benzofurans has been researched along with Fibrosis* in 27 studies
1 trial(s) available for benzofurans and Fibrosis
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Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.
Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis.. HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan. Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks. Topics: Adult; Aged; Amides; Antiviral Agents; Asia; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combination; Europe; Female; Fibrosis; Genotype; Hepacivirus; Hepatitis C; Humans; Imidazoles; Male; Middle Aged; Quinoxalines; Ribavirin; Sulfonamides | 2020 |
26 other study(ies) available for benzofurans and Fibrosis
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Salvianolic acid B attenuates tubulointerstitial fibrosis by inhibiting EZH2 to regulate the PTEN/Akt pathway.
Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.. To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.. Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.. SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both. SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials. Topics: Animals; Benzofurans; Depsides; Enhancer of Zeste Homolog 2 Protein; Fibrosis; Histones; Kidney; Kidney Diseases; Male; Mice; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Transforming Growth Factor beta1; Ureteral Obstruction | 2023 |
Salvianolic Acid B Attenuates Hypertrophic Scar Formation In Vivo and In Vitro.
Hypertrophic scars (HTSs) are a fibroproliferative disorder that occur following skin injuries. Salvianolic acid B (Sal-B) is an extractant from Salvia miltiorrhiza that has been reported to ameliorate fibrosis in multiple organs. However, the antifibrotic effect on HTSs remains unclear. This study aimed to determine the antifibrotic effect of Sal-B in vitro and in vivo.. In vitro, hypertrophic scar-derived fibroblasts (HSFs) were isolated from human HTSs and cultured. HSFs were treated with (0, 10, 50, 100 μmol/L) Sal-B. Cell proliferation and migration were evaluated by EdU, wound healing, and transwell assays. The protein and mRNA levels of TGFβI, Smad2, Smad3, α-SMA, COL1, and COL3 were detected by Western blots and real-time PCR. In vivo, tension stretching devices were fixed on incisions for HTS formation. The induced scars were treated with 100 μL of Sal-B/PBS per day according to the concentration of the group and followed up for 7 or 14 days. The scar condition, collagen deposition, and α-SMA expression were analyzed by gross visual examination, H&E, Masson, picrosirius red staining, and immunofluorescence.. In vitro, Sal-B inhibited HSF proliferation, migration, and downregulated the expression of TGFβI, Smad2, Smad3, α-SMA, COL1, and COL3 in HSFs. In vivo, 50 and 100 μmol/L Sal-B significantly reduced scar size in gross and cross-sectional observations, with decreased α-SMA expression and collagen deposition in the tension-induced HTS model.. Our study demonstrated that Sal-B inhibits HSFs proliferation, migration, fibrotic marker expression and attenuates HTS formation in a tension-induced HTS model in vivo.. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Topics: Animals; Benzofurans; Cicatrix, Hypertrophic; Cross-Sectional Studies; Fibroblasts; Fibrosis; Humans | 2023 |
Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway.
Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear.. This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments.. The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary β2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining.. In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway.. This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF. Topics: Benzofurans; Caffeic Acids; Depsides; Fibrosis; Humans; Kidney Diseases; Lactates; Lymphokines; Platelet-Derived Growth Factor; Signal Transduction | 2022 |
Fraxinellone alleviates kidney fibrosis by inhibiting CUG-binding protein 1-mediated fibroblast activation.
Chronic Kidney Disease (CKD) is a serious threat to human health. In addition, kidney fibrosis is a key pathogenic intermediate for the progression of CDK. Moreover, excessive activation of fibroblasts is key to the development of kidney fibrosis and this process is difficult to control. Notably, fraxinellone is a natural compound isolated from Dictamnus dasycarpus and has a variety of pharmacological activities, including hepatoprotective, anti-inflammatory and anti-cancer effects. However, the effect of fraxinellone on kidney fibrosis is largely unknown. The present study showed that fraxinellone could alleviate folic acid-induced kidney fibrosis in mice in a dose dependent manner. Additionally, the results revealed that fraxinellone could effectively down-regulate the expression of CUGBP1, which was highly up-regulated in human and murine fibrotic renal tissues. Furthermore, expression of CUGBP1 was selectively induced by the Transforming Growth Factor-beta (TGF-β) through p38 and JNK signaling in kidney fibroblasts. On the other hand, downregulating the expression of CUGBP1 significantly inhibited the activation of kidney fibroblasts. In conclusion, these findings demonstrated that fraxinellone might be a new drug candidate and CUGBP1 could be a promising target for the treatment of kidney fibrosis. Topics: Animals; Benzofurans; CELF1 Protein; Cell Line; Disease Models, Animal; Fibroblasts; Fibrosis; Folic Acid; JNK Mitogen-Activated Protein Kinases; Kidney; Kidney Diseases; Male; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Rats; Transforming Growth Factor beta1 | 2021 |
Phlorofucofuroeckol A from Ecklonia cava ameliorates TGF-β1-induced fibrotic response of human tracheal fibroblasts via the downregulation of MAPKs and SMAD 2/3 pathways inactivated TGF-β receptor.
