Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. EKL are composed of polysaccharides (60%), polyphenols (26%), and proteins (11%). EKL present decent potent •OH and DPPH scavenging abilities and Fe²⁺ chelating ability. They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves.

Summary: Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world‐wide. However, the key UDP‐dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two‐step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site‐directed mutagenesis revealed that Gln‐352 may be important for the initial step of glucuronosylation, and His‐22, Trp‐370, Glu‐375 and Gln‐392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two‐step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin.