Herbs-partitioned moxibustion improves intestinal epithelial tight junctions by upregulating A20 expression in a mouse model of Crohn’s disease

• Published in: Biomedicine & pharmacotherapy Vol. 118; p. 109149
• Main Authors: Shi, Yin, Guo, Yajing, Zhou, Jing, Wu, Luyi, Chen, Liu, Sun, Yi, Li, Tao, Zhao, Jimeng, Bao, Chunhui, Wu, Huangan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-10-2019; Elsevier
• Subjects: A20; Animals; Artemisia - chemistry; Colon - metabolism; Colon - ultrastructure; Crohn Disease - metabolism; Crohn Disease - pathology; Crohn Disease - therapy; Crohn’s disease; Disease Models, Animal; Epithelial Cells - metabolism; Epithelial Cells - pathology; Herbs-partitioned moxibustion; Intestinal epithelial barrier; Intestinal Mucosa - metabolism; Intestinal Mucosa - ultrastructure; Mice, Inbred C57BL; Mice, Knockout; Moxibustion - methods; Permeability; Tight Junctions - metabolism; Tight Junctions - ultrastructure; TNF-α-NF-κB-MLCK pathway; Tumor Necrosis Factor alpha-Induced Protein 3 - genetics; Tumor Necrosis Factor alpha-Induced Protein 3 - metabolism; Up-Regulation; TNF-α-NF-κB-MLCK pathway; Intestinal epithelial barrier; Herbs-partitioned moxibustion; Crohn’s disease; A20
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109149

•Herbs-partitioned moxibustion improves intestinal epithelial morphology and epithelial cells structure in a mouse model of Crohn’s disease.•Herbs-partitioned moxibustion reduces FD4 level and improves the permeability of intestinal epithelial barrier by up regulating A20 expression.•Herbs-partitioned moxibustion downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway and increases the expression of tight junction proteins to repair damage of intestinal epithelial barrier by up regulating A20 expression in a mouse model of Crohn’s disease.
To investigate effects moxibustion exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Crohn's disease (CD).
C57BL/6 wild type (WT) and A20IEC−KO mice (48 each) were randomly divided into normal control (NC), model control (MC), mesalazine (MESA) and herbs-partitioned moxibustion (HPM) groups (12 mice per group). An experimental model of CD was established using 2, 4, 6 trinitrobenzene sulfonic acid. MESA and HPM mice were treated with MESA and HPM (at Tianshu (ST25) and Qihai (CV6)), respectively. In HPM group, moxa cones (0.5 cm in diameter and 0.3 cm in height) made of refined mugwort floss were placed on herbal cakes (medicinal formula dispensing [radix] Aconiti praeparata, [cortex] Cinnamomi, etc.) at Tianshu (ST25) and Qihai (CV6) and ignited. The moxa cones were ignited, and two moxa cones were used for each treatment once daily for 10 days. In MESA group, mice were fed MESA, which was prepared at a proportion of 1:0.0026, twice daily for 10 days.
Intestinal epithelial ultrastructure of WT HPM mice improved more than A20IEC−KO HPM mice compared to MC mice. WT HPM mice exhibited greater expression of A20 compared with MC mice (P < 0.01). TNF-α, NF-kB p65, MLCK, MLC, TRAF6 and RIP1 levels in A20IEC−KO and WT HPM mice were all decreased compared to MC mice (Pall < 0.01). NF-κB p65、MLCK and TRAF6 levels were increased in A20IEC−KO HPM mice as compared to WT HPM mice (Pall < 0.05). Intestinal epithelial levels of occludin, claudin-1, ZO-1 and F-actin increased in all HPM mice (Pall  < 0.01–0.05), while occludin, claudin-1, and ZO-1 levels were lower in A20 IEC-KO HPM mice (P < 0.05, P < 0.01, P < 0.01).
HPM downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway by upregulating expression of A20 in a mouse model of CD, thereby protecting intestinal epithelial tight junctions and repairing the damage CD causes to the intestinal epithelial barrier.