Corms are obtained as a byproduct during the cultivation of saffron (Crocus sativus). In a project aimed at the valorization of this waste product, we observed that a 70% EtOH extract of the corms and a sugar-depleted MeOH fraction of the extract inhibited the TNF-α/IFN-γ-induced secretion and gene expression of the chemokines IL-8, MCP-1, and RANTES in human HaCaT cells. The effects were in part stronger than those of the positive control hydrocortisone. For preparative isolation, the 70% EtOH extract was partitioned between n-BuOH and water. Separation of the n-BuOH-soluble fraction by centrifugal partition chromatography, followed by preparative and semipreparative HPLC, afforded a series of bidesmosidic glycosides of echinocystic acid bearing a 3,16-dihydroxy-10-oxo-hexadecanoic acid residue attached to the glycosidic moiety at C-28. They include azafrines 1 and 2, previously reported in saffron, and eight new congeners named azafrines 3-10. Saffron saponins significantly inhibited TNF-α/IFN-γ-induced secretion of RANTES in human HaCaT cells at 1 μM (p < 0.001). Some of them further lowered TNF-α/IFN-γ-induced gene expression.