Effect of Long-term Administration of Cinnamic Acid-Berberine Cocrystal on Intestinal Barrier and Intestinal Flora in Mice
Objective To investigate the effect of long-term oral administration of cinnamic acid-berberine cocrystal (CBBR) versus berberine (BBR)on intestinal barrier and intestinal flora in mice.Methods Mice were randomly divided into control group (CTL group),BBR group (70 mg/kg),and CBBR group (100 mg/kg),and the drugs were given by gavage for 9 con-secutive weeks.Body weight of the mice was measured every week,and after 9 weeks,the mice were anesthetized and sacri-ficed to measure the length of colon.HE staining was used to observe the histopathological changes of the colon;AB-PAS staining was used to measure the thickness of the colonic mucus layer and the number of goblet cells;immunofluorescent stai-ning and Western blot were used to measure the expression levels of the tight junction proteins zonula occluden-1 (ZO-1 ),Clau-din-1,and Occludin in the colon;16S rDNA sequencing was used to analyze the change in intestinal flora.Results Compared with the CTL group,the BBR group and the CBBR group had a significant reduction in body weight (P<0.05). There was no significant difference in the length of the colon between the groups (P>0.05). HE and AB-PAS staining showed no obvious changes in colon structure,goblet cells,and mucus layer.Immunofluorescent staining and Western blot showed no sig-nificant differences in the expression of the tight junction proteins ZO-1,Claudin-1,and Occludin between the administration groups and the control group (P>0.05). The alpha-diversity analysis and the principal coordinate analysis showed alterations in the abun-dance and structural composition of intestinal flora after the administration of BBR and CBBR,with significant increases in the abun-dance of Alistipes,Odoribacter,Roseburia,norank-f-Ruminococcaceae,and Eubacterium xylanophilum group (P<0.05),and com-pared with the BBR group,the CBBR group had significant increases in the abundance of Odoribacter and Eubacterium xylanophilum group (P<0.05)and a significant reduction in the abundance of Bacteroides (P<0.05). Conclusion The long-term administration of CBBR and BBR can significantly reduce the body weight of mice and regulate the composition of intestinal flora and the abundance of certain bacterial genera,with no significant effect on intestinal barrier in mice.
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