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Zhi-Zhi Chen,
Zheng-Lin Wang,
Chong-Yang Deng, Hao Zheng,
Xian-Huo Wang,
Liang Ma,
Xia Ye,
Ying-Hua Ma,
Cai-Feng Xie,
Li-Juan Chen,
Yu-Quan Wei
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ABSTRACT: To evaluate the hepatoprotective roles of (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010) against carbon tetrachloride (CCl₄)-induced acute and chronic liver injury and its underlying mechanisms of action.
In the first experiment, rats were weighed and randomly divided into 5 groups (five rats in each group) to assess the protective effect of SKLB010 on acute liver injury. For induction of acute injury, rats were administered a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl₄ dissolved in olive oil (1:1). Group 1 was untreated and served as the control group; group 2 received CCl₄ for induction of liver injury and served as the model group. In groups 3, 4 and 5, rats receiving CCl₄ were also treated with SKLB010 at doses of 25, 50 and 100 mg/kg, respectively. Blood samples were collected at 6, 12 and 24 h after CCl₄ intoxication to determine the serum activity of alanine amino transferase. Tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay. At 24 h after CCl₄ injection, liver fibrogenesis was evaluated by hematoxylin-eosin (HE) staining and immunohistochemical analyses. Cytokine transcript levels of TNF-α, IL-1β and inducible nitric oxide synthase in the liver tissues of rats were measured using a reverse transcriptase reverse transcription-polymerase chain reaction technique. In the second experiment, rats were randomly divided into 2 groups (15 rats in each group), and liver injury in the CCl₄-administered groups was induced by a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl₄ dissolved in olive oil (1:1). The SKLB010-treated groups received oral 100 mg/kg SKLB010 before CCl₄ administration. Five rats in each group were sacrificed at 2 h, 6 h, 12 h after CCl₄ intoxication and small fortions of livers were rapidly frozen for extraction of total RNA, hepatic proteins and glutathione (GSH) assays. In the hepatic fibrosis model group, rats were randomly divided into 2 groups (5 rats each group). Rats were injected intraperitoneally with a mixture of CCl₄ (1 mL/kg body weight) and olive oil [1:1 (v/v)] twice a week for 4 wk. In the SKLB010-treated groups, SKLB010 (100 mg/kg) was given once daily by oral gavage for 4 wk after CCl₄ administration. The rats were sacrificed one week after the last injection and the livers from each group were harvested and fixed in 10% formalin for HE and immunohistochemical staining.
In this rat acute liver injury model, oral administration of SKLB010 blocked liver tissue injury by down-regulating the serum levels of alanine aminotransferase, suppressing inflammatory infiltration to liver tissue, and improving the histological architecture of liver. SKLB010 inhibited the activation of NF-κB by suppressing the degradation of IκB, and prevented the secretion of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and the reactive free radical, nitric oxide, at the transcriptional and translational levels. In this chronic liver fibrosis model, treatment with 100 mg/kg per day SKLB010 attenuated the degree of hepatic fibrosis and area of collagen, and blocked the accumulation of smooth-muscle actin-expressed cells.
These results suggest that SKLB010 is a potent therapeutic agent for the treatment of CCl₄-induced hepatic injury.
World Journal of Gastroenterology 02/2012; 18(7):654-61. · 2.47 Impact Factor
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ABSTRACT: (Z)2-(5-(4-methoxybenzylidene)-2, 4-dioxothiazolidin-3-yl) acetic acid (MDA) is an aldose reductase (AR) inhibitor. Recent studies suggest that AR contributes to the pathogenesis of inflammation by affecting the nuclear factor κB (NF-κB)-dependent expression of cytokines and chemokines and therefore could be a novel therapeutic target for inflammatory pathology. The current study evaluated the in vivo role of MDA in protecting the liver against injury and fibrogenesis caused by CCl(4) in rats, and the underlying mechanisms.
A single injection of CCl(4) induced acute hepatitis, and repeated injections were used to induce hepatic fibrosis in rats. Therapeutic efficacy was assessed by comparison of the severity of hepatic injury and fibrosis in MDA-treated rats versus untreated controls.
MDA significantly protected the liver from injury by reducing the activity of serum alanine aminotransferase, and improving the histological architecture of the liver. MDA modulated NF-κB-dependent activation of inflammatory cytokines by reducing hepatic mRNA levels of tumor necrosis factor-α, interleukin-1β, inducible nitric oxide (NO) synthase and transforming growth factor-β. In addition, MDA attenuated oxidative stress by increasing the content of hepatic glutathione. These favorable changes were associated with suppressed hepatic NF-κB activation by MDA. MDA treatment improved liver fibrosis in rats that received repeated CCl(4) injections. In vitro, MDA attenuated phosphorylation of IκB and activation of NF-κB, and thus prevented biosynthesis of NO in lipopolysaccharide-activated RAW264.7 cells.
The present study suggests that AR is a novel therapeutic anti-inflammatory target for the treatment of hepatitis and liver fibrosis.
Journal of Gastroenterology and Hepatology 09/2011; 27(5):966-73. · 2.87 Impact Factor
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ABSTRACT: SKLB010 is currently under development as a potential therapeutic agent for the treatment of acute hepatitis and rheumatoid arthritis. The purpose of this paper was to investigate the pre-clinical pharmacokinetics of SKLB010 in beagle dogs. An ultra performance liquid chromatographic tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the quantitative determination of SKLB010 in dog plasma, using rosiglitazone as the internal standard (I.S.). Plasma samples were prepared by a simple solid phase extraction (SPE) method. The analyte and internal standard were separated by an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with a mobile phase of methanol-water (80/20, v/v) over 2 min. Detection was based on the multiple reaction monitoring with the precursor-to-product ion transitions m/z 234.10→147.92 (SKLB010) and m/z 356.15→150.00 (I.S.). The method was validated according to FDA guidelines on bio-analytical method validation. The selectivity, sensitivity, linearity, accuracy, precision, extraction recovery, ion suppression and stability were within the acceptable ranges. The method described above was successfully applied to reveal the single- and multi-pharmacokinetic profiles of SKLB010 in beagle dogs and should be extendable to pharmacokinetic studies in other species as well.
Journal of pharmaceutical and biomedical analysis 05/2011; 56(2):366-72. · 2.45 Impact Factor
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a frequent kind of metabolic syndrome, which included a wide spectrum of liver damage and closely associated with insulin resistance and other metabolic syndromes such as obesity, type II diabetes, hyperglycemia, etc. Recently, a new series of PPARγ ligands based on barbituric acid has been designed, in which 5-(4-(benzyloxy)benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione (SKLB102) showed a high affinity with PPARγ. The current study aimed to evaluate the protective effect of SKLB102 on NAFLD and investigate the underlying mechanisms. In vivo, oral administration of SKLB102 prevented the pathological development, as demonstrated by reducing liver weight and visceral fat effectively, decreasing the serum levels of alanine transaminase, TNF-α and glucose, diminishing the hepatic triglyceride and malondialdehyde content and recovering the abnormal down-regulation of LDL. Histological examination of liver sections by Oil Red O and H&E staining confirmed the protective effect of SKLB102 on NAFLD. Furthermore, SKLB102 elevated the serum level of adiponectin, reduced the serum level of leptin and prevented insulin resistance. Western blots indicated that SKLB102 increased the hepatic AMPK activities and CPT-1 expression. In vitro, SKLB102 showed the ability of significantly enhancing adiponectin expression and inhibiting leptin expression in 3T3-L1 adipocytes. Furthermore, SKLB102 could promote glucose consumption in HepG2 cells in the presence of 0.1 μM insulin. In conclusion, our current study provided strong evidence that SKLB102 had potent ability to reduce fat deposition and protect liver against NAFLD through regulating adipocytokine expression and preventing insulin resistance, which might be of protective value for the prevention of NAFLD.
