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Meanwhile, Wulong Xiaozheng Wan medicated serum could regulate the expression of related proteins and mRNA of TGF-β1/Smad signaling pathway, and inhibit the expressions of EMT transcription factors and EMT markers. CONCLUSION Wulong Xiaozheng Wan medicated serum inhibited epithelial-mesenchymal transition by down-regulated the expression of TβRI and the activation of TGF-β1/Smad signaling pathway.OBJECTIVE To study the active compounds in Jinshui Huanxian formula in the treatment of pulmonary fibrosis with a pharmacological approach. METHODS A systems pharmacology model, incorporating active compounds and targets prediction, and herbal-compound-target-disease network analysis, was established to predict the active substances and therapeutic mechanisms of Jinshui Huanxian formula. All compounds from the herbs of Jinshui Huanxian formula were obtained from drug database and the literature. Then, we analyzed the potential of herbs by predicting oral bioavailability and drug-likeness index. The com- pounds with oral bioavailability ≥ 30% and drug-likeness index ≥ 0.18 were obtained as candidate compounds for further analysis. We then used the systematic drug targeting tool to screen the targets for candidate compounds. The potential targets were projected into Therapeutic Target Database to collect their corresponding diseases. The candidate compounds, potential targets and their related diseases were applied to construct the compound-target and target-disease network. RESULTS Totally 136 compounds from Jinshui Huanxian formula and 265 potential targets were found. Compound-target network analysis suggested that different herbal drugs contained in the Jinshui Huanxian formula could regulate these similar targets to probably exert synergistic effect. Moreover, target proteins were mainly related to oxidoreductase activity, nicotinamide adenine dinucleotide phosphate binding, and G-protein coupled amine receptor activity, which might be associated with the therapeutic mechanisms of Jinshui Huanxian formula. In addition, Jinshui Huanxian formula was probably efficient for many different diseases, such as respiratory tract diseases, neoplasm, nervous system diseases, and cardiovascular diseases, according to target-disease network. CONCLUSION This study may provide a method to explore the potential active compounds in Jinshui Huanxian formula used to treat pulmonary fibrosis.OBJECTIVE To observe the effect of herb-partitioned moxibustion at the Tianshu (ST 25) and Qihai (CV 6) acupoints in rats with Crohn's disease, and explore the underlying mechanism from dopamine (DA) and dopamine receptor 1 (D1R) in the colon, spinal dorsal horn and hypothalamus. METHODS The rats were randomly divided into the normal, model (CD), herb-partitioned moxibustion (Mox) and mesalazine (Mesa) groups. Damage in the colons was scored and observed by hematoxylin and eosin staining. DA and D1R protein expression in the colonic mucosa were detected by immunohistochemistry. The concentrations of DA and D1R in the spinal dorsal horn and hypothalamus were measured by enzyme-linked immunosorbent assay, and D1R mRNA expression was evaluated by quantitative real-time polymerase chain reaction. RESULTS In the colon, compared with the normal group, DA, D1R protein expressions and D1R mRNA expression were significantly higher in the model group, while decreased in the Mox group and the Mesa group. In the spinal dorsal horn and hypothalamus, compared with the normal group, the concentrations of DA and D1R, and the D1R mRNA expressions were significantly higher in the model group, and decreased in the Mox group and the Mesa group. CONCLUSION Herb-partitioned moxibustion at the Tianshu (ST 25) and Qihai (CV 6) acupoints relieved ulceration in CD rats, the underlying mechanism maybe relative with the regulation of DA and D1R in the colon, spinal dorsal horn and hypothalamus by moxibustion.OBJECTIVE To investigate the effect of mitofusin 2 (Mfn2) and its downstream signaling pathway on glomerular mesangial cells (GMCs) proliferation in IgA nephropathy (IgAN), as well as the mechanism of action of Jixuecao (Herba Centellae Asiaticae, HCA) in the treatment of IgAN. METHODS Adenovirus-mediated Mfn2 gene transfection and Mfn2 expression were analyzed by real-time polymerase chain reaction (PCR) and Western blotting. IgA1 induced the proliferation of GMCs, which were then treated with HCA. Cell proliferation was detected with cell counting kit-8 (CCK-8), and Mfn2 expression was analyzed by real-time PCR and western blotting. An IgAN animal model was also established and treated with HCA. GMCs proliferation was detected by hematoxylin-eosin staining, mitochondrial structure was analyzed by electron microscopy, mitochondrial function was determined by the Clark oxygen electrode method, and the expression of Mfn2, Phospho-extracellular regulated protein kinases1/2 (P-ERK1/2), Cyclin-dependent kinase 2 (CDK2), Phospho-p27 (p-p27), and cyclin A was analyzed by Western blotting. RESULTS In vitro, HCA inhibited GMCs in a concentration-dependent manner in association with the upregulation of Mfn2 expression. The overexpression of Mfn2 inhibited IgA1-induced GMCs proliferation and elevated the effect of HCA. In vivo, treatment with HCA could alleviate albuminuria and creatinine and GMCs proliferation. These effects were related to the upregulation of Mfn2, p-p27 and inhibition of p-ERK1/2, CDK2, and cyclinA. Mitochondrial swelling, vacuolar degeneration, and reduction of respiratory control rate were identified in IgAN, but HCA could improve the mitochondrial structure and function. CONCLUSION HCA inhibited GMCs proliferation via the upregulation Mfn2 and the inhibition of Ras-Raf-ERK/MAPK. We revealed that changes of mitochondrial structure and function are associated with IgAN, but that HCA can improve these mitochondrial features.OBJECTIVE