Biomolecules (Jul 2020)

Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-κB Signaling Cascades

  • Md Badrul Alam,
  • Yoon-Gyung Kwon,
  • Shakina Yesmin Simu,
  • Sk Abrar Shahriyar,
  • Sang Han Lee

DOI
https://doi.org/10.3390/biom10071037
Journal volume & issue
Vol. 10, no. 7
p. 1037

Abstract

Read online

Prolonged inflammatory responses can lead to the development of several chronic diseases, such as autoimmune disorders and the development of natural therapeutic agents is required. A murine model was used to assess the anti-inflammatory effects of the megastigmane glucoside, icariside B2 (ICSB), and the assessment was carried out in vitro, and in vivo. The in vitro anti-inflammatory effects of ICSB were tested using LPS-stimulated BV2 cells, and the protein expression levels of inflammatory genes and cytokines were assessed. Mice were subcutaneously injected with 1% carrageenan (CA) to induce acute phase inflammation in the paw. Inflammation was assessed by measuring paw volumes hourly; subsequently, the mice were euthanized and the right hind paw skin was expunged and processed for reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. ICSB inhibits LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) generation by reducing the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). ICSB also inhibits the COX-2 enzyme with an IC50 value of 7.80 ± 0.26 µM. Molecular docking analysis revealed that ICSB had a strong binding affinity with both murine and human COX-2 proteins with binding energies of −8 kcal/mol and −7.4 kcal/mol, respectively. ICSB also reduces the manifestation of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, at their transcriptional and translational level. ICSB hinders inhibitory protein κBα (IκBα) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) nuclear translocation. ICSB also represses the mitogen-activated protein kinases (MAPKs) signaling pathways. ICSB (50 mg/kg) showed an anti-edema effect in CA-induced mice and suppressed the CA-induced increases in iNOS and COX-2 protein levels. ICSB attenuated inflammatory responses by downregulating NF-κB expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-α, IL-1β, and IL-6.

Keywords