Integrated Network Pharmacology and Mice Model to Investigate Qing Zao Fang for Treating Sjögren’s Syndrome

Sjögren’s syndrome (SS) is an autoimmune disease, and its conventional treatment has exhibited limited therapeutic efficacy. Qing Zao Fang (QZF), a traditional Chinese medicine formula, is used in the treatment of Sjögren’s syndrome, but its chemical composition is complex, and its pharmacological mechanism is not clear. Therefore, this study aims to explore the potential mechanism of QZF in the treatment of Sjögren’s syndrome based on network pharmacology and SS mouse model. The main active components and predicted targets of QZF were analyzed by network pharmacology. The SS mouse model was constructed and divided into 6 groups: control, SS, SS + hydroxychloroquine (HCQ)-treated, SS + low-dose QZF-treated, SS + medium-dose QZF-treated, and SS + high-dose QZF-treated group. Immunohistochemical, ELISA, and qRT-PCR assays were performed to detect the expressions of targets associated with SS. TUNEL staining was used to detect apoptosis. Cumulatively, 230 active compounds and 1883 targets of QZF were identified. There were 227 common targets for QZF and SS. The effective active ingredients were stigmasterol, neocryptotanshinone II, neotanshinone C, miltionone I, and beta-pinene. It mainly acts on biological processes such as inflammatory response, chemokine metabolic process, and immune response as well as pathways such as FoxO signaling pathway, Yersinia infection, HIF-1 signaling pathway, and TNF signaling pathway. In SS mice, levels of AKT1, HIF-1α, TNF-α, IL-6, and IL-17A were increased, while decreased after QZF treatment. In contrast, IL-10 levels were decreased in SS mice and increased in QZF-treated mice. In addition, QZF reduced apoptosis in the submandibular gland tissue compared to SS mice. It can be concluded that the QZF in treatment of SS is the result of the combined action of multiple components, multiple targets, and multiple pathways. This study improves the understanding of the link between QZF and SS on molecular mechanisms.

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Faculty Opinions recommendation of IL-17 sequestration via salivary gland gene therapy in a mouse model of Sjogren's syndrome suppresses disease-associated expression of the putative autoantigen Klk1b22.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725703368.793512522 ◽

2015 ◽

Author(s):

Sarah Gaffen ◽

J Agustin Cruz

Keyword(s):

Gene Therapy ◽

Salivary Gland ◽

Mouse Model ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Sjögren‘S Syndrome

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Knockdown of RSAD2 attenuates B cell hyperactivity in patients with primary Sjögren’s syndrome (pSS) via suppressing NF-κb signaling pathway

Molecular and Cellular Biochemistry ◽

10.1007/s11010-021-04070-z ◽

2021 ◽

Author(s):

Hong Zhu ◽

Jian Zheng ◽

Yan Zhou ◽

Tong Wu ◽

Tiantian Zhu

Keyword(s):

B Cell ◽

Signaling Pathway ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Sjögren‘S Syndrome

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Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory Neuronopathy in Sjögren's Syndrome

Case Reports in Immunology ◽

10.1155/2012/186320 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Maria Giovanna Danieli ◽

Lucia Pettinari ◽

Ramona Morariu ◽

Fernando Monteforte ◽

Francesco Logullo

Keyword(s):

Mycophenolate Mofetil ◽

Intravenous Immunoglobulin ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Lower Limbs ◽

High Dose ◽

Sensory Neuronopathy ◽

Sjögren‘S Syndrome

Sensory neuronopathy is described in association with the Sjögren's syndrome (SS). We studied a 55-year-old woman with a 4-year history of progressive asymmetric numbness, distal tingling, and burning sensation in upper and lower limbs. In a few months, she developed ataxia with increased hypoanaesthesia. Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve action potential in upper and lower limbs. Cervical spine magnetic resonance showed a signal hyperintensity of posterior columns. Previous treatment with high-dose glucocorticoids and azathioprine was ineffective. A combined treatment with intravenous immunoglobulin and mycophenolate mofetil was followed by a progressive and persistent improvement. This case documented the efficacy and the safety of the coadministration of intravenous immunoglobulin and mycophenolate mofetil in sensory neuronopathy associated with SS refractory to conventional immunosuppressive therapy.

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The NZB/W F1 mouse model for Sjögren's syndrome: A historical perspective and lessons learned

Autoimmunity Reviews ◽

10.1016/j.autrev.2020.102686 ◽

2020 ◽

Vol 19 (12) ◽

pp. 102686

Author(s):

Harini Bagavant ◽

Aleksandra Michrowska ◽

Umesh S. Deshmukh

Keyword(s):

Mouse Model ◽

Sjögren’S Syndrome ◽

Historical Perspective ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Lessons Learned ◽

Sjögren‘S Syndrome

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Dysregulated co-stimulatory molecule expression in a Sjögren’s syndrome mouse model with potential implications by microRNA-146a

Molecular Immunology ◽

10.1016/j.molimm.2015.09.027 ◽

2015 ◽

Vol 68 (2) ◽

pp. 606-616 ◽

Cited By ~ 4

Author(s):

Adrienne E. Gauna ◽

Yun-Jong Park ◽

Gautam Nayar ◽

Marelys Onate ◽

Jun-o Jin ◽

...

Keyword(s):

Mouse Model ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Sjögren‘S Syndrome

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Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome

AJP Cell Physiology ◽

10.1152/ajpcell.00275.2015 ◽

2016 ◽

Vol 310 (11) ◽

pp. C942-C954 ◽

Cited By ~ 12

Author(s):

Zhen Meng ◽

Maria C. Edman ◽

Pang-Yu Hsueh ◽

Chiao-Yu Chen ◽

Wannita Klinngam ◽

...

Keyword(s):

Mouse Model ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Cathepsin S ◽

Secretory Vesicles ◽

Structured Illumination Microscopy ◽

Tear Proteins ◽

Sjögren‘S Syndrome

The mechanism responsible for the altered spectrum of tear proteins secreted by lacrimal gland acinar cells (LGAC) in patients with Sjögren's Syndrome (SS) remains unknown. We have previously identified increased cathepsin S (CTSS) activity as a unique characteristic of tears of patients with SS. Here, we investigated the role of Rab3D, Rab27a, and Rab27b proteins in the enhanced release of CTSS from LGAC. Similar to patients with SS and to the male nonobese diabetic (NOD) mouse model of SS, CTSS activity was elevated in tears of mice lacking Rab3D. Findings of lower gene expression and altered localization of Rab3D in NOD LGAC reinforce a role for Rab3D in suppressing excess CTSS release under physiological conditions. However, CTSS activity was significantly reduced in tears of mice lacking Rab27 isoforms. The reliance of CTSS secretion on Rab27 activity was supported by in vitro findings that newly synthesized CTSS was detected in and secreted from Rab27-enriched secretory vesicles and that expression of dominant negative Rab27b reduced carbachol-stimulated secretion of CTSS in cultured LGAC. High-resolution 3D-structured illumination microscopy revealed microdomains of Rab3D and Rab27 isoforms on the same secretory vesicles but present in different proportions on different vesicles, suggesting that changes in their relative association with secretory vesicles may tailor the vesicle contents. We propose that a loss of Rab3D from secretory vesicles, leading to disproportionate Rab27-to-Rab3D activity, may contribute to the enhanced release of CTSS in tears of patients with SS.

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