Theaflavin 3,3'-digallate, a major polyphenol found in black tea, is an inducer of oxidative stress which has anti-inflammatory and cancer chemopreventive actions, it reduces tumor angiogenesis by downregulating HIF-1αand VEGF.

Theaflavin 3,3'-digallate (TF-3) significantly reduces viral RNA levels and the expression of NS3 and U87 MG proteins in a dose-dependent manner when used at concentrations of 6.25, 12.5, and 25 μM for 24 hours [1]. Theaflavin 3,3'-digallate demonstrates potent antiviral activity against ZIKV replication in Vero E6 cells (EC50: 7.65 μM), while showing minimal cytotoxicity at doses up to 40 μM. Theaflavin 3,3'-digallate interferes with the post-entry phases of the ZIKV replication cycle, disrupting gene transcription and translation [1]. Theaflavin 3,3'-digallate leads to a rapid and sustained reduction in phospho-ERK1/2 and phospho-MEK1/2 protein levels and inhibits HCT116 cell growth (IC50: 17.26 μM) [2].

In vivo, Theaflavin 3,3'-digallatereduces serum levels of TNF-α, IL-1β, and IL-6 and decreases pulmonary edema, pulmonary congestion, and thickening of the alveolar wall in a mouse model of LPS-induced acute lung injury. It also inhibits osteoclast formation, polarization, and osteoclastic bone resorption in vitro and reduces titanium particle-induced bone erosion and the number of mature osteoclasts in mice in a dose-dependent manner [3].