The Inhibitory Effect of Hedera helix and Coptidis Rhizome Mixture in the Pathogenesis of Laryngopharyngeal Reflux: Cleavage of E-Cadherin in Acid-Exposed Primary Human Pharyngeal Epithelial Cells

Int J Mol Sci. 2024 Nov 14;25(22):12244. doi: 10.3390/ijms252212244.

Abstract

Laryngopharyngeal reflux disease (LPRD) is a prevalent upper airway disorder characterized by inflammation and epithelial damage due to the backflow of gastric contents. Current treatments, primarily proton pump inhibitors (PPIs), often show variable efficacy, necessitating the exploration of alternative or adjunctive therapies. This study investigates the therapeutic potential of a mixture of Hedera helix and Coptidis rhizome (HHCR) in mitigating the pathophysiological mechanisms of LPRD. Using an in vitro model of human pharyngeal epithelial cells exposed to acidic conditions, we observed that acid exposure significantly increased the expression of adenosine A3 receptor (adenosine A3) and matrix metalloproteinase-7 (MMP-7), leading to E-cadherin cleavage and compromised epithelial integrity. Treatment with the HHCR mixture effectively suppressed adenosine A3 expression and MMP-7 activity, thereby reducing E-cadherin cleavage and preserving cellular cohesion. These results highlight the HHCR mixture's ability to modulate the adenosine A3-MMP-7-E-cadherin pathway, suggesting its potential as a valuable adjunctive therapy for LPRD, particularly for patients unresponsive to conventional PPI treatment. This study provides new insights into the molecular interactions involved in LPRD and supports further clinical evaluation of HHCR as a complementary treatment option.

Keywords: adenosine A3; cadherins; hedera and coptidis; laryngopharyngeal reflux; matrix metalloproteinase 7.

MeSH terms

  • Antigens, CD / metabolism
  • Cadherins* / metabolism
  • Cells, Cultured
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Humans
  • Laryngopharyngeal Reflux* / drug therapy
  • Laryngopharyngeal Reflux* / metabolism
  • Matrix Metalloproteinase 7 / metabolism
  • Pharynx / drug effects
  • Pharynx / metabolism
  • Pharynx / pathology
  • Plant Extracts / pharmacology

Substances

  • Cadherins
  • CDH1 protein, human
  • Antigens, CD
  • Plant Extracts
  • Matrix Metalloproteinase 7