The objective of this study was to investigate inhibitory effects of a bioactive compound isolated from Ecklonia cava on fibrotic responses to transforming growth factor-β1 (TGF-β1)-stimulated Hs680. Tr human tracheal fibroblasts and the associated mechanisms of action. Post consecutive purification, a potent bioactive compound was identified phlorofucofuroeckol A. Phlorofucofuroeckol A significantly suppressed protein expression levels of collagen type I and α-smooth muscle actin (α-SMA) on TGF-β1-stimulated Hs680. Tr human tracheal fibroblasts. Further mechanistic studies determined that phlorofucofuroeckol A suppressed the phosphorylation of p38, extracellular regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) and SMAD 2/3 in TGF-β1-stimulated Hs680. Tr human tracheal fibroblasts. Moreover, we could show that phlorofucofuroeckol A inhibits binding of TGF-β1 to its TGF-β receptor by molecular docking. Based on the results, we propose that phlorofucofuroeckol A suppresses the MAPKs and SMAD 2/3 pathways and relieves cellular fibrotic activities, thus preventing tracheal fibrosis. Topics: Benzofurans; Cell Line; Dioxins; Fibroblasts; Fibrosis; Humans; MAP Kinase Signaling System; Phaeophyceae; Signal Transduction; Smad2 Protein; Smad3 Protein; Trachea; Transforming Growth Factor beta1 | 2020 |
Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3.
Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear.. Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B.. Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia.. Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3. Topics: Animals; Base Sequence; Benzofurans; Cell Hypoxia; CpG Islands; Cytoplasm; Diabetic Cardiomyopathies; DNA Methylation; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Mice, Inbred C57BL; Myocardium; Neovascularization, Physiologic; Phosphorylation; Protein Transport; Proto-Oncogene Proteins c-akt; Ventricular Remodeling | 2020 |
Salvianolic acid B attenuates epithelial-mesenchymal transition in renal fibrosis rats through activating Sirt1-mediated autophagy.
Renal fibrosis is a kind of progressive kidney disease leading to end-stage renal damage. Epithelial-mesenchymal transition (EMT) is one of the crucial features of renal fibrosis. Salvianolic acid B (SalB), isolated from traditional Chinese medicine Radix Salviae miltiorrhizae, has been proved to be suitable for renal protection. The aims of this study are to investigate the pharmacological effects of SalB on renal fibrosis and explore the underlying mechanisms. In vivo, our study showed that SalB could improve kidney dysfunction and reduce the expression of EMT-related proteins, including fibronectin (FN), α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β). In addition, SalB activated autophagy and up-regulated the expression of Sirt1. In vitro, our study showed that SalB reversed EMT in TGF-β1-induced human kidney proximal tubular epithelial cells (HK-2 cells). Further mechanism studies showed that the inhibition of Sirt1 and autophagy could reverse the protective effect of SalB on the EMT process in TGF-β1-induced HK-2 cells. Taken together, this study demonstrated that SalB attenuates EMT in the process of renal fibrosis through activating Sirt1-mediated autophagy, and Sirt1 could be a key target for treatment of renal fibrosis. Topics: Actins; Animals; Autophagy; Benzofurans; Cell Line; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibronectins; Fibrosis; Humans; Kidney; Kidney Diseases; Male; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Transforming Growth Factor beta | 2020 |
Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis.
Salvianolic acid B (Sal B) is one of the main water‑soluble components of Salvia miltiorrhiza Bge. Numerous reports have demonstrated that it could exert significant renal‑protective effects, but the underlying mechanism remains unclear. The present study demonstrated that Sal B could alleviate renal injury by regulating the heparanase/syndecan‑1 (HPSE/SDC1) axis. In vivo, the serum creatinine, blood urea nitrogen, transforming growth factor‑β1 (TGF‑β1) and fibroblast growth factor‑2 (FGF‑2) levels, and the histopathological changes of mice kidneys were examined. Sal B could notably reduce the renal injury caused by left ureteral ligation. In vitro, Sal B downregulated the expression levels of HPSE/FGF‑2/TGF‑β1/α‑smooth muscle actin and upregulated the expression levels of SDC1/E‑cadherin in angiotensin II‑stimulated HK‑2 cells in a dose‑dependent manner. In summary, to the best of the authors' knowledge, the present study provided evidence for the first time that Sal B could exert renal‑protective effects via the inhibition of the HPSE/SDC1 axis, and these results suggest that the administration of Sal B may be a novel therapeutic strategy in treating renal interstitial fibrosis. Topics: Animals; Benzofurans; Cell Line; Fibrosis; Glucuronidase; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; Protective Agents; Renal Insufficiency, Chronic; Syndecan-1 | 2020 |
MMP9 inhibition increases autophagic flux in chronic heart failure.
