The influence of crystal facet on the catalytic performance of MOFs-derived NiO with different morphologies for the total oxidation of propane: The defect engineering dominated by solvent regulation effect.

Crystal facet and defect engineering are crucial for designing heterogeneous catalysts. In this study, different solvents were utilized to generate NiO with distinct shapes (hexagonal layers, rods, and spheres) using nickel-based metal-organic frameworks (MOFs) as precursors. It was shown that the exposed crystal facets of NiO with different morphologies differed from each other. Various characterization techniques and density functional theory (DFT) calculations revealed that hexagonal-layered NiO (NiO-L) possessed excellent low-temperature reducibility and oxygen migration ability. The (111) crystal plane of NiO-L contained more lattice defects and oxygen vacancies, resulting in enhanced propane oxidation due to its highest O2 adsorption energy. Furthermore, the higher the surface active oxygen species and surface oxygen vacancy concentrations, the lower the C-H activation energy of the NiO catalyst and hence the better the catalytic activity for the oxidation of propane. Consequently, NiO-L exhibited remarkable catalytic activity and good stability for propane oxidation. This study provided a simple strategy for controlling NiO crystal facets, and demonstrated that the oxygen defects could be more easily formed on NiO(111) facets, thus would be beneficial for the activation of C-H bonds in propane. In addition, the results of this work can be extended to the other fields, such as propane oxidation to propene, fuel cells, and photocatalysis.

p-Synephrine exhibits anti-adipogenic activity by activating the Akt/GSK3ß signaling pathway in 3T3-L1 adipocytes.

This work aimed to investigate the effects of p-synephrine on the differentiation of adipocyte and explore the underlying mechanism. We found that p-synephrine suppressed the 3T3-L1 cell adipogenesis by reducing the expression level of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which subsequently led to a reduction in the fatty acid-binding protein 4 (aP2) expression. p-Synephrine treatment markedly activated the protein kinase B (PKB/Akt) pathway and sequentially inhibited glycogen synthase kinase 3ß (GSK3ß) activity. Inhibition of GSK3ß activity by LiCl was found to partially ameliorate the above-mentioned effects. All these data suggested that p-synephrine exhibited the anti-adipogenic effects via the regulation of Akt signaling pathway and the suppression of adipogenesis-related proteins. PRACTICAL APPLICATIONS: Citrus aurantium often uses as herbal or dietary supplement in various countries around the world, including in Seville, Spain and South Africa. In traditional Chinese herbs, it is referred to as "Fructus aurantii immaturus," "Zhi shi," or "Zhi ke," and has been used for hundreds of years for various digestive problems. Its primary protoalkaloid, p-synephrine, exhibited lipolytic effects and energy expenditure, which has rapidly replaced ephedrine as an "ephedra-free" alternative dietary supplement. The current study firstly demonstrated the anti-adipogenic effects of p-synephrine in 3T3-L1 preadipocytes, which was due to the regulation of Akt signaling pathway and the subsequent suppression of adipogenesis-related proteins. The present study may offer invaluable opinions into the mechanisms of body weight/fat-losing activities of p-synephrine in theory, and scientific experimental evidence on dietary supplement in practice. p-Synephrine could be utilized for the preventive and therapeutic uses against metabolic syndrome.

Paeonol ameliorates monosodium urate-induced arthritis in rats through inhibiting nuclear factor-κB-mediated proinflammatory cytokine production.

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1ß, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.

Flower extracts from Paeonia decomposita and Paeonia ostii inhibit melanin synthesis via cAMP-CREB-associated melanogenesis signaling pathways in murine B16 melanoma cells.

