Ginsenoside Rh1 ameliorates the asthma and allergic inflammation via inhibiting Akt, MAPK, and NF-κB signaling pathways in vitro and in vivo.

Abstract

AIMS:

Overproduction of pro-inflammatory cytokines and its-mediated immune cell infiltration play a crucial role in asthma progression. In this study, we investigated the role of ginsenoside Rh1 (Rh1) in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced allergic asthma both in vitro and in vivo.

MATERIALS AND MAIN METHODS:

The phorbol ester (PMA) and LPS were used to induce inflammation in lung airway cells and macrophage activation, respectively. Western blotting, quantitative reverse transcription-PCR, and immunofluorescence (IF) assays were performed to elucidate the underlying molecular mechanisms. To evaluating the effects of Rh1 in vivo, OVA and LPS were used to establish allergic asthma models.

KEY FINDINGS:

Rh1 significantly suppressed PMA-induced lung inflammation and macrophage activation by suppressing pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1), ICMA-1, and matrix metallopeptidase 9 (MMP9) in A549 cells. Rh1 abolished the PMA-induced inflammation by suppressing MAPK, Akt, and NF-κB p65. Pretreatment with Rh1 blocked PMA-mediated translocation of NF-κB, a key marker of pro-inflammatory cytokine release, into the nucleus. Similar to PMA-induced lung inflammation, Rh1 suppressed LPS-induced macrophage activation by suppressing NF-κB p65 activation and inducible nitric oxide synthase protein and mRNA expression. Consistent with in vitro data, LPS injection enhanced the number of immune cells induced by OVA in bronchoalveolar lavage fluid, whereas 20 mg/kg Rh1 significantly decreased OVA/LPS-mediated immune cell induction. In addition, Rh1 inhibited eosinophil, macrophage, and neutrophil maturation through by IL-4 and OVA-specific IgE production.

SIGNIFICANCE:

Rh1 protects against OVA/LPS-induced allergic asthma by suppressing immune cell infiltration by blocking the activation of MAPK, Akt, and NF-κB signaling pathways.

• Authors: Yujin Jin, Warisraporn Tangchang, Oh Seong Kwon, Ji-Yun Lee, Kyung-Sun Heo, Hwa-Young Son
• Journal: Life sciences (Life Sci) Vol. 321 Pg. 121607 (May 15 2023) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 36958436 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• NF-kappa B
• Proto-Oncogene Proteins c-akt
• ginsenoside Rh1
• Lipopolysaccharides
• Cytokines
• Ovalbumin

Topics

• Humans
• NF-kappa B (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Lipopolysaccharides (pharmacology)
• Asthma (chemically induced, drug therapy)
• Signal Transduction
• Inflammation (drug therapy, metabolism)
• Lung (metabolism)
• Cytokines (metabolism)
• Pneumonia (metabolism)
• Bronchoalveolar Lavage Fluid
• Ovalbumin