Chinese herbal medicine SS-1 inhibits T cell activation and abrogates TH responses in Sjögren's syndrome

Lee, Gilbert; Chang, Ching-Ter; Wāng, Ying; Ma, Ruoyu; Chen, Cheng-Yu; Hsue, Yin-Tzu; Liao, Nan‐Shih; Chang, Hen‐Hong

doi:10.1016/j.jfma.2020.07.024

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…In another study (Lee et al, 2020), we found that SS-1 functioned to reduce the percentages of CD69 + and CD25 + cells among CD8 + and CD4 + T cells upon 24-h activation, as well as the percentages of IL-4 + cells and the levels of IL-4 and IL-13 produced by CD4 + T cells after T H 2 polarization. These findings indicated that SS-1 could inhibit both the activation and the T H 1, T H 2, and IL-17A + IFNγ + T H polarization of murine T cells.…”

Section: Introductionmentioning

confidence: 78%

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

Chang

Lin

et al. 2021

Front. Pharmacol.

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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.

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Section: Introductionmentioning

confidence: 78%

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

Chang

Lin

et al. 2021

Front. Pharmacol.

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“…T cells are known to play an important role in SS [39]. Our previous study pointed out that SS-1 inhibits Th1 (CD4+ IFN-γ+ and CD4+ TNF-α+ cells) and Th2 (CD4+ IL-4+ c cells) polarization of mouse spleen cells and T cell proliferation in Sjögren's syndrome [9]. In this study, we also found that SS-1 inhibited splenic T cell proliferation (Figure 4A), Th1 (CD4+ IFN-γ+) and Th17 (CD4+ IL-17+) cells (Figure 4C,D), and reduced the levels of cytokines (IFN-γ and IL-17) in a salivary gland-induced SS-like symptom mouse model (Figure 4B).…”

Section: Discussionmentioning

confidence: 99%

“…The Chinese herbal formula SS-1 is composed of Gan Lu Yin (GLY), Sang Ju Yin (SJY), and Xuefu Zhuyu decoction (XZD), which exert anti-inflammatory [6], immunomodulatory [7], and antifibrotic [8] effects, respectively. Recently, Lee et al used murine T cell-based assays to investigate the effect of SS-1 on T cell responses [9]. Researchers have concluded that SS-1 inhibits T cell activation and abrogates T H responses in Sjögren's syndrome [9].…”

Section: Introductionmentioning

confidence: 99%

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Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

Lin

Panny

et al. 2021

Life

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Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

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“…Suan-Zao-Ren-Tang (SZRT) could regulate the gammaaminobutyric acid-ergic(GABA) system in plasma which is crucial in the etiology of psychiatric disorders (8). The results of studies conducted on animals have indicated that Gan-Lu-Yin (GLY) can influence vascular smooth muscle activity (9) and exert anti-inflammatory effect (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Traditional Chinese Medicine in Patients With Primary Sjogren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Chen

et al. 2021

Front. Med.

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Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease mainly characterized by dryness, fatigue, and pain. Current therapies for SS in Western medicine are limited. The purpose of this clinical study was to explore the efficacy and safety of using a traditional Chinese medicine (TCM) formula on patients with primary SS.Methods: We performed a 12-week, randomized, double-blinded, placebo-controlled clinical trial at Chung Shan Medical University Hospital. We included 42 patients with SS between the ages of 20 and 80 years who met the classification criteria of the American and European Consensus Group (AECG). Patients who had other severe systemic manifestations or diseases were excluded from this trial. After screening, patients were randomly assigned to the TCM treatment group or placebo group (ratio of 2:1). We treated the TCM group with 6 g of Gan-Lu-Yin granules after breakfast and 6 g of Jia-Wei-Xiao-Yao-San combined with 1 g of Suan-Zao-Ren-Tang and 1 g of Ye-Jiao-Teng every night after dinner. Patients in the control group were treated with a placebo with the same appearance and flavor but only one-tenth the dosage of that received by the treatment group. The European League Against Rheumatism Sjogren's Syndrome Patient-Reported Index (ESSPRI) was used as the primary endpoint at week 12. Secondary endpoints were the Sjogren's Syndrome Disease Activity Index (SSDAI), physician global assessment (PGA), visual analogue scale (VAS), Multidimensional Fatigue Inventory, Medical Outcomes Survey Short Form-36, and the Pittsburgh Sleep Quality Score (PSQI). Adverse events were also recorded.Results: Of the 42 randomized patients, 28 patients were assigned to the TCM treatment group and 14 patients were assigned to the controlled group. During the study period, 5 patients withdrew from the TCM group and 7 withdrew from the control group. At week 12, the ESSPRI scores of both groups had improved. The ESSPRI score of the treatment group decreased by 0.62 (95% CI P = 0.557) and that of the placebo group decreased by 0.91 (P = 0.557). However, no significant difference was observed between the two groups. Sleep duration in the PSQI was −0.61, which exhibited an improvement of more than the −0.21 compared with the placebo group (P = 0.914).Conclusion: At week 12, the ESSPRI scores did not reveal that the use of the TCM formula was efficacious for treating patients with Sjogren's syndrome. However, the PSQI scores indicated that this formula could prolong patient sleep duration. We also found that this formula could decrease the blood pressure of patients.

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Chinese herbal medicine SS-1 inhibits T cell activation and abrogates TH responses in Sjögren's syndrome

Cited by 11 publications

References 34 publications

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

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

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

Traditional Chinese Medicine in Patients With Primary Sjogren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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