Abstract
This study aimed to investigate the molecular mechanism of diabetes mellitus (DM)-induced dry mouth and an application of natural products from Ixeris dentata (IXD), a recently suggested regulator of amylase secretion in salivary cells. Vehicle-treated or diabetic rats were orally treated with either water or an IXD extract for 10 days to observe the effect on salivary flow. We found that the IXD extract increased aquaporin 5 (AQP5) and alpha-amylase protein expression in the submandibular gland along with salivary flow rate. Similarly, the IXD extract and its purified compound increased amylase secretion in high glucose-exposed human salivary gland cells. Furthermore, increased endoplasmic reticulum stress response in the submandibular gland of diabetic rats was inhibited by treatment with the IXD extract, suggesting that IXD extract treatment improves the ER environment by increasing the protein folding capacity. Thus, pharmacological treatment with the IXD extract is suggested to relieve DM-induced dry mouth symptoms.
Highlights
Xerostomia, referred to as dry mouth, is one of the main consequences of diabetes mellitus and is induced by salivary gland dysfunction [1]
Ixeris dentata (IXD) extracted with 100% EtOH had higher amylase than when extracted with low grades of ethanol (Figure 1D,E), suggesting that 100% ethanol extract of IXD had significant influence on amylase extraction
We applied IXD extracts and observed significant increases in salivary flow rate (Figure 3B) and α-amylase expression (Figure 4) in the submandibular gland and in the saliva of diabetic rats
Summary
Xerostomia, referred to as dry mouth, is one of the main consequences of diabetes mellitus and is induced by salivary gland dysfunction [1]. Reduced (Ca2+)ER in salivary glands leads to improper post-translational processing and folding of endoplasmic reticulum (ER) proteins, decreasing salivary amylase activity [6]. The diminished Sarco/endoplasmic-reticulum Ca2+-ATPase (SERCA) was observed in the submandibular gland of STZ-induced diabetic rats which eventually reduced (Ca2+)ER [7]. This decreased (Ca2+)ER led to the improper protein folding in the salivary gland and exhibited xerostomia including low salivary amylase activity [6]. MRNA and protein expression of amylase have been found to be reduced significantly in the parotid glands of diabetic rats [11]. If the translocation of AQP5 to the salivary gland is decreased, the downregulation of protein expression leads to dry mouth symptoms
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