Demethylzeylasteralは、伝統的な漢方薬のTripterygium wilfordiiに由来するトリテルペノイド化合物である[1]。DemethylzeylasteralはＴ細胞の活性化、炎症因子の放出、NF-κBとJAK/STATのシグナル伝達経路を阻害し腫瘍細胞のアポトーシスと細胞周期停止を誘発できる[2-3]。Demethylzeylasteralは有意な免疫抑制、抗炎症性と抗腫瘍生物的な活性を持っている[4]。
MV3とA375細胞におけるDemethylzeylasteral（1μM，5μM，10μM，20μM； 48H）がメラノーマ細胞の増殖を阻害する[5]。SW480細胞におけるDemethylzeylasteral（1μM，5μm，10μm，20μm； 24h，48h，72h，96h）は結腸直腸細胞の悪性腫瘍を阻害する[6]。MKN-45におけるDemethylzeylasteral（50nm，100nm，500nm，1µm，5µm，10µm，10µm，30µm，50µm，100µm，100µM; 24H）は人の胃がん細胞に細胞毒性の効果がある[7]。
DSS誘発性の大腸炎のモデルではDemethylzeylastastal（5mg/kg，10mg/kg，20mg/kg; ip; 9d）は体外で強い抗炎症性が示している[8]。MRL/LPR鼠ではDemethylzeylastastal（0.6mg/10g，1.2mg/10g; Ig; 9d）で処理した24Hのタンパク尿と血清中の抗DSDNA抗体のレベルが有意に改善される[9]。ラットの腎臓移植モデルではDemethylzeylastastal（10mg/kg，20mg/kg; ip; ip; 14d）でそのラットの生存を顕著に延長できる[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.