This investigation seeks to identify the effects of the EtOAc fractions of different flower parts of Paeonia decomposita (Pd) and Paeonia ostii (Po) on melanogenesis and their mechanisms of action in B16 melanoma cells. Cell viability assay showed that Pd-1, Po-1 (the petals of Pd or Po), Pd-3 and Po-3 (the stamens of Pd or Po) at 25 µg/ml produced lower toxic activities in B16 cells. Pd-1 and Po-1 extracts considerably reduced the melanin content and inhibited tyrosinase and DOPA oxidase activity. Moreover, Pd-1 and Po-1 down-regulated the expressions of MC1R, MITF, TRP-1, TRP-2, and tyrosinase. These extracts also reduce cAMP levels and inhibited the phosphorylation of CREB, which might be due to the presence of high concentrations of phenolic compounds and flavonoids. Our results suggested that Pd-1 and Po-1 are able to modulate the cAMP-CREB signaling pathway and down-regulate the melanogenesis-related proteins resulting in the observed anti-melanogenic effects. PRACTICAL APPLICATIONS: In China, the flower of Paeonia is often consumed as a dietary supplement and as an additive in skin whitening products. In November 2013, the National Health and Family Planning Commission of the People's Republic of China has approved the flower of Paeonia ostii as a novel food resource. The current study firstly demonstrated that the effects of EtOAc fractions of the petals of Paeonia decomposita (Pd) and Paeonia ostii (Po) considerably reduced the melanin content in B16 cells, which is due to the modulation of the cAMP-CREB signaling pathway followed by the down-regulation of melanogenesis-related proteins. Pd and Po extracts, as natural tyrosinase inhibitors, may serve as good candidates in food additives, cosmetic materials, or even in treating hyperpigmentation diseases.

Effect of heat treatment under vacuum on structure and visible-light photocatalytic activity of nano-TiO2.

Nano-TiO2 is known as a photocatalyst with high catalytic activity. However, it should be emphasized that the bandgap of nano-TiO2 is wide, which limits its photocatalytic efficiency in response to visible light and thus hinders its potential application. Improving the photocatalytic activity of nano-TiO2 under visible light by the strategy of heat treatment under vacuum was investigated in this study. The structure and photocatalytic activity of nano-TiO2 before and after heat treatment under vacuum were compared and analyzed by XRD, TEM, HRTEM, XPS and UV-Vis-NIR, respectively. The results show that oxygen vacancies were introduced into the crystal structure of nano-TiO2 to change its inherent energy band structure. Particularly, the samples after heat treatment under vacuum exhibited high photocatalytic activity under visible light. In addition, the formation mechanism of non-stoichiometric compound TiO2-x and the mechanism of oxygen vacancy defects to expand the wavelength of light that nano-TiO2 absorbs to the visible portion of the spectrum have also been addressed in this paper.

Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells.

Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPKα expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK-FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis.

Study on preparation method of Zanthoxylum bungeanum seeds kernel oil with zero trans-fatty acids.

The seed of Zanthoxylum bungeanum (Z. bungeanum) is a by-product of pepper production and rich in unsaturated fatty acid, cellulose, and protein. The seed oil obtained from traditional producing process by squeezing or extracting would be bad quality and could not be used as edible oil. In this paper, a new preparation method of Z. bungeanum seed kernel oil (ZSKO) was developed by comparing the advantages and disadvantages of alkali saponification-cold squeezing, alkali saponification-solvent extraction, and alkali saponification-supercritical fluid extraction with carbon dioxide (SFE-CO2). The results showed that the alkali saponification-cold squeezing could be the optimal preparation method of ZSKO, which contained the following steps: Z. bungeanum seed was pretreated by alkali saponification under the conditions of adding 10 %NaOH (w/w), solution temperature was 80 °C, and saponification reaction time was 45 min, and pretreated seed was separated by filtering, water washing, and overnight drying at 50 °C, then repeated squeezing was taken until no oil generated at 60 °C with 15 % moisture content, and ZSKO was attained finally using centrifuge. The produced ZSKO contained more than 90 % unsaturated fatty acids and no trans-fatty acids and be testified as a good edible oil with low-value level of acid and peroxide. It was demonstrated that the alkali saponification-cold squeezing process could be scaled up and applied to industrialized production of ZSKO.

