DST-3 exerts potent antifibrotic effects in vivo and in vitro, primarily through STAT3 pathway inhibition. Its improved pharmacokinetic characteristics further support its potential as a promising candidate for the treatment of pulmonary fibrosis.
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Small
·
2023
·Vol. 19
·期 40
·2302834
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IF 13.3
Kaipei Luo,Lu Yang,Chunmei Yan,Yuxin Zhao,Qiuxia Li,Xing Liu,Long Xie,Qiang Sun,Xiaofang Li
Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.
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PHYTOMEDICINE
·
2023
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IF 7.9
Yinhuang Gao,Ke Ma,Zhibo Zhu,Yan Zhang,Qiong Zhou,Jing Wang,Xiaowen Guo,Liuting Luo,Haitao Wang,Kang Peng,Menghua Liu
Background Vascular dementia (VaD) is one of the most common clinical syndromes of progressive neurocognitive dysfunction with uncertain mechanisms. Modified Erchen decoction (MECD), developed from “Erchen decoction (ECD)” recorded in “Taiping Huimin Heji Jufang”, showed a good effect in the treatment of VaD. However, its therapeutic mechanism is still unclear. Purpose This study aimed to elucidate the multi-target mechanisms of MECD against VaD in vivo and in vitro . Methods VaD model was established by two-vessel obstruction (2-VO) in Sprague-Dawley rats. Six groups, including the control, 2-VO operation, MECD treatment (2.5, 5.0 and 10.0 g kg −1 d −1 ), donepezil hydrochloride (positive control, 0.45 g kg −1 d −1 ) were designed in the whole experiment. After oral administration for 4 weeks, the effects of MECD were verified by behavioral experiments, histological observation, and biochemical index analysis. The chemical profiling of MECD was performed by UHPLC-Orbitrap Fusion-HRMS, and a "compound-target-pathway" multivariate network was constructed to validate and elucidate its pharmacological mechanisms. Results Compared with 2-VO group, MECD treatment significantly alleviated anxiety and improved spatial memory in VaD rats according to the open field test (OFT) and Y-maze test. A significant increase in neuron number was observed from hematoxylin and eosin (H&E) stained images in cornu ammonis 1 (CA1) of the hippocampal region after MECD treatment. On the one hand, MECD reduced the plasma levels of triglyceride (TG), low-density lipoprotein (LDL), malondialdehyde (MDA), and amyloid-beta 42 (Aβ42), and inhibited mRNA expression of interleukin-1 beta ( Il-1β ) and Il-6 in the hippocampus. On the other hand, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were significantly increased after treatment with MECD. Moreover, MECD reduced the mRNA expression and protein expression of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), and BCL2-associated X (BAX) in the brain of 2-VO rats. Furthermore, 71 compounds were identified from the extract of MECD. Among them, liquiritin and isochlorogenic acid C gave inhibiting effects on the mRNA expression of Jnk . In addition, liquiritin and hesperetin were conformed with the inhibition of Jak2 transcription level in vitro experiments. Conclusion MECD has demonstrated a significant amelioration effect on cognitive dysfunction in VaD rats via JAK2/STAT3 and JNK/BAX signaling pathways , which represents an innovative insight into the “activate blood and eliminate phlegm” theory.
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Clinical & Translational Oncology
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2022
·Vol. 25
·期 3
·662-672
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IF 3.34
Chen Jing,Huang Shuting,Li Huawen,Li Yun,Zeng Haishan,Hu Jiemei,Lin Yanchun,Cai Huihua,Deng Pengfei,Song Ting,Guan Tian,Zeng Haoyu,Liu Mubiao
Purpose Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.
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SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Chenxi Zhao,Ruihui Xie,Qiuhui Qian,Jin Yan,Huili Wang,Xuedong Wang
As a broad-spectrum antibacterial agent, triclosan (TCS) has been confirmed to possess potential immunotoxicity to organisms, but the underlying mechanisms remains unclear. Herein, with the aid of transgenic zebrafish strains Tg ( coro 1A: EGFP) and Tg ( rag 2: DsRed), we intuitively observed acute TCS exposure caused the drastic differentiation, abnormal development and distribution of innate immune cells, as well as barriers to formation of adaptive immune T cells. These abnormalities implied occurrence of the cytokine storm, which was further evidenced by expression changes of immune-related genes, and functional biomarkers. Based on transcriptome deep sequencing, target gene prediction and dual luciferase validation, the highly conservative and up-regulated miR-19a was chosen as the research target. Under TCS exposure, miR-19a up-regulation triggered down-regulation of its target gene socs3b , and simultaneously activated the downstream IL-6/STAT3 signaling pathway. Artificial over-expression and knock-down of miR-19a was realized by microinjecting agomir and antagomir, respectively, in 1–2-cell embryos. The miR-19a up-regulation inhibited socs3b expression to activate IL-6/STAT3 pathway, and yielded abnormal changes in the functional cytokine biomarkers, along with the sharp activation of immune responses. These findings disclose the molecular mechanisms regarding TCS-induced immunotoxicity, and offer important theoretical guidance for healthy safety evaluation and disease early warning from TCS pollution.
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Frontiers in Immunology
·
2025
·
IF 5.9
Zhenghao Wu,Guqing Luo,Hongjie Li,Min Chen,Guangbo Wu,Qiang Fan,Chihao Zhang,Jiwei Yu,Jiayun Lin,Jinbo Zhao,Xiaoliang Qi,Haizhong Huo,Meng Luo,Lei Zheng
Introduction: Formononetin regulates intrahepatic fibrogenesis and macrophage polarization to improve portal pressure and liver function in rats with cirrhotic PHT through SMAD3, STAT1, STAT3 and GSK-3β signaling pathways, and modulates lymphangiogenesis through direct action and macrophage polarization-mediated indirect effects. Formononetin has the potential function of treating cirrhotic PHT.Background and aims: Formononetin (FN) has been reported to have anti-fibrotic effects in the kidneys and anti-M1 polarization effects on macrophages. Lymphangiogenesis is closely associated with macrophages, but its role in cirrhosis and portal hypertension (PHT) remains unclear. This study aims to explore the effects of FN on cirrhotic PHT and the disease-related intrahepatic lymphangiogenesis.Methods: In vivo experiments, bile duct ligation (BDL) induced PHT models were conducted in rats, followed by a 4-week FN treatment (50 mg/kg/day) administered via gavage. Hemodynamics, liver fibrosis, infiltration and polarization of intrahepatic macrophages, as well as intrahepatic lymphangiogenesis, were observed. For in vitro experiments, hepatic stellate cells, macrophages and lymphatic endothelial cells were used to observe the multiple effects of FN.Results: FN significantly ameliorated portal pressure in cirrhosis-induced PHT, improved liver function, and reduced liver fibrosis and hepatic stellate cell activation with decreased SMAD3 protein expression. The intrahepatic macrophage infiltration were markedly decreased, and M1-type macrophage polarization was suppressed by FN, accompanied by inhibition of STAT1, STAT3 and GSK-3β signaling pathways. In PHT models, FN reduced VEGF-C and VEGF-D levels in both the liver and blood, inhibiting intrahepatic lymphangiogenesis in portal area. In vitro, high-dose FN significantly inhibited lymphatic endothelial cell proliferation, while the pro-lymphangiogenic effect of conditioned medium from FN-treated M1 macrophages was diminished.Conclusions: FN significantly ameliorates cirrhotic PHT while reducing fibrosis, suppressing macrophage M1 polarization and inhibiting lymphangiogenesis. This may result from its modulation of multiple signaling pathways (SMAD3, STAT1, STAT3 and GSK-3β).
研究领域:
肝病学
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药理学
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细胞生物学
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免疫学
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分子生物学
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