Integrated Therapeutic Strategy Using Ginkgo Biloba and Exercise to Improve Muscle Wasting of Different Origin

Muscle wasting usually is associated with a diversity of diseases, more commonly like aging, neurodamages, chronic kidney disease (CKD), and diabetes mellitus (DM) etc. Clinically different diseases may elicit different type of muscle wasting through varying mechanisms. However the outcome is usually resulting from a complex causality, like vigor-lacking, protein degradation, decreased muscle cross section area, transformation of myofiber type, diminution of vascular density in muscle tissues, elevated oxidative stress, overexpressed inflammatory cytokines, insulin resistance, reduced growth hormone and androgen production, and myocyte apoptosis and fibrosis. Muscle wasting causes loss of independent activity and at the same time increases the health care burdens. Thus to develop a preventive and restoring therapeutic strategy is in need. For thousands of years, Ginkgo biloba has been used as therapeutic medicine on a diversity of diseases including neuro-protective, anti-inflammatory, sedative, tranquilizer, anti-oxidative, anticancer and antibacterial. In addition, it has been shown to exhibit characteristic bioactivity to facilitate transformation of muscle fiber type and improve muscle contractive function. We hypothesize that exercise and Gingko biloba or their combination could be beneficial to restoration of muscle wasting. To explore its effects and the related bioactivity, we will perform both the in vitro C2C12 cell model and the in vivo rat model to investigate its action mechanisms in four muscle wasting types involving the aging, the denervated, CKD and DM. This project covers a two-stage and three-year programs. The first year cell model program and the subsequent 2-year-animal model program. The items to be examined will cover cell viability and growth, cell type and microfine structure (limited to the first year cell model program only), muscular fiber type, antioxidative and anti-inflammatory, de novo protein synthesis, protein degradation, cell apoptosis, energy metabolism and glucose uptake, expression of androgen receptor and the protein signalings associated with myogenesis. Finally, we will carry out proteomic analysis to compare the muscle wasting resulting from the four different causalities. To our believe, the results obtained in this research will be able to provide some, if not entirely, novel improved specific therapeutic managements for preventing or recovering different muscle wasting.