Effects of Chlorogenic Acid on Intestinal Barrier Dysfunction and Intestinal Flora Induced by Cisplatin in Mice

OBJECTIVE To investigate the effect of chlorogenic acid on intestinal barrier dysfunction and intestinal flora disorder induced by cisplatin in mice.

METHODS  Twenty-eight 6-week-old C57BL/6J mice were randomly divided into control group, cisplatin group, low dose of chlorogenic acid group and high dose of chlorogenic acid group. The levels of IL-1β, IL-6 and TNF-α mRNA in colon tissues of each group were detected by RT-qPCR. The expression of Occludin protein was determined by Western blotting and histopathological observation was carried by HE staining. The composition of intestinal flora in cecum contents was determined by 16s rDNA high-throughput sequencing.

RESULTS  Compared with control group, the mRNA levels of IL-1β, IL-6 and TNF-α in colon tissue of cisplatin group were significantly increased(P<0.01), and the expression of Occludin protein in colon tissue was decreased(P<0.01). Chlorogenic acid intervention could significantly reduce the mRNA level of inflammatory factors(P<0.01), increase the expression of Occludin protein(P<0.01), and improve the damage of colonic mucosal barrier and inflammatory injury induced by cisplatin. 16s rDNA high-throughput sequencing results showed that Bacteroidota and firmicutes were dominant in the control group at the phylum level. Compared with the control group, Firmicutes and Verrucomicrobia were significantly more dominant in cisplatin group(P<0.01). In addition, compared with the control group, the ratio of Firmicutes to Bacteroidota was increased in cisplatin group(P<0.01), while the ratio was decreased by low and high doses of chlorogenic acid(P<0.05 or P<0.01). At the genus level, compared with the control group, the relative abundance of Bacteroides, Cillobacterium, Ackermania and Lachnospiraceae_NK4A136 decreased(P<0.05 or P<0.01), and the relative abundance of Citrobacter increased(P<0.01) in cisplatin group. The low dose of chlorogenic acid could partially restore the relative abundances of Bacteroides and Cillobacterium(P<0.05 or P<0.01), inhibit the relative abundances of Citrobacter(P<0.01), and increase the relative abundances of Akermania and Lachnospiraceae_NK4A136(P<0.01).

CONCLUSION Chlorogenic acid can improve intestinal mucosal barrier destruction induced by cisplatin, reduce intestinal inflammation, and partially restore intestinal flora disturbance caused by cisplatin.