Comparative analysis of evolutionarily conserved motifs of epidermal growth factor receptor 2 (HER2) predicts novel potential therapeutic epitopes.

Overexpression of human epidermal growth factor receptor 2 (HER2) is associated with tumor aggressiveness and poor prognosis in breast cancer. With the availability of therapeutic antibodies against HER2, great strides have been made in the clinical management of HER2 overexpressing breast cancer. However, de novo and acquired resistance to these antibodies presents a serious limitation to successful HER2 targeting treatment. The identification of novel epitopes of HER2 that can be used for functional/region-specific blockade could represent a central step in the development of new clinically relevant anti-HER2 antibodies. In the present study, we present a novel computational approach as an auxiliary tool for identification of novel HER2 epitopes. We hypothesized that the structurally and linearly evolutionarily conserved motifs of the extracellular domain of HER2 (ECD HER2) contain potential druggable epitopes/targets. We employed the PROSITE Scan to detect structurally conserved motifs and PRINTS to search for linearly conserved motifs of ECD HER2. We found that the epitopes recognized by trastuzumab and pertuzumab are located in the predicted conserved motifs of ECD HER2, supporting our initial hypothesis. Considering that structurally and linearly conserved motifs can provide functional specific configurations, we propose that by comparing the two types of conserved motifs, additional druggable epitopes/targets in the ECD HER2 protein can be identified, which can be further modified for potential therapeutic application. Thus, this novel computational process for predicting or searching for potential epitopes or key target sites may contribute to epitope-based vaccine and function-selected drug design, especially when x-ray crystal structure protein data is not available.

Asymmetric epoxidation of cis/trans-ß-methylstyrene catalysed by immobilised Mn(salen) with different linkages: heterogenisation of homogeneous asymmetric catalysis.

Immobilised Mn(salen) catalysts with two different linkages were studied in the asymmetric epoxidation of cis/trans-ß-methylstyrene using NaClO as oxidant. The immobilised Mn(salen) complexes inside nanopores can lead to different catalytic behaviour compared with that of homogeneous Jacobsen catalyst. The rigidity of the linkage was found to be a key factor affecting the catalytic performance of immobilised catalysts. The immobilised catalyst with a rigid linkage exhibited comparable chemical selectivity, enantioselectivity and cis/trans ratio of product formation to that obtained with homogeneous Jacobsen catalysts. In contrast, the immobilised catalyst with a flexible linkage gave remarkably lower chemical selectivity, enantioselectivity and inverted cis/trans ratio compared with the results obtained with the homogeneous Jacobsen catalyst and the immobilised catalyst with rigid linkage. Thus, for immobilised Mn(salen) catalysts, a rigid linkage connecting active centres to the support is essential to obtain activity and enantioselectivity as high as those obtained in homogeneous systems.

p-Synephrine: a novel agonist for neuromedin U2 receptor.

In the brain, Neuromedin U2 receptor (NMU2R) is prominent in the hypothalamic regions and is known to be associated with regulation of several important physiological functions, including food intake, energy balance, stress response, and nociception. In this article, by random screening of compounds using the model of high-throughput screening for NMU2R stable expression, NMU2R negative and NMU2R short hairpin RNA (shRNA) knockdown HEK293 cell lines, for the first time, we discovered that p-synephrine, which is the primary protoalkaloid in Citrus aurantium (bitter orange) and is widely used in weight loss and weight management products, is a highly potent and selective NMU2R agonist. In NMU2R activating ability experiments, p-synephrine was found binding to NMU2R with high efficacy and potency; the efficacy, 50% of the maximum possible effect (EC50) and potency values were determined to be 7.207, 6.604 and 0.227 µmol/L for the NMU2R, respectively. Our researches have important theoretical value for elucidating the mechanisms of p-synephrine in body weight and energy balance regulation. These data provide further evidence for widespread roles for p-synephrine and its receptors in the brain.

