scholarly journals Characterization of the Physiological Response followingIn VivoAdministration ofAstragalus membranaceus

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Karen Denzler ◽  
Jessica Moore ◽  
Heather Harrington ◽  
Kira Morrill ◽  
Trung Huynh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Temperature ◽  
Dynamic Change ◽  
Baseline Values ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Necrosis Factor

The botanical,Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overallin vivoeffects ofA. membranaceuson the human body. This study evaluates the physiological responses toA. membranaceusby measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after thein vivoadministration ofA. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γand tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role ofA. membranaceusin priming for a potential immune response as well as its effect on blood flow and wound healing.

scholarly journals Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice

2019 ◽  
Vol 316 (1) ◽  
pp. F128-F133 ◽  
Author(s):  
Felix Knauf ◽  
Heino Velazquez ◽  
Victoria Pfann ◽  
Zhirong Jiang ◽  
Peter S. Aronson
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Fractional Excretion ◽  
Wild Type ◽  
Nacl Transport ◽  
Lower Blood ◽  
Urine Oxalate

The apical membrane Cl−/oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl− absorption were similar in surface proximal tubules of wild-type and Slc26a6−/− mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6−/− mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6−/− compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6−/− mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.

Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An in vitro and in vivo Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Acute Experiment ◽  
Antihypertensive Activity ◽  
Mentha Pulegium ◽  
In Vitro Experiment ◽  
Arterial Blood ◽  
Dose Dependent ◽  
Ca2 Channels

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

Role Of Cyclic Amp In The Inhibition Of Human Platelet Functions By Quercetin, A Flav0N0Id That Potentiates PGI2 Effect

1981 ◽  
Author(s):  
J P Cazenave ◽  
A Beretz ◽  
A Stierlé ◽  
R Anton
Keyword(s):  
Maximum Level ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Pde Inhibitors ◽  
Pde Inhibition ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Dose Dependent

Injury to the endothelium (END) and subsequent platelet (PLAT)interactions with the subEND are important steps in thrombosis and atherosclerosis. Thus,drugs that protect the END from injury and also inhibit PLAT function are of interest. It has been shown that some flavonoids(FLA), a group of compounds found in plants, prevent END desquamation in vivo, inhibit cyclic nucleotide phosphodiesterases(PDE)and inhibit PLAT function. We have studied the structure-activity relationships of 13 purified FLA on aggregation and secretion of 14c-5HT of prelabeled washed human PLAT induced by ADP, collagen(COLL) and thrombin(THR). All the FLA were inhibitors of the 3 agents tested. Quercetin(Q), was the second best after fisetin. It inhibited secretion and aggregation with I50 of 330µM against 0.1 U/ML.THR, 102µM against 5µM ADP and 40 µM against COLL. This inhibitory effect is in the range of that of other PDE inhibitors like dipyridamole or 3-isobutyl-l- methylxanthine. The aggregation induced by ADP, COLL and THR is at least mediated by 3 mechanisms that can be inhibited by increasing cAMP levels. We next investigated if Q, which is a PDE inhibitor of bovine aortic microsomes,raises PLAT cAMP levels. cAMP was measured by a protein-binding method. ADP- induced aggregation(5µM) was inhibited by PGI2 (0.1 and 0.5 nM) . Inhibition was further potentiated(l.7 and 3.3 times) by lOµM Q, which alone has no effect on aggregation. The basal level of cAMP(2.2 pmol/108PLAT) was not modified by Q (50 to 500µM). Using these concentrations of Q,the rise in cAMP caused by PGI2(0.1 and 0.5nM) was potentiated in a dose dependent manner. Q potentiated the effect of PGI2 on the maximum level of cAMP and retarded its breakdown. Thus Q and possibly other FLA could inhibit the interaction of PLAT with the components of the vessel wall by preventing END damage and by inhibiting PLAT function through a rise in cAMP secondary to PDE inhibition and potentiation of the effect of vascular PGI2 on PLAT adenylate cyclase.

Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockade

2006 ◽  
Vol 290 (6) ◽  
pp. H2554-H2559 ◽  
Author(s):  
Ryan M. Fryer ◽  
Pamela A. Rakestraw ◽  
Patricia N. Banfor ◽  
Bryan F. Cox ◽  
Terry J. Opgenorth ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Type B ◽  
Selective Antagonist ◽  
Relevant Role ◽  
Basal Blood Pressure ◽  
Baseline Values

