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

ABSTRACT: 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 fluid-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.

SUBMITTER: Bhattarai KR

PROVIDER: S-EPMC5546769 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Xerostomia is a subjective condition of dryness of the oral cavity that may lead to several oral problems deteriorating oral health-related quality of life. This study aimed to (1) determine the prevalence of xerostomia, (2) compare the general health status, unstimulated salivary flow rate, and oral health-related quality of life in xerostomics and non-xerostomics, and (3) investigate the potential of salivary aquaporin-3 (AQP-3) as a screening biomarker for xerostomia in patients with periodontal disease. Demographics and systemic health data were collected from 109 healthy participants, 20 to 55 years old, with Community Periodontal Index (CPI) score ≥ 3. For subjective assessment of xerostomia, Shortened Xerostomia Inventory (SXI) was used. For objective assessment of xerostomia, unstimulated salivary flow rate was measured. Shortened Oral Health Impact Profile (S-OHIP) was utilized for oral health-related quality of life assessment. The collected saliva samples were processed and stored at -80°C. Quantification of salivary AQP-3 protein was done with enzyme-linked immunosorbent assay. Xerostomia was reported in 78% of the subjects based on SXI score. Median concentration of AQP-3 was significantly higher in xerostomics compared to non-xerostomics, p = 0.001. Moreover, oral health-related quality of life was significantly poor in xerostomics compared to non-xerostomics, p = 0.002. Furthermore, there were significant correlations between AQP-3 and SXI (r = 0.21, p = 0.025), AQP-3 and S-OHIP (r = 0.2, p = 0.042), S-OHIP and SXI (r = 0.37, p < 0.001), unstimulated salivary flow rate and random blood glucose level (r = 0.32, p = 0.001), and body mass index and mean arterial pressure (r = 0.44, p < 0.001). Regression analysis showed that body mass index, CPI score 3, and salivary AQP-3 were suitable predictors for presence of xerostomia. AQP-3 could be a potential screening biomarker for xerostomia in patients with periodontal disease for its early identification may help improve oral health-related quality of life of the individuals.

Project description:Xerostomia is a common symptom in menopausal women, suggesting the role of sex steroids in disease development. Shreds of literature had reported the potential use of herbal extracts to relieve xerostomia. However, a cocktail of multiple components in herbal extract makes it difficult to understand the exact mechanism of action. Aquaporin5 (AQP5), the specific aquaporin expressed in salivary glands, plays an important role in salivary secretion as a downstream of estrogen signaling. In this study, we aimed to unravel a single active herbal component as a therapeutic for xerostomia and investigate its mechanism of action. The effects of apigenin (flavonoid), dauricine (alkaloids), protopine (alkaloids), and lentinan (polysaccharides) on AQP5 transcription were screened in vitro. Only apigenin robustly induced AQP5 transcription and expression, and this effect was even robust compared to the effect of estradiol (E2, a positive control). Overexpression of estrogen receptor α (ERα) in the human salivary gland cell line (HSG) upregulated the AQP5 transcription and expression and the knockdown ERα reversed this effect, suggesting the role of ERα signaling on AQP5 activation in HSG cells. Docking results showed apigenin-specific binding sites in ERα. We further analyzed the therapeutic effect of apigenin on ovariectomized mice as a xerostomia model. The saliva secretion in the xerostomia group was reduced to one-third of the sham group, whereas the apigenin or E2 treatment for 12 weeks reversed this effect. Meanwhile, the water consumption in the xerostomia group was augmented obviously compared to the sham group, whereas the water consumption in the apigenin and E2 group was declined to the level of the sham group. Immunohistochemistry of submandibular glands revealed the downregulation of AQP5 expression in xerostomia mice compared to control. Apigenin, or E2 treatment, upregulated AQP5 expression in xerostomia mice. In conclusion, apigenin, a single active component of herbal extract, upregulated AQP5 expression in HSG cells via activation of ERα signaling and restored saliva flow rates in OVX mice. These results revealed apigenin as a single active component of herbal extract with the potential to treat xerostomia.

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

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