Deciphering the catalytic and pharmacological mechanisms of Coptis chinensis herbzymes to renovate intestinal microenvironment for colitis alleviation

Abstract Leveraging the traditional medicinal properties of the intestinal meridian herb Coptis chinensis (CC), CC carbon dots nanozymes (CCzymes) are developed for the treatment of ulcerative colitis (UC). The CC precursors provide functional fragments and oxygenated functional groups that endow CCzymes with pharmacological activity and potent scavenging ability of free radicals. Targeting UC, CCzymes can effectively promote the restoration of the intestinal microenvironment. CCzymes inhibit the secretion of pro‐inflammatory cytokines downstream of the MAPK and PI3K‐Akt signaling pathways by suppressing the expression of the gene encoding the receptor tyrosine kinase protein (Kit). At the same time, CCzymes inhibited the HIF‐1 and JAK‐STAT signaling pathways, which in turn inhibited M1‐type polarization of macrophages. In addition, CCzymes selectively inhibit pathogenic bacteria while promoting the growth of beneficial microbiota, thus achieving a balanced gut microbiota. Importantly, CCzymes also increased the levels of bile acids and indole derivatives, thereby contributing to the restoration of intestinal barrier integrity. This study provides a novel approach to harness the therapeutic potential of herbal nano‐enzymes, offering a powerful strategy for treating inflammatory diseases through targeted antioxidant therapy. Targeting UC, CCzymes can be effective in treating inflammatory diseases.