Transformation of Ergosterol Peroxide to Cytotoxic Substances by Rat Intestinal Bacteria

Abstract

Ergosterol peroxide (EPO, 1) is a major antitumor sterol produced by edible or medicinal mushrooms. Following oral administration of 1 to rats or anaerobic in vitro incubation of 1 with rat fecal bacteria, three metabolites were detected and their structures were identified to be 5a a,6a a-epoxyergosta-8(14),22-diene-3b b,7a a-diol (M1, 2), 5a a,6a a-epoxyergosta-8,22-diene-3b b,7a a-diol (M2, 3), and 5a a,6a a-epoxy-3b b-hydroxyergosta-22-ene-7-one (M3, 4) by spectroscopic analysis. Of these, M2 and M3 showed more potent inhibitory activity than the original compound 1 against proliferation of CACO-2, WiDr, DLD-1 and Colo320 human colorectal adenocarcinoma cells. These findings suggest that bacterial metabolites of EPO play a significant role in its cytotoxic activity against human colorectal cancer cells.Key words ergosterol peroxide; rat intestinal bacteria; cytotoxic activity Biol. Pharm. Bull. 31(5) 949-954 (2008)

Oxysterols from Free Radical Chain Oxidation of 7-Dehydrocholesterol: Product and Mechanistic Studies

“…Many of these natural oxysterols have shown diverse biological activities, such as being cytotoxic,95-100,104,108,109 antimalarial,104 antitubercular,110 anti-inflammatory,111 and an agonist of the liver X receptor (LXR) 112. LXRs are nuclear receptors that control cellular cholesterol efflux 113.…”

Sterols from Hericium erinaceum and their inhibition of TNF-α and NO production in lipopolysaccharide-induced RAW 264.7 cells

“…Their structures were identified as erinarol G (1), erinarol H (2), erinarol I (3), erinarol J (4), (3b,5a,22E) ergosta- 6,8(14),22-triene-3,5-diol (5), fomentarol A (6) (Zang et al, 2013), (3b,7a,22E) ergosta-8(14),22-diene-3,7-diol (7) (Notaro et al, 1992b), 7-ketobrassicasterol (8) (Notaro et al, 1992a), (3b,22E) ergosta-5,8(14),22-triene-7-one (9) (Lin et al, 1999) 5a,6a-epoxy-3b-hydroxy ergosta-22-ene-7-one (10) (Lee et al, 2008), 5a,6a-epoxy-(22E,24R)-ergosta-8(14),22-diene-3b,7b-diol (11) (Ishizuka et al, 1997), 5a,6a-epoxy-(22E,24R)-ergosta-7,22-diene-3b-ol (12) (Bok et al, 1999), 5a,6a;8a,9a-diepoxy-(22E,24R)-ergosta-22-ene-3b-7a-diol (13) (Yaoita et al, 1999), and 5a,6a;8a,9a-diepoxy-(22E,24R)-ergosta-22-ene-3b-7b-diol (14) (Yaoita et al, 1999). Among them, compounds 1-4 were novel.…”

Sterols from the Stems of Momordica charantia

“…As part of our program aimed at the discovery of bioactive secondary metabolites from Taiwanese M. charantia, we had reported the isolation and structure elucidation of twenty-five cucurbitane-type triterpenoids from the MeOH extract of the stems of this plant. [18][19][20][21][22] In the continuing phytochemical investigation on M. charantia, we further identified one new ergostane sterol, 5a,6a-epoxy-3b-hydroxy-(22E,24R)-ergosta-8,22-dien-7-one (1), along with eight known sterols, 5a,6a-epoxy-(22E,24R)-ergosta-8,22-diene-3b,7a-diol (2), 23 5a,6a-epoxy-(22E,24R)-ergosta-8,22-diene-3b,7b-diol (3), 24 5a,6a-epoxy-(22E,24R)-ergosta-8(14),22-diene-3b,7a-diol (4), 23 3b-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one (5), 25 ergosterol peroxide (6), 26 clerosterol (7), 27,28 decortinol (8), 27 and decortinone (9). 27 We describe in this paper the extraction, isolation, purification, and structure elucidation of compound 1 and the cytotoxic activity of compounds 1, 4, 5, 8, and 9.…”