Ginsenoside Rb1 Upregulating AQP5 Protein Expression and Alleviating Salivary Secretion Impairment in Ovariectomized Sjögren’s Syndrome Mice

Abstract

Sjogren’s syndrome(SS) is an autoimmune disease characterized as the impairment of salivary secretion mediated by abnormal aquaporin 5(AQP5). Here we used AQP5 promoter as the target to screen the effective components from natural drugs. Panax quinquefolius and its specific ingredient, Rb1, were identified to increase the AQP5 transcriptional activity and AQP5 expression. Then we investigated the possibility of Rb1 binding to sex hormone receptors and demonstrated that Rb1 bound specifically to estrogen receptor alpha(ERα), but not to androgen receptor. Next, we found that ERα overexpression magnified the effect of Rb1 induced AQP5 transcription, and the silence of ERα blocked this effect, demonstrating that Rb1 activated AQP5 transcription via ERα pathway. Importantly, we constructed SS mouse model and investigated the effects of Rb1 on salivary secretion in vivo. SS mice exhibited significant impairment in salivary secretion and decreased AQP5 expression in the submandibular gland. Intriguingly, SS mice administered with Rb1 exhibited dramatically increased salivary secretion, followed by decreased diary water consumption. In particular, Rb1 up-regulated AQP5 expression localized in the submandibular gland, almost similar to the SS mice administered with estrogen. Our data demonstrated that Rb1 bound with ERα to up-regulate AQP5 to increase saliva secretion, thus functioned as a potential natural phytoestrogen for the therapy of salivary secretion impairment in SS patients.