To investigate the underlying mechanism of Bailian (Radix Ampelopsis Japonicae, BL) extract action on colorectal cancer (CRC). METHODS We explored the involvement of β-catenin signaling on the anti-CRC effects of an BL ethanolic extract (BLE) in cell models by using the 3-(4,5-dimethylthiazol-2-yl)-2,5- iphenyltetrazolium bromide assay, immunofluorescent staining, luciferase assay, Western blot analysis and real-time quantitative polymerase chain reaction analysis. Anti-CRC compounds were quantified by high performance liquid chromatography. RESULTS The contents of gallic acid, catechin, and epicatechin in the BLE were 0.23, 1.25, and 0.18 g/kg, respectively. BLE-mediated cytotoxic and apoptotic effects were accompanied by lowered β-catenin/Tcf transcriptional activity, reduced β-catenin nuclear localization, and downregulated protein and mRNA levels of both β-catenin and molecules regulated by β-catenin. CONCLUSION The mechanism underpinning the anti-CRC effects of BLE may involve inhibition of β-catenin signaling. Further studies are necessary to establish the role of β-catenin signaling in the action of BLE-mediated anti-CRC effects.OBJECTIVE To study the absorption and biotransformation of liquiritin, cinnamic acid, paeoniflorin, and glycyrrhizic acid in the Guizhi decoction (GZD) in the gastrointestinal tracts of rats. METHODS A simple and reliable high-performance liquid chromatography method was established and validated for the analysis of the four components of GZD simultaneously in the gastrointestinal tracts of rats. Rats were randomly divided into in situ gastrointestinal loop model, in vitro anaerobic culture model, and blank control groups. All rats were fasted for 12 h and anesthetized using 20% urethane. Subsequently, the abdominal cavity of each rat was opened, and the stomach, duodenum, jejunum, ileum, cecum, and colon were ligated. For the in situ gastrointestinal loop model group, 2.5 mL of GZD (1.0 g crude drug/mL, 37 ℃) were injected into the gastrointestinal tract. The abdominal incision was covered with warm, wet cotton, and animals were maintained at 25 ℃ . Then, we collected the gastrointestinal tract content aftern rates in the distal small intestine than that in the proximal small intestine. CONCLUSION Although a portion of the glycosides in GZD was directly absorbed as the prototype forms in the gastrointestinal tract, they were primarily metabolized and transformed into their corresponding metabolites by intestinal flora near the distal small intestine before their absorption.OBJECTIVE To investigate the radioprotective effect of tea polyphenols (TP 50) against radiation-induced organ and tissue damage. METHODS Beagle dogs were exposed to a single acute dose of whole-body γ-radiation (3 Gy) and orally administered TP 50 (80 or 240 mg·kg-1·d-1) for 28 consecutive days. A hemogram was obtained from experimental dogs every other day for 42 d. At the end of the experiment, enzyme activities of the antioxidants superoxide-dismutase andglutathione peroxidase, serum levels of inflamma- tory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), colony-forming units of bone marrow hematopoietic progenitor cells, andorgan coefficients were measured. RESULTS Dogs exposed to γ-radiation alone exhibited typical hematopoietic syndrome. In contrast, irradiated dogs that received TP 50 exhibited an improved blood profile with reduced leucopenia, thrombocytopenia (platelet counts), and reticulocyte levels. TP 50 also significantly elevated levels of the endogenous antioxidant enzyme superoxide-dismutase, reduced the increased levels of serum cytokine in response to radiation-induced toxicity, and increased colony-forming units of bone marrow hematopoietic progenitor cells. In addition, TP 50 repaired radiation-induced organ damage. CONCLUSION The current findings suggest that oral administration of TP 50 to beagle dogs effectively alleviated hematopoietic bone marrow dam- age induced by γ-radiation.OBJECTIVE To investigate the therapeutic mechanism of compound Yindan decoction (CYD) in a rat model of acute intrahepatic cholestatic (AIC). METHODS A total of 108 adult male rats were randomly divided into control (n = 18) and AIC groups (n = 90). AIC was induced in rats using alpha-naphthylisothiocyanate (ANIT) (75 mg/kg, 10 mL/kg in corn oil, p. o. ). Then, 90 AIC rats were randomly divided into five groups a control group (n = 18), a CYD high dose group (n = 18), a CYD middle dose group (n = 18), a CYD low dose group (n = 18), and a ursodeoxycholic acid (UDCA) group (n = 18). According to sampling time, each group was subdivided into three subgroups 24 h (n = 6), 48 h (n = 6), and 72 h groups (n = 6). The CYD-high, -middle and -low groups were orally administered 24.48, 12.24, and 6.12 g·kg-1·d-1 modified CYD, respectively, while the model group was given 20 mL/kg of body weight of distilled water once a day. The UDCA group was given 67. 5 mg·kg - 1·d - 1 UDCA once a day. Radioimmunity assay was used to group. CYD and UDCA treatment ameliorated ANIT-induced biliary epithelial cell proliferation. selleck chemicals Neutrophil infiltration was rare and little focal necrosis was observed in lobules in the CYD-high and -medium dose groups and UDCA group at 72 h. Compared with the control group, the expression of MRP2 mRNA and MRP2 protein in the liver tissue of the CYD groups was significantly increased (P less then 0. 05 and P less then 0. 01, respectively). MRP2 expression and RXRα nuclear receptor mRNA and protein levels in the CYD groups were significantly increased compared with the control and UDCA groups (P less then 0. 01). CONCLUSION CYD can alleviate cholestasis in ANIT-induced AIC rats, and the mechanism underlying this action might involve increases in ALT, AST, GGT, ALP, TBil, and DBil and upregulation of MRP2 and RXRα mRNA and protein levels.

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