Increased matrix metalloprotease 9 (MMP9) after myocardial infarction (MI) exacerbates ischemia-induced chronic heart failure (CHF). Autophagy is cardioprotective during CHF; however, whether increased MMP9 suppresses autophagic activity in CHF is unknown. This study aimed to determine whether increased MMP9 suppressed autophagic flux and MMP9 inhibition increased autophagic flux in the heart of rats with post-MI CHF. Sprague-Dawley rats underwent either sham surgery or coronary artery ligation 6-8 wk before being treated with MMP9 inhibitor for 7 days, followed by cardiac autophagic flux measurement with lysosomal inhibitor bafilomycin A1. Furthermore, autophagic flux was measured in vitro by treating H9c2 cardiomyocytes with two independent pharmacological MMP9 inhibitors, salvianolic acid B (SalB) and MMP9 inhibitor-I, and CRISPR/cas9-mediated MMP9 genetic ablation. CHF rats showed cardiac infarct, significantly increased left ventricular end-diastolic pressure (LVEDP), and increased MMP9 activity and fibrosis in the peri-infarct areas of left ventricular myocardium. Measurement of the autophagic markers LC3B-II and p62 with lysosomal inhibition showed decreased autophagic flux in the peri-infarct myocardium. Treatment with SalB for 7 days in CHF rats decreased MMP9 activity and cardiac fibrosis but increased autophagic flux in the peri-infarct myocardium. As an in vitro corollary study, measurement of autophagic flux in H9c2 cardiomyocytes and fibroblasts showed that pharmacological inhibition or genetic ablation of MMP9 upregulates autophagic flux. These data are consistent with our observations that MMP9 inhibition upregulates autophagic flux in the heart of rats with CHF. In conclusion, the results in this study suggest that the beneficial outcome of MMP9 inhibition in pathological cardiac remodeling is in part mediated by improved autophagic flux. Topics: Animals; Autophagy; Benzofurans; Cell Line; Disease Models, Animal; Fibroblasts; Fibrosis; Heart Failure; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Myocytes, Cardiac; Rats, Sprague-Dawley; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling | 2020 |
Salvianolic acid B attenuates experimental skin fibrosis of systemic sclerosis.
Systemic sclerosis (SSc) is a connective tissue disease characterized mainly by fibrosis of skin and internal organs. Our previous study has shown that salvianolic acid B (SAB), a bioactive component extracted from Salvia miltiorrhiza (SM), was one of the essential ingredients in the traditional Chinese medicine Yiqihuoxue formula, which has been used to treat SSc-related dermal and pulmonary fibrosis. The aim of the present study was to evaluate the effect of SAB on skin fibrosis and explore its underlying anti-fibrotic mechanism. We found that SAB was capable of alleviating skin fibrosis in a bleomycin-induced SSc mouse model, alleviating skin thickness and reducing collagen deposition. in vitro studies indicated that SAB reduced SSc skin fibroblast proliferation and downregulated extracellular matrix gene transcription and collagen protein expression. TGF-β/SMAD and MAPK/ERK pathway activation were also shown to be suppressed in SAB treated fibroblasts. Moreover, RNA-seq revealed that the anti-fibrotic effect of SAB might be related to antioxidant activity, the cell cycle, and the p53 signaling pathway. Taken together, our results suggest that SAB has the ability to alleviate SSc-related skin fibrosis both in vivo and in vitro. Topics: Animals; Benzofurans; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Fibroblasts; Fibrosis; Mice; Mice, Inbred C57BL; Random Allocation; Scleroderma, Systemic; Skin | 2019 |
Twist1 in Infiltrating Macrophages Attenuates Kidney Fibrosis
Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix. To study Twist1 functions in different macrophage subsets during kidney scar formation, we used two conditional mutant mouse models in which. Twist1 in infiltrating inflammatory macrophages but not in resident macrophages limited kidney fibrosis after ureteral obstruction by driving extracellular matrix degradation. Moreover, deletion of Twist1 in infiltrating macrophages attenuated the expression of MMP13 in CD11b. Twist1 in infiltrating myeloid cells mitigates interstitial matrix accumulation in the injured kidney by promoting MMP13 production, which drives extracellular matrix degradation. These data highlight the complex cell-specific actions of Twist1 in the pathogenesis of kidney fibrosis. Topics: Actins; Animals; Benzofurans; Collagen Type I; CX3C Chemokine Receptor 1; Disease Models, Animal; Extracellular Matrix; Fibrosis; Gene Expression; Hydroxyproline; Kidney; Kidney Diseases; Macrophages; Macrophages, Peritoneal; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; Mice; Morpholines; Myeloid Cells; Twist-Related Protein 1; Ureteral Obstruction | 2019 |
DL-3-n-butylphthalide improves ventricular function, and prevents ventricular remodeling and arrhythmias in post-MI rats.