Application of low-cost algal nitrogen source feeding in fuel ethanol production using high gravity sweet potato medium.

Protein-rich bloom algae biomass was employed as nitrogen source in fuel ethanol fermentation using high gravity sweet potato medium containing 210.0 g l(-1) glucose. In batch mode, the fermentation could not accomplish even in 120 h without any feeding of nitrogen source. While, the feeding of acid-hydrolyzed bloom algae powder (AHBAP) notably promoted fermentation process but untreated bloom algae powder (UBAP) was less effective than AHBAP. The fermentation times were reduced to 96, 72, and 72 h if 5.0, 10.0, and 20.0 g l(-1) AHBAP were added into medium, respectively, and the ethanol yields and productivities increased with increasing amount of feeding AHBAP. The continuous fermentations were performed in a three-stage reactor system. Final concentrations of ethanol up to 103.2 and 104.3 g l(-1) with 4.4 and 5.3 g l(-1) residual glucose were obtained using the previously mentioned medium feeding with 20.0 and 30.0 g l(-1) AHBAP, at dilution rate of 0.02 h(-1). Notably, only 78.5 g l(-1) ethanol and 41.6 g l(-1) residual glucose were obtained in the comparative test without any nitrogen source feeding. Amino acids analysis showed that approximately 67% of the protein in the algal biomass was hydrolyzed and released into the medium, serving as the available nitrogen nutrition for yeast growth and metabolism. Both batch and continuous fermentations showed similar fermentation parameters when 20.0 and 30.0 g l(-1) AHBAP were fed, indicating that the level of available nitrogen in the medium should be limited, and an algal nitrogen source feeding amount higher than 20.0 g l(-1) did not further improve the fermentation performance.

[Activating effect of citrus flavonoids on neuromedin U2 receptor and analysis on siRNA interference].

OBJECTIVE: To screen out active substances on Neuromedin U2 receptor (NMU2R) by using stable NMU2R cell lines and negative cell lines and analyzing siRNA interference. METHOD: NMU2R cells were used to observe the activating effect of nine nine citrus flavonoids on NMU2R cell. Afterwards, false-positive interference of citrus flavonoids that showed higher activating effect was eliminated by using negative cells and analyzing the efficiency of siRNA interference. RESULT: Hesperidin and nobiletin contained in citrus flavonoids were found to effectively activate NMU2R. The efficacy, EC50 and potency values of hesperidin were 4.688, 318.970 micromol x L(-1) and 200.933 micromol x L(-1), while the efficacy, EC50 and potency values of nobiletin were 4.758, 5.832 micromol x L(-1) and 3.124 micromol x L(-). CONCLUSION: Hesperidin and nobiletin contained in citrus flavonoids can activate NMU2R. Nobiletin shows such a low EC50 that it has medicinal value.

Visible light responsive N-F-codoped TiO2 photocatalysts for the degradation of 4-chlorophenol.

N-F-codoped TiO2 (NFTO) photocatalysts were synthesized by a simple sol-gel process with tetrabutyl titanate (Ti(OBu)4) as the precursor of TiO2 and ammonium fluoride (NH4F) as the source of N and F. The synthesized photocatalysts were investigated by Xray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) and photodegradation reaction tests of 4-chlorophenol under visible light irradiation to understand the relationship between the structure of NFTO catalyst and corresponding photocatalytic activity. The crystal phase and particle size of catalysts were found to be largely affected by the calcination temperature. In addition, N-F-codoping could inhibit phase transition of TiO2 from anatase to rutile. The presence of N and F atoms in the lattice of TiO2 is responsible for the visible light catalytic activity. In UV-Vis DRS tests, the spectrum of NFTO exhibited red shift compared with Degussa P25 and the band gap was reduced to around 2.92 eV. Under optimal calcination temperature and dopant concentration conditions, the NFTO photocatalyst exhibited the highest activity in the photodegradation reaction tests of 4-chlorophenol under visible light irradiation with a degradation rate of 75.84%. Besides, the 5-recycle test showed that NFTO photocatalyst could be reused and its activity kept stable under visible light irradiation.

