Gallotannin (Tannic acid) is a natural polyphenolic compound that has been found in various plants and has antioxidant, anti-inflammatory, anti-angiogenic, antiviral and anti-tumor biological activities[1]. Gallotannin inhibits the activity of DNA polymerase α, β and κ with IC50 values of 13, 130 and 30nM, respectively [2]. Gallotannin is a novel human Ether-à-go-go-Related Gene (hERG) blocker with an IC50 value of 3.4 μM[3]. Gallotannin is a potent inhibitor of the CXCL12/CXCR4 signaling pathway[4]. Gallotannin is a direct inhibitor of poly (ADP-ribose) glycohydrolase (PARG) [5]. Gallotannin is an inhibitor of NOS3 (eNOS) and a weak inhibitor of NOS2 (iNOS) and NOS1(nNOS)[6]. Gallotannin can induce cyclooxygenase-2 (Cox-2) expression and is a free radical scavenger[7].
In vitro, Gallotannin (0-100 μM) treatment of HEK293 cells rapidly inhibited intracellular hERG channels with an IC50 of 3.4±0.8 μM, and at a concentration of 10 μM, the activation curve of hERG current was significantly shifted to a more positive potential[3]. Gallotannin (100μM) treatment of AML12 cells for 1 h significantly inhibited the intracellular NAD+ level after nicotinamide riboside (NRH) treatment [8].
In vivo, Gallotannin (25 mg/kg) was treated with intraperitoneal injection of colon cancer xenograft mice for 4 weeks, significantly inhibiting tumor growth, reducing the proliferation index (Ki67), and reducing the mRNA expression levels of IL-6, TNF-α and IL-1α and angiogenesis (VEGFA) proteins [9].
References:
[1] Fraga-Corral M, Otero P, Cassani L, et al. Traditional applications of tannin rich extracts supported by scientific data: Chemical composition, bioavailability and bioaccessibility[J]. Foods, 2021, 10(2): 251.
[2] Savelyev N, Baykuzina P, Dokudovskaya S, et al. Comprehensive analysis of telomerase inhibition by gallotannin[J]. Oncotarget, 2018, 9(27): 18712.
[3] Chu X, Guo Y, Xu B, et al. Effects of tannic acid, green tea and red wine on hERG channels expressed in HEK293 cells[J]. PLoS One, 2015, 10(12): e0143797.
[4] Chen X, Beutler J A, McCloud T G, et al. Tannic acid is an inhibitor of CXCL12 (SDF-1α)/CXCR4 with antiangiogenic activity[J]. Clinical Cancer Research, 2003, 9(8): 3115-3123.
[5] Ying W, Swanson R A. The poly (ADP-ribose) glycohydrolase inhibitor gallotannin blocks oxidative astrocyte death[J]. Neuroreport, 2000, 11(7): 1385-1388.
[6] Olmos A, Giner R M, Máñez S. Drugs modulating the biological effects of peroxynitrite and related nitrogen species[J]. Medicinal Research Reviews, 2007, 27(1): 1-64.
[7] Go J, Kim J E, Koh E K, et al. Hepatoprotective effect of gallotannin-enriched extract isolated from gall on hydrogen peroxide-induced cytotoxicity in HepG2 cells[J]. Pharmacognosy Magazine, 2017, 13(Suppl 2): S294.
[8] Giroud-Gerbetant J, Joffraud M, Giner M P, et al. A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor[J]. Molecular metabolism, 2019, 30: 192-202.
[9] Al-Halabi R, Bou Chedid M, Abou Merhi R, et al. Gallotannin inhibits NFĸB signaling and growth of human colon cancer xenografts[J]. Cancer biology & therapy, 2011, 12(1): 59-68.
单宁酸（Gallotannin；Tannic acid）是一种天然多酚化合物，已在各种植物中发现，具有抗氧化、抗炎、抗血管生成、抗病毒和抗肿瘤等生物活性[1]。Gallotannin抑制DNA聚合酶α、β和κ的活性，IC50值分别为13、130和30nM[2]。Gallotannin是一种新型的人延迟整流钾离子通道（hERG）阻塞剂，其IC50 值为3.4 μM[3]。Gallotannin是一种有效的 CXCL12/CXCR4 信号通路抑制剂[4]。Gallotannin是聚（ADP-核糖）糖水解酶（PARG）的直接抑制剂[5]。Gallotannin 是NOS3（eNOS）的抑制剂以及NOS2（iNOS）和NOS1（nNOS）的弱抑制剂[6]。Gallotannin可诱导环氧合酶-2（Cox-2）表达，是一种自由基清除剂[7]。
在体外，Gallotannin（0-100μM）处理HEK293细胞，迅速抑制了细胞内hERG通道， IC50为3.4±0.8μM，10μM浓度下明显将hERG电流的活化曲线转移到更正的电位[3]。Gallotannin（100μM）处理AML12细胞1h，显著抑制了烟酰胺核苷（NRH）治疗后的细胞内NAD+水平[8]。
在体内，Gallotannin（25mg/kg）通过腹腔注射治疗结肠癌异种移植小鼠4周，显著抑制了肿瘤生长，降低了增殖指数（Ki67），降低了 IL-6、TNF-α 和 IL-1α 和血管生成（VEGFA）蛋白的mRNA表达水平[9]。