Studies in Natural Products Chemistry

Brassinosteroids (BRs), a group of plant hormones, have been found in a wide range of organisms from lower to higher plants. BRs have been detected in all plant organs such as pollen, anthers, seeds, leaves, stems, roots, flowers, and grain. BRs are polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones. They are implicated in the promotion of plant growth and development, including regulation of gene expression, cell division and expansion, differentiation, programmed cell death, and homeostasis. BRs play a significant role in amelioration of various environmental stresses. BRs are not only implicated in plant response to abiotic and biotic stresses but also have medicinal applications. At present, our knowledge of the effects of BRs in animals or human is still rather fragmentary. However, it is known that BRs have an anabolic action and anticancer and antiproliferative properties. For example, BR treatment produced anabolic effects and improved physical fitness in healthy animals without detrimental androgenic effects, that is, increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass. BRs stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells mediated in part by the PI3K/Akt (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway. Natural BRs also inhibited growth of several human cancer cell lines without affecting the growth of normal cells. Application of BRs showed high cytotoxic activity in breast (MCF-7/MDA-MB-468) and prostate cancer (LNCaP/DU-145) cell lines. BRs have a favorable safety profile because no treatment-related effect was observed at LD50 (the dosage causing death in 50% of exposed animals) up to 1000mg/kg body weight in mice and 2000mg/kg body weight in Wistar rats when applied orally or subcutaneously. BRs have also antiviral activities against herpes simplex viruses type I and II, arenaviruses, measles viruses, and vesicular stomatitis virus. BRs may prove to be promising leads for the development of new generation of drugs, especially against cancer or viral infection.