Theaflavin 3,3'-digallate (TF-3; ZP10) is a potent inhibitor of Zika virus (ZIKV) protease with an IC50 value of 2.3μM[1]. Theaflavin 3,3'-digallate is a polyphenolic compound with multiple biological activities such as anti-inflammatory, antioxidant, anti-tumor, and anti-angiogenic[2, 3].
In vitro, Theaflavin 3,3'-digallate (0-25μM) treated OVCAR-3 cells for 24h dose-dependently inhibited cell viability, ranging from 100% to 48.3%, and downregulated vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) to reduce angiogenesis[4]. Theaflavin 3,3'-digallate (0-50µM) treated platinum-resistant human ovarian cancer cell line A2780/CP70 cells for 24h, inhibited cell viability in a dose-dependent manner, ranging from 100% to 11.38%, induced G2 cell cycle arrest, reduced Akt phosphorylation without affecting total Akt protein expression, and reduced mouse double minute 2 (MDM2) protein levels[5].
In vivo, Theaflavin 3,3'-digallate (20, 40mg/kg) was intranasally administered to treat LPS-induced lung injury mice, inhibited the concentrations of TNF-α and IL-6 in serum in a dose-dependent manner, significantly reduced the ratio of lung wet weight to dry weight, and improved pulmonary edema in mice[6]. Theaflavin 3,3'-digallate (5mg/kg) was orally administered to mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis, which inhibited the nuclear localization of NF-κB and the increase in cytoplasmic IκB kinase (IKK) activity, and retained NF-κB inhibitory protein (IκBα) in colon tissue, thereby improving colitis in mice[7].
References:
[1] Cui X, Zhou R, Huang C, et al. Identification of theaflavin-3, 3’-digallate as a novel Zika virus protease inhibitor[J]. Frontiers in pharmacology, 2020, 11: 514313.
[2] Ko H J, Lo C Y, Wang B J, et al. 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[J]. Journal of Functional Foods, 2015, 17: 271-282.
[3] Seo E J, Wu C F, Ali Z, et al. Both phenolic and non-phenolic green tea fractions inhibit migration of cancer cells[J]. Frontiers in Pharmacology, 2016, 7: 398.
[4] Gao Y, Rankin G O, Tu Y, et al. Theaflavin-3, 3'-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and Notch-1 pathways, not via MAPK pathways[J]. International journal of oncology, 2016, 48(1): 281-292.
[5] Tu Y, Kim E, Gao Y, et al. Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells[J]. International journal of oncology, 2016, 48(6): 2657-2665.
[6] Wu Y, Jin F, Wang Y, et al. In vitro and in vivo anti-inflammatory effects of theaflavin-3, 3′-digallate on lipopolysaccharide-induced inflammation[J]. European Journal of Pharmacology, 2017, 794: 52-60.
[7] Ukil A, Maity S, Das P K. Protection from experimental colitis by theaflavin‐3, 3′‐digallate correlates with inhibition of IKK and NF‐κB activation[J]. British journal of pharmacology, 2006, 149(1): 121-131.
Theaflavin 3,3'-digallate（茶黄素-3,3'-双没食子酸; TF-3; ZP10）是一种有效的寨卡病毒（ZIKV）蛋白酶抑制剂，IC50值为2.3μM[1]。Theaflavin 3,3'-digallate是一种多酚类化合物，具有抗炎、抗氧化、抗肿瘤、抗血管生成等多种生物活性[2, 3]。
在体外，Theaflavin 3,3'-digallate（0-25µM）处理OVCAR-3细胞24h，剂量依赖性地抑制了细胞活力，抑制范围为100%至48.3%，下调了血管内皮生长因子（VEGF）和缺氧诱导因子1-α（HIF-1α）来减少血管生成[4]。Theaflavin 3,3'-digallate（0-50µM）处理铂抗性人卵巢癌细胞系A2780/CP70细胞24h，剂量依赖性地抑制了细胞活力，抑制范围为100%至11.38%，诱导了G2细胞周期停滞，降低Akt的磷酸化而不影响总Akt蛋白表达，降低鼠双微体2（MDM2）的蛋白水平[5]。
在体内，Theaflavin 3,3'-digallate（20、40mg/kg）通过鼻腔给药治疗LPS诱导的肺损伤小鼠，剂量依赖性方式抑制了血清中TNF-α和IL-6的浓度, 显著降低了肺湿重与干重之比，改善了小鼠肺水肿[6]。Theaflavin 3,3'-digallate（5mg/kg）通过口服治疗三硝基苯磺酸（TNBS）诱导的结肠炎的小鼠，抑制了NF-κB核定位、胞质IκB激酶（IKK）活性的增加，并在结肠组织中保留了NF-κB抑制蛋白（IκBα），改善了小鼠结肠炎[7]。