1,2,3,4,6-pentagalloylglucose(Pentagalloylglucose;PGG) is a polyphenolic compound with powerful antioxidant, anti-inflammatory, antibacterial, antiviral, and antitumor effects [1-2]. 1,2,3,4,6-pentagalloylglucose is a potent and cellular active inhibitor of the PALB2-BRCA2 protein-protein interaction (PPI). 1,2,3,4,6-pentagalloylglucose binds PALB2 at the BRCA2 binding site and significantly suppresses HR repair by inhibiting BRCA2 recruitment to the DNA damage site.
1,2,3,4,6-pentagalloylglucose (5, 10, or 20µM; 1h) blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs) in vitro[3]. 1,2,3,4,6-pentagalloylglucose (10μM; 4h) suppresses HR-mediated DNA repair in U2OS cells[4]. 1,2,3,4,6-pentagalloylglucose (0-60µM; 24h) dose-dependently inhibited the proliferation of CNE1 and CNE2 cells. PGG regulated the cell cycle by altering p53, cyclin D1, CDK2, and cyclin E1 protein levels[5].
1,2,3,4,6-pentagalloylglucose (20 and 40mg/kg; i.p) treatment significantly reduced the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels in mice with AILI, and protect Acetaminophen-induced acute liver injury in mice[3]. Pre-treatment with 1,2,3,4,6-pentagalloylglucose (5 and 10mg/kg; i.p; 7days) showed significant, and dose dependent protection against I/R-induced brain injury by alleviating all the behavioral, neurological, morphological, and histological changes induced by I/R. The protective effect of 1,2,3,4,6-pentagalloylglucose is thought to be due to its powerful antioxidant properties[6].
References:
[1]. Ashibe S, Ikeuchi K, et,al. Non-Enzymatic Oxidation of a Pentagalloylglucose Analogue into Members of the Ellagitannin Family. Angew Chem Int Ed Engl. 2017 Nov 27;56(48):15402-15406. doi: 10.1002/anie.201708703. Epub 2017 Nov 2. PMID: 29024258.
[2]. Mikolajczyk TP, Nosalski R, et,al. 1,2,3,4,6-Penta-O-galloyl-β-d-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension. Br J Pharmacol. 2019 Jun;176(12):1951-1965. doi: 10.1111/bph.14583. Epub 2019 Mar 14. PMID: 30658013; PMCID: PMC6534792.
[3]. Zheng C, Chen Y, et,al. Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway. Mol Med. 2024 Sep 27;30(1):160. doi: 10.1186/s10020-024-00924-6. PMID: 39333876; PMCID: PMC11428449.
[4]. Zeng J, Han J, et,al. Pentagalloylglucose disrupts the PALB2-BRCA2 interaction and potentiates tumor sensitivity to PARP inhibitor and radiotherapy. Cancer Lett. 2022 Oct 10;546:215851. doi: 10.1016/j.canlet.2022.215851. Epub 2022 Aug 1. PMID: 35926819.
[5]. Fan CW, Tang J, et,al. Pentagalloylglucose suppresses the growth and migration of human nasopharyngeal cancer cells via the GSK3β/β-catenin pathway in vitro and in vivo. Phytomedicine. 2022 Jul 20;102:154192. doi: 10.1016/j.phymed.2022.154192. Epub 2022 May 21. PMID: 35636179.
[6]. Viswanatha GL, Shylaja H, et,al. Alleviation of transient global ischemia/reperfusion-induced brain injury in rats with 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose isolated from Mangifera indica. Eur J Pharmacol. 2013 Nov 15;720(1-3):286-93. doi: 10.1016/j.ejphar.2013.10.016. Epub 2013 Oct 22. PMID: 24157980.
1,2,3,4,6-pentagalloylglucose(五没食子酰葡萄糖; Pentagalloylglucose; PGG)是一种多酚化合物，具有抗氧化、抗炎、抗菌、抗病毒和抗肿瘤效果[1-2]。1,2,3,4,6-pentagalloylglucose作为强效的细胞活性抑制剂，能够干扰PALB2-BRCA2蛋白-蛋白相互作用（PPI）。 1,2,3,4,6-pentagalloylglucose通过结合PALB2的BRCA2结合位点，显著抑制BRCA2向DNA损伤部位的募集，从而抑制同源重组（HR）修复。
1,2,3,4,6-pentagalloylglucose(5, 10, or 20µM; 1h)可以阻断巨噬细胞(BMDMs)中的cGAS-STING通路激活[3]。 1,2,3,4,6-pentagalloylglucose(10μM; 4h) 在U2OS细胞中抑制了HR介导的DNA修复[4]。1,2,3,4,6-pentagalloylglucose(0-60µM; 24h)以剂量依赖性方式抑制了CNE1和CNE2细胞的增殖，并通过调节p53、Cyclin D1、CDK2和Cyclin E1蛋白水平调控细胞周期[5]。
1,2,3,4,6-pentagalloylglucose(20 and 40mg/kg; i.p)显著降低了AILI(对乙酰氨基酚诱导的急性肝损伤)小鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)和碱性磷酸酶(ALP)水平，保护小鼠免受急性肝损伤[3]。1,2,3,4,6-pentagalloylglucose预处理 (5 and 10mg/kg; i.p; 7days)能以剂量依赖性方式显著保护I/R(缺血再灌注)诱导的脑损伤，通过缓解I/R诱导的行为学、神经学、形态学和组织学改变发挥作用。这种保护作用可能归因于其强大的抗氧化特性[6]。