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Ginsenoside Rg3 Alleviates Xerostomia in Orchiectomized Mice via AR/AQP5.

B Chen1, Y Sun2, W Wei3

  • 1School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Medical University, Guangzhou, China.

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Summary

Dihydrotestosterone (DHT) and the natural compound ginsenoside Rg3 upregulate salivary aquaporin 5 (AQP5) expression through androgen receptor (AR) signaling. This finding offers a new therapeutic approach for treating Sjögren

Keywords:
Sjögren’s diseaseandrogen receptoraquaporin 5dihydrotestosteronenatural productsubmandibular gland

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Area of Science:

  • Endocrinology
  • Immunology
  • Cell Biology

Background:

  • Sjögren's disease (SjD) is an autoimmune disorder linked to decreased androgen levels.
  • Current testosterone replacement therapies for SjD have unclear mechanisms and potential side effects.

Purpose of the Study:

  • To investigate the role of dihydrotestosterone (DHT) in regulating salivary gland function in SjD.
  • To identify natural compounds that mimic DHT's effects on salivary aquaporin 5 (AQP5) expression.

Main Methods:

  • Studied DHT's effect on AQP5 transcription in human salivary gland epithelial cells via androgen receptor (AR) signaling.
  • Utilized orchiectomized mice to model androgen deficiency and SjD progression.
  • Screened DHT-like compounds and identified ginsenoside Rg3 for its effects on AQP5 and salivary function.

Main Results:

  • DHT/AR complex binding to the AQP5 promoter upregulates AQP5 expression.
  • Ginsenoside Rg3 mimics DHT's action by binding to AR, upregulating AQP5 and restoring saliva secretion in mouse models.
  • Rg3 treatment normalized submandibular gland morphology and modulated signaling pathways related to salivation and inflammation.

Conclusions:

  • Ginsenoside Rg3 effectively restores androgen deficiency-induced xerostomia (dry mouth) by upregulating AQP5 via AR signaling.
  • Rg3 presents a promising natural therapeutic agent for managing SjD-related salivary dysfunction.