title: Polydatin attenuated food allergy via store-operated calcium channels in mast cell.
abstract: OBJECTIVE
  To investigate the effect of polydatin (PD), a resveratrol glucoside, on mast cell degranulation and anti-allergic activity.
  
  
  METHODS
  After the rats were orally sensitized with ovalbumin (OVA) for 48 d and underwent PD treatment for 4 d, all the rats were stimulated by 100 mg/mL OVA for 24 h and then sacrificed for the following experiments. The small intestines from all the groups were prepared for morphology examination by hematoxylin and eosin staining. We also used a smooth muscle organ bath to evaluate the motility of the small intestines. The OVA-specific immunoglobulin E (IgE) production and interleukin-4 (IL-4) levels in serum or supernatant of intestinal mucosa homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA). Using toluidine blue stain, the activation and degranulation of isolated rat peritoneal mast cells (RPMCs) were analyzed. Release of histamine from RPMCs was measured by ELISA, and regulation of PD on intracellular Ca(2+) mobilization was investigated by probing intracellular Ca(2+) with fluo-4 fluorescent dye, with the signal recorded and analyzed.
  
  
  RESULTS
  We found that intragastric treatment with PD significantly reduced loss of mucosal barrier integrity in the small intestine. However, OVA-sensitization caused significant hyperactivity in the small intestine of allergic rats, which was attenuated by PD administration by 42% (1.26 ± 0.13 g vs OVA 2.18 ± 0.21 g, P < 0.01). PD therapy also inhibited IgE production (3.95 ± 0.53 ng/mL vs OVA 4.53 ± 0.52 ng/mL, P < 0.05) by suppressing the secretion of Th2-type cytokine, IL-4, by 34% (38.58 ± 4.41 pg/mL vs OVA 58.15 ± 6.24 pg/mL, P < 0.01). The ratio of degranulated mast cells, as indicated by vehicles (at least five) around the cells, dramatically increased in the OVA group by 5.5 fold (63.50% ± 15.51% vs phosphate-buffered saline 11.15% ± 8.26%, P < 0.001) and fell by 65% after PD treatment (21.95% ± 4.37% vs OVA 63.50% ± 15.51%, P < 0.001). PD mediated attenuation of mast cell degranulation was further confirmed by decreased histamine levels in both serum (5.98 ± 0.17 vs OVA 6.67 ± 0.12, P < 0.05) and intestinal mucosa homogenates (5.83 ± 0.91 vs OVA 7.35 ± 0.97, P < 0.05). Furthermore, we demonstrated that administration with PD significantly decreased mast cell degranulation due to reduced Ca(2+) influx through store-operated calcium channels (SOCs) (2.35 ± 0.39 vs OVA 3.51 ± 0.38, P < 0.01).
  
  
  CONCLUSIONS
  Taken together, our data indicate that PD stabilizes mast cells by suppressing intracellular Ca(2+) mobilization, mainly through inhibiting Ca(2+) entry via SOCs, thus exerting a protective role against OVA-sensitized food allergy.
authors.affiliation: Allergy Branch of the State Key Laboratory of Respiratory Disease, School of Medicine, Shenzhen University, Shenzhen 518060, Guangdong Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Jian-Jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Ji-Juan
authors.initials: JJ
authors.lastname: Cao
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qiong-Mei
authors.initials: QM
authors.lastname: Ji
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005512:Food Hypersensitivity / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use*; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000009:adverse effects; D051381:Rats; D011914:Rats, Inbred BN; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D013267:Stilbenes; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D010047:Ovalbumin; D002118:Calcium; C058229:polydatin
keywords: Ca2+; Food allergy; Mast cells; Polydatin; Store-operated calcium channels