PMID- 33887491 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20210929 IS - 1522-9629 (Electronic) IS - 1094-5539 (Linking) VI - 68 DP - 2021 Jun TI - Gentiopicroside ameliorates ovalbumin-induced airway inflammation in a mouse model of allergic asthma via regulating SIRT1/NF-kappaB signaling pathway. PG - 102034 LID - S1094-5539(21)00046-8 [pii] LID - 10.1016/j.pupt.2021.102034 [doi] AB - Allergic asthma is a common airway inflammatory disorder with increasing morbidity and mortality worldwide. Gentiopicroside (GPS) is a secoiridoid glycoside compound that exhibits anti-inflammatory property. However, the effect of GPS on allergic asthma has not been reported yet. In this study, we investigated the role of GPS in a mouse model of ovalbumin (OVA)-induced allergic asthma and explored its potential mechanism. Mice were sensitized with OVA and gavaged with 20, 40, or 80 mg/kg GPS. Administration of GPS decreased lung wet-to-dry weight ratio. Histological analysis of H&E and PAS staining showed that GPS treatment alleviated inflammatory cell infiltration and goblet cell hyperplasia in lung tissue of OVA-sensitized mice. Moreover, GPS inhibited the recruitment of inflammatory cells including total cells, macrophages, eosinophils, lymphocytes and neutrophils and the secretion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) of OVA-sensitized mice in a dose dependent manner. The levels of OVA-specific immunoglobulin E (IgE) and pro-inflammatory tumor necrosis factor (TNF)-alpha were also attenuated by GPS treatment. Interestingly, GPS upregulated the expression of silent information regulator 1 (SIRT1) while downregulated the expression of acetyl-nuclear factor kappa B (NF-kappaB) p65 in lung tissue of OVA-sensitized mice. Furthermore, treatment with an SIRT1 inhibitor (EX-527) partially abolished the inhibitory effect of GPS on OVA-induced airway inflammation, suggesting that the anti-inflammation of GPS might be achieved through regulating SIRT1/NF-kappaB p65 signaling pathway. These findings indicate that GPS might be a novel drug candidate in the treatment of allergic asthma. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Zou, Bo AU - Zou B AD - Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China; Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China. FAU - Fu, Yue AU - Fu Y AD - Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China. FAU - Cao, Chaofan AU - Cao C AD - Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China; Department of Respiratory Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People's Republic of China. FAU - Pan, Dianzhu AU - Pan D AD - Department of Respiratory Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning Province, People's Republic of China. FAU - Wang, Wei AU - Wang W AD - Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China. FAU - Kong, Lingfei AU - Kong L AD - Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China. Electronic address: cmukonglf@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210419 PL - England TA - Pulm Pharmacol Ther JT - Pulmonary pharmacology & therapeutics JID - 9715279 RN - 0 (Cytokines) RN - 0 (Iridoid Glucosides) RN - 0 (NF-kappa B) RN - 0WE09Z21RC (gentiopicroside) RN - 9006-59-1 (Ovalbumin) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - *Asthma/drug therapy MH - Bronchoalveolar Lavage Fluid MH - Cytokines MH - Disease Models, Animal MH - Inflammation/drug therapy MH - Iridoid Glucosides MH - Lung/metabolism MH - Mice MH - Mice, Inbred BALB C MH - *NF-kappa B/metabolism MH - Ovalbumin MH - Signal Transduction MH - Sirtuin 1 OTO - NOTNLM OT - Airway inflammation OT - Allergic asthma OT - Gentiopicroside OT - NF-kappaB OT - SIRT1 EDAT- 2021/04/23 06:00 MHDA- 2021/09/30 06:00 CRDT- 2021/04/22 20:16 PHST- 2021/01/14 00:00 [received] PHST- 2021/04/09 00:00 [revised] PHST- 2021/04/15 00:00 [accepted] PHST- 2021/04/23 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2021/04/22 20:16 [entrez] AID - S1094-5539(21)00046-8 [pii] AID - 10.1016/j.pupt.2021.102034 [doi] PST - ppublish SO - Pulm Pharmacol Ther. 2021 Jun;68:102034. doi: 10.1016/j.pupt.2021.102034. Epub 2021 Apr 19.