Five new 14,15-secopregnane derivatives, named argelosides K-O (1-5), have been isolated from Solenostemma argel leaves. Their structures were established by a detailed spectroscopic analysis. In particular, argeloside N (1) showed in the sugar portion an unusual 3-O-methyl-2,6-dideoxyhexopyranose unit characterized by the occurrence of a Delta3 double bond, and argeloside O (5) displayed an unusual moiety linked to position 3 probably derived by the oxidation of a 3-O-methyl-2,6-dideoxyhexopyranose unit. The propensity of compounds 2, 3, and 5 and argeloside F (6) to inhibit TNF-alpha release by LPS-stimulated RAW 264.7 mouse cells was evaluated.