Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

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.

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner.

Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory failure associated with extensive pulmonary infiltrates. The pathological characterization of ALI includes injuries of alveolar epithelial cells (AECs), alveolar neutrophilic infiltration, and increases in proinflammatory cytokines, which cause destruction of the alveolar capillary barrier and subsequent devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment of patients with gastrointestinal symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of RKT on organ inflammation and fibrosis remain unknown. We investigated the pharmacological potential of RKT in the treatment of ALI by using a bleomycin-induced ALI model in mice. RKT or distilled water (DW) was given to mice daily starting 12 h after bleomycin administration. The RKT-treated mice showed a definitively higher survival rate than the DW-treated mice after injury. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of proinflammatory cytokines, activation of the NF-κB pathway, apoptosis of AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT administration increased the plasma ghrelin levels in wild-type mice, and it also mitigated the ALI response in both ghrelin-deficient mice and growth hormone secretagogue receptor-deficient mice after lung injury. Our results indicate that RKT administration exerts protective effects against ALI by protecting the AECs and regulating lung inflammation independently of the ghrelin system, and they highlight RKT as a promising therapeutic agent for the management of this intractable disease.

Estimation of caffeine intake in Japanese adults using 16 d weighed diet records based on a food composition database newly developed for Japanese populations.

OBJECTIVE: Previous studies in Western populations have linked caffeine intake with health status. While detailed dietary assessment studies in these populations have shown that the main contributors to caffeine intake are coffee and tea, the wide consumption of Japanese and Chinese teas in Japan suggests that sources of intake in Japan may differ from those in Western populations. Among these teas, moreover, caffeine content varies widely among the different forms consumed (brewed, canned or bottled), suggesting the need for detailed dietary assessment in estimating intake in Japanese populations. Here, because a caffeine composition database or data obtained from detailed dietary assessment have not been available, we developed a database for caffeine content in Japanese foods and beverages, and then used it to estimate intake in a Japanese population. DESIGN: The caffeine food composition database was developed using analytic values from the literature, 16 d weighed diet records were collected, and caffeine intake was estimated from the 16 d weighed diet records. SETTING: Four areas in Japan, Osaka (Osaka City), Okinawa (Ginowan City), Nagano (Matsumoto City) and Tottori (Kurayoshi City), between November 2002 and September 2003. SUBJECTS: Two hundred and thirty Japanese adults aged 30-69 years. RESULTS: Mean caffeine intake was 256.2 mg/d for women and 268.3 mg/d for men. The major contributors to intake were Japanese and Chinese teas and coffee (47 % each). Caffeine intake above 400 mg/d, suggested in reviews to possibly have negative health effects, was seen in 11 % of women and 15 % of men. CONCLUSIONS: In this Japanese population, caffeine intake was comparable to the estimated values reported in Western populations.