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

Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there has been no way to relieve these symptoms. This study’s aim was to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin (STZ)-induced diabetes model, the dry mouth condition was established as a model. Here, rats were treated with water or IXD through the sublingual spray, and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na+/H+ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than in each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes, glutathione assay (GSH: GSSG) ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx), were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia.

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Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0282 ◽

2019 ◽

Vol 44 (4) ◽

pp. 365-372

Author(s):

Taye Jemilat Lasisi ◽

Shehu Tijani Shittu ◽

Akinola Rasak Alada

Keyword(s):

Nitric Oxide ◽

Total Protein ◽

Immunoglobulin A ◽

Salivary Secretion ◽

Normal Diet ◽

Secretion Rate ◽

Control Group ◽

Aquaporin 5 ◽

Submandibular Glands ◽

Nitric Oxide Level

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey’s post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

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

International Journal of Molecular Sciences ◽

10.3390/ijms19041059 ◽

2018 ◽

Vol 19 (4) ◽

pp. 1059 ◽

Cited By ~ 10

Author(s):

Kashi Bhattarai ◽

Hwa-Young Lee ◽

Seung-Hyun Kim ◽

Hyung-Ryong Kim ◽

Han-Jung Chae

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Rat Model ◽

Salivary Secretion ◽

Ixeris Dentata

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Effects of Phenylephrine on Transplanted Submandibular Gland

Journal of Dental Research ◽

10.1177/154405910608501208 ◽

2006 ◽

Vol 85 (12) ◽

pp. 1106-1111 ◽

Cited By ~ 18

Author(s):

B. Xiang ◽

Y. Zhang ◽

Y.M. Li ◽

K. Zhang ◽

Y.Y. Zhang ◽

...

Keyword(s):

Submandibular Gland ◽

Apical Membrane ◽

Rabbit Model ◽

Acinar Cells ◽

Salivary Secretion ◽

Secretory Function ◽

Aquaporin 5 ◽

Receptor Signal ◽

Wharton’S Duct ◽

Structural Injury

Autotransplantation of the submandibular gland is a potential treatment for severe kerato-conjunctivitis sicca. However, one of the major barriers to this procedure is that secretions from the transplanted gland decrease shortly after the operation, which may lead to obstruction of Wharton’s duct, or even to transplantation failure. Using a rabbit model, we investigated whether phenylephrine could improve the secretion from the transplanted gland. We found that phenylephrine treatment significantly reversed the decrease in salivary secretion after transplantation, enhanced the expressions of α1A-, α1B-, and α1D-adrenoceptor mRNA, and ameliorated atrophy of acinar cells. Furthermore, phenylephrine also induced translocation of aquaporin-5 from the cytoplasm to the apical membrane, and increased the levels of phospho-ERK1/2, ERK1/2, phospho-PKCζ, and PKCζ in the transplanted gland. These results indicate that phenylephrine treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through promoting α1-adrenoceptor expression and post-receptor signal transduction.

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The Synergistic Effects of Ixeris dentata and Lactobacillus gasseri Extracts on a Diabetes-induced Dry Mouth Model by Enhancing Antioxidation

10.20944/preprints202003.0230.v1 ◽

2020 ◽

Author(s):

Hwa Young Lee ◽

Mingkun Gu ◽

Jinhua Cheng ◽

Joo Won Suh ◽

Han-Jung Chae

Keyword(s):

Synergistic Effects ◽

Salivary Flow ◽

Diabetic Rats ◽

Dry Mouth ◽

Oxidative Enzymes ◽

Diabetic Patients ◽

Aquaporin 5 ◽

Diabetes Model ◽

Streptozotocin Induced Diabetes ◽

Ixeris Dentata

Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there was no way to relieve these symptoms. This study was aimed to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin-induced diabetes model, dry mouth condition was established as a model. Both control and diabetic rats were treated with a sublingual spray of either water or IXD and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na+/H+ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes; GSH:GSSG ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia.

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Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2018-0006 ◽

2018 ◽

Vol 30 (1) ◽

pp. 111-120 ◽

Cited By ~ 4

Author(s):

Taye Jemilat Lasisi ◽

Shehu-Tijani Toyin Shittu ◽

Akinola Rasak Alada

Keyword(s):

Nitric Oxide ◽

Total Protein ◽

High Fat Diet ◽

Salivary Secretion ◽

Normal Diet ◽

Obese Group ◽

High Fat ◽

Aquaporin 5 ◽

Diet Induced Obesity ◽

M3 Receptor

Abstract Background Obesity has been implicated in impaired salivary secretion. This study aimed at evaluating the influence of diet-induced obesity on salivary secretion and how re-feeding with normal diet would affect changes in salivary secretion associated with diet-induced obesity. Methods Weaning rats weighing 55–65 g were randomly divided into three groups (control, diet-induced obese, re-fed obese) of seven rats each. The diet-induced obese group was fed a high-fat diet for 15 weeks, whereas the re-fed obese group received normal diet for another 15 weeks following the 15 weeks of high-fat diet. After treatment, blood and stimulated saliva samples were collected for the analyses of total protein, electrolytes, amylase, Immunoglobulin A (IgA), leptin and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor and aquaporin 5 in the submandibular glands were determined. Data were presented as mean±SEM and compared using independent student t-test and ANOVA with Tukey’s post-hoc test. Results Results indicated increases in the levels of salivary calcium, phosphate, bicarbonate and leptin, whereas the levels of salivary amylase and ghrelin showed reduction in the obese group compared with the control. Most of these changes were reversed in the re-fed obese group. There were no significant differences in salivary lag time, flow rate, levels of tissue total protein, nitric oxide and the relative expressions of M3 receptor, Na++/K+-ATPase and aquaporin 5 in the submandibular glands between the obese and control groups. Conclusions Diet-induced obesity lead to some changes in salivary factors which were reversed by returning to normal diet.

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Potential Application of Ixeris dentata in the Prevention and Treatment of Aging-Induced Dry Mouth

Nutrients ◽

10.3390/nu10121989 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1989 ◽

Cited By ~ 1

Author(s):

Kashi Bhattarai ◽

Hwa-Young Lee ◽

Seung-Hyun Kim ◽

Jong-Sug Park ◽

Hyung-Ryong Kim ◽

...

Keyword(s):

Submandibular Gland ◽

The Elderly ◽

Salivary Flow ◽

Treated Group ◽

Dry Mouth ◽

Aquaporin 5 ◽

Aging Rats ◽

Gland Weight ◽

Oral Dryness ◽

Ixeris Dentata

Dry mouth is a common complaint among the elderly population. The aim of this study was to investigate the effect of Ixeris dentata (IXD) extract on aging-induced dry mouth. We used young (two months) and aged (20 months) SD rats in our study. Using water as the vehicle, IXD extract (25, 50, and 100 mg/kg) was given via oral gavage to the young and aged rats for eight weeks. We found that the salivary flow rate relative to the submandibular gland weight was differently influenced by IXD extract treatment. IXD extract augmented the submandibular gland acinar cells, which are depleted during aging. In addition, the decreased salivary alpha-amylase, inositol triphosphate receptor, and aquaporin-5 in the aging rats were upregulated by IXD treatment. Free radical-induced oxidative stress in the aging rats was also alleviated in the IXD-treated group. The formation of high molecular weight complexes of protein disulfide isomerase, decreased expression of an ER chaperone (GRP78), and increased ER stress response (ATF-4, CHOP and p-JNK) in aging rats was regulated with IXD treatment, and eventually increased salivary secretions from the aging submandibular glands. These are the first data to suggest that IXD extract might ameliorate aging-associated oral dryness by regulating the ER environment.

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