Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review)

Theaflavin‑3,3'‑digallate (TF3) is a major galloylated theaflavin generated during black tea fermentation and has been reported to exhibit a range of biological activities, including antioxidant, anti‑inflammatory, antimicrobial, antiviral and anticancer properties. However, due to its chemical instability, low bioavailability and complex biotransformation in the gastrointestinal tract, the in vivo effects of TF3 remain inconsistent across studies. The present review summarizes the structural characteristics, degradation behavior and gut microbiota‑mediated metabolic processes of TF3, and discusses its pharmacological actions at multiple targets, particularly its regulatory effects on signaling pathways such as the NF‑κB, MAPK and nuclear factor erythroid 2‑related factor 2 signaling pathways. Specifically, the present review addresses the issue of whether the biological effects of TF3 are predominantly driven by the parent compound per se or are mediated by its metabolites (such as theaflavin, gallic acid). Finally, key directions for future research are proposed, including comparative evaluations of the bioactivities of TF3 and its metabolites, and the integration of pharmacokinetic‑pharmacodynamic investigations to facilitate the development of TF3‑based therapeutic agents.