Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway. (30th January 2022)

• Record Type: Journal Article
• Authors: Liang, Rongyao; Tong, Xiyang; Dong, Zhikui; Qin, Weiwei; Fan, Lingling; Bai, Ziyu; Zhang, Zhihao; Xiang, Ting; Wang, Zhen; Tan, Ninghua
• Is Part Of: Journal of ethnopharmacology. Volume 283(2021)
• Publication Date: 2022-01-30
• Subjects: Suhuang antitussive capsule -- Post-infectious cough -- AhR -- Nrf2 -- Oxidative stress; AhR Aryl hydrocarbon receptor -- ARE antioxidant response elements -- BCA bicinchoninic acid -- COPD chronic obstructive pulmonary disease -- COVID-19 coronavirus disease 2019 -- CS cigarettes smoke -- CVA cough variant asthma -- CYP1A1 cytochrome P450 1A1 -- DAPI 4′, 6-diamidino-2-phenylindole -- DMSO dimethyl sulfoxide -- EGFR epidermal growth factor receptor -- ELISA enzyme-linked immunosorbent assay -- ERK extracellular signal-regulated kinase -- GSH glutathione -- HGF hepatocyte growth factor -- HO-1 heme oxygenase-1 -- i.g. intragastrically -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- i.p. intraperitoneally -- JAK2 janus kinase 2 -- Keap1 Kelch-like ECH associated protein 1 -- LPS lipopolysaccharide -- MON Montelukast sodium tablets -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- MUC5AC mucin 5AC -- NLRP3 Nod-like receptor protein 3 -- NQO1 NAD(P)H dehydrogenase 1 -- Nrf2 NF-E2-related factor 2 -- PAGE polyacrylamide gel electrophoresis -- PBS phosphate buffered saline -- PIC post-infectious cough -- Q-PCR Quantitative-polymerase chain reaction -- SDS sodium dodecyl sulfate -- SEM standard error of mean -- SH capsule Suhuang antitussive capsule -- SOD superoxide dismutase -- STAT3 signal transducer and activator of transcription 3 -- T-AOC total antioxidant capacity -- TCMs traditional Chinese medicines -- TNF-α tumor necrosis factor-α -- XRE xenobiotic-responsive element; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114664
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: 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. Aim of the study: This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. Materials and methods: 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 . Results: 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. Conclusion: 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. Graphical abstract: Image 1 Highlights: Suhuang antitussive capsule significantly ameliorated cough symptoms and pulmonary histological damage in mice. Suhuang antitussive capsule down-regulated the expressions of inflammatory mediators in vitro and in vivo. Suhuang antitussive capsule exerted the ameliorative effect on post-infectious cough mice via activating AhR-Nrf2 pathway. AhR-Nrf2 pathway may be exploited as a novel therapeutic target for post-infectious cough.