Xinqin exhibits the anti-allergic effect through the JAK2/STAT5 signaling pathway

Zhang, Qian; Xiong, Ying; Li, Guobing�; Tang, Qin; Cao, Min; Huang, Jingbin�; Mao, Xing; Hu, Changpeng�; Gong, Ya; Wang, Qinghua; Gao, Ning; Zhang, Rong

doi:10.1016/j.jep.2016.09.045

Cited by 13 publications

(3 citation statements)

References 27 publications

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“…Numerous studies have explored the relationship between SOCS3 and AR in clinical patients and animal experiments [24,25]. Previous experiments conducted by our team indicated that SOCS3 is upregulated in persistent AR, suggesting the potential significance of SOCS proteins as regulators in AR pathogenesis [26].…”

Section: Discussionmentioning

confidence: 88%

Identification of Hit Compounds Using Artificial Intelligence for the Management of Allergic Diseases

Byun,

Tai,

Kim

et al. 2024

IJMS

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This study aimed to identify and evaluate drug candidates targeting the kinase inhibitory region of suppressor of cytokine signaling (SOCS) 3 for the treatment of allergic rhinitis (AR). Utilizing an artificial intelligence (AI)-based new drug development platform, virtual screening was conducted to identify compounds inhibiting the SH2 domain binding of SOCS3. Luminescence assays assessed the ability of these compounds to restore JAK-2 activity diminished by SOCS3. Jurkat T and BEAS-2B cells were utilized to investigate changes in SOCS3 and STAT3 expression, along with STAT3 phosphorylation in response to the identified compounds. In an OVA-induced allergic rhinitis mouse model, we measured serum levels of total IgE and OVA-specific IgE, performed real-time PCR on nasal mucosa samples to quantify Th2 cytokines and IFN-γ expression, and conducted immunohistochemistry to analyze eosinophil levels. Screening identified 20 hit compounds with robust binding affinities. As the concentration of SOCS3 increased, a corresponding decrease in JAK2 activity was observed. Compounds 5 and 8 exhibited significant efficacy in restoring JAK2 activity without toxicity. Treatment with these compounds resulted in reduced SOCS3 expression and the reinstatement of STAT3 phosphorylation in Jurkat T and BEAS-2B cells. In the OVA-induced allergic rhinitis mouse model, compounds 5 and 8 effectively alleviated nasal symptoms and demonstrated lower levels of immune markers compared to the allergy group. This study underscores the promising nonclinical efficacy of compounds identified through the AI-based drug development platform. These findings introduce innovative strategies for the treatment of AR and highlight the potential therapeutic value of targeting SOCS3 in managing AR.

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Section: Discussionmentioning

confidence: 88%

Identification of Hit Compounds Using Artificial Intelligence for the Management of Allergic Diseases

Byun,

Tai,

Kim

et al. 2024

IJMS

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“…It is believed that those inflammatory processes can increase the risk of cancer if the patients are not treated effectively. Extensive investigations have been exploring the association between AR and NPC [ 20 , 21 ]. However, the exact molecular mechanisms involved remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Biyuanling suppresses the toluene-2, 4-diisocyanate induced allergic rhinitis in guinea pigs

Xiang

et al. 2017

Oncotarget

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Allergic rhinitis (AR), one of the common diseases of the upper respiratory system, is associated with high risk of nasopharyngeal carcinoma. Biyuanling Granules (BLG), a formulated preparation of traditional Chinese medicine, has been used in China for treatment of AR for more than a decade; however, its exact action against allergic rhinitis and the mechanism involved remain unclear. In this study, we studied the effects of BLG on allergic rhinitis induced by toluene-2, 4- diisocyanate (TDI) in guinea pigs. The anti-AR effects of BLG were evaluated by behavior observations, histological examinations of the nasal tissues stained with hematoxylin and eosin staining (H&E), immunohistochemical analyses of pulmonary surfactant associated protein (SP), Bcl-2 Associated X Protei (Bax), tumor necrosis factor (TNF-α) and vascular cell adhesion molecule-1 (VCAM-1) in the nasal mucosa, and serum tests of interleukin-4 (IL-4) and human SARS-specific immunoglobulin (SIgE) levels. We observed that in the AR-positive animals treated with BLG, the symptom scores were significantly higher (P < 0.01), the nasal mucosa edemas and inflammatory infiltrates were significantly alleviated (P < 0.01) and the serum IL-4 and SIgE levels were significantly decreased (P < 0.05) as compared with the control group. Immunohistochemical examinations of the nasal mucosa demonstrated that the expressions of TNF-α, SP and VCAM-1 were significantly decreased (P < 0.01), whereas Bax expression was increased in the BLG treatment groups (P < 0.05). These results indicate that BLG can effectively suppress the TDI-induced AR, and that the protective effects of BLG were associated with reductions of TNF-α, SP and VCAM-1, and an elevation of Bax, suggesting that BLG exerts its AR-suppressive effects through inhibition of inflammatory response.

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“…Research has shown that the JAK2/STAT5 signaling pathway can promote in ammatory response by regulating the homeostasis, proliferation, and secretion of in ammatory mediators of in ammatory cells, playing an important role in the occurrence and development of allergic diseases (Wang L et al, 2019). Xinqin herbal medicine can regulate mast cell mediated allergic reaction by downregulating JAK2/STAT5 signaling pathway to play an anti allergic role (Zhang Q et al, 2016). The expression of speci c transcription factor Foxp3 can also regulate the immunosuppressive function of Treg cells (Lifshitz et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Role of JAK2/STAT5/Foxp3 signaling pathway in Jurkat T cells secretion of cytokines induced by traffic-related PM 2.5 and different components

Wang,

Zhao,

Kong

et al. 2024

Preprint

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Studies have shown that traffic-related PM2.5 (TRPM2.5) can damage the immune system and reduce resistance to various diseases. However, the specific mechanisms remain unclear. In this study, Jurkat T cells were used as immune cells model. Exposure to different concentrations of TRPM2.5, water-soluble ions (WSI), and organic extract (OE) aggravated the inflammation of Jurkat T cells, increased the mRNA and protein expressions of JAK2 (Janus kinase 2), reduced signal transducer and activator of transcription (STAT5) and forkhead box P3 (Foxp3), decreased the proportions of Treg cells, and then diminished the release of cytokine IL-10 and TGF-β. However, after AG490 treatment, JAK2 and p-JAK2 mRNA and protein levels were inhibited, and STAT5 and Foxp3 mRNA and protein expressions were improved. Moreover, after transfection with STAT5 plasmid, the mRNA and protein expression of STAT5 and Foxp3 was significantly enhanced. Therefore, JAK2/STAT5/Foxp3 signaling pathway may play a critical regulatory role in the alteration of inflammatory mediators of Jurkat T cells induced by TRPM2.5 and its different components, which provides a scientific reference for the immune-inflammatory diseases caused by PM2.5.

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Xinqin exhibits the anti-allergic effect through the JAK2/STAT5 signaling pathway

Cited by 13 publications

References 27 publications

Identification of Hit Compounds Using Artificial Intelligence for the Management of Allergic Diseases

Identification of Hit Compounds Using Artificial Intelligence for the Management of Allergic Diseases

Biyuanling suppresses the toluene-2, 4-diisocyanate induced allergic rhinitis in guinea pigs

Role of JAK2/STAT5/Foxp3 signaling pathway in Jurkat T cells secretion of cytokines induced by traffic-related PM 2.5 and different components

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