Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway

Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling.This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice.To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)-NF-E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro.SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice.Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress.