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Molecular Neurobiology

, Volume 55, Issue 7, pp 5798–5808 | Cite as

Role of 3-Acetyl-11-Keto-Beta-Boswellic Acid in Counteracting LPS-Induced Neuroinflammation via Modulation of miRNA-155

  • Aya Shoukry Sayed
  • Iman Emam Omar GomaaEmail author
  • Michael Bader
  • Nesrine Salah El Dine El Sayed
Article

Abstract

Neuroinflammation is one of the most important mechanisms underlying neurodegeneration. Lipopolysaccharide (LPS) is a potent inflammogen which causes cognitive dysfunction. Boswellia serrata is known since many years as a powerful anti-inflammatory herbal drug. Its beneficial effect mainly arises from inhibition of 5-lipoxygenase (5-LO) enzyme. 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent 5-LO inhibitor extracted from the oleo-gum-resin of Boswellia serrata. The aim of the present work is to study the molecular mechanisms underlying the anti-inflammatory and neuroprotective effects of AKBA and dexamethasone (DEX) in LPS-induced neuroinflammatory model. A single intraperitoneal (i.p.) dose of LPS (0.8 mg/kg) was injected to induce cognitive dysfunction. The LPS-treated mice were administered for 7 days with either AKBA or DEX at intraperitoneal doses of 5 and 1 mg/kg, respectively. Cognitive, locomotor functions, and anxiety level were first examined. The level of the phosphorylated inhibitory protein for NF-κB, IκB-α (P-IκB-α), was measured, and the expression levels of the inflammatory microRNA-155 (miR-155) and its target gene, suppressor of cytokine signaling-1 (SOCS-1), were determined in the brain. Moreover, the level of carbonyl proteins as a measure of oxidative stress and several cytokines as well as markers for apoptosis and amyloidogenesis was detected. Results showed that AKBA and DEX reversed the behavioral dysfunction induced by LPS. AKBA decreased P-IκB-α, miRNA-155 expression level, and carbonyl protein content. It restored normal cytokine level and increased SOCS-1 expression level. It also showed anti-apoptotic and anti-amyloidogenic effects in LPS-injected mice. These findings suggest AKBA as a therapeutic drug for alleviating the symptoms of neuroinflammatory disorders.

Keywords

LPS AKBA DEX Molecular markers Inflammatory markers 

Notes

Acknowledgements

Thanks are directed to Gabin Sihn, Phillip Schiele, and Karolina Wszołek-Meißner for their technical assistance at the western blot analysis both at Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13125, Berlin, Germany.

Authors’ Contribution

German University in Cairo (GUC) led the conception, design acquisition of all experimental work, and the manuscript preparation. All authors read and approved the final manuscript. Conceived and designed the experiments: IG, MB, and NS. Participated at the experimental work: AS and IG. Contributed with reagents/materials/analysis equipment and tools: AS, IG, and MB. Analyzed the data: AS and IG. Wrote the paper: AS, IG, MB, and NS.

Funding Information

This work has been partially supported by equipment grants from the Centre for Special Studies and Programs (CSSP), Bibliotheca Alexandrina, grant no. “145”, as well as DAAD equipment funding, project no. “134.104401.347”, grant no. “ga43213.”

Compliance with Ethical Standards

The study received ethical approval on the animals’ procedures that were held according to the guidelines of the Animals Ethics Committee at the German University in Cairo in association with the recommendations of the National Institutes of Health (NIH) Guide for Care and Use of Laboratory Animals (Publication No. 85-23, revised 1985).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Aya Shoukry Sayed
    • 1
  • Iman Emam Omar Gomaa
    • 2
    • 3
    • 4
    • 5
    Email author
  • Michael Bader
    • 6
  • Nesrine Salah El Dine El Sayed
    • 7
    • 8
  1. 1.Department of Pharmaceutical Biology, Faculty of Pharmacy and BiotechnologyGerman University in CairoNew Cairo CityEgypt
  2. 2.Biotechnology Sector, Faculty of Pharmacy and BiotechnologyGerman University in CairoCairoEgypt
  3. 3.School of Engineering and Applied SciencesNile UniversityCairoEgypt
  4. 4.Nano Science and Technology InstituteKafr El-Sheikh UniversityKafr El-SheikhEgypt
  5. 5.CairoEgypt
  6. 6.Max-Delbrück-Center for Molecular Medicine (MDC)BerlinGermany
  7. 7.Department of Pharmacology and Toxicology, Faculty of PharmacyCairo UniversityGizaEgypt
  8. 8.Department of Pharmacology and Toxicology, Faculty of Pharmacy and BiotechnologyGerman University in CairoNew Cairo CityEgypt

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