Evaluation of the effects of quercetin on damaged salivary secretion.

With the aim of discovering an effective method to treat dry mouth, we analyzed the effects of quercetin on salivary secretion and its mechanism of action. We created a mouse model with impaired salivary secretion by exposure to radiation and found that impaired secretion is suppressed by quercetin intake. Moreover, secretion levels were enhanced in quercetin-fed normal mice. To elucidate the mechanisms of these effects on salivary secretion, we conducted an analysis using mouse submandibular gland tissues, a human salivary gland epithelial cell line (HSY), and mouse aortic endothelial cells (MAECs). The results showed that quercetin augments aquaporin 5 (AQP5) expression and calcium uptake, and suppresses oxidative stress and inflammatory responses induced by radiation exposure, suggesting that quercetin intake may be an effective method to treat impaired salivary secretion

Effects of quercetin on proinflammatory cytokine expression in SMGs.

<p>SMG tissues from each group were harvested 1 week after the completion of the salivary secretion measurement, and RNA samples extracted from these tissues were used for real-time RT-PCR quantification. (A) TNF-α expression levels are shown. (B) IL-10 expression levels are shown. β-actin was used as an internal control. Data are shown as the mean ± standard deviation (n = 5). Significant differences are expressed as **P <0.01. Cont, fed a normal diet; Q, fed quercetin (1.25 g/kg/day or 0.25 g/kg/day); IR, 15 Gy radiation; Q+IR, fed quercetin plus 15 Gy radiation.</p

Effects of quercetin on calcium uptake into HSY cells.

<p>Carbachol (cch)-induced intracellular calcium concentrations were measured in HSY cells that were pretreated with quercetin (Q, 1 μM, 10 μM, 100 μM) for 2 minutes or left untreated. (A, B) Time points at which cch was added onto fura-2-loaded cells are indicated by arrows. (A) Changes in intracellular calcium upon 30 μM cch stimulation are shown. (B) Changes in intracellular calcium upon 100 μM cch stimulation are shown. (C, D) Changes in the ratios of baseline values prior to cch stimulation and top peak values after stimulation are shown. (C) Upon 30 μM cch stimulation. (D) Upon 100 μM cch stimulation. Data are shown as the mean ± standard deviation (n = 3). Significant differences are expressed as *P <0.05, **P <0.01.</p

Effects of quercetin on MDA.

<p>SMG tissues from each group were harvested one week after completion of the salivary secretion measurements and were used for MDA measurements. Total protein in SMG tissues was used in the MDA detection assessment. Data are shown as the mean ± standard deviation (n = 5). Significant differences are expressed as *P <0.05. Cont, fed a normal diet; Q, fed quercetin (1.25 g/kg/day or 0.25 g/kg/day); IR, 15 Gy radiation; Q+IR, fed quercetin plus 15 Gy radiation.</p

Effects of quercetin on eNOS expression in MAECs.

<p>Samples of RNA extracted from radiation-exposed (IR, 30 Gy) and quercetin-treated (Q, 50 μM, 100 μM) MAECs were used for RT-PCR, and band intensities were quantified using Quantity One 1-D software (Bio-Rad, Hercules, CA). β-actin was used as an internal control. Data are shown as the mean ± standard deviation (n = 5). Significant differences are expressed as *P <0.05.</p

Effects of quercetin on salivary secretion.

<p>Quercetin was given at a dose of 1.25 g/kg/day for 2 weeks from the start of the experiment and subsequently at 0.25 g/kg/day for 8 weeks. Radiation exposure was conducted 2 weeks after the start of the experiment. Salivary secretion levels were measured for 15 min after pilocarpine stimulation, and the total saliva amount was corrected for body weight. Data are shown in terms of salivary secretion levels per g body weight. (A) Comparison between control group (fed a normal diet, Cont) and irradiated group (15 Gy radiation, IR). (B) Comparison between quercetin-fed group (1.25 g/kg/day or 0.25 g/kg/day, Q) and control group. (C) Comparison between quercetin + irradiated group (1.25 g/kg/day or 0.25 g/kg/day and 15 Gy radiation, Q+IR) and exposure group. Data are shown as the mean ± standard deviation (n = 5). Significant differences are expressed as *P <0.05, **P <0.01.</p