PMID- 35401244
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Isorhamnetin Alleviates Airway Inflammation by Regulating the Nrf2/Keap1 Pathway 
      in a Mouse Model of COPD.
PG  - 860362
LID - 10.3389/fphar.2022.860362 [doi]
LID - 860362
AB  - Chronic obstructive pulmonary disease (COPD) is a severely disabling chronic lung 
      disease characterized by persistent airway inflammation, which leads to limited 
      expiratory airflow that deteriorates over time. Isorhamnetin (Iso) is one of the 
      most important active components in the fruit of Hippophae rhamnoides L. and 
      leaves of Ginkgo biloba L, which is widely used in many pulmonary disease studies 
      because of its anti-inflammatory effects. Here, we investigated the 
      pharmacological action of Iso in CS-induced airway inflammation and dissected the 
      anti-inflammation mechanisms of Iso in COPD mice. A mouse model of COPD was 
      established by exposure to cigarette smoke (CS) and intratracheal inhalation of 
      lipopolysaccharide (LPS). Our results illustrated that Iso treatment 
      significantly reduced leukocyte recruitment and excessive secretion of 
      interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated 
      upon activation, normal T-cell expressed and secreted (RANTES) in BALF of 
      CS-induced COPD mice in a dose-dependent manner. This improved airway collagen 
      deposition and emphysema, and further alleviated the decline in lung functions 
      and systemic symptoms of hypoxia and weight loss. Additionally, Iso treatment 
      obviously improves the T lymphocyte dysregualtion in peripheral blood of COPD 
      mice. Mechanistically, Iso may degrade Keap1 through ubiquitination of p62, 
      thereby activating the nuclear factor erythroid 2-related factor (Nrf2) pathway 
      to increase the expression of protective factors, such as heme oxygenase-1 
      (HO-1), superoxide dismutase (SOD) 1, and SOD2, in lungs of CS-exposed mice, 
      which plays an anti-inflammatory role in COPD. In conclusion, our study indicates 
      that Iso significantly alleviates the inflammatory response in CS-induced COPD 
      mice mainly by affecting the Nrf2/Keap1 pathway. More importantly, Iso exhibited 
      anti-inflammatory effects comparable with Dex in COPD and we did not observe 
      discernible side effects of Iso. The high safety profile of Iso may make it a 
      potential drug candidate for COPD.
CI  - Copyright (c) 2022 Xu, Li, Lin, Liang, Qin, Ding, Chen and Zhou.
FAU - Xu, Yifan
AU  - Xu Y
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
AD  - Institute of Combination Chinese and Western Medicine, Guangzhou Medical 
      University, Guangzhou, China.
FAU - Li, Jing
AU  - Li J
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
AD  - Institute of Combination Chinese and Western Medicine, Guangzhou Medical 
      University, Guangzhou, China.
FAU - Lin, Zhiwei
AU  - Lin Z
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Liang, Weiquan
AU  - Liang W
AD  - Department of Respiratory Medicine, The Second People's Hospital of Foshan, 
      Foshan, China.
FAU - Qin, Lijie
AU  - Qin L
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Ding, Jiabin
AU  - Ding J
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
FAU - Chen, Shuqi
AU  - Chen S
AD  - Institute of Combination Chinese and Western Medicine, Guangzhou Medical 
      University, Guangzhou, China.
AD  - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 
      China.
FAU - Zhou, Luqian
AU  - Zhou L
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220324
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8988040
OTO - NOTNLM
OT  - COPD
OT  - Nrf2
OT  - inflammation
OT  - isorhamnetin
OT  - keap1
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/12 06:00
MHDA- 2022/04/12 06:01
PMCR- 2022/03/24
CRDT- 2022/04/11 05:27
PHST- 2022/01/22 00:00 [received]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/04/11 05:27 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/12 06:01 [medline]
PHST- 2022/03/24 00:00 [pmc-release]
AID - 860362 [pii]
AID - 10.3389/fphar.2022.860362 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Mar 24;13:860362. doi: 10.3389/fphar.2022.860362. 
      eCollection 2022.