DL-3-n-butylphthalide (NBP) is used in the treatment of ischemic stroke. It was demonstrated NBP also has a cardioprotective effect in acute myocardial infarction (MI) model. However, the chronic effects of NBP on ventricular function, remodeling, and arrhythmias in post-MI stage are unknown. This study was to investigate the effect of NBP on reducing ventricular remodeling and arrhythmias in post-MI stage. Post-MI rats were randomly treated with 100 mg/kg NBP daily (n = 21) or vehicle (n = 21) for 5 weeks. Sham-operated rats were treated with the same dose vehicle (n = 18). Echocardiographic assessment, ventricular arrhythmias inducibility test, morphological and collagen analysis, immunohistochemistry, and western blot were studied. NBP significantly improved cardiac function, inhibited the severity and inducibility of ventricular arrhythmias, reduced cardiac index, fibrosis and hypertrophy, improved the protein expression and distribution of Cx43 gap junction, and upregulated PI3k/Akt/Nrf2 pathway and the downstream antioxidant response elements (ARE), including heme oxygenase-1, Glutathione, Cu-Zn superoxide dismutase, and Fe/Mn superoxide dismutase. These results suggest NBP improves LV function and reduces ventricular arrhythmias by mitigating LV fibrosis, hypertrophy, and Cx43 gap junction remodeling. PI3k/Akt/Nrf2/ARE signaling pathway may contribute to its anti-ventricular remodeling effects. Topics: Animals; Arrhythmias, Cardiac; Benzofurans; Cardiotonic Agents; Connexin 43; Fibrosis; Heart Ventricles; Myocardial Infarction; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Ventricular Function; Ventricular Remodeling | 2018 |
Salvianolic Acid B-Alleviated Angiotensin II Induces Cardiac Fibrosis by Suppressing NF-κB Pathway In Vitro.
BACKGROUND Salvianolic acid B (SalB) is the representative component of phenolic acids derived from the roots and rhizomes of Salvia miltiorrhiza Bge (Labiatae), which has been used widely in Asian countries for clinical therapy of various cardiovascular dysfunction-related diseases. However, cardiac protection effects and the underlying mechanism for clinical application are still poorly understood. Here, we investigated the potential anti-myocardial fibrosis effect and mechanism of SalB on Angiotensin II (Ang II)-induced cardiac fibrosis in vitro. MATERIAL AND METHODS The proliferation and migration capacity of cardiac fibroblasts (CFBs) were measured by MTT assay and scratch analysis, respectively. The colorimetric assay determined the hydroxyproline content in medium. Western blotting detected the protein expressions of nuclear transcription factor-kappa B (NF-κB) pathway-associated proteins, fibronectin (FN), collagen type I (Coll I), α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). The expression of α-SMA protein was observed by immunofluorescence staining. qRT-PCR detected the mRNA expression of NF-κB. RESULTS SalB attenuated Ang II-induced the proliferation and the migration ability of CFBs. Ang II-induced the extracellular matrix protein Coll I, FN, and α-SMA, the pro-fibrotic cytokine CTGF protein expression was inhibited, and the nuclear translocation of NF-κB p65 subunit was reduced by SalB. Western blotting and qRT-PCR confirmed that SalB blocked the activation of NF-κB induced by Ang II. PDTC (the NF-κB inhibitor) also inhibited proliferation of CFBs and reduced α-SMA and Coll I expression induced by Ang II. CONCLUSIONS SalB can alleviate Ang II-induced cardiac fibrosis via suppressing the NF-κB pathway in vitro. Topics: Angiotensin II; Animals; Benzofurans; Cell Movement; Cell Proliferation; Collagen Type I; Fibroblasts; Fibrosis; Heart; I-kappa B Proteins; Myocardium; NF-kappa B; Rats; Rats, Sprague-Dawley | 2018 |
Sanggenon C protects against pressure overload‑induced cardiac hypertrophy via the calcineurin/NFAT2 pathway.