European journal of pharmacology 04/2011; 659(2-3):244-51. · 2.59 Impact Factor
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Liang Ma,
Caifeng Xie,
Yinghua Ma,
Juan Liu,
Mingli Xiang,
Xia Ye, Hao Zheng,
Zhizhi Chen,
Qinyuan Xu,
Tao Chen,
Jinying Chen,
Jincheng Yang,
Neng Qiu,
Guangcheng Wang,
Xiaolin Liang,
Aihua Peng,
Shengyong Yang,
Yuquan Wei,
Lijuan Chen
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ABSTRACT: Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E(2) (PEG(2)). (Z)-N-(3-chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC(50) = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE(2) production (IC(50) = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
Journal of Medicinal Chemistry 03/2011; 54(7):2060-8. · 4.80 Impact Factor
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ABSTRACT: Entrapping inclusion complexes in liposomes has been proposed to increase the entrapment efficiency (EE) and stability of liposomes compared with conventional liposomes. In the present study, a stable honokiol-in-hydroxypropyl-β-cyclodextrin-in-liposome (honokiol-in-HP-β-CD-in-liposome) was developed as honokiol delivery system by a novel method. The final molar ratio of honokiol/HP-β-CD/lipid was selected as 1:2:2. The mean particle size was 123.5 nm, the zeta potential was -25.6 mV, and the EE was 91.09 ± 2.76%. The release profile in vitro demonstrated that honokiol is released from honokiol-in-HP-β-CD-in-liposome with a sustained and slow speed. Crystallographic study indicated that honokiol was first bound within HP-β-CD and then the inclusion complex was encapsulated within liposomes. Honokiol-in-HP-β-CD-in-liposome without freeze dry kept stable for at least 6 months at 4°C. Pharmacokinetic study revealed that honokiol-in-HP-β-CD-in-liposome significantly retarded the elimination and prolonged the residence time in circulating system. The data of bioactivity showed that honokiol-in-HP-β-CD-in-liposome remained similar antiproliferative activity in A549 and HepG2 tumor cells compared to free honokiol. These results suggested that we had successfully prepared honokiol-in-HP-β-CD-in-liposome. The novel honokiol formulation was easy to push industrialization forward and might be a potential carrier for honokiol delivery in tumor chemotherapy.
Journal of Pharmaceutical Sciences 03/2011; 100(8):3357-64. · 3.06 Impact Factor
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ABSTRACT: PEGylated liposomal honokiol had been developed with the purpose of improving the solubility and pharmacokinetics compared with free honokiol. Human plasma protein binding ability of honokiol was also investigated. PEGylated liposomal honokiol was prepared by thin film evaporation-sonication method. Its mean particle size was 98.68 nm, mean zeta potential was -20.6 mV and encapsulation efficiency were 87.68±1.56%. The pharmacokinetics of PEGylated liposomal honokiol was studied after intravenous administration in Balb/c mice. There were significant differences of parameters T(1/2β) and AUC(0→∞) between them and liposome lengthened T(1/2β) and AUC(0→∞) values. The mean T(1/2β) value of PEGylated liposomal honokiol and free honokiol were 26.09 min and 13.46 min, respectively. The AUC(0→∞) ratio of PEGylated liposomal honokiol to free honokiol was about 1.85-fold (219.24 μg/mL min/118.68 μg/mL min) (P=0.000). Examination of protein binding ability showed that honokiol with 0.5, 8.0 and 20 μg/mL concentrations in human plasma achieved the percent of bound between 60% and 65%. The results suggested that PEGylated liposomal honokiol improved the solubility, increased the drug concentration in plasma, and withstanded the clearance. Besides, the percent of protein bound of honokiol in human plasma was between 60% and 65%.
