Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways

Abstract Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the phar...

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Main Authors: Chang Xu, Yilan Song, Zhiguang Wang, Jingzhi Jiang, Yihua Piao, Li Li, Shan Jin, Liangchang Li, Lianhua Zhu, Guanghai Yan
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
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Online Access:https://doi.org/10.1002/iid3.490
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author Chang Xu
Yilan Song
Zhiguang Wang
Jingzhi Jiang
Yihua Piao
Li Li
Shan Jin
Liangchang Li
Lianhua Zhu
Guanghai Yan
author_facet Chang Xu
Yilan Song
Zhiguang Wang
Jingzhi Jiang
Yihua Piao
Li Li
Shan Jin
Liangchang Li
Lianhua Zhu
Guanghai Yan
author_sort Chang Xu
collection DOAJ
description Abstract Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Methods Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Results Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Conclusion Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways.
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spelling doaj-art-3feb79822e494617bb2f7bcff4f7c01c2025-08-20T03:15:35ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941406141710.1002/iid3.490Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathwaysChang Xu0Yilan Song1Zhiguang Wang2Jingzhi Jiang3Yihua Piao4Li Li5Shan Jin6Liangchang Li7Lianhua Zhu8Guanghai Yan9Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaDepartment of Dermatology Yanbian University Hospital Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaDepartment of Dermatology Yanbian University Hospital Yanji Jilin ChinaJilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University Yanji Jilin ChinaAbstract Introduction Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways. Methods Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels. Results Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways. Conclusion Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways.https://doi.org/10.1002/iid3.490AMPKHO‐1Nrf2oxidative stressPterostilbene (Pts)Sirt 1
spellingShingle Chang Xu
Yilan Song
Zhiguang Wang
Jingzhi Jiang
Yihua Piao
Li Li
Shan Jin
Liangchang Li
Lianhua Zhu
Guanghai Yan
Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
Immunity, Inflammation and Disease
AMPK
HO‐1
Nrf2
oxidative stress
Pterostilbene (Pts)
Sirt 1
title Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
title_full Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
title_fullStr Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
title_full_unstemmed Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
title_short Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
title_sort pterostilbene suppresses oxidative stress and allergic airway inflammation through ampk sirt1 and nrf2 ho 1 pathways
topic AMPK
HO‐1
Nrf2
oxidative stress
Pterostilbene (Pts)
Sirt 1
url https://doi.org/10.1002/iid3.490
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