PMID- 34342160
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 9
IP  - 4
DP  - 2021 Dec
TI  - Pterostilbene suppresses oxidative stress and allergic airway inflammation 
      through AMPK/Sirt1 and Nrf2/HO-1 pathways.
PG  - 1406-1417
LID - 10.1002/iid3.490 [doi]
AB  - 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 siAMPKalpha2, 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 gamma (IFN-gamma). 
      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-gamma 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-alpha, COX-2, IL-1beta, 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.
CI  - (c) 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & 
      Sons Ltd.
FAU - Xu, Chang
AU  - Xu C
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
FAU - Song, Yilan
AU  - Song Y
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
FAU - Wang, Zhiguang
AU  - Wang Z
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, 
      Yanji, Jilin, China.
FAU - Jiang, Jingzhi
AU  - Jiang J
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
FAU - Piao, Yihua
AU  - Piao Y
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Intensive Care Unit, Affiliated Hospital of Yanbian University, 
      Yanji, Jilin, China.
FAU - Li, Li
AU  - Li L
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
FAU - Jin, Shan
AU  - Jin S
AD  - Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China.
FAU - Li, Liangchang
AU  - Li L
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
FAU - Zhu, Lianhua
AU  - Zhu L
AD  - Department of Dermatology, Yanbian University Hospital, Yanji, Jilin, China.
FAU - Yan, Guanghai
AU  - Yan G
AUID- ORCID: 0000-0001-8058-7822
AD  - Jilin Key Laboratory for Immune and Targeting Research on Common Allergic 
      Diseases, Yanbian University, Yanji, Jilin, China.
AD  - Department of Anatomy Histology and Embryology, Yanbian University Medical 
      College, Yanji, Jilin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210802
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - 0 (Cytokines)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Stilbenes)
RN  - 26R60S6A5I (pterostilbene)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Animals
MH  - Cytokines/metabolism
MH  - Inflammation/drug therapy
MH  - Lung
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress
MH  - *Sirtuin 1
MH  - Stilbenes
PMC - PMC8589405
OTO - NOTNLM
OT  - AMPK
OT  - HO-1
OT  - Nrf2
OT  - Pterostilbene (Pts)
OT  - Sirt 1
OT  - oxidative stress
COIS- The authors declare that there are no conflict of interests.
EDAT- 2021/08/04 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/08/02
CRDT- 2021/08/03 07:01
PHST- 2021/07/02 00:00 [revised]
PHST- 2021/04/27 00:00 [received]
PHST- 2021/07/06 00:00 [accepted]
PHST- 2021/08/04 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/08/03 07:01 [entrez]
PHST- 2021/08/02 00:00 [pmc-release]
AID - IID3490 [pii]
AID - 10.1002/iid3.490 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2021 Dec;9(4):1406-1417. doi: 10.1002/iid3.490. Epub 2021 Aug 
      2.