This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Shoseiryuto May Prevent Bronchial Epithelial Tight Junction Disruption by Inhibiting the Inflammatory NF-κB Signaling Pathway
by
, , ,
Jingya Lu
1,2,*
,
Ailing Hu
1,
Yunhai Lin
1,
Yi Luo
1,
Wenshu Yuan
1,
Takuji Yamaguchi
1,
Zenji Kawakami
1,
Yasushi Ikarashi
1,
Masaaki Abe
2,
Hajime Orita
2 and
Hiroyuki Kobayashi
1 1
Department of Personalized Kampo Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
2
International Collaborative Research Administration, Juntendo University School of Medicine, Tokyo 113-8431, Japan
*
Author to whom correspondence should be addressed.
Biology 2026, 15(8), 603; https://doi.org/10.3390/biology15080603
Submission received: 18 February 2026
/
Revised: 4 April 2026
/
Accepted: 8 April 2026
/
Published: 11 April 2026
(This article belongs to the Section Cell Biology)
Simple Summary
This study investigated the mechanisms responsible for the protective effects of Shoseiryuto (SST) on bronchial epithelial tight junction (TJ) barrier dysfunction using cultured human bronchial epithelial cells. SST effectively suppressed inflammation and TJ barrier dysfunction induced by inflammatory agents such as lipopolysaccharide (LPS), hydrogen peroxide (H2O2), tumor necrosis factor-α (TNF-α), and polyinosinic–polycytidylic acid (Poly I:C). Further analyses were conducted using the Poly I:C model as a representative inflammation model. The protective effects of SST against inflammation and TJ barrier dysfunction were comparable to those of nuclear factor κB (NF-κB) inhibitors and were attributed to the inhibition of NF-κB signaling activation. The SST components isoliquiritigenin (ILQG) and glycyrrhizin (GL) suppressed inflammation, TJ barrier dysfunction, and NF-κB signaling activation, consistent with the effects of SST. These findings suggest that (1) activation of the NF-κB signaling pathway might contribute to both inflammatory responses and TJ barrier disruption, (2) SST could reduce these effects, potentially through the modification of NF-κB signaling, and (3) ILQG and GL may contribute, in part, to these activities. Overall, this study suggests that SST may be a Kampo medicine that possesses both anti-inflammatory and TJ barrier-protecting properties for the treatment of respiratory diseases.
Abstract
Shoseiryuto (SST) is a Kampo medicine widely used to treat respiratory diseases. We previously showed that SST attenuates lipopolysaccharide (LPS)-induced tight junction (TJ) barrier disruption in human bronchial epithelial (16HBE) cells. However, the underlying mechanisms remain unclear. This study aimed to clarify the mechanisms underlying the protective effects of SST. SST attenuated inflammatory responses (increased IL-6 protein and mRNA levels) and TJ disruption (decreased transepithelial electrical resistance, increased sodium fluorescein permeability, and decreased occludin mRNA and protein expression) induced by LPS, hydrogen peroxide (H2O2), tumor necrosis factor-α (TNF-α), and polyinosinic–polycytidylic acid (Poly I:C). Further analyses using the Poly I:C model confirmed that the effects of SST were comparable to those of the nuclear factor κB (NF-κB) inhibitors SC-514 and BAY11-7085. SST reduced the activation of NF-κB signaling (increased phosphorylation of NF-κB and IκB), similar to BAY11-7085. SST components, isoliquiritigenin (ILQG) and glycyrrhizin (GL), also attenuated inflammation, barrier dysfunction, and NF-κB signaling activity. These findings suggest that (1) activation of the NF-κB signaling pathway might be associated with both inflammatory responses and TJ barrier disruption; (2) SST could reduce these effects, potentially through modulation of NF-κB signaling; and (3) ILQG and GL may contribute, in part, to these activities. Overall, this study provides the first evidence suggesting that SST may exert anti-inflammatory and epithelial barrier-protective effects, possibly via the suppression of the NF-κB signaling pathway.
