Demethylzeylasteral is a triterpenoid compound derived from the traditional Chinese medicine Tripterygium wilfordii [1]. Demethylzeylasteral can inhibit T cell activation, inflammatory factor release, NF-κB and JAK/STAT signaling pathways, and induce tumor cell apoptosis and cell cycle arrest [2-3]. Demethylzeylasteral has significant immunosuppressive, anti-inflammatory and anti-tumor biological activities [4].
In MV3 and A375 cells, Demethylzeylasteral (1μM, 5μM, 10μM, 20μM; 48h) inhibits cell proliferation in melanoma cells [5]. In SW480 cells, Demethylzeylasteral (1μM, 5μM, 10μM, 20μM; 24h, 48h, 72h, 96h) inhibited the colorectal cell malignancy [6]. In MKN-45 cells, Demethylzeylasteral (50nM, 100nM, 500nM, 1µM, 5µM, 10µM, 30µM, 50µM, 100µM; 24h) has cytotoxic effects on human gastric cancer cells [7].
In DSS-induced colitis model, Demethylzeylasteral (5mg/kg, 10mg/kg, 20mg/kg; ip; 9d) exhibited a robust anti-inflammatory activity in vitro [8]. In MRL/lpr mice, treated with Demethylzeylasteral (0.6mg/10g, 1.2mg/10g; ig; 9d) showed a significant improvement in 24h proteinuria and the levels of anti-dsDNA antibody in serum [9]. In the rat kidney transplant model, treated with Demethylzeylasteral (10mg/kg, 20mg/kg; ip; 14d)significantly prolonged the survival of kidney-transplanted rats [10].
References:
[1]. Sun X, Shen B, Yu H, et al. Therapeutic potential of demethylzeylasteral, a triterpenoid of the genus Tripterygium wilfordii. Fitoterapia. 2022 Nov 1; 163: 105333.
[2]. Lv L, Zhou F, Quan Y, et al. Demethylzeylasteral exerts potent efficacy against non-small-cell lung cancer via the P53 signaling pathway. Translational Oncology. 2024 Aug 1; 46: 101989.
[3]. Pan L, Feng F, Wu J, et al. Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacological research. 2022 Jul 1; 181: 106270.
[4]. Li W, Han F, Tang K, et al. Inhibiting NF-κB-S100A11 signaling and targeting S100A11 for anticancer effects of demethylzeylasteral in human colon cancer. Biomedicine & Pharmacotherapy. 2023 Dec 1; 168: 115725.
[5]. Zhao Y, He J, Li J, et al. Demethylzeylasteral inhibits cell proliferation and induces apoptosis through suppressing MCL1 in melanoma cells. Cell death & disease. 2017 Oct; 8(10): e3133.
[6]. Yang Y, Han J, Ma Y, et al. Demethylzeylasteral inhibits cell proliferation and enhances cell chemosensitivity to 5-fluorouracil in Colorectal Cancer cells. Journal of Cancer. 2020 Aug 19; 11(20): 6059.
[7]. Yang Y, Zhao M, Hu T, et al. Identification of an antitumor effect of demethylzeylasteral on human gastric cancer cells. Oncology Letters. 2021 Jan; 21(1): 49.
[8]. Wen T, Liu T, Chen H, et al. Demethylzeylasteral alleviates inflammation and colitis via dual suppression of NF-κB and STAT3/5 by targeting IKKα/β and JAK2. International Immunopharmacology. 2024 Dec 5; 142: 113260.
[9]. Hu Q, Yang C, Wang Q, et al. Demethylzeylasteral (T-96) treatment ameliorates mice lupus nephritis accompanied by inhibiting activation of NF-κB pathway. PloS one. 2015 Jul 24; 10(7): e0133724.
[10]. Xu W, Lin Z, Yang C, et al. Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model. International immunopharmacology. 2009 Jul 1; 9(7-8): 996-1001.
Demethylzeylasteral是从传统中药雷公藤中提取的三萜类化合物 [1]。Demethylzeylasteral能够抑制T细胞活化、炎症因子释放、NF-κB和JAK/STAT信号通路，并诱导肿瘤细胞凋亡和细胞周期阻滞 [2-3]。Demethylzeylasteral具有显著的免疫抑制、抗炎和抗肿瘤生物活性 [4]。
在MV3和A375细胞中，Demethylzeylasteral（1μM、5μM、10μM、20μM；48h）可抑制黑色素瘤细胞的增殖 [5]。在SW480细胞中，Demethylzeylasteral（1μM、5μM、10μM、20μM；24h、48h、72h、96h）可抑制结肠直肠细胞恶性肿瘤 [6]。在MKN-45细胞中，Demethylzeylasteral（50nM、100nM、500nM、1µM、5µM、10µM、30µM、50µM、100µM；24h）对人胃癌细胞具有细胞毒作用 [7]。
在DSS诱发的结肠炎模型中，Demethylzeylasteral（5mg/kg、10mg/kg、20mg/kg；ip；9d）表现出强大的体外抗炎活性 [8]。在MRL/lpr小鼠中，Demethylzeylasteral（0.6mg/10g、1.2mg/10g；ig；9d）治疗后，24小时蛋白尿和血清抗双链DNA抗体水平显著改善 [9]。在大鼠肾移植模型中，用Demethylzeylasteral（10mg/kg，20mg/kg；ip；14d）治疗可显著延长肾移植大鼠的存活期 [10]。