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.