The effects of Sanggenon C on oxidative stress and inflammation have previously been reported; however, little is currently known regarding the effects of Sanggenon C on cardiac hypertrophy and fibrosis. In the present study, aortic banding (AB) was performed on mice to induce cardiac hypertrophy. After 1 week AB surgery, mice were treated daily with 10 or 20 mg/kg Sanggenon C for 3 weeks. Subsequently, cardiac function was detected using echocardiography and catheter‑based measurements of hemodynamic parameters. In addition, the extent of cardiac hypertrophy was evaluated by pathological staining and molecular analysis of heart tissue in each group. After 4 weeks of AB, vehicle‑treated mice exhibited cardiac hypertrophy, fibrosis, and deteriorated systolic and diastolic function, whereas treatment with 10 and 20 mg/kg Sanggenon C treatment ameliorated these alterations, as evidenced by attenuated cardiac hypertrophy and fibrosis, and preserved cardiac function. Furthermore, AB‑induced activation of calcineurin and nuclear factor of activated T cells 2 (NFAT2) was reduced following Sanggenon C treatment. These results suggest that Sanggenon C may exert protective effects against cardiac hypertrophy and fibrosis via suppression of the calcineurin/NFAT2 pathway. Topics: Animals; Benzofurans; Biomarkers; Biopsy; Calcineurin; Cardiomegaly; Cardiotonic Agents; Cell Culture Techniques; Cell Line; Chromones; Disease Models, Animal; Fibrosis; Hypertension; Immunohistochemistry; Male; Mice; Myocytes, Cardiac; NFATC Transcription Factors; Signal Transduction | 2017 |
New strategy for renal fibrosis: Targeting Smad3 proteins for ubiquitination and degradation.
Smad3 is a critical signaling protein in renal fibrosis. Proteolysis targeting chimeric molecules (PROTACs) are small molecules designed to degrade target proteins via ubiquitination. They have three components: (1) a recognition motif for E3 ligase; (2) a linker; and (3) a ligand for the target protein. We aimed to design a new PROTAC to prevent renal fibrosis by targeting Smad3 proteins and using hydroxylated pentapeptide of hypoxia-inducible factor-1α as the recognition motif for von Hippel-Lindau (VHL) ubiquitin ligase (E3).. Computer-aided drug design was used to find a specific ligand targeting Smad3. Surface plasmon resonance (SPR) was used to verify and optimize screening results. Synthesized PROTAC was validated by two-stage mass spectrometry. The PROTAC's specificity for VHL (E3 ligase) was proved with two human renal carcinoma cell lines, 786-0 (VHL(-)) and ACHN (VHL(+)), and its anti-fibrosis effect was tested in renal fibrosis cell models.. Thirteen small molecular compounds (SMCs) were obtained from the Enamine library using GLIDE molecular docking program. SPR results showed that #8 SMC (EN300-72284) combined best with Smad3 (KD=4.547×10(-5)M). Mass spectrometry showed that synthesized PROTAC had the correct peptide molecular weights. Western blot showed Smad3 was degraded by PROTAC with whole-cell lysate of ACHN but not 786-0. Degradation, but not ubiquitination, of Smad3 was inhibited by proteasome inhibitor MG132. The upregulation of fibronectin and Collagen I induced by TGF-β1 in both renal fibroblast and mesangial cells were inhibited by PROTAC.. The new PROTAC might prevent renal fibrosis by targeting Smad3 for ubiquitination and degradation. Topics: Amino Acid Motifs; Benzofurans; Binding Sites; Cell Line, Tumor; Drug Design; Fibrosis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney; Ligands; Models, Molecular; Molecular Docking Simulation; Molecular Targeted Therapy; Peptide Fragments; Protein Interaction Domains and Motifs; Proteolysis; Pyridines; Recombinant Fusion Proteins; Renal Insufficiency, Chronic; Smad3 Protein; Small Molecule Libraries; Surface Plasmon Resonance; Ubiquitin-Protein Ligases; Ubiquitination | 2016 |
Salvianolic acid B reduced the formation of epidural fibrosis in an experimental rat model.
Salvianolic acid B (Sal B) was newly reported to be able to attenuate fibrosis in the animal model. The aim of the present study was to investigate the effect of the intragastric application of Sal B on the prevention of epidural fibrosis (EF).. Forty healthy adult male Wistar rats were divided into four treatment groups (n = 10 per group): (1) 10 mg/kg Sal B, (2) 30 mg/kg Sal B, (3) 50 mg/kg Sal B and (4) Saline (vehicle treatment, control group). All animals underwent a laminectomy at the lumbar 1-2 (L 1-2) level. After intragastric treatment, all rats were sacrificed at post-operative week 8. The extent of the epidural scar, the regeneration of the vasculature and the expression levels of vascular endothelial growth factor (VEGF) were analysed.. The animals' recovery was uneventful during the experimental period. The extent of the epidural scar, the regeneration of the vasculature and the expression levels of VEGF suggested better outcomes in the Sal B-treated groups. Sal B exerted the ability to prevent the formation of an epidural scar and vascularization at the laminectomy sites. The effects of Sal B were dose-dependent, with the 50 mg/kg Sal B group showing the best outcomes compared with the other groups.. Post-operative intragastric application of Sal B can prevent the formation of epidural scarring. Sal B exerted these effects in a dose-dependent manner, and 50 mg/kg dose was shown to be the best effect in the present study. The results of this study reveal that Sal B could be a potential therapy for EF and valuable for further research. Topics: Animals; Benzofurans; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Epidural Space; Fibrosis; Male; Rats; Rats, Wistar | 2016 |
Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.
Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Topics: Administration, Oral; Amygdalin; Animals; Area Under Curve; Benzofurans; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Drugs, Chinese Herbal; Fibrosis; Kidney; Lactates; Liver Cirrhosis; Lung; Male; Rats; Rats, Wistar; Rosmarinic Acid; Tandem Mass Spectrometry; Tissue Distribution | 2015 |
Study on salvianolic acid B in the reduction of epidural fibrosis in laminectomy rats.
Epidural fibrosis (EF) is a common complication after laminectomy. Salvianolic acid B (Sal B) is a major bioactive component of a traditional Chinese medical agent, Salvia miltiorrhiza, which has shown anti-inflammatory, anti-fibrotic and anti-proliferative properties. The object of this study was to investigate the effect of Sal B on the prevention of epidural fibrosis in laminectomy rats.. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. The rats were randomly divided into 3 groups of 20: (1) Sal B treatment group; (2) Vehicle group; (3) Sham group (laminectomy without treatment). All rats were sacrificed 4 weeks post-operatively. The extent of epidural fibrosis, fibroblast proliferation and the expression of vascular endothelial growth factor (VEGF) and inflammatory factors were analyzed.. The recovery of all rats was uneventful. In the laminectomy sites treated with Sal B, the dura mater showed no adhesion. Collagen deposition was significantly lower in the Sal B group than the other two groups. In addition, both fibroblast and inflammatory cell counting in the laminectomy sites treated with Sal B showed better grades than the other two groups. The expression of VEGF and inflammatory factors in operative sites also suggested better results in the Sal B group than the other two groups.. Sal B inhibits fibroblast proliferation, blood vessel regeneration, and inflammatory factor expression. Thus, Sal B is able to prevent epidural scar adhesion in post-laminectomy rats. Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cell Proliferation; Cicatrix; Double-Blind Method; Drugs, Chinese Herbal; Epidural Space; Fibroblasts; Fibrosis; Hydroxyproline; Interleukin-6; Laminectomy; Male; Rats, Wistar; Tissue Adhesions; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A | 2014 |
Inhibition of protease-activated receptor 1 ameliorates intestinal radiation mucositis in a preclinical rat model.
To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects.. Rats underwent fractionated X-irradiation (5 Gy×9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation. The effect of PAR1 inhibition on development of chronic intestinal radiation fibrosis was evaluated in animals receiving SCH602539 (0, 15, or 30 mg/kg/d) until 2 weeks after irradiation, or continuously until termination of the experiment 26 weeks after irradiation.. Blockade of PAR1 ameliorated early intestinal toxicity, with reduced overall intestinal radiation injury (P=.002), number of myeloperoxidase-positive (P=.03) and proliferating cell nuclear antigen-positive (P=.04) cells, and collagen III accumulation (P=.005). In contrast, there was no difference in delayed radiation enteropathy in either the 2- or 26-week administration groups.. Pharmacological blockade of PAR1 seems to reduce early radiation mucositis but does not affect the level of delayed intestinal radiation fibrosis. Early radiation enteropathy is related to activation of cellular thrombin receptors, whereas platelet activation or fibrin formation may play a greater role in the development of delayed toxicity. Because of the favorable side-effect profile, PAR1 blockade should be further explored as a method to ameliorate acute intestinal radiation toxicity in patients undergoing radiotherapy for cancer and to protect first responders and rescue personnel in radiologic/nuclear emergencies. Topics: Animals; Benzofurans; Carbamates; Fibrosis; Intestinal Mucosa; Intestine, Small; Male; Mucositis; Peroxidase; Proliferating Cell Nuclear Antigen; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; Receptor, PAR-1 | 2013 |
Salvianolic acid B reverses the epithelial-to-mesenchymal transition of HK-2 cells that is induced by transforming growth factor-β.