Geniposide induces the expression of heme oxygenase-1 via PI3K/Nrf2-signaling to enhance the antioxidant capacity in primary hippocampal neurons.

Oxidative stress in brain is emerging as a potential causal factor in aging and age-related neurodegenerative disorders. A large body of evidence shows that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In this study, geniposide upregulates the expression of heme oxygenase-1 (HO-1) to attenuate the cell apoptosis induced by 3-morpholinosydnonimine hydrochloride (SIN-1) in primary cultured hippocampal neurons. Furthermore, geniposide induces the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and activation of phosphatidylinositol 3'-kinase (PI3K) in the presence of oxidative stress, and both LY294002 (a specific inhibitor of PI3K) and Zinc protoporphyrin (ZnPP, an inhibitor of HO-1) decrease the cytoprotective action of geniposide in hippocampal neurons. Taken together, the novel cytoprotective mechanism of geniposide to antagonize oxidative stress may be involved in PI3K- and Nrf2-mediated upregulation of the antioxidative enzyme HO-1.

[Effect and mechanism of total flavonoids of orange peel on rat adjuvant arthritis].

OBJECTIVE: To investigate the effect of the total flavonoids of orange peel (TFO) against adjuvant arthritis (AA) and the underlying mechanism. METHOD: AA model was induced in male Wistar (correction of SD) rats by immunization with Freund's complete adjuvant Pad thickness was assayed by caliper. Pathological impairment of ankle joint was analysised by hematoxylin and eosin (H&E) staining. Levels of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and prostaglandin (PG) E2 in serum was detected by radioimmunoassay method. Cyclooxygenase (COX)-2 expression in synovium tissues was measured by Western blot assay. RESULT: The 75 mg x kg(-1) and 150 mg x kg(-1) TFO treatment obviously decreased the pad thickness and improve the pathological impairment of ankle joint of AA rats. In addition, abnormal elevation of TNF-alpha, IL-1beta and PGE2 in serum and COX-2 expression in synovium tissues of AA rats were markedly repressed by TFO treatment. CONCLUSION: TFO can inhibit the development of AA in rats, and the mechanism were likely due to depressing inflammatory mediators production.

[High throughput screening method of identifying D5 receptor agonist from Chinese herbs].

D5 receptor is a subtype of dopamine D1-like receptor, and it plays a functional role in many neurological disorders. Some natural compounds from Chinese herbs, which were shown to have the property as that of receptor agonist, might provide a rich source in search of new candidates for therapeutic use. For exploring this possibility, we developed a cell-based high throughput (HTS) D5 receptor assay to screen the herb-based natural compound library established in our centre. The D5 receptor plasmid (hD5R/pcDNA3.1) and reporter gene plasmid (4 x CRE/TK/Luci/pGL3) were co-transfected into HEK293 cell line. After G418 being selected, the monoclonal cell lines bearing hD5R and the reporter gene were established and used for agonist screening. To optimize the assay condition, the effects of some factors such as cell number per well, incubation time, and the doses of SKF38393 (a potent selective partial D1-like agonist) were examined by using forskolin, a positive compound for cAMP response element. The best condition for this HTS assay included: the cell number at 5 x 10(4)/mL, the dose of forskolin at 5-20 micromol/L, the dose of SKF38393 at 100 nmol/L-100 micromol/L, and the agonist incubation time at 6 -8 h. Thereafter, water extracts from more than 200 Chinese herbs in our library were screened and three of these water extracts showed positive activity, with higher or similar activity as SKF38393. In conclusion, we have established a cell-based HTS assay for D5 receptor agonist screening, and by use of this HTS assay, 3 Chinese herbs maybe contain components exhibiting D5 receptor agonist property. This work provides an alternative vision of how to use herb medicines and a way to develop potential drugs for treatment of neurological disorders.

GLP-1 receptor plays a critical role in geniposide-induced expression of heme oxygenase-1 in PC12 cells.

AIM: To explore the role of activation of glucagon-like peptide 1 receptor (GLP-1R) and its relative cell signaling pathway in the cytoprotection of geniposide. METHODS: Cell viability was determined by MTT assay. Knockdown of the Glp-1r gene was carried out with shRNA. The levels of HO-1 protein and cAMP response element binding protein (CREB) phosphorylation were measured by Western blotting. RESULTS: Geniposide protected PC12 cells from oxidative damage induced by 3-morpholinosydnonimine hydrochloride (SIN-1) by enhancing the expression of heme oxygenase 1 (HO-1) via the cAMP-PKA-CREB signal pathway. After transfecting PC12 cells with the AB1 enhancer from the HO-1 gene, luciferase activity induced by geniposide increased in a dose-dependent manner, but not in the PC12 cells whose Glp-1r gene was disrupted. Additionally, inhibition of HO-1 activity by Sn-protoporphyrin IX (SnPP) or shRNA-mediated knockdown of Glp-1r decreased the neuroprotection of geniposide in PC12 cells. CONCLUSION: GLP-1R plays a critical role in geniposide-induced HO-1 expression to attenuate oxidative insults in PC12 cells.

Characterization and antitumor activity of triethylene tetramine, a novel telomerase inhibitor.

Triethylene tetramine (TETA) is a novel ligand for G-quadruplex and has been reported to have many kinds of biological activities, including telomerase inhibition, inducing the senescence of tumor cells, etc. In this study, tumor inhibiting activity of TETA and its mechanism were investigated in HeLa cells, MCF-7 cells and mice transplanted with S180 tumor. Results indicated that TETA inhibited telomerase activity involved in decreasing the expression of human telomerase reverse transcriptase (hTERT). We also observed that a low concentration of TETA had limited ability to inhibit the growth of tumor cells in short-term culture, but it could significantly enhance antitumor activity of traditional antitumor drugs in vitro and in vivo.

Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.

Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide-1 (GLP-1) gives a new genre in therapeutic targets for intervention in AD with its neurotrophic and neuroprotective functions. In previous work, we identified that geniposide is a novel agonist for GLP-1 receptor, which shows neurotrophic characteristics to induce the neuronal differentiation of PC12 cells. The aim of this study is to determine whether geniposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide. LY294002 (a PI3K inhibitor) inhibited the effect of geniposide increasing of Bcl-2 level by activation of MAPK, MEK and c-Raf phosphorylation in hydrogen peroxide treated PC12 cells. U0126 (a selective inhibitor of MEK) also attenuated the enhancement of geniposide on Bcl-2 level by inhibiting the phosphorylation of p90RSK in the hydrogen peroxide treated PC12 cells. All these data demonstrate that geniposide, an agonist for GLP-1 receptor, regulates expression of anti-oxidative proteins including HO-1 and Bcl-2 by activating the transcriptor of p90RSK via MAPK signaling pathway in PC12 cells.

Neurotrophic property of geniposide for inducing the neuronal differentiation of PC12 cells.

The emerging data show that the insulinotrophic hormone glucagon-like peptide-1(GLP-1) and its agonist extendin-4 have neurotrophic function to inducing neuronal differentiation of PC12 cells and prevent neurons damage challenged by oxidative stress. Here, with the model of high throughput screen for GLP-1 receptor agonists, we screen and identify that geniposide is a novel agonist for GLP-1 receptor. Furthermore, geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43. U0126, a selective MEK inhibitor, prevents neurites out growth and phosphorylation of mitogen-activated kinase proteins in PC12 cells induced by geniposide. All these results show that activation of GLP-1 receptor by geniposide to induce the neuronal differentiation of PC12 cells involves in MAPK signaling cascade.