Protective effects of l-pGlu-(2-propyl)-l-His-l-ProNH2, a newer thyrotropin releasing hormone analog in in vitro and in vivo models of cerebral ischemia

Peptides ◽  
2011 ◽  
Vol 32 (6) ◽  
pp. 1225-1231 ◽  
Author(s):  
Satyendra Kumar Rajput ◽  
Maqsood Ahmad Siddiqui ◽  
Vivek Kumar ◽  
Chhuttan Lal Meena ◽  
Aditya Bhushan Pant ◽  
...  
Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.


2021 ◽  
Vol 36 (1) ◽  
pp. 964-976
Author(s):  
Ilaria Dettori ◽  
Irene Fusco ◽  
Irene Bulli ◽  
Lisa Gaviano ◽  
Elisabetta Coppi ◽  
...  

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 349 ◽  
Author(s):  
Katalin Prokai-Tatrai ◽  
Daniel L. De La Cruz ◽  
Vien Nguyen ◽  
Benjamin P. Ross ◽  
Istvan Toth ◽  
...  

Using thyrotropin-releasing hormone (TRH) as a model, we explored whether synergistic combination of lipoamino acid(s) and a linker cleaved by prolyl oligopeptidase (POP) can be used as a promoiety for prodrug design for the preferential brain delivery of the peptide. A representative prodrug based on this design principle was synthesized, and its membrane affinity and in vitro metabolic stability, with or without the presence of a POP inhibitor, were studied. The in vivo formation of TRH from the prodrug construct was probed by utilizing the antidepressant effect of the peptide, as well as its ability to increase acetylcholine (ACh) synthesis and release. We found that the prototype prodrug showed excellent membrane affinity and greatly increased metabolic stability in mouse blood and brain homogenate compared to the parent peptide, yet a POP inhibitor completely prevented prodrug metabolism in brain homogenate. In vivo, administration of the prodrug triggered antidepressant-like effect, and microdialysis sampling showed greatly increased ACh release that was also antagonized upon a POP inhibitor treatment. Altogether, the obtained promising exploratory data warrant further investigations on the utility of the prodrug approach introduced here for brain-enhanced delivery of small peptides with neurotherapeutic potential.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67063 ◽  
Author(s):  
Virginie Desestret ◽  
Adrien Riou ◽  
Fabien Chauveau ◽  
Tae-Hee Cho ◽  
Emilie Devillard ◽  
...  

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Tao Tao ◽  
Guang-Jie Liu ◽  
Xuan Shi ◽  
Yan Zhou ◽  
Yue Lu ◽  
...  

Abstract Background Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. Methods We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. Results In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. Conclusions DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qiang Liang ◽  
Xiaoran Li ◽  
Wangning Zhou ◽  
Yu Su ◽  
Shenbao He ◽  
...  

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract’s antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule-1 (KIM-1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis-related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate- (CaOx-) induced OPN expression, KIM-1 expression, and OS compared with the positive control group (P<0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P<0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P<0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone-forming constituents and urolithiasis-related protein expression, and elevating urinary citrate levels.


2014 ◽  
Vol 2 (3) ◽  
pp. 189-198
Author(s):  
Ajay H. Bahl ◽  
Wanda Lee

Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs). Some of these peptides can assume an alpha-helical conformation, others contain one or two disulfide bonds, still others are Pro- and Arg-rich, or Trp-rich. Higher levels of human cathelicidin antimicrobial protein (hCAP18), which are up-regulated by vitamin D, appear to significantly reduce the risk of death from infection in dialysis patients. Using in vitro and in vivo models of kidney infection, we demonstrate key antimicrobial and host immunomodulatory properties of cathelicidins. To directly assess the role of endogenous cathelicidin in the development of glomerulonephritis, WT and mCRAMP KO mice were provided with 5% DSS to induce glomerulonephritis. Some mice groups were administered with E. coli DNA I.P. Our findings showed that mCRAMP KO mice develop more severe glomerulonephritis. These data demonstrate key roles for cathelicidins in host defense against glomerulonephritis and the potential to inform the development of synthetic analogues to modulate specific host-pathogen interactions as novel antimicrobial therapeutics.


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