Hesperidin Improves Colonic Motility in Loeramide-Induced Constipation Rat Model via 5-Hydroxytryptamine 4R/cAMP Signaling Pathway

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 692-705 ◽  
Author(s):  
Minna Wu ◽  
Youran Li ◽  
Yunfei Gu

Fructus has motivation effect on gastrointestinal tract. Hesperidin is extracts of Fructus, and we attempted to prove its effects on improving the gastrointestinal transmission function and determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. Constipation phenotypes were measured in rats with Lop-induced constipation after treatment with hesperidin. The amounts and water content of stool were significantly higher in the hesperidin-treated group than the loperamide-induced model group, whereas food intake was maintained at constant levels. Moreover, intestinal transit rate was increased in the treatment group of hesperidin. Histological alteration was detected by H&E staining, we found that the colon smooth muscle cells and neuron cells of the rats were increased, and the infiltration of inflammatory cells was decreased in the hesperidin-treated group compared with the loperamide-induced model group. 5-Hydroxytryptamine (5-HT) receptor4 fluorescence intensity and intracellular-free calcium ions in colon tissue were increased, and relative protein of cAMP/PKA pathway and p-cAMP response component-binding protein (CREB) pathway were upregulated in the hesperidin-treated group compared with the loperamide-induced model group. Further, SMCs from colon tissue of rats were cultured and identified. We found hesperidin could significantly promote tegaserod-induced increase of 5-HTR4 fluorescence intensity, intracellular calcium ions, relative protein of cAMP/PKA pathway and p-CREB pathway, and cell proliferation and inhibit GR113808-induced decrease of 5-HTR4 fluorescence intensity, 5-HTR4 pathway-related proteins (ADCY3, cAMP, PKA, and p-CREB), intracellular calcium ions, and cell proliferation. The analysis of our data suggested that hesperidin could obviously improve the gastrointestinal transmission function in loperamide-induced STC rat model via increasing the 5-HTR4 and intracellular-free calcium ions to enhance the expression of relative protein of cAMP/PKA pathway and p-CREB pathway. Hesperidin could be used in the treatment of STC, and our data not only provide experimental basis for the treatment of STC in hesperidin but also provides a theoretical reference for clinical treatment.

2013 ◽  
Vol 295-298 ◽  
pp. 78-81
Author(s):  
Hua Liu ◽  
Hua Guang Li ◽  
Su Liu

AIM: To investigate the mechanism of hyaluronic acid on rabbit chondrocyte apoptosis in vitro induced by NO. METHODS: We cultured rabbit chondrocytes as normal group and added SNP after cultured 24 h as model group. Treated group was added HA. We used cell culture experiment. We tested the activity of mitochondria though MTT. The flow cytometry detected mitochondrial membrane potential, the percentage of apoptosis and intracellular free calcium concentration.RESULTS: HA could elevate the active of chondrocyte mitochondria and MMP; it could decrease the rate of chondrocyte apoptosis and intracellular free calcium concentration.CONCLUSION: HA can inhibit the lowering of the MMP in chondrocyte, which has a stable role on MMP and inhibit apoptosis occurred. This effect may be related to inhibiting of intracellular calcium overload chondrocytes.


Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Ki Park ◽  
Hye-Jin Park

The effect ofCordyceps militaris(CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-)αmRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.


2021 ◽  
Vol 11 (9) ◽  
pp. 1792-1798
Author(s):  
Li Yan ◽  
Ge Jingping ◽  
Yin Yuanyuan ◽  
Li Xiaomei ◽  
Zhao Boxiang ◽  
...  

Aim: This research was to investigate the effects and mechanisms of HSYA in vascular endothelial injury by vitro study. Methods: Dividing HUVECs as Normal Control (NC), Model (LPS treated) group, HSYA-L, HSYA-M and HSYA-H groups. Cells in the HSYA treatment groups were treated with LPS, followed by 40 mg/ml, 80 mg/ml, and 120 mg/ml HSYA intervention (HSYA-L, HSYA-M, and HSYA -H groups), respectively. Measuring the cell proliferation, apoptosis, relative proteins and mRNA (TLR4, MyD88 and NF-κB(p65)) expressions by MTT, Flow cytometry, WB and RT-qPCR assay. Using cellular immunofluorescence to evaluate NF-κB(p65) nuclear volume of difference groups. Results: With HSYA supplement, the cell proliferation rates were significantly up-regulation with cell apoptosis significantly down-regulation with TLR4 relatived mRNA and proteins and NF-κB(p65) nuclear significantly depressed with dose-dependent (P <0.05, respectively). Conclusion: HSYA improved vascular endothelial injury induced by LPS via TLR4 pathway In Vitro.


2021 ◽  
Author(s):  
Yi-yi Wang ◽  
Hua Duan ◽  
Sha Wang ◽  
Yong-jun Quan ◽  
Jun-hua Huang ◽  
...  

Abstract Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a central role in contributing the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the development of ADS and presents an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with β-estradiol (β-E2) presented stronger proliferative and proangiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins, compared with the controls. Meanwhile, these promoting effects were abrogated in the presence of Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly Upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of Talin1 overexpression plus β-E2 treatment. Results from the xenograft model showed that the hypodermic endometrial lesions from the co-treatment group with OV-Talin1 and β-E2 had the highest mean weight and volume, compared with that of individual OV-Talin1 or β-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated most significantly in the co-treated group. Our findings unveiled that abnormally overexpressed Talin1 cooperated with E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xiaosong He ◽  
Yongting Wang ◽  
Yaning Li ◽  
Yifang Lv ◽  
Yaohui Tang ◽  
...  

Introduction: oligodendrocyte injury after ischemic stroke influences the integrity of white matter, which ultimately leads to neurological deficits. Netrin-1 (NT-1) plays a crucial role in axon guidance during neural development. Also, it promotes oligodendrocyte progenitor cell proliferation. Our previous study demonstrates that netrin-1 overexpression improves neurobehavioral outcomes after ischemia by promoting focal angiogenesis. In this study, we investigate whether netrin-1 facilitates white matter recovery during focal ischemia and further to explore which specific receptor involves in the white matter reconstruction. Methods: sixty adult male ICR mice underwent adeno-associated virus (AAV) mediated AAV-Netrin-1 or AAV-GFPgene transfer. These mice received one hour transient middle artery occlusion (MCAO) and 7, 14, 28 days reperfusion at one week after the gene transfer. Western blot and immunohischemistry were used to determine the location and quantification of exogenous NT-1 expression. Neuronalbehavior test were performed to eveluate the neuralbehavioral outcomes. Oligodendrocyte progenietor cell proliferation, maturation and myelination were examined by immunohischemistry. Results: NT-1 was highly expressed in the mouse brain after two weeks of AAV-NT-1 gene transfer, which mainly expressed in neurons and astrocytes. Neurobehavioral outcomes were greatly improved at 7, 14 and 28 days after reperfusion in AAV-NT-1 treated mice compared to the GFP control mice ( p <0.05), The number of proliferated oligodendrocyte progenietor cells, mature oligodendrocytes and MBP positive neurofilaments in the corpus callosum and the striatum in the ipsilateral hemisphere at 7, 14 and 28 days after reperfusion were increased in the NT-1 treated group compared to GFP control mice ( p <0.01). NT-1 receptor DCC and Unc5H2 are involved in the proliferation of oligodendrocyte progenitor cells,But only Unc5h2 was involved in the re-myelination process. Conclusion: NT-1 overexpression improves neurobehavioral outcomes and promotes oligodendrocyte progenietor cell proliferation and maturation. Oue results suggest that netrin-1 not only promotes angiogenesis but also enchances remyelination.


1979 ◽  
Vol 178 (1) ◽  
pp. 187-193 ◽  
Author(s):  
I B Täljedal

Suspensions rich in pancreatic beta-cells were prepared from non-inbred ob/ob-mice, incubated with 10 micrometer-chlorotetracycline, and analysed for fluorescence polarization in a microscope. Throughout the temperature range 16–38 degrees C, fluorescence was enhanced by 5 mM-Ca2+ in the incubation medium; 20 mM-D-glucose decreased the fluorescence measured in the presence of Ca2+. Fluorescence showed a curvilinear negative regression on temperature. The curves were rectified to a virtually ideal degree by Arrhenius transformations of data. Non-parametric testing of differences between linearized regression lines forms the basis for the following conclusions. The temperature-dependence of fluorescence intensity appeared to be smaller for Ca2+-specific signals than for the background fluorescence of chlorotetracycline in Ca2+-deficient cells. D-Glucose significantly diminished the polarization of fluorescence in cells incubated with Ca2+. It is suggested that D-glucose increases the mobility of Ca2+ in beta-cell plasma membranes; this mobility increase may help to explain previously reported effects of D-glucose on 45Ca2+ fluxes and membrane electric potential.


1991 ◽  
Vol 112 (4) ◽  
pp. 711-718 ◽  
Author(s):  
N Grandin ◽  
M Charbonneau

In Xenopus embryos, previous results failed to detect changes in the activity of free calcium ions (Ca2+i) during cell division using Ca2(+)-selective microelectrodes, while experiments with aequorin yielded uncertain results complicated by the variation during cell division of the aequorin concentration to cell volume ratio. We now report, using Ca2(+)-selective microelectrodes, that cell division in Xenopus embryos is accompanied by periodic oscillations of the Ca2+i level, which occur with a periodicity of 30 min, equal to that of the cell cycle. These Ca2+i oscillations were detected in 24 out of 35 experiments, and had a mean amplitude of 70 nM, around a basal Ca2+i level of 0.40 microM. Ca2+i oscillations did not take place in the absence of cell division, either in artificially activated eggs or in cleavage-blocked embryos. Therefore, Ca2+i oscillations do not represent, unlike intracellular pH oscillations (Grandin, N., and M. Charbonneau. J. Cell Biol. 111:523-532. 1990), a component of the basic cell cycle ("cytoplasmic clock" or "master oscillator"), but appear to be more likely related to some events of mitosis.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Zhong-Xia Lu ◽  
Wen-Jun Xu ◽  
Yang-Sheng Wu ◽  
Chang-Yu Li ◽  
Yi-Tao Chen

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.


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