Demethylzeylasteral

Demethylzeylasteral is a nortriterpenoid originally isolated from T. wilfordii that has diverse biological activities, including enzyme inhibitory, anti-angiogenic, antiproliferative, anti-inflammatory, and immunosuppressive properties.^1,2,3,4 Demethylzeylasteral inhibits the UDP-glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7 (K_is = 0.6 and 17.3 μM, respectively).² It inhibits growth of bovine aortic endothelial cells (BAEs) and U251 human glioma cancer cells in vitro (IC₅₀s = 0.21 and ~6.2 μM, respectively), as well as inhibits tumor growth and neovascularization in vivo in a B16/F10 melanoma mouse allograft model when administered at a dose of 30 mg/kg per day.¹ Demethylzeylasteral (0.12 mg/kg per day) decreases renal proteinuria, lesions, immune cell infiltration, and protein levels of TNF-α, COX-2, and ICAM-1 in lupus-prone MRL/lpr mice.³ Demethylzeylasteral (10 mg/kg per day) also increases survival of recipient rats in a model of kidney transplant.⁴

1.Ushiro, S., Ono, M., Nakayama, J., et al.New nortriterpenoid isolated from anti-rheumatoid arthritic plant, Tripterygium wilfordii, modulates tumor growth and neovascularizationInt. J. Cancer72(4)657-663(1997) 2.Zhao, J.-W., Wang, G.-H., Chen, M., et al.Demethylzeylasteral exhibits strong inhibition towards UDP-glucuronosyltransferase (UGT) 1A6 and 2B7Molecules17(8)9469-9475(2012) 3.Hu, Q., Yang, C., Wang, Q., et al.Demethylzeylasteral (T-96) Treatment Ameliorates Mice Lupus Nephritis Accompanied by Inhibiting Activation of NF-κB PathwayPLoS One10(7)e0133724(2015) 4.Xu, W., Lin, Z., Yang, C., et al.Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation modelInt. Immunopharmacol.9(7-8)996-1001(2009)