International journal of pharmaceutics 03/2011; 410(1-2):169-74. · 2.96 Impact Factor
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Liang Ma,
Shilin Li, Hao Zheng,
Jinying Chen,
Lin Lin,
Xia Ye,
Zhizhi Chen,
Qinyuan Xu,
Tao Chen,
Jincheng Yang,
Neng Qiu,
Guangcheng Wang,
Aihua Peng,
Yi Ding,
Yuquan Wei,
Lijuan Chen
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ABSTRACT: Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.
European journal of medicinal chemistry 02/2011; 46(6):2003-10. · 3.27 Impact Factor
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ABSTRACT: Idiopathic pulmonary fibrosis is regarded as a lethal chronic disease accompanied with excessive collagen disposition. In the early stage, monocyte chemotactic protein-1 (MCP-1) plays a crucial role in the process. Our previously screening with a vitro assay through inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1 proved that several analogues of thiazolidinediones, especially (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010), had potency of protecting acute liver injury in vivo without obvious toxicity. The present study aimed to investigate the preventive effect of SKLB010 in bleomycin-induced pulmonary fibrosis and further explore the underlying mechanisms. Bleomycin (BLM) was injected intratracheally at a single dose of 5 U kg(-1) for pulmonary fibrosis induction. SKLB010 (25, 50 mg/kg/d) was respectively administrated by gavages 1 d prior to BLM administration and continued to the end of the study (for 4 weeks). Our results demonstrated that SKLB010 diminished the increase of macrophage, neutrophil and lymphocyte counts as well as the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid on day 14 (p<0.05). Moreover, oral gavages of SKLB010 also ameliorated histological changes and significantly suppressed collagen deposition on day 28. The treatment with SKLB010 exerted approximately 34.6% the hydroxyproline content reduction for 25 mg/kg dose and 56.7% reduction for 50 mg/kg dose in contrast to bleomycin-induced group (p<0.05). Meanwhile, SKLB010 inhibited the overexpression of tumor growth factor (TGF)-β1 and Smad3 in a dose-dependent manner. In conclusion, our results showed that SKLB010 could attenuate the BLM-induced pulmonary fibrosis in vivo and therefore be a promising anti-fibrogenic candidate.
Biological & Pharmaceutical Bulletin 01/2011; 34(2):219-25. · 1.66 Impact Factor
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Xianhuo Wang,
Xingmei Duan,
Guangli Yang,
Xiaoyan Zhang,
Linyu Deng, Hao Zheng,
Chongyang Deng,
Jiaolin Wen,
Ning Wang,
Cheng Peng,
Xia Zhao,
Yuquan Wei,
Lijuan Chen
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ABSTRACT: Gliosarcoma is one of the most common malignant brain tumors, and anti-angiogenesis is a promising approach for the treatment of gliosarcoma. However, chemotherapy is obstructed by the physical obstacle formed by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Honokiol has been known to possess potent activities in the central nervous system diseases, and anti-angiogenic and anti-tumor properties. Here, we hypothesized that honokiol could cross the BBB and BCSFB for the treatment of gliosarcoma. METHODOLOGIES: We first evaluated the abilities of honokiol to cross the BBB and BCSFB by measuring the penetration of honokiol into brain and blood-cerebrospinal fluid, and compared the honokiol amount taken up by brain with that by other tissues. Then we investigated the effect of honokiol on the growth inhibition of rat 9L gliosarcoma cells and human U251 glioma cells in vitro. Finally we established rat 9L intracerebral gliosarcoma model in Fisher 344 rats and human U251 xenograft glioma model in nude mice to investigate the anti-tumor activity.
