Ninjin’yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression

Abstract

Atsushi Miyamoto, Kazuhisa Asai, Hideaki Kadotani, Naomi Maruyama, Hiroaki Kubo, Atsuko Okamoto, Kanako Sato, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Tomoya Kawaguchi Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, JapanCorrespondence: Kazuhisa AsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-Machi, Abeno-ku, Osaka-City, Osaka 545-8585, JapanTel [phone]Fax [phone]Email [email protected]: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice.Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks.Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution.Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.Keywords: chronic obstructive pulmonary disease, sarcopenia, peroxisome proliferator-activated receptor γ coactivator-1α, Ninjin’yoeito, muscle dysfunction

Keywords

• chronic obstructive pulmonary disease
• sarcopenia
• peroxisome proliferator-activated receptor γ coactivator-1α
• ninjin’yoeito
• muscle dysfunction