FICZ (Formyl-indolo [3,2-b] carbazole), as an endogenous ligand for the aryl hydrocarbon receptor (AhR), can exert pleiotropic effects including protection against inflammation, fibrosis, and oxidative stress[1].
In vitro, treatment with 0.01 nM-1 µM FICZ in HepG2 cells, FICZ stimulated cell growth at low concentrations but inhibited cell growth at high concentrations[2]. In vitro experiment it demonstrated that treatment LPS combined with 200 nM FICZ in YAMC cells did not influence LPS-induced IL-6 release[3]. In vitro, 50 µM FICZ obviously induced apoptosis, whereas all tested compounds in higher concentrations (L-KYN 1 mM, KYNA 5 mM, FICZ 50 µM) increased necrosis in melanoma A375 cells. Statistically, FICZ obviously inhibited DNA synthesis in A375 cells at a concentration range of 10-6-50 µM, but there is only observed inhibitory effect on RPMI7951 cells in the highest tested micromolar concentrations[4].
In vivo efficacy test it shown that per mouse was treatment with 1 µg (50 µg/kg) intraperitoneally enhanced the level of IL-22 in colonic samples, and ameliorated colitis induced by TNBS (trinitrobenzene sulfonic acid) or DSS (dextran sulfate sodium)[5]. In vivo, 10 µg/kg FICZ in mice orally resulted in transient AhR activation, with the effect waning in less than 18h[6].
[1]Tamayo M, et al. The Aryl Hydrocarbon Receptor Ligand FICZ Improves Left Ventricular Remodeling and Cardiac Function at the Onset of Pressure Overload-Induced Heart Failure in Mice. Int J Mol Sci. 2022 May 12;23(10):5403.
[2]Mohammadi-Bardbori A, et al. The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro. Arch Toxicol. 2017 Oct;91(10):3365-3372.
[3]Li X, et al. 6-Formylindolo (3, 2-b) Carbazole (FICZ)-mediated protection of gut barrier is dependent on T cells in a mouse model of alcohol combined with burn injury. Biochim Biophys Acta Mol Basis Dis. 2020 Nov 1;1866(11):165901.
[4]Walczak K, et al. Effect of Tryptophan-Derived AhR Ligands, Kynurenine, Kynurenic Acid and FICZ, on Proliferation, Cell Cycle Regulation and Cell Death of Melanoma Cells-In Vitro Studies. Int J Mol Sci. 2020 Oct 26;21(21):7946.
[5]Rannug A. How the AHR Became Important in Intestinal Homeostasis-A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology. Int J Mol Sci. 2020 Aug 8;21(16):5681.
[6]Wheeler JL, et al. Differential consequences of two distinct AhR ligands on innate and adaptive immune responses to influenza A virus. Toxicol Sci. 2014 Feb;137(2):324-34.
FICZ（甲酰吲哚 [3,2-b] 咔唑）作为芳基烃受体 (AhR) 的内源性配体，可以发挥多效性作用，包括防止炎症、纤维化和氧化应激[1 ]。
在体外，用 0.01 nM-1 µM FICZ 处理 HepG2 细胞，FICZ 在低浓度下刺激细胞生长，但在高浓度下抑制细胞生长[2]。体外实验表明，LPS联合200 nM FICZ处理YAMC细胞不影响LPS诱导的IL-6释放[3]。在体外，FICZ 50 77777#181;M FICZ 明显诱导细胞凋亡，而所有测试化合物（L-KYN 1 mM，KYNA 5 mM，FICZ 50 µM）增加黑色素瘤 A375 细胞的坏死。据统计，FICZ在10-6-50 µM的浓度范围内明显抑制A375细胞的DNA合成，但仅在最高测试微摩尔浓度下观察到对RPMI7951细胞的抑制作用[4] .
体内药效试验表明，每只小鼠用1 µg (50 µg/kg)腹腔注射可提高结肠样本中IL-22的水平，并改善TNBS诱导的结肠炎（三硝基苯磺酸）或 DSS（葡聚糖硫酸钠）[5]。在体内，小鼠口服 10 µg/kg FICZ 导致短暂的 AhR 激活，效果在不到 18 小时内减弱[6]。