Isoliquiritigenin is a flavonoid compound derived from licorice. Isoliquiritigenin can activate the Nrf2 pathway to reduce oxidative stress and inflammation, while also inhibiting cancer progression by inducing apoptosis[1-2]. Isoliquiritigenin can also inhibit the activity of aldose reductase, neutralize free radicals to reduce oxidative damage, and is used in research related to the nervous system, antiviral, antitumor, and other areas[3-4].
In vitro, treatment of SK-MEL-28 human melanoma cells with Isoliquiritigenin (1–50µM) for 24–72 hours, Isoliquiritigenin significantly induced apoptosis and reduced cell viability by triggering the mitochondrial pathway (activating caspase-9/-7/-3, PARP cleavage, regulating the Bax/Bcl-2 balance, promoting cytochrome C release) and inhibiting the ROS-mediated p38/mTOR/STAT3 signaling pathway[5]. Treatment of NOZ and SGC-996 human gallbladder cancer cells with Isoliquiritigenin (20–100µM) for 24–72 hours, Isoliquiritigenin induced ferroptosis and inhibited cell proliferation by activating the p62-Keap1-Nrf2-HMOX1 axis, downregulating GPX4 expression, leading to iron accumulation, lipid peroxidation, and disruption of the GSH/GSSG ratio[6].
In vivo, intragastric administration of Isoliquiritigenin (5–20mg/kg/day) to ICR mice with cerebral ischemia-reperfusion injury (pretreated for 7 days, assessed 24 hours post-surgery), Isoliquiritigenin significantly reduced cerebral infarct volume and neurological deficits, and ameliorated oxidative stress and mitochondrial dysfunction by activating the Nrf2 pathway[7]. Intragastric administration of Isoliquiritigenin (20mg/kg/day) to high-fat diet-induced obese C57BL/6 mice (continued for 8 weeks), Isoliquiritigenin significantly reduced weight gain and white adipose tissue deposition, and activated the expression of thermogenesis-related genes in brown adipose tissue[8].
References:
[1] Chen Z, Ding W, Yang X, et al. Isoliquiritigenin, a potential therapeutic agent for treatment of inflammation-associated diseases. J Ethnopharmacol. 2024 Jan 10;318(Pt B):117059.
[2] Qiu M, Ma K, Zhang J, et al. Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications. Front Pharmacol. 2024 Oct 9;15:1395735.
[3] Wang KL, Yu YC, Hsia SM. Perspectives on the Role of Isoliquiritigenin in Cancer. Cancers (Basel). 2021 Jan 1;13(1):115.
[4] Zhang Z, Yung KK, Ko JK. Therapeutic Intervention in Cancer by Isoliquiritigenin from Licorice: A Natural Antioxidant and Redox Regulator. Antioxidants (Basel). 2022 Jul 11;11(7):1349.
[5] Kwon MJ, Raut PK, Jang JH, et al. Isoliquiritigenin Induces Apoptosis via ROS-Mediated Inhibition of p38/mTOR/STAT3 Pathway in Human Melanoma Cells. Biomol Ther (Seoul). 2025 Mar 1;33(2):378-387.
[6] Wang Z, Li W, Wang X, et al. Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells. Chin Med J (Engl). 2023 Sep 20;136(18):2210-2220.
[7] Lan X, Wang Q, Liu Y, et al. Isoliquiritigenin alleviates cerebral ischemia-reperfusion injury by reducing oxidative stress and ameliorating mitochondrial dysfunction via activating the Nrf2 pathway. Redox Biol. 2024 Nov;77:103406.
[8] Zhao L, Li M, Zhu Q, et al. Isoliquiritigenin Ameliorates High-Fat Diet-Induced Obesity in Mice by Activating Brown Adipose Tissue. Int J Mol Sci. 2025 Feb 14;26(4):1616.
Isoliquiritigenin是一种来源于甘草的黄酮类化合物，Isoliquiritigenin可激活Nrf2通路以减少氧化应激和炎症，同时通过诱导细胞凋亡来抑制癌症进展[1-2]。Isoliquiritigenin还可以抑制aldose reductase的活性，可中和自由基来减少氧化损伤，Isoliquiritigenin被用于神经系统、抗病毒、抗肿瘤等相关研究[3-4]。
在体外，Isoliquiritigenin（1–50μM）处理SK-MEL-28人黑色素瘤细胞24–72小时，Isoliquiritigenin通过诱导线粒体途径（激活caspase-9/-7/-3、PARP裂解，调控Bax/Bcl-2平衡，促进细胞色素C释放）和ROS介导的p38/mTOR/STAT3信号通路抑制，显著诱导细胞凋亡并降低细胞存活率[5]。Isoliquiritigenin（20–100μM）处理NOZ和SGC-996人胆囊癌细胞24–72小时，Isoliquiritigenin通过激活p62-Keap1-Nrf2-HMOX1轴、下调GPX4表达，引起铁离子积累、脂质过氧化和GSH/GSSG比率失衡，从而诱导铁死亡并抑制细胞增殖[6]。
在体内，Isoliquiritigenin（5–20mg/kg/day）灌胃处理脑缺血再灌注损伤模型ICR小鼠（预处理7天，术后24小时评估），Isoliquiritigenin显著减轻脑梗死体积和神经功能缺损，并通过激活Nrf2通路改善氧化应激和线粒体功能障碍[7]。Isoliquiritigenin（20mg/kg/day）灌胃处理高脂饮食诱导的肥胖C57BL/6小鼠（持续8周），Isoliquiritigenin显著降低体重增长和白色脂肪组织沉积，并激活棕色脂肪组织产热相关基因表达[8]。