Publications (6)

  • [Show abstract] [Hide abstract] ABSTRACT: Rationale The mechanism involved in AD is complex, which has prompted to develop compounds that could simultaneously interact with several potential targets. Here, we report a new synthesized compound SCR-1693 which is designed to target both AChE and calcium channels that are potential for AD therapy. Objectives We investigated the effects of SCR-1693 on AChE and calcium channels, the effects of neuroprotection and anti-amnesia in icv-Aβ25–35-injected mice, and the potential mechanisms. Methods AChE activity assay, intracellular Ca2+ content and calcium currents measurement, and Aβ25–35-induced cellular death determine were performed for validation of designed targets and neuroprotection of SCR-1693. Mice were orally administrated with SCR-1693 once daily after an Aβ25–35 injection. The Morris water maze and Y-maze test, and hippocampal protein detection were conducted on days 5–10, day 11, and day 8. The pyramidal neuron number, hippocampal AChE activity, and synaptic transmission were measured on day 12. Results SCR-1693 acted as a selective, reversible, and noncompetitive inhibitor of AChE, and a nonselective voltage-gated calcium channel blocker. SCR-1693 also inhibited the increase of AChE activity in the mouse hippocampus. SCR-1693 was more effective than donepezil and memantine in preventing Aβ25–35-induced long-term and short-term memory impairment, maintaining the basal transmission of Schaffer collateral-CA1 synapses, and sustaining LTP in mouse hippocampus. SCR-1693 attenuated Aβ25–35-induced death of SH-SY5Y cell and the loss of hippocampal pyramidal neurons, and regulated Aβ25–35-induced signal cascade in neurons. Conclusions All these findings indicated that SCR-1693, as a double-target-direction agent, is a considerable candidate for AD therapy.
    Article · Nov 2015 · Psychopharmacology
  • Dataset · Nov 2015
  • Zhuan Hong · Aijing Bi · Dan Chen · [...] · Lan Luo
    [Show abstract] [Hide abstract] ABSTRACT: The activation of the hedgehog pathway, which is an important signaling mechanism crucial in embryogenesis, has strong links to carcinogenesis. Aberrant regulation of this pathway can result in the development of tumors. The present study was designed to investigate Hh related protein expression in non-small cell lung cancers. Fifty five non-small cell lung cancers samples were used in the study. By reverse transcription-polymerase chain reaction (RT-PCR), the expression of Shh, Ptch-1, and Gli-1 in tumor and adjacent normal tissues was examined and associated to clinical pathologic features. The expression levels of Shh, Ptch-1, Gli-1 in non-small cell lung cancer tissues were 63.64, 69.09, 43.64 %, respectively, higher than that in the adjacent normal tissues. Survival analysis showed that both Ptch-1 and Gli-1 expression were associated with poor survival (both P <0.05, log-rank test). Shh and Ptch-1 expression were correlated with lymph node metastasis. These results suggest that dysregulation of Hh signaling pathway plays an important role in the development of human NSCLCs. The expression of Ptch-1 and Gli-1 is possibly involved in NSCLCs progression, which may be a useful prognostic indicator of NSCLCs.
    Article · Apr 2014 · Pathology & Oncology Research
  • Dan Chen · Aijing Bi · Xiaoliang Dong · [...] · Lan Luo
    [Show abstract] [Hide abstract] ABSTRACT: Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases.
    Article · Dec 2013 · Biochemical and Biophysical Research Communications
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    Dan Chen · Jinjiao Liu · Bing Rui · [...] · Lan Luo
    [Show abstract] [Hide abstract] ABSTRACT: Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation.
    Full-text Article · Dec 2013 · Biochimica et Biophysica Acta
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    Wei Jiang · Min Gao · Shuai Sun · [...] · Lan Luo
    [Show abstract] [Hide abstract] ABSTRACT: We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1β in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.
    Full-text Article · May 2012 · Biochemical and Biophysical Research Communications