Ixeris dentata Extract Increases Salivary Secretion through the Regulation of Endoplasmic Reticulum Stress in a Diabetes-Induced Xerostomia Rat Model

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.

Compliance with Saliva Collection Protocol in Healthy Volunteers: Strategies for Managing Risk and Errors

“…If saliva is handled wisely, salivary biomarkers such as enzymes and proteins (e.g., alpha-amylase) 4 , stress proteins (e.g., GRP78) 3 , 88 and HSP70 89 , infectious diseases (e.g., HIV), oral squamous cell carcinoma 90 , 91 , and CA125 markers of neoplasia 92 can be effectively assessed. Additionally, analytes such as hormones, steroids, antibodies, growth factors, cytokines, chemokines, nucleic acids, and proteins related to different systemic diseases, psychological research, autoimmune diseases, and oral diseases (caused by fungus, viruses, and bacteria) can be successfully implemented in diagnostic applications 87 .…”

“…Saliva is an important specimen in dental research and in the oral physiology field due to its suitability as a non-invasive diagnostic tool. Saliva has been used to diagnose various autoimmune diseases, diabetes, cardiovascular diseases, dental caries, and other oral diseases 1 - 3 . Saliva volume and biochemical composition differ among individuals; these parameters are influenced by age 4 , sex 5 , and diet 6 .…”

Protective Effect and Mechanism of Action of Rosmarinic Acid on Radiation-Induced Parotid Gland Injury in Rats

“…Rats were injected intraperitoneally with 0.6 mg/kg pilocarpine hydrochloride (Sigma-Aldrich), and then stimulated saliva was collected 4 days before and 3, 10, 30, 60, and 120 days after IR according to a previously described procedure. 26 Cotton balls, which were preweighed and kept in the oral cavity for 10 minutes to absorb saliva, were immediately weighed on an electronic balance to prevent moisture loss. Assuming the specific gravity of saliva to be 1.0 g/cm 3 , the difference of pre and postcollection cotton ball mass in grams was substituted by milliliters.…”

IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases

“…In this disease, secretory cells are the main type affected, which leads to reduced secretion, resulting in pathologies such as dry mouth and dry skin ( 309 ). Normally, salivary gland acinar cells, due to their secretory function, are highly susceptible to ER stress under physiological circumstances due to their high rate of protein synthesis ( 310 – 312 ). Therefore, activation of IRE1α and other UPR molecules is expected due to their regulation of secretion and also to alleviate the ER folding load ( 87 , 313 ).…”