Treatment with the Biscoclaurine Alkaloid Cepharanthine Significantly Increases Salivary Secretion in Primary Sjögren's Syndrome Patients

• Material Type: 博士論文
• Title: Treatment with the Biscoclaurine Alkaloid Cepharanthine Significantly Increases Salivary Secretion in Primary Sjögren's Syndrome Patients
• Author/Editor: Yamanoi, Tomoko; Aota, Keiko; Momota, Yukihiro; Azuma, Masayuki
• Author Heading: Yamanoi, Tomoko; Aota, Keiko; Momota, Yukihiro; Azuma, Masayuki
• Publication, Distribution, etc.: 四国歯学会
• Publication Date: 2017-04-04
• Publication Date (W3CDTF): 2017-04-04
• Alternative Title: 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
• Periodical title: Journal of Oral Health and Biosciences
• No. or year of volume/issue: 29 2
• Volume: 29
• Issue: 2
• Pages: 39-48
• ISSN (Periodical Title): ISSN : 2189-6682; ISSN : 2188-7888
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-23
• Dissertation Number: 甲第3070号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: Primary Sjögren's syndrome; NF-κB; MMP-9; Type IV collagen; Acinar structure; salivary gland; sjögren's syndrome; salivary secretion; cepharanthin
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.20738/johb.29.2_39
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

http://repo.lib.tokushima-u.ac.jp/files/public/11/111058/20190820160914154468/LID201704251010.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/111058/20190820160914651517/LID201704251011.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/111058/20190820160915163773/LID201704251012.pdf fulltext