Glycyrrhizic acid

Glycyrrhizic acid is the active ingredient triterpenoid saponin in licorice. It is an antagonist of high mobility group protein 1 (HMGB1) with a Kd value of 4.03 µM [1]. Glycyrrhizic acid inhibits monoamine oxidase (MAO) with an IC50 of 0.1µM[2]. Glycyrrhizic acid can regulate a variety of signaling proteins, including caspase family, Bcl-2 family, NF-κB protein, HMGB1 protein, ERK kinase, PI3K/AKT kinase and JNK kinase [3].

In vitro, Glycyrrhizic acid (10-100µM) treated BV2 cells for 18 h, inhibited LPS-stimulated NO production in a dose-dependent manner, and significantly reduced the expression of pro-inflammatory genes TNF-α, IL-1β, and IL-6 [4]. Glycyrrhizic acid (0, 0.1, 1, 10µM) treats Vero E6 cells and dose-dependently inhibits the cytopathic effect induced by DENV-2 virus, with an IC50 of 8.1 µM and low cytotoxicity [5]. Glycyrrhizic acid (10µM) treated intestinal NCI-H716 cells, stimulated GLP-1 secretion and increased intracellular calcium levels [6].

In vivo, Glycyrrhizic acid (50, 100, 150 mg/kg) treated STZ-induced diabetic rats via intraperitoneal injection, attenuating hyperglycemia in a dose-dependent manner and causing an increase in plasma GLP-1 levels [6]. Glycyrrhizic acid (50 or 500 mg/kg) treated mice with EL-4 lymphoma by intraperitoneal injection, significantly reducing tumor volume and reducing tumor burden indicators [7].

References:
[1] Okuma Y U, Liu K, Wake H, et al. Glycyrrhizin inhibits traumatic brain injury by reducing HMGB1-RAGE interaction[J]. Neuropharmacology, 2014, 85: 18-26.
[2] Hatano T, Fukuda T, Miyase T, et al. Phenolic constituents of licorice [Glycyrrhiza]. III. Structures of glicoricone and licofuranone and inhibitory effects of licorice constituents on monoamine oxidase[J]. 1991.
[3] Wang H, Ge X, Qu H, et al. Glycyrrhizic acid inhibits proliferation of gastric cancer cells by inducing cell cycle arrest and apoptosis[J]. Cancer management and research, 2020: 2853-2861.
[4] Yu J Y, Ha J Y, Kim K M, et al. Anti-inflammatory activities of licorice extract and its active compounds, glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver[J]. Molecules, 2015, 20(7): 13041-13054.
[5] Baltina L A, Tasi Y T, Huang S H, et al. Glycyrrhizic acid derivatives as Dengue virus inhibitors[J]. Bioorganic & Medicinal Chemistry Letters, 2019, 29(20): 126645.
[6]Wang L Y, Cheng K C, Li Y, et al. Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats[J]. Biomedicine & Pharmacotherapy, 2017, 95: 599-604.
[7]Hostetler B J, Uchakina O N, Ban H, et al. Treatment of hematological malignancies with glycyrrhizic acid[J]. Anticancer Research, 2017, 37(3): 997-1004.

Glycyrrhizic acid是甘草里面的活性成分三萜皂苷,是高迁移率族蛋白1( HMGB1 )的拮抗剂,Kd值为4.03µM[1]。Glycyrrhizic acid抑制单胺氧化酶(MAO),IC50为0.1µM[2]。Glycyrrhizic acid可以调节多种信号蛋白,包括caspase家族、Bcl-2家族、NF-κB蛋白、HMGB1蛋白、ERK激酶、PI3K/AKT激酶和JNK激酶[3]。

在体外,Glycyrrhizic acid(10-100µM)处理BV2 细胞18h,以剂量依赖性方式抑制了LPS刺激的NO产生,并显著降低了促炎基因TNF-α、IL-1β和IL-6的表达[4]。Glycyrrhizic acid(0、0.1、1、10µM)处理Vero E6细胞,剂量依赖性地抑制DENV-2病毒诱导的细胞病变效应,IC50为8.1µM,且具有低细胞毒性[5]。Glycyrrhizic acid(10µM)处理肠道NCI-H716细胞,刺激了GLP-1分泌,升高了细胞内钙水平[6]。

在体内,Glycyrrhizic acid(50,100,150mg/kg)通过腹腔注射治疗STZ诱导的糖尿病大鼠,以剂量依赖性方式减弱高血糖, 且引起血浆GLP-1水平升高[6]。Glycyrrhizic acid(50或500mg/kg)通过腹腔注射治疗患有EL-4淋巴瘤的小鼠,显著减小了肿瘤体积,降低了肿瘤负荷指标[7]。