Salvianolic acid B (Sal B) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae, and has recently been used for treating renal fibrosis in traditional Chinese medicine. Here we investigated the ability reversal of Sal B to reverse the transdifferentiation of human kidney proximal tubular epithelial cells that was induced by transforming growth factor-beta 1 (TGF-β1). The effects of Sal B on HK-2 cell morphology were observed by phase contrast microscopy, while alpha smooth muscle actin and E-cadherin were studied by immunocytochemistry and real-time reverse transcription polymerase chain reaction, respectively. Exposure of HK-2 cells to TGF-β1 for 72 h induced a complete conversion of the epithelial cells to myofibroblasts. When HK-2 cells were co-incubated with Sal B and TGF-β1 for a further 72 h, the morphology of myofibroblasts returned to that of proximal tubular epithelial cells, whereas the myofibroblast phenotype was maintained after exposure of cells to TGF-β1 for 144 h. Sal B reduced alpha smooth muscle actin levels and increased E-cadherin levels compared with their epithelial-to-mesenchymal transition controls. The reversal effect of Sal B was dose-dependent. That Sal B reverses the epithelial-to-mesenchymal transition in vitro suggests that it could possibly facilitate the repair of tubular epithelial structures and the regression of renal fibrosis in injured kidneys. Topics: Benzofurans; Cell Culture Techniques; Cell Line; Drugs, Chinese Herbal; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Kidney; Mesoderm; Microscopy, Phase-Contrast; Transforming Growth Factor beta | 2011 |
Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27.
Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicin-induced cardiotoxicity.. Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50% decrease of mortality.. These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity. Topics: Animals; Apoptosis; Benzofurans; Cardiotonic Agents; Culture Media, Serum-Free; Cytoprotection; Doxorubicin; Fibrosis; HSP27 Heat-Shock Proteins; Male; Mice; Mice, Inbred BALB C; Myocytes, Cardiac; Phosphorylation | 2011 |
Salvianolic acid B prevents epithelial-to-mesenchymal transition through the TGF-beta1 signal transduction pathway in vivo and in vitro.
Salvianolic Acid B (Sal B) is a water-soluble component from Danshen (a traditional Chinese herb widely used for chronic renal diseases) with anti-oxidative and cell protective properties. Sal B also has potential protective effects on renal diseases. Tubular epithelial cells can undergo epithelial-to-mesenchymal transition (EMT), which plays an important role in the pathogenesis of renal interstitial fibrosis (RIF) and is mainly regulated by TGF-beta1/Smads pathway. The aims of the study are to investigate the effect of Sal B on tubular EMT in vivo and in vitro, and to elucidate its underlying mechanism against EMT related to TGF-beta1/Smads pathway.. For in vivo experiments, RIF was induced in rats by oral administration of HgCl2 and prophylaxised with Sal B and vitamin E. The protein expression of E-cadherin was down-regulated, while the expression of alpha-SMA, TGF-beta1, TbetaR-I, p-Smad2/3 and the activity of matrix metalloproteinase-2 (MMP-2) were up-regulated in kidneys of model rats when compared with those of normal rats. In contrast, Sal B and vitamin E significantly attenuated the expression of alpha-SMA, TGF-beta1, TbetaR-I, p-Smad2/3, and MMP-2 activity, but increased E-cadherin expression. For in vitro experiments, HK-2 cells were incubated with TGF-beta1 to induce EMT, and the cells were co-cultured with 1 and 10 microM Sal B or SB-431542 (a specific inhibitor of TbetaR-I kinase). TGF-beta1 induced a typical EMT in HK-2 cells, while it was blocked by Sal B and SB-431542, as evidenced by blocking morphologic transformation, restoring E-cadherin and CK-18 expression, inhibiting alpha-SMA expression and F-actin reorganization, and down-regulating MMP-2/9 activities in TGF-beta1 mediated HK-2 cells. Furthermore, Sal B and SB-431542 profoundly down-regulated the expressions of TbetaR-I and p-Smad2/3 but prevented the decreased expression of Smad7 in TGF-beta1 stimulated HK-2 cells.. Sal B can prevent tubular EMT in the fibrotic kidney induced by HgCl2 as well as HK-2 cells triggered by TGF-beta1, the mechanism of Sal B is closely related to the regulation of TGF-beta1/Smads pathway, manifested as the inhibition of TGF-beta1 expression, suppression of TbetaR-I expression and function, down-regulation of Smad2/3 phosphorylation, and restoration of the down-regulation of Smad7, as well as inhibition of MMP-2 activity. Topics: Actins; Animals; Benzofurans; Cell Differentiation; Cell Line; Drugs, Chinese Herbal; Epithelial Cells; Fibrosis; Humans; Kidney; Mesoderm; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad7 Protein; Transforming Growth Factor beta1; Up-Regulation | 2010 |
Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling.
Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9).. Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis.. As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. Topics: Animals; Benzofurans; Binding Sites; Computer Simulation; Down-Regulation; Drug Design; Drugs, Chinese Herbal; Fibrosis; Heart Ventricles; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Molecular Conformation; Myocardial Contraction; Myocardial Infarction; Protease Inhibitors; Random Allocation; Rats; Rats, Wistar; Recombinant Fusion Proteins; Ventricular Remodeling | 2010 |
[Protection and mechanisms of salvianolic-acid B on experimental renal interstitial fibrosis in rats].
