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

Tomoko Yamanoi, Keiko Aota, Yukihiro Momota, Masayuki Azuma
2017 Journal of oral health and biosciences  
キーワード:Primary Sjögren's syndrome, NF-κB, MMP-, Type IV collagen, Acinar structure Abstract:Objective: Our previous findings suggested that the suppression of tumor necrosis factoralpha (TNF-α)-induced matrix metalloproteinase (MMP)-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
more » ... gren's syndrome (pSS) patients. Methods: In this single-center, open-label pilot study, patients with pSS ( women, man) received mg/day orally cepharanthine for months. Standard clinical assessments and stimulated salivary flow were examined at baseline and each month for months in all 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 p , phosphorylated IκB-α, MMP-, 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 patients with an anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro) antibody value that was either negative or < U/ml responded significantly well to this treatment, whereas the patients with anti-SSA/Ro antibody values > U/ml did not. The immunohistochemical analysis demonstrated that although p , phosphorylated IκB-α, and MMP-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-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.
doi:10.20738/johb.29.2_39 fatcat:qfwagyfrqvfdzblbktl4giecz4