The net contribution of endothelin type A (ETA) and type B (ETB) receptors in blood pressure regulation in humans and experimental animals, including the conscious mouse, remains undefined. Thus we assessed the role of ETA and ETB receptors in the control of basal blood pressure and also the role of ETA receptors in maintaining the hypertensive effects of systemic ETB blockade in telemetry-instrumented mice. Mean arterial pressure (MAP) and heart rate were recorded continuously from the carotid artery and daily (24 h) values determined. At baseline, MAP ranged from 99 ± 1 to 101 ± 1 mmHg and heart rate ranged between 547 ± 15 and 567 ± 19 beats/min ( n = 6). Daily oral administration of the ETB selective antagonist A-192621 [10 mg/kg twice daily] increased MAP to 108 ± 1 and 112 ± 2 mmHg on days 1 and 5, respectively. Subsequent coadministration of the ETA selective antagonist atrasentan (5 mg/kg twice daily) in conjunction with A-192621 (10 mg/kg twice daily) decreased MAP to baseline values on day 6 (99 ± 2 mmHg) and to below baseline on day 8 (89 ± 3 mmHg). In a separate group of mice ( n = 6) in which the treatment was reversed, systemic blockade of ETB receptors produced no hypertension in animals pretreated with atrasentan, underscoring the importance of ETA receptors to maintain the hypertension produced by ETB blockade. In a third group of mice ( n = 10), ETA blockade alone (atrasentan; 5 mg/kg twice daily) produced an immediate and sustained decrease in MAP to values below baseline (baseline values = 101 ± 2 to 103 ± 2 mmHg; atrasentan decreased pressure to 95 ± 2 mmHg). Thus these data suggest that ETA and ETB receptors play a physiologically relevant role in the regulation of basal blood pressure in normal, conscious mice. Furthermore, systemic ETB receptor blockade produces sustained hypertension in conscious telemetry-instrumented mice that is absent in mice pretreated with an ETA antagonist, suggesting that ETA receptors maintain the hypertension produced by ETB blockade.

Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells

1996 ◽  
Vol 271 (6) ◽  
pp. L1014-L1022 ◽  
Author(s):  
R. Rajah ◽  
S. E. Nunn ◽  
D. J. Herrick ◽  
M. M. Grunstein ◽  
P. Cohen
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Igf Binding Proteins ◽  
Leukotriene D4 ◽  
Igf Binding ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Insulin Like Growth Factors

We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is comitogenic with insulin-like growth factors (IGF) in airway smooth muscle (ASM) cells. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced inhibitory IGF-binding proteins (IGFBP). In this report, we analyzed the conditioned media (CM) from LTD4-treated human ASM cells (ASM-LTD4-CM) by Western ligand blotting and demonstrated a marked LTD4-induced reduction in the levels of the intact IGFBP (predominantly IGFBP-2) secreted by these cells. The IGFBP-2 in the ASM-LTD4-CM was identified as lower-molecular-weight fragments by Western immunoblotting. Incubation with 125I-labeled IGFBP demonstrated that an IGFBP protease was induced in the ASM cells in response to LTD4 treatment. Immunodepletion of ASM-LTD4-CM with anti-matrix metalloproteinase (MMP)-1 antibodies demonstrated a dose-dependent reduction of IGFBP proteolysis. Tissue inhibitor of MMP-1 and Batimastat (synthetic) inhibited proteolysis of IGFBP. Immunoblotting the ASM-LTD4-CM with anti-MMP-1 demonstrated a dose-dependent increase in MMP-1 protein. Similar results were also obtained by immunocytochemistry. Collectively, these observations demonstrate that MMP-1 is an IGFBP protease induced by leukotrienes that plays a significant role in modulating IGF action in ASM cells. A similar mechanism may be applicable in vivo in the airways of patients with asthma.

Toward heterogeneity in feedforward network with synaptic delays based on FitzHugh–Nagumo model

2018 ◽  
Vol 32 (01) ◽  
pp. 1750274 ◽  
Author(s):  
Ying-Mei Qin ◽  
Cong Men ◽  
Jia Zhao ◽  
Chun-Xiao Han ◽  
Yan-Qiu Che
Keyword(s):  
Neuronal Excitability ◽  
Temporal Coding ◽  
Feedforward Network ◽  
Firing Patterns ◽  
In Vivo Experiments ◽  
Connection Probability ◽  
Rate Coding

We focus on the role of heterogeneity on the propagation of firing patterns in feedforward network (FFN). Effects of heterogeneities both in parameters of neuronal excitability and synaptic delays are investigated systematically. Neuronal heterogeneity is found to modulate firing rates and spiking regularity by changing the excitability of the network. Synaptic delays are strongly related with desynchronized and synchronized firing patterns of the FFN, which indicate that synaptic delays may play a significant role in bridging rate coding and temporal coding. Furthermore, quasi-coherence resonance (quasi-CR) phenomenon is observed in the parameter domain of connection probability and delay-heterogeneity. All these phenomena above enable a detailed characterization of neuronal heterogeneity in FFN, which may play an indispensable role in reproducing the important properties of in vivo experiments.

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