| Description: |
Theaflavin-3,3'-digallate is a potent AMP-activated protein kinase (AMPK) activator with anti-adiposity activity in adipocytes, suggesting its potential application in functional foods and nutraceuticals for obesity management. Theaflavin-3,3'-digallate is also an inducer of oxidative stress and apoptosis, it has strong antioxidant and antiangiogenic activities, it inhibits the tube formation of endothelial cells via decreased both MMP-2 and MMP-9 activities in vitro. A combination microbicide containing theaflavin-3,3'-digallate and lactic acid can reduce herpes simplex virus (HSV) transmission. Theaflavin-3,3'-digallate may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IkappaB kinase (IKK) activity. Theaflavin-3,3'-digallate can repress osteoclastogenesis and prevent wear debris-induced osteolysis via suppression of ERK pathway, it is a promising candidate for the treatment of osteoclast-related osteolytic diseases, such as wear debris-induced peri-implant osteolysis (PIO). |
| In vitro: |
| Antimicrob Agents Chemother,2013 Aug,57(8): 3806-14. | | Theaflavin-3,3'-digallate and lactic acid combinations reduce herpes simplex virus infectivity.[Reference: WebLink] | The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining Theaflavine-3,3'-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract.
METHODS AND RESULTS:
Six clinical isolates of HSV-2 and two clinical isolates of HSV-1 were almost completely inactivated when Theaflavine-3,3'-digallate (100 μM) was present with LA over the pH range of 4.5 to 5.7, whereas four additional HSV-1 clinical isolates required Theaflavine-3,3'-digallate concentrations of 250 to 500 μM for comparable virus titer reduction. Theaflavine-3,3'-digallate reduced HSV-2 titers by 5 log10 in 20 to 30 min at pH 4.5, whereas HSV-1 required 60 min for comparable inactivation. Mixtures of Theaflavine-3,3'-digallate and LA stored at 37 °C for 1 month at pH 4.0 to 5.7 maintained antiviral activity. Semen, but not cervical vaginal fluid, decreased LA-dependent antiviral activity at pH 4.0, but adding Theaflavine-3,3'-digallate to the mixture reduced HSV titers by 4 to 5 log10.
CONCLUSIONS:
These results indicate that a combination microbicide containing Theaflavine-3,3'-digallate and LA could reduce HSV transmission. | | J.Funct.Foods,2015,17:271-82. | | Theaflavin-3,3′-digallate, a black tea polyphenol, stimulates lipolysis associated with the induction of mitochondrial uncoupling proteins and AMPK–FoxO3A–MnSOD pathway in 3T3-L1 adipocytes.[Reference: WebLink] | Phytochemicals have gained an immense interest in obesity management. Previously, we have shown that theaflavin-3,3′-digallate (Theaflavine-3,3'-digallate,TF3), a black tea polyphenol, prevents adipocyte-triggered metaflammation.
METHODS AND RESULTS:
Here, we demonstrate that TF3 attenuates triacylglycerol accumulation in adipocytes, concomitant with promoting gene expression profile that favors lipolysis and β-oxidation, and inducing energy dissipation-related genes, mitochondrial uncoupling protein-1 (UCP-1) and UCP-2. The gene expression is in line with the upregulation of peroxisome proliferator-activated receptor α (PPARα), a primary transactivator for the expression of lipolytic genes. TF3 activates AMP-activated protein kinase (AMPK), which is required for TF3 effects of PPARα upregulation, and the reversal of the inactivation of Forkhead-box-O 3A (FoxO3A) and insulin-induced suppression of manganese superoxide dismutase (MnSOD). The role of MnSOD in adipogenesis is verified in MnSOD-overexpressing adipocytes.
CONCLUSIONS:
Thus, our results demonstrate TF3 as a potent AMPK activator with anti-adiposity activity in adipocytes, suggesting its potential application in functional foods and nutraceuticals for obesity management. | | Showa Univ. J. Med. Sci.,2007,19(2):59-72. | | Theaflavin-3, 3'-digallate Inhibits Tube Formation in Cocultured Endothelial Cells with Fibroblasts[Reference: WebLink] | Several tea polyphenols, particularly those containing galloyl, have antitumor affects via strong antioxidant and antiangiogenic activi-ties. Theaflavin-3, 3'-digallate (Theaflavine-3,3'-digallate,TF3), a theaflavin derivative in black tea, has 2 galloyl groups. Matrix metalloproteinases (MMPs) are associated with extracellular matrix degradation, cellular migration, and angiogenesis, and (-) -epigallocatechin-3-gallate (EGCG) is an inhibitor of MMP activity and secretion; thus one of its major actions is the inhibition of angiogenesis. However, there are few studies of angiogenesis in theaflavin derivatives.
METHODS AND RESULTS:
We investigated the effects of TF3 on angiogenesis in vitro. Angiogenesis was assayed using cocultured human umbilical vein endothelial cells with fibroblasts. Cells were cultivated in various concentrations of TF3 and EGCG in the presence or absence of vascular endothelial growth factor-A. After 11 days, MMP-2 and MMP-9 activities and the pro-MMP-2 protein in the medium were measured by gelatin zymography and immunoassay, respectively. Tube formation was markedly inhibited by 100 μmol/L TF3 or EGCG. Even at 10 iumolIL, TF3 or EGCG inhibited tube formation. The MMP-2 and MMP-9 activities were inhibited and pro-MMP-2 protein concentrations were reduced by TF3 or EGCG in a concentration-dependent manner, regardless of the presence of vascular endothelial growth factor. The effect of TF3 was similar to that of EGCG, indicating that the tube formation of endothelial cells was suppressed via decreased both MMP-2 and MMP-9 activities in vitro.
CONCLUSIONS:
Our results demonstrate antiangiogenic activity of TF3 in vitro, and suggest possible anti-tumor effects of TF3. |
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| In vivo: |
| Acta Biomater. 2017 Jan 15;48:479-488. | | Theaflavin-3,3'-digallate represses osteoclastogenesis and prevents wear debris-induced osteolysis via suppression of ERK pathway.[Pubmed: 27838465 ] | Peri-implant osteolysis (PIO) and the following aseptic loosening is the leading cause of implant failure. Emerging evidence suggests that receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast formation and osteoclastic bone resorption are responsible for particle-stimulated PIO.
METHODS AND RESULTS:
Here, we explored the effect of theaflavin-3,3'-digallate (Theaflavine-3,3'-digallate,TF3) on titanium particle-induced osteolysis in vivo and in vitro. Twenty-eight male C57BL/6 mice were randomly separated into four groups: sham control (sham), titanium particles only (titanium), titanium particles with low TF3 concentration (low-TF3, 1mg/kg TF3), and titanium particles with high TF3 concentration (high-TF3, 10mg/kg TF3). Two weeks later, micro-computed tomography and histological analysis were performed. Bone-marrow-derived macrophages and RAW264.7 murine macrophages were applied to examine osteoclast formation and differentiation. TF3 significantly inhibited titanium particle-induced osteolysis and prevented bone destruction compared with titanium group. Interestingly, the number of mature osteoclasts reduced after treatment with TF3 in vivo, suggesting osteoclast formation might be inhibited by TF3. In vitro, TF3 suppressed osteoclast formation, polarization and osteoclastic bone resorption by specifically targeting the RANKL-induced ERK signal pathway.
CONCLUSIONS:
Collectively, these results suggest that TF3, a natural active compound derived from black tea, is a promising candidate for the treatment of osteoclast-related osteolytic diseases, such as wear debris-induced PIO. |
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