Ursolic Acid and Chlorogenic Acid from Boehmeria nivea Drive Aquaporin-5 Upregulation in Salivary Gland Systems

Abstract

Background: Xerostomia, often linked to radiation therapy and autoimmune disorders, arises from impaired salivary gland function with limited therapeutic options. Aquaporin-5 (AQP5) is a critical water channel protein for salivary secretion, yet it remains underexplored as a pharmacological target. Objective: To evaluate Boehmeria nivea–derived phytocompounds for their potential to modulate AQP5 expression using combined in silico and in vitro approaches. Methods: Phytocompounds were screened for drug-likeness, ADMET properties, and pharmacokinetics. Molecular docking was performed against the crystal structure of human AQP5, and gene interaction analysis was conducted using GeneMANIA. Lead compounds were validated in human salivary gland epithelial cells using qRT-PCR and ELISA/Western blotting. Results: Ursolic acid and chlorogenic acid showed strong binding affinity to AQP5, interacting with key residues (Leu47, Leu51, Leu163, Leu167, Thr170, Ser160, Gly159, and Gln58) within the active site. Both compounds significantly upregulated AQP5 at the transcriptional (qRT-PCR: ~2–2.8-fold increase) and protein levels (ELISA/Western: ~2.5–2.8-fold increase), with ursolic acid showing the highest potency. Gene interaction analysis further confirmed AQP5’s linkage with other salivary gland–related proteins (AQP4, AQP3, AQP7, ELF5). Conclusion: B. nivea–derived phytocompounds, particularly ursolic acid and chlorogenic acid, demonstrate strong AQP5-binding potential and significantly enhance its expression at both mRNA and protein levels. These findings establish a foundation for in vivo validation and the translational development of green therapeutics for xerostomia.