Tomatidine

Tomatidine is a steroidal alkaloid that has been found in the skins and leaves of tomatoes.¹ It suppresses NF-κB signaling in LPS-stimulated macrophages, blocking induced expression of inducible nitric oxide synthase (iNOS) and COX-2. Tomatidine inhibits acid sphingomyelinase activity by 84.2% when used at a concentration of 10 mM.² It also has antibacterial properties, preferentially blocking the replication of S. aureus variants that are pathogenic in cystic fibrosis over normal strains (MICs = 0.12 and >16 ?g/ml, respectively).³ It prevents skeletal muscle atrophy associated with fasting or spinal cord injury in mice.⁴ Tomatidine has also been used as a negative control for cyclopamine in studies involving signaling mediated by the hedgehog pathway.⁵

1.Chiu, F.L., and Lin, J.K.Tomatidine inhibits iNOS and COX-2 through suppression of NF-κB and JNK pathways in LPS-stimulated mouse macrophagesFEBS Lett.582(16)2407-2412(2008) 2.Kornhuber, J., Muehlbacher, M., Trapp, S., et al.Identification of novel functional inhibitors of acid sphingomyelinasePLoS One6(8)1-13(2011) 3.Mitchell, G., Gattuso, M., Grondin, G., et al.Tomatidine inhibits replication of Staphylococcus aureus small-colony variants in cystic fibrosis airway epithelial cellsAntimicrob. Agents Chemother.55(5)1937-1945(2011) 4.Dyle, M.C., Ebert, S.M., Cook, D.P., et al.Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophyJ. Biol. Chem.289(21)14913-14924(2014) 5.Zhao, C., Chen, A., Jamieson, C.H., et al.Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemiaNature458(7239)776-779(2009)