ID 111058
Title Alternative
ビスコクラウリン型アルカロイドであるセファランチンは、1次性シェーグレン症候群患者の唾液分泌量を著明に増加させる
Author
Keywords
Primary Sjögren's syndrome
NF-κB
MMP-9
Type IV collagen
Acinar structure
salivary gland
sjögren's syndrome
salivary secretion
cepharanthin
Content Type
Thesis or Dissertation
Description
Objective: Our previous findings suggested that the suppression of tumor necrosis factoralpha (TNF-α)-induced matrix metalloproteinase (MMP)-9 production by the biscoclaurine alkaloid cepharanthine could prevent the destruction of the acinar structure in the salivary glands of murine Sjögren's syndrome. Here, we examined the effect of cepharanthine on the salivary secretion in primary Sjögren's syndrome (pSS) patients.
Methods: In this single-center, open-label pilot study, 29 patients with pSS (28 women, 1 man) received 6 mg/day orally cepharanthine for 12 months. Standard clinical assessments and stimulated salivary flow were examined at baseline and each month for 12 months in all 29 patients. In eight of the patients, inflammatory lesions in the salivary glands were histologically investigated before and after the cepharanthine treatment. We analyzed the expressions of p65, phosphorylated IκB-α, MMP-9, and type IV collagen immunohistochemically.
Results: All patients completed the study without any adverse events. A significant increase in salivary flow was observed after the cepharanthine treatment compared to baseline. The serological analysis revealed that the 14 patients with an anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro) antibody value that was either negative or <64 U/ml responded significantly well to this treatment, whereas the 15 patients with anti-SSA/Ro antibody values >64 U/ml did not. The immunohistochemical analysis demonstrated that although p65, phosphorylated IκB-α, and MMP-9 were more strongly stained in the acinar cells of the patients at baseline compared to the staining at the completion of cepharanthine treatment, the continuity of type IV collagen was observed following the cepharanthine treatment. These results indicate that cepharanthine could inhibit the phosphorylation of IκB-α, followed by the prevention of MMP-9 activation and the stabilization of type IV collagen.
Conclusions: Our findings suggest that cepharanthine could be a promising agent for improving salivary secretion in pSS patients.
Journal Title
Journal of Oral Health and Biosciences
ISSN
21896682
21887888
NCID
AA12713630
Publisher
四国歯学会
Volume
29
Issue
2
Start Page
39
End Page
48
Sort Key
39
Published Date
2017-04-04
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨:LID201704251010.pdf
審査要旨:LID201704251011.pdf
論文本文:LID201704251012.pdf
本論文は,著者Tomoko Yamanoiの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3070号
Diploma Number
甲口第413号
Granted Date
2017-03-23
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences
University Hospital