To investigate the effect and mechanism of salvianolic acid B (SA-B) on renal interstitial fibrosis in rats induced by unilateral ureteral obstruction (UUO).. 18 male SD rats were randomly divided into 3 groups, 6 in each group. After the models were established, the rats were treated with SA-B for 2 weeks. Then their renal pathology were examined by hight microscope and electron microscopy Protein expression levels of alpha-smooth muscle actin (alpha-SMA) and E-cadherin (E-cad) in the obstructed kidney were analyzed by Western blot and Biochemistry assay.. Pathological examination of the kidney in model group showed tubules lumen widened and many inflammatory cells infiltrated, a part of renal tubule expanded and part of them atrophied. The tubular epithelial cells were karyorrhexis or karyolysis, some tubulars were atrophy. The protein expression of alpha-SMA were significantly up-regulated (P < 0.01) and E-cad were significantly down-regulated (P < 0.01) in the model group. After intervention with SA-B, the renal pathological status in the treatment group was significantly improved, the expression of alpha-SMA were significantly down-regulated (P < 0.05), but E-cad only a little up-regulated (P > 0.05).. SA-B could antagonize renal interstitial fibrosis mainly by maintaining epithelial phenotype, inhibiting the protein of alpha-SMA which is the principal effect cells that are responsible for the progressive kidney fibrosis. Topics: Actins; Animals; Benzofurans; Blotting, Western; Cadherins; Disease Models, Animal; Fibrosis; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Tubules; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Ureteral Obstruction | 2010 |
Preventive effects of salvianolic acid B on transforming growth factor-beta1-induced epithelial-to-mesenchymal transition of human kidney cells.
Epithelial-mesenchymal transition (EMT) is an important mechanism in kidney fibrosis. While Salvianolic acid-B (Sal B) has been well appreciated to show a protective effect of tissue fibrosis, the objective of this study was to investigate the influence of Sal B on the transdifferentiation of renal tubular epithelial cells. Human kidney proximal tubular cell line (HK-2) was used as the proximal tubular cell model and EMT was induced with 5 ng/ml of human transforming growth factor (TGF)-beta1. The effects of the Sal B on cell morphology were observed by phase contrast microscopy, and the possible mechanisms were studied by immunocytochemistry and real-time reverse transcription-polymerase chain reaction. Our results revealed that Sal B could inhibit TGF-beta1-induced myofibroblast phenotype and restored the epithelial morphology in a dose-dependent manner. It was partially through modulating alpha-smooth muscle actin (SMA) increase and E-cadherin reduction. These observations strongly suggest that Sal B is a potent inhibitor of TGF-beta1-induced EMT and might be a promising agent for treating tubulointerstitial fibrosis. Topics: Benzofurans; Cell Line; Cell Transdifferentiation; Epithelial Cells; Fibrosis; Humans; Immunohistochemistry; Kidney Tubules, Proximal; Mesoderm; Nephritis, Interstitial; Protective Agents; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta1 | 2009 |
[Effect of salvianolic acid B on generation and activation of myofibroblast in rat with renal interstitial fibrosis].
To investigate the effect of salvianolic acid B (SA-B) on renal interstitial fibrosis due to unilateral ureteral obstruction.. Thirty-six SD male rats were randomly divided into 3 groups, 12 in each group, the sham-operated group, the model group and the SA-B treated group. The rat model of renal interstitial fibrosis was successfully established by unilateral ureteral obstruction (UUO). Rats in the SA-B treated group was intragastrically administrated with SA-B (12.5 mg x kg(-1)) daily after modeling. Rats of each group were killed respectively at day 14 and day 21 after UUO. Pathological changes of renal tissue were observed by hematoxylin and eosin (HE) staining. The expression of alpha-smooth muscle actin (alpha-SMA) in kidney was determined with immunohistochemistry. And the expressions of cytokeratinl9 (ck19) mRNA in renal tissue were detected using reverse transcription polymerase chain reaction (RT-PCR).. Renal interstitial fibrosis was obviously ameliorate in SA-B treated group. The expression of alpha-SMA was significantly decreased in SA-B treated group as compared with that in model group at day 14. And the expression of ck19 was significantly lower than that determined in model group at day 21.. SA-B could ameliorate renal interstial fibrosis due to UUO, probable by inhibiting epithelial-to-myofibroblast transdifferentiation and the activation of myofibroblast. Topics: Animals; Benzofurans; Disease Models, Animal; Drugs, Chinese Herbal; Fibroblasts; Fibrosis; Gene Expression; Humans; Keratin-19; Kidney Diseases; Male; Muscle, Smooth; Random Allocation; Rats; Rats, Sprague-Dawley | 2009 |