Japanese herbal medicine Hochu-ekki-to (TJ-41) attenuates lung inflammation in lung emphysema

Background: Chronic Obstructive Pulmonary Disease (COPD) is a systemic inflammatory disease, and often causes weight loss, which is considered as a poor prognostic factor. A Japanese herbal medicine, Hochu-ekki-to (TJ-41), was reported to prevent weight loss in a small study of COPD patients, while its biological mechanism is unknown. Objective: The objective of our study was to evaluate the role of TJ-41 using mouse lung emphysema model, and to investigate its biological mechanism in vivo and in vitro. Methods: We used lung epithelial specific Taz conditional knockout mice (Taz CKO mice) as emphysema model mice, and fed a diet containing 2% TJ-41 or a control diet for 12 weeks. During administration, body weights were measured. After seeding, Taz CKO mice and control mice were subjected to BALF analysis, and lung mRNA expressions of inflammatory cytokines were analysed by RT-PCR. Results: After treatment, Taz CKO mice showed higher body weights in TJ-41 group compared to control diet group. BALF analysis showed decreased number of inflammatory cells in TJ-41 group, and among inflammatory cytokines, IL-8 expression was also significantly decreased. Conclusion: Our results suggest the possibility that TJ-41 attenuates lung inflammation, and thereby prevents weight loss of COPD patients. Among inflammatory cytokines, IL-8 is downregulated by administration of TJ-41, which coincided with decreased number of inflammatory cells in BALF in TJ-41 group. Our study sheds light on the biological mechanism of TJ-41 in lung emphysema, and suggests its potential for anti-inflammatory therapy for COPD patients.