Cancer cachexia pathophysiology and translational aspect of herbal medicine

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.