Pudilan xiaoyan oral liquid alleviates LPS-induced respiratory injury through decreasing nitroxidative stress and blocking TLR4 activation along with NF-ΚB phosphorylation in mice

J Ethnopharmacol. 2018 Mar 25:214:292-300. doi: 10.1016/j.jep.2017.07.009. Epub 2017 Jul 6.

Abstract

Ethnopharmacological relevance: Pudilan xiaoyan oral liquid (PDL), collected in Chinese Pharmacopoeia, has been used clinically for treating inflammatory diseases such as upper respiratory tract infection diseases. However, its potential anti-inflammation and the mechanism are still unclear.

Materials and methods: lipopolysaccharide (LPS) was used to induce respiratory inflammation of mice by intratracheal administration. UPLC/MS was performed for components analysis of PDL. Enzyme-linked immune sorbent assay (ELISA) was conducted for determining interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in serum and supernatant of tracheal tissue while Nitric oxide assay kit for nitric oxide (NO) content. Hematoxylin-Eosin (HE) staining was applied to evaluate pathological lesions. Western blotting analysis (WB) and Immunohistochemistry(IHC) were employed for the determination of Toll-like receptors 4(TLR4), TNF-α, IL-6, inducible nitric oxide synthase(iNOS) and nuclear factor-kappa B p65 (NF-κB p65) protein expressions.

Results: Seven major compounds of PDL were analyzed simultaneously. The treatment of PDL could attenuate LPS-induced histopathological damage of tracheal tissues, followed by reducing pro-inflammation mediators including TNF-α and IL-6 in serum and supernatant of tracheal tissue. LPS-induced nitroxidative stress including NO content and iNOS expression was inhibited significantly by PDL. Furthermore, PDL also down-regulated NF-kB p65 phosphorylation and TLR4 expressions.

Conclusion: The results indicated that the PDL had a protective effect on LPS-induced respiratory inflammation injury in mice. Our findings for the first time provide experimental evidence for the application of PDL on respiratory inflammation injury in clinical practice.

Keywords: Adenosine(PubChem CID:60961); Anti-inflammation; Baicalin(PubChem CID:64982); Caffeic Acid (PubChem CID: 1549111); Chlorogenic Acid (PubChem CID:1794427); Cichoric Acid(PubChem CID: 5281764); Corynoline(PubChem CID:177014); Nitroxidative stress; Pudilan xiaoyan oral liquid; Respiratory disease; Wogonin (PubChem CID:5281703).

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage*
  • Inflammation Mediators / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides*
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / chemically induced
  • Lung Injury / immunology
  • Lung Injury / metabolism
  • Lung Injury / prevention & control*
  • Male
  • Mice, Inbred ICR
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitrosative Stress / drug effects*
  • Phosphorylation
  • Signal Transduction / drug effects
  • Time Factors
  • Toll-Like Receptor 4 / drug effects*
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / immunology
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • IL1B protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Pudilan xiaoyan
  • Rela protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse