title: Akt-dependent anabolic activity of natural and synthetic brassinosteroids in rat skeletal muscle cells.
abstract: Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids. In this study, we synthesized a set of brassinosteroid analogues of a natural brassinosteroid (22S,23S)-homobrassinolide (HB, 1), including (22S,23S)-homocastasterone (2), (22S,23S)-3α-fluoro-homobrasinolide (3), (22S,23S)-3α-fluoro-homocastasterone (4), (22S,23S)-7-aza-homobrassinolide (5), and (22S,23S)-6-aza-homobrassinolide (6) and studied their anabolic efficacy in the L6 rat skeletal muscle cells in comparison to other synthetic and naturally occurring brassinosteroids (22R,23R)-homobrassinolide (7), (22S,23S)-epibrassinolide (8), and (22R,23R)-epibrassinolide (9). Presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were critical for the anabolic activity, possibly due to higher cytotoxicity of the 22β,23β-hydroxylated brassinosteroids. All anabolic brassinosteroids tested in this study selectively activated PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.
authors.affiliation: Biotech Center, SEBS, Rutgers University, 59 Dudley Road, New Brunswick, New Jersey 08901, United States.
authors.forename: Debora
authors.initials: D
authors.lastname: Esposito
authors.forename: Thirumurugan
authors.initials: T
authors.lastname: Rathinasabapathy
authors.forename: Alexander
authors.initials: A
authors.lastname: Poulev
authors.forename: Slavko
authors.initials: S
authors.lastname: Komarnytsky
authors.forename: Ilya
authors.initials: I
authors.lastname: Raskin
mesh_terms: D045930:Anabolic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002778:Cholestanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D045930:Anabolic Agents; D002778:Cholestanones; C070163:homobrassinolide; D051057:Proto-Oncogene Proteins c-akt