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 <i>in vivo</i> 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 <i>per se</i> 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.

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Publication Details

Journal
Molecular Medicine Reports
Published
2026-03-04
DOI
https://doi.org/10.3892/mmr.2026.13837
Primary Topic
Nuts composition and effects
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Siwei Zhang, Teng Ma, Junhong Guan, Miaomiao Xiao et al.
Molecular Medicine Reports
Nuts composition and effects
article

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

Siwei Zhang, Teng Ma, Junhong Guan, Miaomiao Xiao, Zhijian Ma
article en

Abstract

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 <i>in vivo</i> 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 <i>per se</i> 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.

Molecular Medicine ReportsVol. 33(5)
Sun Yat-sen University (CN), Lanzhou University Second Hospital (CN), Weinan Central Hospital (CN), Sun Yat-sen University Cancer Center (CN), Lanzhou University (CN)
Lanzhou University, National Natural Science Foundation of China, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities
Zero hunger
Openalex Percentile: Top 34%
Nuts composition and effects
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