We showed for the first time that honokiol could effectively cross BBB and BCSFB. The ratios of brain/plasma concentration were respectively 1.29, 2.54, 2.56 and 2.72 at 5, 30, 60 and 120 min. And about 10% of honokiol in plasma crossed BCSFB into cerebrospinal fluid (CSF). In vitro, honokiol produced dose-dependent inhibition of the growth of rat 9L gliosarcoma cells and human U251 glioma cells with IC(50) of 15.61 µg/mL and 16.38 µg/mL, respectively. In vivo, treatment with 20 mg/kg body weight of honokiol (honokiol was given twice per week for 3 weeks by intravenous injection) resulted in significant reduction of tumor volume (112.70±10.16 mm(3)) compared with vehicle group (238.63±19.69 mm(3), P = 0.000), with 52.77% inhibiting rate in rat 9L intracerebral gliosarcoma model, and (1450.83±348.36 mm(3)) compared with vehicle group (2914.17±780.52 mm(3), P = 0.002), with 50.21% inhibiting rate in human U251 xenograft glioma model. Honokiol also significantly improved the survival over vehicle group in the two models (P<0.05).
This study provided the first evidence that honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. It suggested a significant strategy for offering a potential new therapy for the treatment of gliosarcoma.
PLoS ONE 01/2011; 6(4):e18490. · 4.09 Impact Factor
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Yinghua Ma,
Xianhuo Wang,
Xiaohua Wu,
Xin Wei,
Liang Ma, Hao Zheng,
Baowen Qi,
Wei Zhu,
Youfu Luo,
Yuquan Wei,
Lijuan Chen
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ABSTRACT: In our previous study, we have demonstrated that (Z)-5-(4-methoxybenzylidene) thiazolidine-2, 4-dione (SKLB010), a novel analogue of thiazolidinediones, showed protection against concanavalin A (Con A)-induced hepatitis via inhibiting the migration of macrophages and the expression of pro-inflammatory mediators. In present study, Transwell assay was applied to study the effects of SKLB010 on macrophage-like Raw264.7 cell migration and we investigated the effects of SKLB010 on NO generation in vitro. We also studied in vivo effects of SKLB010 on adjuvant-induced arthritis in Lewis rats by oral administration. It was proved that SKLB010 depressed cells migration and the production of NO in Raw264.7 cells in a dose-dependent way. Our results also indicated that oral administration of 50 mg/kg SKLB010 markedly resulted in a clear suppression of clinical signs compared to untreated groups, showing as markedly reduction of paw swelling and inhibition of body weight decreasing. The improvement in disease severity was accompanied by suppression of CD68-positive cells in knee joint and by inhibition of production in pro-inflammatory cytokines of TNF-α, IL-1β and IL-6 in serum. The elevated TNF-α, IL-1β and iNOS mRNA expression in tissue were down-regulated after treatment with SKLB010. SKLB010 also significantly inhibited the histological progress of RA. These data indicate that SKLB010 is a potent anti-inflammatory therapeutic agent targeting the inflammatory response of macrophages.
International immunopharmacology 11/2010; 10(11):1456-62. · 2.21 Impact Factor
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ABSTRACT: We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell lung cancer (NSCLC) patients with malignant pleural effusions after a single administration. Paclitaxel concentrations were measured in pleural fluid and plasma using a simple and rapid ultra performance liquid chromatography (UPLC) method following intra- and inter-day validations. In subjects, AUC(0-96 h) values in pleural fluid and plasma were 17831 ± 6439 µg h/mL and 778 ± 328 µg h/mL, respectively, and T(max) values were initial time and 6.67 h after administration and the corresponding C(max) values were 558 ± 44 µg/mL and 12.89 ± 6.86 µg/mL, respectively. The T(1/2,IP), CL(IP) and Vd(IP) values in pleural fluid were 76 ± 48 h, 0.005 ± 0.002 L/h m(2) and 0.53 ± 0.23 L/m(2), respectively. The T(1/2,pla), CL(pla), and Vd(pla) values in plasma were 68.34 ± 56.74 h, 0.184 ± 0.080 L/h m(2), and 17.53 ± 16.57 L/m(2), respectively. However, some paclitaxel concentrations from several patients in plasma could not be detected at some designed time-points. Our results might offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile.
