Front. Pharmacol., 24 September 2021 | https://doi.org/10.3389/fphar.2021.645437IF: 5.988 Q1

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

Ching-Mao Chang (張清貿)1,2,3, Po-Chang Wu4,5, Jr-Rung Lin6, Yeong-Jian Jan Wu7, Shue-Fen Luo7, Yin-Tzu Hsue8, Joung-Liang Lan4,5, Tai-Long Pan9,10,11, Yu-Ting Wu12, Kuang-Hui Yu7*, Yau-Huei Wei12,13,14* and Hen-Hong Chang15,16*

• 1Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
• 2Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
• 3Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
• 4Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan
• 5College of Medicine, China Medical University, Taichung, Taiwan
• 6Clinical Informatics and Medical Statistics Research Center, Graduate Institute of Clinical Medical, Chang Gung University, Taoyuan, Taiwan
• 7Department of Medicine, Division of Allergy, Immunology, and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan
• 8Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Changhua Christian Hospital, Changhua, Taiwan
• 9School of Traditional Chinese Medicine and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
• 10Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
• 11Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
• 12Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua, Taiwan
• 13Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
• 14Department of Medicine, Mackay Medical College, Taipei, Taiwan
• 15Graduate Institute of Integrated Medicine, College of Chinese Medicine, and Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
• 16Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan

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.

中文摘要

背景：修格蘭氏症 (Sjögren’s syndrome)是一種自身免疫性炎症性疾病，主要影響外分泌腺，導致腺體功能障礙。修格蘭氏症的主要侵犯眼睛和口腔乾燥症狀，影響患者的生活質量，並降低他們進行日常活動的能力。

目的：本研究旨在評估中藥複方 SS-1 對修格蘭氏症患者的潛在治療益處的功效。

材料和方法： 中藥複方SS-1 藉由 BioMAP生物活性系統中 12 個人類細胞系統中建構的四種不同中藥複方 SS-1確定濃度。接著進行了一項隨機、雙盲、交叉、安慰劑對照臨床試驗，其中納入 57 名接受 SS-1 治療 28 週的修格蘭氏症患者。

結果：基於細胞的模型中的生物多重活性分析表明中藥複方 SS-1 在 B 細胞中具有抗增生活性、促進抗發炎和免疫調節活性。在臨床試驗中，Schirmer's test結果顯示雙眼有顯著改善，分別增加了 3.42 mm（95% CI，2.44-4.41 mm）和 3.45 mm（95% CI，2.32-4.59 mm），並且可顯著降低在人工淚液使用中。此外，B 細胞激活因子 (BAFF) 和 B 細胞成熟抗原 (BCMA) 水平的增加分別降低了 53.20%（295.29 對 555.02 pg/ml）和 58.33%（99.16 對 169.99 pg/ml）。

結論：中藥複方SS-1可顯著抑制B細胞成熟抗原。無觀察到嚴重的藥物相關不良反應。口服中藥複方SS-1藥可作為是修格蘭氏症之補充及另類治療。