To make this discovery, Komarnytsky and colleagues exposed rat skeletal muscle cells to different amounts of homobrassinolide and measured protein synthesis in cell culture. The result was increased protein synthesis and decreased protein degradation in these cells. Healthy rats then received oral administration of homobrassinolide daily for 24 days. Changes in body weight, food consumption, and body composition were measured. Rats receiving homobrassinolide gained more weight and slightly increased their food intake. Body composition was measured using dual-emission X-ray absorptiometry analysis and showed increased lean body mass in treated animals over those who were not treated. This study was repeated in rats fed high protein diet and similar results were observed. Additionally, researchers used surgically castrated peri-pubertal rat models to examine the ability of homobrassinolide to restore androgen-dependent tissues after androgen deprivation following castration. Results showed increased grip strength and an increase in the number and size of muscle fibers crucial for increased physical performance.
"The temptation is to see this discovery as another quick fix to help you go from fat to fit," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "and to a very small degree, this may be true. In reality, however, this study identifies an important drug target for a wide range of conditions that cause muscle wasting."
Anabolic effect of plant brassinosteroid
Author Affiliations- 1 Correspondence and current address: Plants for Human Health Institute, FBNS, North Carolina State University, 600 Laureate Way, Kannapolis, NC 28081, USA. E-mail: komarnytsky@ncsu.edu
- Abstract
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 (EC50 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.—Esposito, D., Komarnytsky, S., Shapses, S., Raskin, I. Anabolic effect of plant brassinosteroid.