Piscroside C, a novel iridoid glycoside isolated from Pseudolysimachion rotundum var. subinegrum suppresses airway inflammation induced by cigarette smoke

Abstract

Ethnopharmacological relevance: Pseudolysimachion rotundum var. subintegrum (Speedwell, Plantaginaceae) is used as a traditional herbal medicine for treating bronchitis, cough and asthma in Korea, China, Russia, and Europe. Aim of the study: In this study, we investigated the protective effects of the novel iridoid glycoside, piscroside C (compound 1) isolated from the methanolic extract of P. rotundum var. subintegrum against inflammatory responses using a cigarette smoke induced chronic obstructive pulmonary disease (COPD) and TNF-alpha-stimulated human airway epithelial NCI-H292 cells. Materials and methods: The novel iridoid glycoside piscroside C was isolated from the methanolic extract of P. rotundum var. subintegrum. The chemical structure was established by NMR, HRESIMS, and optical rotation. In in vivo experiment, the mice received 1 h of cigarette smoke for 3 days. Piscroside C was administered to mice by oral gavage I h before cigarette smoke exposure for 3 days. In in vitro experiment, we evaluated the effect of piscroside C on proinflammatory mediators in H292 cells stimulated with TNF-alpha. Results: Piscroside C significantly reduced the neutrophil influx, reactive oxygen species production, IL-6, TNF-alpha, and elastase activity in bronchoalveolar lavage fluid in COPD animals. In addition, piscroside C attenuated NF-kappa B and ha phosphorylation, leading to reduced recruitment of inflammatory cells into the lung tissue. Consistent with the results of in vivo experiment, piscroside C significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and IL-10) by inhibiting NF-kappa B activation, as resulting decrease in the phosphorylation of IKK beta, I kappa B alpha and TAK1 in TNF-alpha-stimulated H292 cells. Conclusion: These findings indicate that piscroside C effectively inhibits inflammatory responses, which is an important process in the development of COPD through suppression of IKK/NF-kappa B activation. Our study suggest that piscroside C might represent a useful therapeutic for the treatment of inflammatory airway disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved.