Sjögren’s syndrome is an autoimmune disease, and its conventional treatment has exhibited limited therapeutic efficacy. Qing Zao Fang, 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 Qing Zao Fang in the treatment of Sjögren’s syndrome based on network pharmacology and Sjögren’s syndrome mouse model.
The main active components and predicted targets of Qing Zao Fang were analyzed by network pharmacology. The Sjögren’s syndrome mouse model was constructed and divided into 6 groups: control, Sjögren’s syndrome, Sjögren’s syndrome + hydroxychloroquine (HCQ)-treated, Sjögren’s syndrome + low-dose Qing Zao Fang-treated, Sjögren’s syndrome + medium-dose Qing Zao Fang-treated, and Sjögren’s syndrome + high-dose Qing Zao Fang-treated group. Immunohistochemical, ELISA, and qRT-PCR assays were performed to detect the expressions of targets associated with Sjögren’s syndrome. TUNEL staining was used to detect apoptosis. Cumulatively, 230 active compounds and 1883 targets of Qing Zao Fang were identified.
There were 227 common targets for Qing Zao Fang and Sjögren’s syndrome. 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 Sjögren’s syndrome mice, levels of AKT1, HIF-1α, TNF-α, IL-6, and IL-17A were increased, while decreased after Qing Zao Fang treatment. In contrast, IL-10 levels were decreased in Sjögren’s syndrome mice and increased in Qing Zao Fang-treated mice.
In addition, Qing Zao Fang reduced apoptosis in the submandibular gland tissue compared to Sjögren’s syndrome mice. It can be concluded that the Qing Zao Fang in treatment of Sjögren’s syndrome is the result of the combined action of multiple components, multiple targets, and multiple pathways. This study improves the understanding of the link between Qing Zao Fang and Sjögren’s syndrome on molecular mechanisms.