Luan Shu

China Academy of Chinese Medical Sciences, Peping, Beijing, China

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Publications (12)23.58 Total impact

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    ABSTRACT: Diabetes is characterized by a loss and dysfunction of the β-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in β-cell survival and function. It is meaningful to identify promising agents from natural products which might activate GLP-1R signaling. In this study, puerarin, a diet isoflavone, was evaluated its beneficial effects on β-cell survival and GLP-1R pathway. We showed that puerarin reduced the body weight gain, normalized blood glucose and improved glucose tolerance in high-fat-diet (HFD) induced and db/db diabetic mice. Most importantly, increased β-cell mass and β-cell proliferation, but decreased β-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immuno-staining of mice pancreatic sections. The protective effect of puerarin on β-cell survival was confirmed in isolated mouse islets treated with high glucose. Further mechanism studies showed that the circulating level of GLP-1 in mice was unaffected by puerarin. However, puerarin enhanced GLP-1R signaling by up-regulating expressions of GLP-1R and Pdx-1, which subsequently led to Akt activation but Foxo1 inactivation, and promoted β-cell survival. The protective effect of puerarin was remarkably suppressed by Exendin(9-39), an antagonist of GLP-1R. Our study demonstrated puerarin improved glucose homeostasis in obese diabetic mice, and identified a novel role of puerarin in protecting β-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.
    No preview · Article · Jan 2016 · Molecular Endocrinology
  • X. Jiang · Y. Wang · L. Shu · B. Luo
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    ABSTRACT: Ice melting of transmission line with AC or DC widely adopted at present cannot adapt well to development of power grid in security, reliability and intelligentization. Anti-icing and de-icing with line impedance regulation, which can be operated in real time without disconnection of line sections to be de-iced, is a very promising technology in protecting lines from icing disaster. This paper makes a special study on concrete application method in anti-icing and de-icing with line impedance regulation. For both anti-icing and de-icing methods, their rationale is illustrated with characteristics of impedanceregulation for bundled conductor; the key parameters, i.e. maximum interval time, minimum load current for anti-icingand ice-melting time for de-icing, are calculated. On this basis, specific method of anti-icing and de-icing of line impedance simulation is obtained, including determination of number of conducting subconductors and their conducting time. Anti-icing and de-icing of this method are validated preliminarilywith laboratory investigation conducted in artificial climate chamber. The results of this research can be employed to line impedance regulation in anti-icing and de-icingin practical engineering as a reference.
    No preview · Article · Oct 2015
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    D D Yao · L Yang · Y Wang · C Liu · Y J Wei · X B Jia · W Yin · L Shu
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    ABSTRACT: T-cell factor 7-like 2 (TCF7L2) is an important transcription factor of Wnt/β-catenin signaling, which has critical roles in β-cell survival and regeneration. In preliminary screening assay, we found geniposide, a naturally occurring compound, was able to increase TCF7L2 mRNA level in Min6 cells. Here we aimed to investigate the role of geniposide in β-cell and underlying mechanism involved. Geniposide was found to promote β-cell survival by increasing β-cell proliferation and decreasing β-cell apoptosis in cultured mouse islets after challenge with diabetic stimuli. Geniposide protected β-cell through activating Wnt signaling, enhanced expressions of TCF7L2 and GLP-1R, activated AKT, inhibited GSK3β activity, and promoted β-catenin nuclear translocation. The protective effect of geniposide was remarkably suppressed by siRNAs against β-catenin, or by ICG001 (β-catenin/TCF-mediated transcription inhibitor). Moreover, geniposide promoted β-cell regeneration in vivo to normalize blood glucose in high-fat diet and db/db mice. Increased β-cell proliferation was observed in pancreatic sections of geniposide-treated diabetic mice. Most importantly, geniposide triggered small islet-like cell clusters formation as a result of β-cell neogenesis from ductal epithelium, which was well correlated with the increase in TCF7L2 expression. In exocrine cells isolated from mouse pancreas, geniposide could induce duct cell differentiation through upregulating TCF7L2 expression and activating JAK2/STAT3 pathway. Taken together, we identified a novel role of geniposide in promoting β-cell survival and regeneration by mechanisms involving the activation of β-catenin/TCF7L2 signaling. Our finding highlights the potential value of geniposide as a possible treatment for type 2 diabetes.
    Preview · Article · May 2015 · Cell Death & Disease
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    ABSTRACT: Objective: To prepare polysaccharides, alkaloids, and polyphenols from fresh Portulaca oleracea and study their hypoglycemic effects. Methods: The suitable macroporous resin and adequate separation and purification technology were selected to prepare polysaccharides, alkaloids, and polyphenols from fresh P. oleracea; Then their hypoglycemic effects were studied by analyzing fasting blood serum, insulin, and MDA and SOD from STZ induced diabetic mice. Results: All these three compositions can low fasting blood serum of diabetic mice. What's more, polysaccharides and polyphenols can obviously improve the content of SOD and degrade the content of MDA, while alkaloids can promote pancreatic β echylosis. Conclusion: Polysaccharides, alkaloids, and polyphenols from fresh P. oleracea possess anti-diabetic effects, and the integral administration of the three compositions has better hypoglycemic effect. ©, 2014, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.
