scholarly journals Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

2013 ◽  
Vol 190 (11) ◽  
pp. 5689-5701 ◽  
Author(s):  
Ana P. Girol ◽  
Kallyne K. O. Mimura ◽  
Carine C. Drewes ◽  
Simone M. Bolonheis ◽  
Egle Solito ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4288-4296 ◽  
Author(s):  
Magali Pederzoli-Ribeil ◽  
Francesco Maione ◽  
Dianne Cooper ◽  
Adam Al-Kashi ◽  
Jesmond Dalli ◽  
...  

Abstract Human polymorphonuclear leukocytes adhesion to endothelial cells during the early stage of inflammation leads to cell surface externalization of Annexin A1 (AnxA1), an effector of endogenous anti-inflammation. The antiadhesive properties of AnxA1 become operative to finely tune polymorphonuclear leukocytes transmigration to the site of inflammation. Membrane bound proteinase 3 (PR3) plays a key role in this microenvironment by cleaving the N terminus bioactive domain of AnxA1. In the present study, we generated a PR3-resistant human recombinant AnxA1—named superAnxA1 (SAnxA1)—and tested its in vitro and in vivo properties in comparison to the parental protein. SAnxA1 bound and activated formyl peptide receptor 2 in a similar way as the parental protein, while showing a resistance to cleavage by recombinant PR3. SAnxA1 retained anti-inflammatory activities in the murine inflamed microcirculation (leukocyte adhesion being the readout) and in skin trafficking model. When longer-lasting models of inflammation were applied, SAnxA1 displayed stronger anti-inflammatory effect over time compared with the parental protein. Together these results indicate that AnxA1 cleavage is an important process during neutrophilic inflammation and that controlling the balance between AnxA1/PR3 activities might represent a promising avenue for the discovery of novel therapeutic approaches.


2020 ◽  
Author(s):  
Yanlei Zheng ◽  
Ronghua Hu ◽  
Li Zhang

Abstract BackgroundInflammation and apoptosis contribute to the development of sepsis-induced acute kidney injury. Annexin A1 (ANXA1) is the calcium-dependent phospholipid-binding protein known to play an important role in a variety of cellular functions, including inflammation, apoptosis, migration and proliferation. However, the effect of ANXA1 on sepsis-induced acute injury has not been reported. Herein, we investigated the role and underlying mechanism of the mimetic peptide Ac2-26 of annexin A1 in sepsis-induce acute kidney injury in vivo and in vitro.MethodsIn vivo, a mouse model was established by cecal ligation and puncture (CLP), and the Ac2-26 peptide of ANXA1 (1 mg/kg) was intraperitoneally administered 2 hours before CLP. In vitro, A model of HK-2 cells was established by treatment with 10 μg/ml lipopolysaccharide (LPS), and the Ac2-26 peptide of ANXA1 (0.5 μmol/L) was administered 2 hours before LPS. The kidney function of mice detected by Elisa. The kidney tissue was examined by HE and TEM. The inflammatory cytokines and apoptotic molecules were measured by PCR, Elisa, Western blotting and Immunohistochemistry. The apoptosis was detected by TUNEL and flow cytometry.ResultsThe studies demonstrated that ANXA1 markedly improved kidney function and kidney tissue injury and enhanced 7-day survival in CLP-induced septic mice, which was accompanied by a significant decrease the inflammatory molecules. ANXA1 obviously downregulated the apoptosis-associated proteins and inhibited apoptosis in kidney tissue in vivo. In vitro studies showed that ANXA1 increased the viability of HK-2 cells, reduced the levels of the inflammatory molecules, downregulated the apoptosis-associated proteins Bax, upregulated the antiapoptotic protein Bcl-2 and inhibited the apoptosis of HK-2 cells.ConclusionsThe mimetic peptide Ac2-26 of annexin A1 protects against sepsis-induced inflammation, apoptosis, and kidney dysfunction via regulating the LXA4/PI3K/IKK-β/NF-κB signaling pathway.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
S Fuchs ◽  
LT Hsieh ◽  
W Saarberg ◽  
CAJ Erdelmeier ◽  
TA Wichelhaus ◽  
...  
Keyword(s):  

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.


2020 ◽  
Vol 21 (15) ◽  
pp. 1688-1698
Author(s):  
Germeen N.S. Girgis

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.


2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.


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