Journal of ethnopharmacology · 2026
Xue-Jie-San alleviates Crohn's disease through suppressing endothelial cell pyroptosis via the TLR4/NF-κB/NLRP3 pathway.
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Gao Ying, Zhu Yi-Qian, Liu Ke-Hua, Wu Dan, Wang Zhuo, Zheng Hong-Yan, Yang Xiao, Wen Ke, Sun Xue-Liang
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbs with the effects of promoting blood circulation and removing stasis play a vital role in CD treatment. However, research on the mechanisms by which they work is rare. Xue-Jie-San (XJS) has exhibited excellent efficacy in ameliorating CD, but how it works is unclearly known.
AIM OF THE STUDY: The present study attempted to investigate whether XJS treating CD by restoring the function of the endothelial barrier through hindering NLRP3 inflammasome-mediated pyroptosis and uncover the potential mechanisms of blood-activating and stasis-removing herbs in treating CD.
MATERIALS AND METHODS: Lipopolysaccharide-stimulated human umbilical vein endothelial cells and CD rats were subjected to XJS treatment. Colitis symptoms were recorded and histopathological damages were evaluated by hematoxylin-eosin staining. The function of vascular endothelial barrier was assessed via detecting vascular permeability and the levels of tight junction proteins through immunofluorescence staining and Western blot. Enzyme-linked immunosorbent assay was utilized to detect IL-1β and IL-18 concentrations. Endothelial cell pyroptosis and NLRP3 inflammasome activation mediated by TLR4 signaling were detected through multiple detection techniques.
RESULTS: XJS treatment mitigated the symptoms and histopathological damages of CD-like colitis. The function of vascular endothelial barrier was restored by XJS via reducing its permeability and upregulating the expressions of tight junction protein ZO-1 and OCLN. Pyroptosis-mediated inflammatory response was suppressed as reflected by decreased IL-1β and IL-18 concentrations. Meanwhile, the upregulated expressions of pyroptosis executor GSDMD and GSDMD-N were also precluded by XJS. Additionally, XJS administration inhibited the NLRP3 inflammasome activation via diminishing the expressions of NLRP3, ASC, pro-caspase1 and caspase1. The canonical upstream TLR4/MyD88/NF-κB signal that transcriptionally regulated NLRP3 expression was also blocked. In vitro, overexpressing TLR4 abolished the effect of XJS on inhibiting endothelial cell pyroptosis.
CONCLUSION: XJS might ameliorate CD-like colitis via restoring vascular endothelial barrier through regulating TLR4 signaling and debilitating the activity of NLRP3 inflammasome. This work disclosed a potential mechanism of blood-activating and stasis-removing herbs in treating CD.
AIM OF THE STUDY: The present study attempted to investigate whether XJS treating CD by restoring the function of the endothelial barrier through hindering NLRP3 inflammasome-mediated pyroptosis and uncover the potential mechanisms of blood-activating and stasis-removing herbs in treating CD.
MATERIALS AND METHODS: Lipopolysaccharide-stimulated human umbilical vein endothelial cells and CD rats were subjected to XJS treatment. Colitis symptoms were recorded and histopathological damages were evaluated by hematoxylin-eosin staining. The function of vascular endothelial barrier was assessed via detecting vascular permeability and the levels of tight junction proteins through immunofluorescence staining and Western blot. Enzyme-linked immunosorbent assay was utilized to detect IL-1β and IL-18 concentrations. Endothelial cell pyroptosis and NLRP3 inflammasome activation mediated by TLR4 signaling were detected through multiple detection techniques.
RESULTS: XJS treatment mitigated the symptoms and histopathological damages of CD-like colitis. The function of vascular endothelial barrier was restored by XJS via reducing its permeability and upregulating the expressions of tight junction protein ZO-1 and OCLN. Pyroptosis-mediated inflammatory response was suppressed as reflected by decreased IL-1β and IL-18 concentrations. Meanwhile, the upregulated expressions of pyroptosis executor GSDMD and GSDMD-N were also precluded by XJS. Additionally, XJS administration inhibited the NLRP3 inflammasome activation via diminishing the expressions of NLRP3, ASC, pro-caspase1 and caspase1. The canonical upstream TLR4/MyD88/NF-κB signal that transcriptionally regulated NLRP3 expression was also blocked. In vitro, overexpressing TLR4 abolished the effect of XJS on inhibiting endothelial cell pyroptosis.
CONCLUSION: XJS might ameliorate CD-like colitis via restoring vascular endothelial barrier through regulating TLR4 signaling and debilitating the activity of NLRP3 inflammasome. This work disclosed a potential mechanism of blood-activating and stasis-removing herbs in treating CD.