Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-kappa B Signaling Cascades
- Authors
- Alam, Md Badrul; Kwon, Yoon-Gyung; Simu, Shakina Yesmin; Shahriyar, Sk Abrar; Lee, Sang Han
- Issue Date
- Jul-2020
- Publisher
- MDPI
- Keywords
- anti-inflammatory effects; icariside B2; NF-kappa B signaling; MAP-kinase
- Citation
- BIOMOLECULES, v.10, no.7
- Journal Title
- BIOMOLECULES
- Volume
- 10
- Number
- 7
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/81254
- DOI
- 10.3390/biom10071037
- ISSN
- 2218-273X
- Abstract
- 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 (PGE(2)) 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 mu M. 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-alpha, IL-6, and IL-1 beta, at their transcriptional and translational level. ICSB hinders inhibitory protein kappa B alpha (I kappa B alpha) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappa B) 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-kappa B expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-alpha, IL-1 beta, and IL-6.
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