Herbal Formula SS-1 Increases Tear Secretion for Sjögren's Syndrome

Abstract

Background: Sjögren's syndrome (SS) is an autoimmune inflammatory disease that primarily affects the exocrine glands, leading to glandular dysfunction. The hallmark symptoms of SS are dry eyes and mouth, compromising the quality of life of patients and decreasing their capacity to perform their daily activities. Objective: This study aims to evaluate the efficacy of the herbal formula SS-1 for its potential therapeutic benefits for patients with Sjögren's syndrome. Materials and Methods: The bioactivity profile of SS-1 was determined using four different SS-1 concentrations across 12 human primary cell systems of the BioMAP profile. After that, a randomized, double-blind, crossover, placebo-controlled trial was performed including 57 patients treated with SS-1 for 28 weeks. Results: Biologically multiplexed activity profiling in cell-based models indicated that SS-1 exerted anti-proliferative activity in B cells and promoted anti-inflammatory and immunomodulatory activity. In the clinical trial, Schirmer's test results revealed significant improvements in both eyes, with increases of 3.42 mm (95% CI, 2.44-4.41 mm) and 3.45 mm (95% CI, 2.32-4.59 mm), respectively, and a significant reduction in artificial tear use, which was -1.38 times/day, 95% CI, -1.95 to -0.81 times/day. Moreover, the increases in B-cell activating factor (BAFF) and B-cell maturation antigen (BCMA) levels were dampened by 53.20% (295.29 versus 555.02 pg/ml) and 58.33% (99.16 versus 169.99 pg/ml), respectively. Conclusion: SS-1 treatment significantly inhibited B-cell maturation antigen. No serious drug-related adverse effects were observed. Oral SS-1 administration may be a complementary treatment for Sjögren's syndrome.

Keywords: Herbal formula; Integrative therapy; SS-1; Sjögren’s syndrome; Xerophthalmia.

FIGURE 1

The protocol for this integrated clinical trial. The recruited patients were randomly divided into two groups of “Group SS-1-Placebo” and “Group Placebo-SS-1.” SS-1 was administered in an add-on design, and all the subject’s still required the same HCQ treatment throughout the trial. Both groups did not receive additional pilocarpine or cevimeline, which were administered in the patient’s respective rheumatology OPDs. The “Group SS-1-Placebo” patients first received SS-1 for 12 weeks, after which they underwent a 4-weeks washout period, followed by placebo treatment for 12 weeks; and vice versa for the “Group Placebo-SS-1” patients.

FIGURE 2

The analysis of bioactivities in each BioMAP assay systems. The cytotoxic and anti-proliferative activities are illustrated by thin black arrow and grey arrows, respectively.

FIGURE 3

Flowchart of recruitment of patients with Sjögren’s syndrome in this integrated clinical trial.

FIGURE 4

The outcome improvements in (A) Schirmer’s test, (B) Artificial tear usage after the integrated treatment, and (C) serum levels of BAFF and BCMA after the integrated treatment.