Journal of Pharmaceutical Sciences 11/2010; 99(11):4746-52. · 3.06 Impact Factor
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ABSTRACT: Phosphoinositide 3-kinase-gamma (PI3Kgamma) has been identified to play the critical roles in inflammatory cells activation and recruitment in multiply inflammatory diseases and it promised to be a prospective target for relevant inflammatory diseases therapy. AS605240, a selective PI3Kgamma inhibitor, has been proved effective on several inflammatory diseases. In this study, we investigated the protective effect of AS605240 on bleomycin-induced pulmonary fibrosis in rats. Our results showed that orally administration of AS605240 significantly prevented lung inflammation and reduced collagen deposition. AS605240 also inhibited augmented expression of TNF-alpha and IL-1beta induced by bleomycin instillation. Moreover, the mRNA levels of TNF-alpha and IL-1beta in lung were remarkably suppressed. Histological assessment found that AS605240 reduced the expression of TGF-beta(1) and prevented T lymphocytes infiltration to lung. Phospho-Akt level in inflammatory cells by blocking PI3Kgamma was down-regulated and the inhibition of Akt phosphorylation was further confirmed by Western blot. Our findings illustrated that AS605240 was effective for preventing pulmonary fibrosis by suppressing inflammatory cells recruitment and production of inflammatory cytokines. These findings also suggest that PI3Kgamma may be a useful target in treating inflammation diseases and AS605240 may represent a promising novel agent for the future therapy of pulmonary fibrosis.
Biochemical and Biophysical Research Communications 06/2010; 397(2):311-7. · 2.48 Impact Factor
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Youfu Luo,
Liang Ma, Hao Zheng,
Lijuan Chen,
Rui Li,
Chunmei He,
Shengyong Yang,
Xia Ye,
Zhizhi Chen,
Zicheng Li,
Yan Gao,
Jing Han,
Gu He,
Li Yang,
Yuquan Wei
Journal of Medicinal Chemistry 04/2010; · 4.80 Impact Factor
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Youfu Luo,
Liang Ma, Hao Zheng,
Lijuan Chen,
Rui Li,
Chunmei He,
Shengyong Yang,
Xia Ye,
Zhizhi Chen,
Zicheng Li,
Yan Gao,
Jing Han,
Gu He,
Li Yang,
Yuquan Wei
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ABSTRACT: A large amount of evidence suggests that monocytes/macrophages infiltration is implicated in a variety of inflammatory diseases including acute liver injury. Monocyte chemoattractant protein 1 (MCP-1) plays a crucial role in the process of macrophages recruitment. We herein presented a small-molecule library and a feasible quick screening method of evaluating potency of inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1. Fifty-three small molecules were synthesized and screened, and four compounds (2g, 2h, 4f, and 6h) showed inhibitory effects with IC(50) values range from 0.72 to 20.47 microM, with compound 4f being the most efficient. Further in vivo studies demonstrated that oral administration of 2g, 2h, 4f, or 6h decreases, most significantly for 4f, the serum levels of alanine aminotransaminase (ALT) and asparate aminotransaminase (AST) in ConA-induced acute livery injury BALB/c mice. Histopathological evaluation liver sections confirmed 4f as a potent, orally active compound for hepatoprotective effects against ConA-induced acute liver injury in BALB/c mice.
Journal of Medicinal Chemistry 11/2009; 53(1):273-81. · 4.80 Impact Factor
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ABSTRACT: To test the effect of 5-(4-methoxybenzylidene)-2-thioxo-dihydropyrimidine-4, 6 (1H, 5H)-dione (SKLB-102) on acute hepatic inflammatory induced by concanavalin A (ConA) in mice.
The inhibitive effect of SKLB-102 on RAW264.7 cell migration induced by recombinant rat monocyte chemotactic protein-1 (MCP-1) was tested. The serum from the ConA-treated mice was collected after intragastric administration of SKLB-102 at the dose of 50 mg/kg bodyweight. The serum AST and ALT were determined by an automatic analyzer, and the serum TNF-alpha was determined with enzyme-linked immunosorbent assay (ELISA) kits. The liver samples were fixed in 10% formalin, embedded in paraffin, sectioned and then stained with hematoxylin and eosin for histological examinations.
