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Function of hesperidin alleviating inflammation and oxidative stress responses in COPD mice might be related to SIRT1/PGC-1α/NF-κB signaling axis.

Abstract
Purpose: Hesperidin has anti-inflammatory and anti-oxidant stress effects, but its functions in chronic obstructive pulmonary disease (COPD) remains unknown. This study analyzed the role of hesperidin in COPD mice, aiming to provide a basis for the hesperidin application.Materials and methods: Mice were injected with cigarette smoke extract (CSE) to construct COPD models and then treated with budesonide or hesperidin. Hematoxylin-eosin (HE) and TUNEL assays were used to observe the pathological changes and cell death of lung tissue. The levels of interleukin (IL)-6, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in bronchoalveolar lavage fluid (BLAF), as well as myeloperoxidase (MPO) content in lung tissues were confirmed. The expression levels of SIRT1, PGC-1α, and p65 proteins were measured by western blotting (WB) analysis.Results: CSE induced inflammatory cell infiltration and cell death in the lung tissues of mice, whereas budesonide and hesperidin effectively alleviated these pathological changes. The levels of IL-6, IL-8, and MDA in BLAF and pulmonary MPO content in the COPD mice were effectively increased, while the levels of SOD and CAT in BLAF were decreased, which could be reversed by budesonide and hesperidin. Moreover, the addition of budesonide or hesperidin reliably accelerated the expression levels of PGC-1α and SIRT1 but suppressed the phosphorylation of p65 in COPD mice. In general, high-dose hesperidin had a stronger regulatory effect on COPD mice.Conclusions: Hesperidin alleviated inflammation and oxidative stress responses in CES-induced COPD mice, associated with SIRT1/PGC-1α/NF-κB signaling axis, which might become a new direction for COPD treatment.
AuthorsShuyun Wang, Ning He, Haiyan Xing, Yuemei Sun, Juan Ding, Liping Liu
JournalJournal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 40 Issue 4 Pg. 388-394 (Aug 2020) ISSN: 1532-4281 [Electronic] England
PMID32164488 (Publication Type: Journal Article)
Chemical References
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • RELA protein, human
  • Smoke
  • Transcription Factor RelA
  • Hesperidin
  • Peroxidase
  • Superoxide Dismutase
  • Sirt1 protein, mouse
  • Sirtuin 1
Topics
  • Animals
  • Bronchoalveolar Lavage Fluid (chemistry)
  • Disease Models, Animal
  • Hesperidin (pharmacology)
  • Humans
  • Inflammation (drug therapy, genetics, pathology)
  • Interleukin-6 (chemistry)
  • Interleukin-8 (chemistry, isolation & purification)
  • Lung (drug effects, metabolism)
  • Mice
  • NF-kappa B (genetics)
  • Oxidative Stress (drug effects)
  • Peroxidase (chemistry, isolation & purification)
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (genetics)
  • Pulmonary Disease, Chronic Obstructive (drug therapy, genetics, metabolism, pathology)
  • Signal Transduction (drug effects)
  • Sirtuin 1 (genetics)
  • Smoke (adverse effects)
  • Superoxide Dismutase (chemistry, isolation & purification)
  • Transcription Factor RelA (genetics)

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