Last update 01 Nov 2024

NF-κB x STAT x JAK

Last update 01 Nov 2024

Basic Info

Related Targets

NF-κBSTATJAK

Drugs associated with NF-κB x STAT x JAK

C498-0670

Target

JAK x NF-κB x STAT

Mechanism

JAK inhibitors [+2]

Active Org.

Ocean University of China [+1]

Originator Org.

The Affiliated Hospital of Qingdao University [+1]

Active Indication

Sepsis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NF-κB x STAT x JAK

100 Translational Medicine associated with NF-κB x STAT x JAK

0 Patents (Medical) associated with NF-κB x STAT x JAK

1,399

Literatures (Medical) associated with NF-κB x STAT x JAK

01 Jan 2025·Journal of Ethnopharmacology

Xuetongsu ameliorates synovial inflammatory hyperplasia in rheumatoid arthritis by inhibiting JAK2/STAT3 and NF-κB signaling pathways

Article

Author: Li, Bin ; Chen, Yuxin ; Zheng, Hao ; Yu, Huanghe ; Su, Wei ; Deng, Yasi ; Ahmad, Bilal ; Liang, Ling ; Yuan, Hanwen ; Wang, Wei ; Yang, Yupei

ETHNOPHARMACOLOGICAL RELEVANCESynovial inflammatory hyperplasia is the key pathological process that leads to further joint damage in rheumatoid arthritis (RA) progress. Kadsura heteroclita (Roxb) Craib, also called Xuetong in Chinese Tujia ethnomedicine, is utilized for its medicinal properties, including promoting blood circulation, dispelling "wind evil", and relieving "damp evil". It has been used in the treatment of arthralgia and RA, within Tujia ethnomedicinal practices. Xuetongsu (XTS), the main component of Xuetong, has been shown to inhibit the proliferation of RA fibroblast-like synovial cells (RAFLS) cells. However, the molecular mechanism of XTS in RA treatment requires further investigation.AIM OF THE STUDYTo observe the therapeutic effect of XTS on synovial inflammatory hyperplasia in rheumatoid arthritis, focusing on its underlying molecular mechanisms involving the janus kinase 2 (JAK2)/transducer/activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways.MATERIALS AND METHODSProtein-protein interaction (PPI) and molecular docking were used to find the main targets of XTS treatment for RA. In lipopolysaccharide (LPS)-induced RAFLS and RAW264.7 cells in vitro models, the levels of inflammatory cytokines were analyzed using enzyme linked immunosorbent assay (ELISA), and the expression of JAK2, STAT3, and NF-κB signaling pathways, as well as cyclooxygenase-2 (COX-2), were analyzed through western blotting test. A hemolysis assay was used to certify the biosecurity of XTS. A model of adjuvant arthritis (AIA) was established in 40 male rats, and different doses of XTS were administered, followed by an automatic blood routine, ELISA assay, hematoxylin and eosin (H&E) staining, and radiological analysis of the effect of no XTS on blood cytokines, histological changes, and improvement of posterior paw bone destruction in AIA rats. The protein levels of inflammatory cytokines were analyzed by immunofluorescence, immunohistochemistry, or Western blot. Finally, H&E staining was used to detect the damage of XTS on the heart, liver, spleen, lung, and kidney of AIA rats.RESULTSOur results demonstrate that XTS effectively inhibited LPS-induced inflammatory responses in RAFLS and RAW264.7 cells by modulating the JAK2/STAT3 and NF-κB signaling pathways. Moreover, XTS administration in the AIA rats model significantly ameliorated paw swelling. Histological analysis revealed that XTS also suppressed the inflammatory response in paw tissue by modulating the JAK2/STAT3 and NF-κB signaling pathways. Importantly, during the treatment, XTS exhibited excellent safety profiles, as it did not induce any abnormalities in blood routine parameters or cause organ damage in the rats.CONCLUSIONSOur findings highlight XTS as a promising natural agent for inhibiting synovial hyperplasia in RA. XTS holds great potential as an unprecedented natural agent for developing novel therapeutic strategies to target synovial hyperplasia in RA.

01 Jan 2025·Journal of Ethnopharmacology

Exploring antiviral effect and mechanism of Jinye Baidu granules（JYBD）against influenza A virus through network pharmacology and in vitro and in vivo experiments

Article

Author: Liu, Menghua ; Liu, Shuwen ; Jiang, Feng ; Zhang, Chunyu ; Chen, Zhixuan ; Gao, Yinhuang ; Mo, Qinxian ; Liang, Jinlong ; Yang, Jie ; Yang, Sizu ; Luo, Siqi ; Ma, Jun ; Jiang, Linrui ; Li, Yinyan

ETHNOPHARMACOLOGICAL RELEVANCEJinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus.AIM OF THE STUDYThis study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism.MATERIALS AND METHODSUltra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated.RESULTSA total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice.CONCLUSIONSJYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

01 Jan 2025·Journal of Ethnopharmacology

Botany, phytochemistry, pharmacologic activities, traditional applications, pharmacokinetics, quality control and toxicity of Zanthoxyli Radix: An updated review

Review

Author: Zeng, Fen-Fen ; Yang, Xia ; Luo, Fu-Hui ; Zhang, Feng-Xiang ; Shi, Wei ; Li, Jin-Jin ; Chen, Zi-Hao

ETHNOPHARMACOLOGICAL RELEVANCEZanthoxyli Radix (ZR), the dry root of Zanthoxylum nitidum (Roxb.) DC (ZN) is known as Liang Mian Zhen in China and has been the preferred Chinese medicine for the treatment of inflammation and cancer disease at home and abroad. ZR has been used as the core ingredient in anti-inflammatory traditional medicines, such as Sanjiuweitai granules and Jinji tablets, etc. AIM OF THE WORK: This review aimed to provide a comprehensive overview of ZR in terms of traditional uses, quality control, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics. Meanwhile, the anti-inflammatory substances and mechanism of ZR were emphasized, to offer new perspectives and broad scopes for future studies.MATERIALS AND METHODSThe information was retrieved from Web of Science, Researchgate, Google Scholar, SciFinder, X-MOL, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Masters and Doctoral Dissertations, and Elsevier between 1984 and 2024.RESULTSTill now, a total of 184 chemical components have been identified in ZR, including 91 alkaloids, 22 lignans, 4 flavonoids, 19 coumarins, 17 terpenoids, and 31 other types. Pharmacological studies have proved that ZR had a variety of biological activities, such as anti-tumour, antibacterial, antioxidant and other activities, particularly in anti-inflammation. ZR exerts anti-inflammatory disease effects by modulating various signaling pathways, including MAPK, NF-κB, P13/AKT and JAK/STAT. Pharmacokinetic studies have shown that ZR exhibits low absorption rates, broad distribution, and rapid metabolism. Additionally, this review also revealed the shortcomings of current research on ZR and possible future research directions.CONCLUSIONExtensive literature analysis indicates that ZR and its bioactive constituents possess diverse pharmacological activities, especially anti-inflammation. Moreover, in order to promote the safety and adaptability of ZR in clinical application, it is also strongly recommended that further research should focus on toxicity studies, pharmacokinetic studies of herb-drug interactions, and quality control.

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