Cytosporone B is a natural fungal metabolite with broad-spectrum antifungal activity and has strong inhibitory effects on various pathogenic fungi, including Candida and Aspergillus species[1]. Cytosporone B is also an agonist for Nur77/NR4A1, with an EC50 of 0.278nM[2]. Cytosporone B can regulate the cell cycle, exert anti-inflammatory effects, and modulate immune functions[3]. Additionally, Cytosporone B has demonstrated inhibit tumor cell growth[4]
In vitro, treatment of MCF-7 cells with Cytosporone B (10µM) for 24 hours activates Nur77, downregulates the transcriptional activity and mRNA levels of CD36 and FABP4 in MCF-7 cells, reduces lipid droplet accumulation, and inhibits cell proliferation[5]. Treatment of human vocal fold fibroblasts (HVOX cell line) with Cytosporone B (1µM) for 24 hours significantly downregulates the expression of COL1A1 and ACTA2 under TGF-β1 (10ng/ml) stimulation. Cytosporone B also reduces TGF-β1-mediated collagen gel contraction[6].
In vivo, Cytosporone B (10mg/kg) was administered orally once daily to C57BL/6N mice starting on day 14 after induction of experimental autoimmune encephalomyelitis (EAE) and continued until day 21. Cytosporone B significantly alleviated clinical symptoms in EAE mice, reduced the percentages of CD4⁺ T cells and F4/80⁺ cells in the central nervous system[7]. In mice infected with influenza virus (IAV), Cytosporone B (5mg/kg) was administered intraperitoneally once daily. Cytosporone B significantly reduced lung viral loads, improved pulmonary function, increased the production of type I interferons (IFN-β and IFN-α), and reduced inflammatory cell infiltration and lung tissue damage[8].
References:
[1] Yin C, Liu H, Shan Y, et al. Cytosporone B as a Biological Preservative: Purification, Fungicidal Activity and Mechanism of Action against Geotrichum citri-aurantii. Biomolecules. 2019 Mar 29;9(4):125.
[2] Zhan Y, Du X, Chen H, et al. Cytosporone B is an agonist for nuclear orphan receptor Nur77. Nat Chem Biol. 2008 Sep;4(9):548-56.
[3] Xiong Y, Ran J, Xu L, et al. Reactivation of NR4A1 Restrains Chondrocyte Inflammation and Ameliorates Osteoarthritis in Rats. Front Cell Dev Biol. 2020 Mar 17;8:158.
[4] Guan YF, Huang QL, Ai YL, et al. Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis. Oncogene. 2020 Mar;39(11):2408-2423.
[5] Yang PB, Hou PP, Liu FY, et al. Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression. Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27412-27422.
[6] Hiwatashi N, Mukudai S, Bing R, et al. The effects of cytosporone-B, a novel antifibrotic agent, on vocal fold fibroblasts. Laryngoscope. 2018 Dec;128(12):E425-E428.
[7] Yu HZ, Zhu BQ, Zhu L, et al. NR4A1 agonist cytosporone B attenuates neuroinflammation in a mouse model of multiple sclerosis. Neural Regen Res. 2022 Dec;17(12):2765-2770.
[8] Egarnes B, Blanchet MR, Gosselin J. Treatment with the NR4A1 agonist cytosporone B controls influenza virus infection and improves pulmonary function in infected mice. PLoS One. 2017 Oct 20;12(10):e0186639.
Cytosporone B是一种具有广谱抗真菌活性的天然真菌代谢产物，对多种病原真菌（包括念珠菌属和曲霉菌属）具有较强的抑制作用[1]。Cytosporone B也是一种Nur77/NR4A1激动剂，EC50为0.278nM[2]。Cytosporone B可以调节细胞周期、抗炎以及调节免疫功能等[3]。此外，Cytosporone B还显示出抑制肿瘤细胞生长的功能[4]。
在体外，Cytosporone B（10µM）处理MCF-7细胞24小时，Cytosporone B通过激活Nur77活性，抑制MCF-7细胞中CD36和FABP4的转录活性及mRNA水平，减少脂滴积累，抑制细胞增殖 [5]。Cytosporone B（1µM）处理人声带成纤维细胞（HVOX细胞系）24小时，在TGF-β1（10ng/ml）刺激下，Cytosporone B显著下调COL1A1和ACTA2的表达，同时Cytosporone B还减少了TGF-β1介导的胶原凝胶收缩现象[6]。
在体内，诱导实验性自身免疫性脑脊髓炎（EAE）C57BL/6N小鼠后第14天开始，每日一次经口灌胃给药Cytosporone B（10mg/kg），持续至第21天。Cytosporone B显著减轻了EAE小鼠的临床症状，减少了中枢神经系统中CD4⁺ T细胞和F4/80⁺细胞的百分比[7]。Cytosporone B（5mg/kg）每日一次腹腔注射，用于处理感染流感病毒（IAV）的小鼠。Cytosporone B显著降低了肺部病毒载量，改善了肺功能，增加了I型干扰素（IFN-β和IFN-α）的产生，减少了炎症细胞浸润和肺组织损伤[8]。