    No preview · Article · Sep 2014 · Chinese Traditional and Herbal Drugs
  • D.-D. Yao · L. Shu · L. Yang · X.-B. Jia · M. Sun
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    ABSTRACT: Objective: To investigate the hypoglycemic effect of geniposide and to explore the mechanism. Methods: The diabetic mice were induced by a single dose of 90 mg/kg streptozotocin (STZ) injection followed by four-week high-fat diets and randomly divided into three groups: normal control (con), diabetic model (diab), and geniposide (gen, 100 mg/kg) groups. Body weight and fasting blood glucose were measured during the treatment. Thirty days later, the oral glucose tolerance test (OGTT) was performed, blood samples were collected to measure insulin concentration in plasma. The morphological changes of pancreas pathology and β-cell proliferation were examined by immuno-fluorescent staining of insulin and Ki67. The phosphorylations of AKT and GSK-3β (p-AKT and p-GSK-3β) in liver tissues were detected by Western blotting assay. Results: Compared with the diab group, geniposide showed significantly hypoglycemic effect, together with lowering body weight, increasing the insulin content in plasma, and improving OGTT. The immuno-fluorescent staining showed the islets destruction caused by hyperglycemia was recovered by geniposide. The β-cell proliferation presented by Ki67 staining increased as compared with that in the diab group. Moreover, both p-Akt and p-GSK-3β levels in the liver tissue were upregulated by geniposide remarkably. Conclusion: The present study demonstrates that geniposide could ameliorate the hyperglycemia in diabetic mice by enhancing the pancreatic β-cell proliferation and activation of AKT signaling pathway in liver.
    No preview · Article · Apr 2014 · Chinese Traditional and Herbal Drugs
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    Dong-Dong Yao · Luan Shu · Lei Yang · Xiao-Bin Jia
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    ABSTRACT: The diabetes is mainly treated by the oral administration of western medicines at present. Despite their rapid curative effect, there have been still many reports for the western medicines about their clinical adverse reactions, failure of effective prevention and treatment of complications and drug resistance. Hence, they are not suitable for long-term administration. Traditional Chinese medicines have a long history in treating diabetes mellitus (DM) , which is commonly known as Xiaokezheng in the theory of traditional Chinese medicines. In recent years, many scholars have taken extracts from traditional Chinese medicines or separated active constituents as the study objects in the expectation of developing new-type drugs for treating and preventing diabetes. Therefore, a large number of study reports have been emerged in this field. Due to their significant glucose-reducing effect and specific effect in treating complications of diabetes, traditional Chinese medicine Gardeniae Fructus and its iridoid component geniposide shall be given full attention. This paper summarized the advance in studies on the curative effect and action mechanism of Gardeniae Fructus and geniposide in preventing and treating diabetes.
    Preview · Article · Apr 2014 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
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    ABSTRACT: Unlabelled: Luteolin, one of the most common abundant flavonoids in vegetables and herbs, has antitumor effects on various tumors by inducing apoptosis, antioxidant effects and inhibition of angiogenesis. However, the potential chemoprevention of luteolin on lung cell damage and its related mechanism(s) are not fully known. The present study evaluated the protective effects of luteolin on cigarette smoke extract (CSE)-induced toxicity and apoptosis in normal human bronchial epithelial (NHBE) cells and explored its underlying mechanism(s). MTT assay showed that pretreatment with luteolin increased CSE-decreased cell viability (p<0.05). Luteolin increased cellular glutathione (GSH) levels but decreased reactive oxygen species (ROS) generation (p<0.05). Cytometry assay and western blot analysis showed that luteolin attenuated CSE-induced apoptosis and apoptosis‑related protein activation, including caspase‑3, -8 and -9 (p<0.05). The expression of CSE-induced Nad(p)h: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were decreased significantly by luteolin (p<0.05). Furthermore, luteolin attenuated CSE-induced apoptosis, noticeably reduced CSE-induced expression of NF-E2-related factor 2 (Nrf2), NQO1 and HO-1 using a small interfering RNA (siRNA) transfection assay. The data demonstrated that CSE-induced oxidative damage and apoptosis through the Nrf2 pathway was inhibited by luteolin and it may serve as a chemopreventive agent for the prevention and treatment of lung cancer.
