Cachexia is a frequent complication in patients with
respiratory failure, such as lung
fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in
body weight and skeletal muscle mass are key features of
cachexia that are resistant to current
therapies.
Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate
ghrelin secretion. By using
bleomycin (BLM)-induced lung
fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary
cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and
body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung
fibrosis.
Rikkunshito administration restored the plasma concentrations of
ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a
ghrelin receptor antagonist.
Rikkunshito administration did not decrease the degree of loss of
body weight or food intake reduction in either
ghrelin-deficient mice or
growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary
cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the
ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung
fibrosis.