FASEB J. 2011 Oct;25(10):3708-19. Epub 2011 Jul 11.
Anabolic effect of plant brassinosteroid.
Esposito D, Komarnytsky S, Shapses S, Raskin I.
Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane,
structurally similar to cholesterol-derived animal steroid hormones and insect
ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a
steroidal lactone with potent plant growth-promoting property, stimulated protein
synthesis and inhibited protein degradation in L6 rat skeletal muscle cells
(EC(50) 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration
of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein
content 23.9%) increased food intake, body weight gain, lean body mass, and
gastrocnemius muscle mass as compared with vehicle-treated controls. The effect
of HB administration increased slightly in animals fed a high-protein diet
(protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4
mg/kg) administration of HB showed low androgenic activity when tested in the
Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor
in vitro. HB treatment was also associated with an improved physical fitness of
untrained healthy rats, as evident from a 6.7% increase in lower extremity
strength, measured by grip test. In the gastrocnemius muscle of castrated
animals, HB treatment significantly increased the number of type IIa and IIb
fibers and the cross-sectional area of type I and type IIa fibers. These findings
suggest that oral application of HB triggers selective anabolic response with
minimal or no androgenic side-effects and begin to elucidate the putative
cellular targets for plant brassinosteroids in mammals.