Ixeris dentata extract regulates salivary secretion through the activation of aquaporin-5 and prevents diabetes-induced xerostomia

The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na⁺/H⁺ exchangers in the salivary gland, which suggests that Na⁺/H⁺ exchangers modulate salivary secretions and aid in the fuid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia.