Screening Drugs Which Can Promote Salivary Gland Secretion Based On The Target Of AQP5 And Its Mechanism Of Action

Oral dryness caused by Sjogren's syndrome(SS)and menopause is characterized by the objective reductions of salivary flow rate.Salivary disorder could impair oral function.It leads to oral mucosal atrophy and trauma,rampant dental caries,and denture removal difficulties,which cause a negative impact on the quality of life.At present,there is no specific drug for the treatment of oral dryness.Hydroxychloroquine(HCQ)and estrogens are still the most commonly used drugs for oral dryness so far,but they both increase the risk of organ injury,infection and breast cancer.To overcome the defects of contemporary medicine,scientists focus on the natural medicines and have made remarkable achievements.Some scientifically validated extracts have been widely used in clinical treatments.Aquaporin 5(AQP5)is one of the most important aquaporins involved in the secretory function of salivary glands.It has become a target for controlling salivary secretion.To identify compounds that can specifically promote salivary secretion,we used AQP5 as a target and established a drug screening system.We used the functional extracts of widely used Chinese prescriptions as the first scope to screen compounds that promote saliva secretion.Then,we analyzed the structures of all the functional extracts from the prescription and selected the compounds with similar structures to estrogen and HCQ.After deleting the compounds that have already been identified,we chose 15 compounds for the following experiments.What's more,we also found that Apigenin notably activated the transcriptional activity and the expression levelof the AQP5 promoter in a dose-dependent manner.Based on the preliminary results obtained in cellular level,we carried out administration by HCQ,Apigenin,and estrogen for 12 weeks in 8-week-old menopausal mice and SS model mice.The body weight,saliva volume,and water consumption of mice were continues measured during the drug administration.The water consumption and saliva secretion index were further calculated and recorded.As time goes by,the oral dryness symptom was more and more obvious in menopausal mice and SS mice.Compared with the control group,the salivary secretion was increased and the water consumption was decreased by the administration of Apigenin,suggesting the oral dryness symptom was alleviated.Additionally,blood analysis results of SS mice showed that Apigenin could increase the count of immune cell,thereby enhancing the immunity function.Apigenin could activate the transcriptional activity and the expression level of AQP5.Above results verified that Apigenin promotes salivary secretion and reduces water consumption,thereby alleviating oral dryness caused by SS and menopause.The results provide a new direction for drug research and the findings are significant for the clinical treatment of oral dryness.