    No preview · Article · Jan 2014 · Oncology Reports
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    ABSTRACT: The zebrafish model organism was applied first in a metabolic study of icariin, baohuoside I, epimedin A and epimedin C, which are flavonoids in Herba Epimedii. Metabolites of these compounds in zebrafish after exposure for 24 h were identified by HPLC-ESI-MS, whereby the separation was performed with a Zorbax C-18 column using a gradient elution of 0.05% formic acid acetonitrile-0.05% formic acid water. The quasi-molecular ions of compounds were detected in simultaneous negative and positive ionization modes. Metabolic products of icariin and epimedin C via cleavage of glucose residue instead of rhamnose residues were found, which coincided with the results using regular metabolic analysis methods. In addition, the zebrafish model was used to predict the metabolism of the trace component epimedin A, whose metabolic mechanisms haven't been clearly elucidated with the current metabolism model. The metabolic pathway of epimedin A in zebrafish was similar to those of its homologue icariin and epimedin C. Our study demonstrated that the zebrafish model can successfully imitate the current models in elucidating metabolic pathways of model flavonoids, which has advantages of lower cost, far less amount of compound needed, easy set up and high performance. This novel model can also be applied in quickly predicting the metabolism of Chinese herb components, especially trace compounds.
    Preview · Article · Dec 2012 · Molecules
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    ABSTRACT: Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.
    Preview · Article · Dec 2012 · Molecules
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    ABSTRACT: The study aimed to investigate the potential of zebrafish in imitating mammal phase I metabolism of natural compounds. Three diterpenoid quinones from Radix Salvia miltiorrhiza, namely tanshinone IIA (TIIA), cryptotanshinone (Cry) and tanshinone I (TI) were selected as model compounds, and their metabolites mediated by zebrafish were characterized using a high-performance liquid chromatography coupled ion-trap mass spectrometry (HPLC/IT-MSn) method with electrospray ionization in positive mode. The separation was performed with a Zorbax C-18 column using a binary gradient elution of 0.05% formic acid acetonitrile/0.05% formic acid water. According to the MS spectra and after comparison with reference standards and literature reports, hydroxylation, dehydrogenation or D-ring hydrolysis metabolites of TIIA and Cry but not of TI were characterized, which coincided with those reported using regular in vivo or in vitro metabolic analysis methods, thus verifying that zebrafish can successfully imitate mammalian phase I metabolism which instills further confidence in using zebrafish as a novel and prospective metabolism model.
    Preview · Article · Dec 2012 · Molecules
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    ABSTRACT: Baohuoside I (also known as Icariside II) is a flavonoid isolated from Epimedium koreanum Nakai. Although Baohuoside I exhibits anti-inflammatory and anti-cancer activities, its molecular targets/pathways in human lung cancer cells are poorly understood. Therefore, in the present study, we investigated the usefulness of Baohuoside I as a potential apoptosis-inducing cytotoxic agent using human adenocarcinoma alveolar basal epithelial A549 cells as in vitro model. The apoptosis induced by Baohuoside I in A549 cells was confirmed by annexin V/propidium iodide double staining, cell cycle analysis and dUTP nick end labeling. Further research revealed that Baohuoside I accelerated apoptosis through the mitochondrial apoptotic pathway, involving the increment of BAX/Bcl-2 ratio, dissipation of mitochondrial membrane potential, transposition of cytochrome c, caspase 3 and caspase 9 activation, degradation of poly (ADP-ribose) polymerase and the over-production of reactive oxygen species (ROS). A pan-caspase inhibitor, Z-VAD-FMK, only partially prevented apoptosis induced by Baohuoside I, while NAC, a scavenger of ROS, diminished its effect more potently. In addition, the apoptotic effect of Baohuoside I was dependent on the activation of ROS downstream effectors, JNK and p38(MAPK), which could be almost abrogated by using inhibitors SB203580 (an inhibitor of p38(MAPK)) and SP600125 (an inhibitor of JNK). These findings suggested that Baohuoside I might exert its cytotoxic effect via the ROS/MAPK pathway.
    No preview · Article · Jun 2012 · Chemico-biological interactions
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    ABSTRACT: Zebrafish, a common model organism for studies of vertebrate development and gene function, has been used in pharmaceutical research as a new and powerful tool in recent years. In the present study, we applied zebrafish for the first time in a metabolic study of notoginsenoside (R1), ginsenoside (Rg1) and ginsenoside (Rb1), which are saponins isolated from Panax notoginseng. Metabolites of these three saponin compounds in zebrafish after exposure for 24 h were identified by high performance liquid chromatography - electrospray mass spectrometry (HPLC-ESI-MS) with a Zorbax C-18 column for separation using a binary gradient elution of 0.05% formic acid acetonitrile - 0.05% formic acid water. The quasi-molecular ions of compounds were detected in negative mode. Step-wise deglycosylation metabolites and hydroxylation metabolites of the three saponins were found, which were coincide with regular methods for metabolic analysis. Our study demonstrated that the zebrafish model can successfully imitate the current metabolic model with advantages of lower cost, far less amount of compound needed, easy set up and high performance. Our data suggests that the zebrafish metabolic model has the potential for developing a novel method for quickly predicting the metabolism of Chinese herb components, including those of trace compounds.
    Preview · Article · Dec 2011 · Molecules