SKLB-102 markedly reduced cell migrations, successfully reduced serum AST, ALT and down-regulated TNF-alpha.
SKLB-102 is likely to suppress the occurrence of Con A-induced hepatitis by suppressing macrophages migration and TNF-alpha releases.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 07/2009; 40(4):697-9, 711.
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ABSTRACT: A new type of voltammetric sensor, Langmuir–Blodgett film of p-tert-butylthiacalix[4]arene modified glassy carbon electrode, was advanced and used for determining copper at trace levels by differential pulse stripping voltammetry. Calibration plot was found to be linear in the range of 2×10−8 M to 5×10−6 M; the detection limit was 2×10−9 M. Possible recognition mechanism was also discussed. From determination of Copper in real samples (river, lake and tap water) it can be concluded that the method is rapid, sensitive in determining of copper and can be used in the analysis of natural water samples.
Electroanalysis 11/2006; 18(21):2115 - 2120. · 2.87 Impact Factor
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ABSTRACT: A new type of current sensor, Langmuir–Blodgett (LB) film of calixarene on the surface of glassy carbon electrode (GCE) was prepared for determination of mercury by anodic stripping voltammetry (ASV). An anodic stripping peak was obtained at 0.15 V (vs. SCE) by scanning the potential from −0.6 to +0.6 V. Compared with a bare GCE, the LB film coated electrode greatly improves the sensitivity of measuring mercury ion. The fabricated electrode in a 0.1 M H2SO4+0.01 M HCl solution shows a linear voltammetric response in the range of 0.07–40 μg L−1 and detection limit of 0.04 μg L−1 (ca. 2×10−10 M). The high sensitivity, selectivity, and stability of this LB film modified electrode demonstrates its practical application for a simple, rapid and economical determination of Hg2+ in a water sample.
Electroanalysis 05/2006; 18(12):1202 - 1207. · 2.87 Impact Factor
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ABSTRACT: A glassy carbon electrode (GCE) coated with Langmuir–Blodgett (LB) film of p-allylcalix[4]arene is described for simultaneous determination of traces of thallium and cadmium in environmental water. The LB film electrode in a 0.1 M KH2PO4 solution shows a linear voltammetric response in the range of 5–250 μg l−1 for thallium and 10–300 μg l−1 for cadmium. The detection limits of thallium(I) and cadmium(II) are estimated to be 1.0 μg l−1 (ca. 5.0 × 10−9 M) and 2.2 μg l−1 (ca. 2.0 × 10−8 M), respectively. Above all, the indium does not respond to this LB film electrode.
Sensors and Actuators B: Chemical.
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ABSTRACT: A glassy carbon electrode (GCE) modified with a Langmuir–Blodgett (LB) film of p-tert-butylthiacalix[4]arene (TCA) has been investigated as a disposable sensor for measuring the trace levels of lead and cadmium. The possibility of determining lead and cadmium at trace levels was examined with differential pulse stripping voltammetry in the measurement step. The electrochemical response was characterized with respect to supporting electrolyte, pH of solution, accumulation time, accumulation potential, layers of the LB films, and possible interferences. Calibration plots were found to be linear in the range 2 × 10−7 to 5 × 10−5 mol l−1 (Cd2+) and 1 × 10−7 to 2.5 × 10−5 mol l−1 (Pb2+); the detection limits were 2 × 10−8 mol l−1 (Cd2+) and 8 × 10−9 mol l−1 (Pb2+). Possible recognition mechanism was also discussed. From the analysis of real samples (river, lake and tap water) it can be concluded that the method is sensitive and reproducible in determining of these elements and can be used in the analysis of natural water samples.
Sensors and Actuators B: Chemical.
