Dual mechanisms of pomelo peel extract in combating cough and lung injury: Inhibition of MAPK/NF-κB and restoration of gut microbiota.

Cough, a common symptom of respiratory diseases, is often accompanied by pulmonary inflammation. Pomelo peels as the by-products of pomelo have anti-inflammatory, anti-oxidative, antibacterial, and other properties. This study investigates its therapeutic potential in alleviation of ammonia-induced cough and lung inflammation. As a result, UPLC-Q/TOF-MS indicates that there are 15 compounds in pomelo peel extracts (PPE), such as 7-methoxycou-marin, iristetrigenin B, marmesin, lysionotin, scoparone, naringenin, hesperetin, diosmin, and so forth. Naringin as the main compound occupies 84.73 % of PPE. PPE treatment significantly reduces cough frequency, suppresses TLR4/MyD88/MAPK/AP-1 and NF-κB signaling pathways, and decreases the levels of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α in both bronchoalveolar lavage fluid and serum. Notably, PPE restores gut microbiota homeostasis, and increases the abundance of Lactobacillus murinus (L. murinus) and its metabolites like lactic acid and short-chain fatty acids, highlighting its role in modulating the gut-lung axis. Interestingly, L. murinus used alone also exerts pulmonary protective effect in ammonia-induced mice. Vancomycin intervention doesn't inhibit the anti-inflammatory effects of PPE. Crucially, our findings propose that PPE has a dual mechanism involved inhibition of MAPK/NF-κB signaling and gut microbiota-dependent restoration of the gut-lung axis. All in all, it has potential research and development values in combating cough and lung injury in the future.