Shoseiryuto May Prevent Bronchial Epithelial Tight Junction Disruption by Inhibiting the Inflammatory NF-κB Signaling...

Area of Science:

• Pharmacology
• Immunology
• Cell Biology

Background:

• Shoseiryuto (SST) is a Kampo medicine used for respiratory conditions.
• Previous studies indicated SST's role in attenuating lipopolysaccharide (LPS)-induced tight junction (TJ) disruption in bronchial epithelial cells.
• The precise mechanisms behind SST's protective effects remained unclear.

Purpose of the Study:

• To elucidate the mechanisms underlying the anti-inflammatory and epithelial barrier-protective effects of SST.
• To investigate SST's impact on inflammatory responses and TJ integrity.
• To identify potential signaling pathways modulated by SST.

Main Methods:

• Utilized human bronchial epithelial (16HBE) cells.
• Induced inflammation and TJ disruption using LPS, hydrogen peroxide (H₂O₂), tumor necrosis factor-α (TNF-α), and polyinosinic-polycytidylic acid (Poly I:C).
• Assessed inflammatory markers (IL-6), TJ integrity (TEER, permeability, occludin expression), and NF-κB signaling pathway activation (NF-κB and IκB phosphorylation).
• Compared SST effects with NF-κB inhibitors (SC-514, BAY11-7085) and analyzed active components (isoliquiritigenin, glycyrrhizin).

Main Results:

• SST attenuated inflammatory responses and TJ disruption induced by various stimuli.
• SST's effects were comparable to NF-κB inhibitors.
• SST reduced NF-κB signaling activation, including phosphorylation of NF-κB and IκB.
• SST components, isoliquiritigenin (ILQG) and glycyrrhizin (GL), also demonstrated anti-inflammatory and barrier-protective effects.

Conclusions:

• NF-κB signaling pathway activation is linked to inflammatory responses and TJ barrier disruption.
• SST mitigates inflammation and epithelial barrier dysfunction, likely through modulation of the NF-κB pathway.
• Isoliquiritigenin and glycyrrhizin may be key contributors to SST's therapeutic actions.