Triterpene Acids of Loquat Leaf Improve Inflammation in Cigarette Smoking Induced COPD by Regulating AMPK/Nrf2 and NFκB Pathways

Nutrients. 2020 Feb 28;12(3):657. doi: 10.3390/nu12030657.

Abstract

Cigarette smoking (CS) is believed to be an important inducement in the pathological development of chronic obstructive pulmonary disease (COPD), a progressive lung disease. Loquat is an Asian evergreen tree commonly cultivated for its fruit. Its leaf has long been used as an important material for both functional and medicinal applications in the treatment of lung disease in China and Japan. As the principal functional components of loquat leaf, triterpene acids (TAs) have shown notable anti-inflammatory activity. However, their protective activity and underlying action of mechanism on CS-induced COPD inflammation are not yet well understood. In the present study, male C57BL/6 mice were challenged with CS for 12 weeks, and from the seventh week of CS exposure, mice were fed with TAs (50 and 100 mg/kg) for 6 weeks to figure out the therapeutic effect and molecular mechanism of TAs in CS-induced COPD inflammation. The results demonstrate that TA suppressed the lung histological changes in CS-exposed mice, as evidenced by the diminished generation of pro-inflammatory cytokines, including interleukin 1β (IL-1β), IL-2, IL-6, and tumor necrosis factor α (TNF-α). Moreover, TA treatment significantly inhibited the malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity. In addition, TAs increased the phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor erythroid-2-related factor-2 (Nrf2) expression level, while inhibiting phosphorylation of nuclear factor kappa B (NFκB) and inducible nitric oxide synthase (iNOS) expression in CS-induced COPD. In summary, our study reveals a protective effect and putative mechanism of TA action involving the inhibition of inflammation by regulating AMPK/Nrf2 and NFκB pathways. Our findings suggest that TAs could be considered as a promising functional material for treating CS-induced COPD.

Keywords: AMPK; Keywords loquat leaf; NFκB; Nrf2; chronic obstructive pulmonary disease; cigarette smoke; iNOS; inflammation; triterpene acids.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Body Weight
  • Cigarette Smoking / adverse effects*
  • Cytokines / metabolism
  • Eriobotrya / chemistry*
  • Inflammation / drug therapy*
  • Inflammation Mediators / metabolism
  • Lung / pathology
  • Male
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Plant Leaves / chemistry
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Signal Transduction
  • Triterpenes / analysis
  • Triterpenes / chemistry
  • Triterpenes / therapeutic use*
  • Weight Loss

Substances

  • Cytokines
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Triterpenes
  • Nitric Oxide Synthase Type II
  • AMP-Activated Protein Kinases