Ellagic acid is a naturally occurring polyphenolic dilactone widely found in various fruits and nuts, which effectively inhibits the activity of CK2 (IC50=40nM) and SHP2 (Ki=20nM)[1-2]. Ellagic acid demonstrates potential research value in multiple disease models, including anti-cancer, anti-inflammatory, antioxidant, liver protection, and neuroprotection[3-4].
In vitro, treatment of esophageal squamous cell carcinoma (ESCC) cells (EC9706 and KYSE450) with Ellagic acid (0-40μM) for 24-72 hours, Ellagic acid significantly inhibited cell survival and induced apoptosis in a concentration-dependent manner. Ellagic acid markedly promoted PARP cleavage, downregulated the expression of anti-apoptotic proteins Bcl-2 and Mcl-1, and upregulated SHP-1 expression to inhibit STAT3 signaling pathway activity[5]. Treatment of renal cell carcinoma (RCC) cells (786-O and ACHN) with Ellagic acid (50μM) for 24 hours, Ellagic acid significantly inhibited cell migration and invasion capabilities. Ellagic acid downregulated the expression of transcription factor RUNX2, thereby reducing the mRNA and protein levels of matrix metalloproteinase MMP1, thus inhibiting the metastatic potential of RCC cells[6].
In vivo, pretreatment of C57BL/6 mice with Ellagic acid (60mg/kg/day) via oral gavage for 14 consecutive days (followed by establishment of a hepatic ischemia-reperfusion model), Ellagic acid significantly inhibited caspase-1-GSDMD pathway-mediated pyroptosis, reduced serum ALT, AST, and LDH levels, decreased the expression of IL-1β and IL-18 in liver tissue, and alleviated pathological damage such as hepatic congestion and necrosis[7]. Treatment of STZ-induced diabetic ICR mice with Ellagic acid (100mg/kg/day) via oral gavage for 8 consecutive weeks, Ellagic acid significantly improved gastrocnemius muscle fiber cross-sectional area and grip strength, reduced serum CK, LDH, TC, TG, and LDL levels while increasing HDL, and alleviated muscle atrophy by inhibiting Atrogin-1/MuRF-1-mediated protein degradation, enhancing NRF-1/PGC-1α mitochondrial function, reducing CHOP/GRP-78 endoplasmic reticulum stress, and regulating the BAX/Bcl-2 apoptosis pathway[8].
References:
[1] Yoganathan S, Alagaratnam A, Acharekar N, et al. Ellagic Acid and Schisandrins: Natural Biaryl Polyphenols with Therapeutic Potential to Overcome Multidrug Resistance in Cancer. Cells. 2021 Feb 21;10(2):458.
[2] Zeb A. Ellagic acid in suppressing in vivo and in vitro oxidative stresses. Mol Cell Biochem. 2018 Nov;448(1-2):27-41.
[3] Zhu H, Yan Y, Jiang Y, et al. Ellagic Acid and Its Anti-Aging Effects on Central Nervous System. Int J Mol Sci. 2022 Sep 19;23(18):10937.
[4] Shakeri A, Zirak MR, Sahebkar A. Ellagic Acid: A Logical Lead for Drug Development? Curr Pharm Des. 2018;24(2):106-122.
[5] Xu YY, Wang WW, Huang J, et al. Ellagic acid induces esophageal squamous cell carcinoma cell apoptosis by modulating SHP-1/STAT3 signaling. Kaohsiung J Med Sci. 2020 Sep;36(9):699-704.
[6] Huang PY, Hung TW, Hsieh YH, et al. Ellagic acid suppresses the human renal carcinoma cell migration and invasion by targeting the RUNX2/MMP1 expression. Int J Med Sci. 2025 Apr 22;22(10):2308-2317.
[7] Wang H, Miao F, Ning D, et al. Ellagic acid Alleviates hepatic ischemia-reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway. BMC Vet Res. 2022 Jun 18;18(1):229.
[8] Liu X, Cheng C, Deng B, et al. Ellagic acid attenuates muscle atrophy in STZ-induced diabetic mice. Physiol Res. 2022 Nov 28;71(5):631-641.
Ellagic acid是一种天然存在的多酚二内酯，广泛存在于多种水果和坚果中，可有效抑制CK2（IC50=40nM）和SHP2（Ki=20nM）的活性[1-2]。Ellagic acid对多种疾病模型展现出潜在的研究价值，包括抗癌、抗炎、抗氧化、肝保护及神经保护等[3-4]。
在体外，Ellagic acid（0-40μM）处理食管鳞状细胞癌（ESCC）细胞（EC9706和KYSE450）24-72小时，Ellagic acid以浓度依赖性方式显著抑制细胞存活并诱导细胞凋亡，Ellagic acid显著促进PARP裂解和下调凋亡蛋白Bcl-2、Mcl-1表达，上调SHP-1表达抑制STAT3信号通路活性[5]。Ellagic acid（50μM）处理肾细胞癌（RCC）细胞（786-O和ACHN）24小时，Ellagic acid显著抑制细胞迁移和侵袭能力，Ellagic acid通过下调转录因子RUNX2表达，进而降低基质金属蛋白酶MMP1的mRNA和蛋白水平，从而抑制RCC细胞的转移潜能[6]。
在体内，Ellagic acid（60mg/kg/天）经口灌胃预处理C57BL/6小鼠（连续14天，随后建立肝脏缺血再灌注模型），Ellagic acid显著抑制Caspase-1-GSDMD通路介导的细胞焦亡，降低血清ALT、AST、LDH水平及肝组织中IL-1β、IL-18的表达，并减轻肝组织充血和坏死病理损伤[7]。Ellagic acid（100mg/kg/天）经口灌胃处理STZ诱导的糖尿病ICR小鼠（连续8周），Ellagic acid显著改善腓肠肌纤维横截面积和握力，降低血清CK、LDH、TC、TG、LDL水平并提升HDL，同时通过抑制Atrogin-1/MuRF-1介导的蛋白降解、增强NRF-1/PGC-1α线粒体功能、减少CHOP/GRP-78内质网应激及调节BAX/Bcl-2凋亡通路缓解肌肉萎缩[8]。