Recent Advances in Biosynthesis and Bioactivity of Plant Caffeoylquinic Acids

Caffeoylquinic acids (CQAs), a class of phenolic acid metabolites widely distributed in plants, encompass 15 positional isomers from mono- to tetra-esters, with 5-O-caffeoylquinic acid (5-CQA) as the predominant form. The biosynthesis of 5-CQA from phenylalanine proceeds through five primary pathways, which are finely regulated by environmental, hormonal, and transcription factors from families such as MYB, WRKY, and bHLH. These regulators control 5-CQA synthesis by binding specifically to the promoter regions of key structural genes, including PAL, 4CL and HCT/HQT. Subsequently, 5-CQA serves as a central precursor for the biosynthesis of other CQAs. In terms of bioactivity, CQAs possess remarkable pharmacological activities, encompassing antioxidant, antimicrobial, anti-diabetic, anti-inflammatory and anti-tumor properties. For instance, anti-inflammatory effects are demonstrated by the ability of 5-CQA to reduce key pro-inflammatory cytokines (e.g., TNF-α and IL-1β) and downregulate the TLR4/NF-κB pathway. The synergistic action of 5-CQA with ultraviolet-A reduced succinate-coenzyme Q reductase activity by approximately 72%, highlighting its potential to disrupt bacterial metabolism and combat antibiotic resistance. Furthermore, 3,4,5-triCQA exhibits potent anti-influenza virus activity, potentially through a mechanism distinct from existing neuraminidase inhibitors. Beyond medicine, CQAs show promise in light industry. They serve as antibiotic alternatives in livestock feed to enhance gut health, extend food shelf life through their antioxidant activity, and function as active ingredients in UV-protective skincare formulations. CQAs also enhance plant stress tolerance to cold, arsenic, and pests by mechanisms such as scavenging reactive oxygen species and inhibiting pest mobility. While this review consolidates progress in the biosynthesis and bioactivity of CQAs specifically with caffeoyl substituents, future efforts should leverage modern biotechnological tools and interdisciplinary approaches to bridge critical knowledge gaps in their biosynthesis, transport, and clinical translation.