Last update 01 Nov 2024

NF-κB x STAT1 x HMOX1

Last update 01 Nov 2024

Basic Info

Related Targets

NF-κBSTAT1HMOX1

Drugs associated with NF-κB x STAT1 x HMOX1

CKD-712

Target

HMOX1 x NF-κB x STAT1

Mechanism

HMOX1 modulators [+2]

Active Org.-

Originator Org.

Chong Kun Dang Pharmaceutical Corp.

Active Indication-

Inactive Indication

Sepsis

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NF-κB x STAT1 x HMOX1

100 Translational Medicine associated with NF-κB x STAT1 x HMOX1

0 Patents (Medical) associated with NF-κB x STAT1 x HMOX1

Literatures (Medical) associated with NF-κB x STAT1 x HMOX1

01 Jul 2024·Journal of Ethnopharmacology

Exocarpium Citri Grandis ameliorates LPS-induced acute lung injury by suppressing inflammation, NLRP3 inflammasome, and ferroptosis

Article

Author: Hu, Yingjie ; Li, Jiayu ; Wang, Kongyan ; Gao, Yong ; Huang, Jiawen ; Xu, Zaibin ; Hu, Huiyu ; Zhou, Kaili ; Luo, Zhuohui

ETHNOPHARMACOLOGICAL RELEVANCEExocarpium Citri Grandis (ECG), the epicarp of C. grandis 'Tomentosa' which is also known as Hua-Ju-Hong in China, has been widely used for thousands of years to treat inflammatory lung disorders such as asthma, and cough as well as dispelling phlegm. However, its underlying pharmacological mechanisms in acute lung injury (ALI) remain unclear.AIM OF THE STUDYTo explore the therapeutic effect of ECG on ALI and reveal the potential mechanisms based on experimental techniques in vivo and in vitro.MATERIALS AND METHODSLipopolysaccharides (LPS) induced ALI in mice and induced RAW 264.7 cell inflammatory model were established to investigate the pharmacodynamics of ECG. ELISA kits, commercial kits, Western Blot, qPCR, Hematoxylin and Eosin (H&E) staining, immunohistochemistry, and immunofluorescence technologies were used to evaluate the pharmacological mechanisms of ECG in ameliorating ALI.RESULTSECG significantly attenuated pulmonary edema in LPS-stimulated mice and decreased the levels of IL1β, IL6, and TNF-α in serum and BALF, reduced MDA and iron concentration as well as increased SOD and GSH levels in lung tissues, and also decreased the ROS level in BALF and Lung tissue. Further pharmacological mechanism studies showed that ECG significantly inhibited mRNA expression of inflammatory signaling factors and chemokines, and down-regulated the expression of TLR4, MyD88, NF-κB p65, NF-κB p-p65 (S536), COX2, iNOS, Txnip, NLRP3, ASC, Caspase-1, JAK1, p-JAK1 (Y1022), JAK2, STAT1, p-STAT1 (S727), STAT3, p-STAT3 (Y705), STAT4, p-STAT4 (Y693), and Keap1, and also up-regulated the expression of Trx-1, Nrf2, HO-1, NQO1, GPX4, PCBP1, and SLC40A1. In the LPS-induced RAW264.7 cell inflammatory model, ECG showed similar results to animal experiments.CONCLUSIONSOur results showed that ECG alleviated ALI by inhibiting TLR4/MyD88/NF-κB p65 and JAK/STAT signaling pathway-mediated inflammatory response, Txnip/NLRP3 signaling pathway-mediated inflammasome activation, and regulating Nrf2/GPX4 axis-mediated ferroptosis. Our findings provide an experimental basis for the application of ECG.

01 Apr 2024·Heliyon

Alleviation of taurine on liver injury of type 2 diabetic rats by improving antioxidant and anti-inflammatory capacity

Article

Author: Ouyang, Guangyi ; Wu, Gaofeng ; Sun, Wenke ; Tong, Jihang ; Wang, Nannan ; Yang, Jiancheng

Type 2 diabetes mellitus (T2DM) is a serious metabolic disease characterized by insulin resistance and reduced insulin production, which causes abnormally elevated blood glucose. It has been reported that T2DM can enhance oxidative stress and inflammatory responses, and stimulate a variety of complications including liver injury. Studies have shown that taurine has antioxidant and anti-inflammatory effects that can not only ameliorate diabetes but also alleviate liver injury caused by various diseases. However, its effect on liver injury in T2DM is not clear. In our study, a high-fat diet and intraperitoneal injection of streptozotocin (STZ) was used to induce liver injury in T2DM rats, and taurine was given as a treatment. Through the use of HE staining on paraffin sections, ELISA, and qRT-PCR, the effects of taurine on liver pathological alterations, antioxidant capacity, and inflammatory response were investigated. We found that: hepatic transaminase levels of rats were reduced significantly following taurine administration; histopathological observations revealed that the morphology of rat hepatocytes was close to normal, and the number of inflammatory cells around liver vessels was significantly reduced; antioxidant-related indicators were significantly increased, including SOD, CAT, GSH-Px and T-AOC, while related factors of the Nrf2 signalling pathway and its downstream HO-1, NQO1 and γ-GCS were significantly increased; the expression of the JAK2-STAT1 signalling pathway, TLR4/NF-κB signalling pathway and NLRP3 inflammatory vesicle-related factors were significantly reduced. Our results suggest taurine can alleviate T2DM-induced liver injury by improving the antioxidant capacity of the liver and inhibiting macrophage M1-type polarization and the inflammatory response mediated thereby.

01 Jan 2022·The American Journal of Chinese Medicine

Anti-Inflammatory and Anti-oxidant Functions of Cornuside by Regulating NF-κB, STAT-1, and Nrf2-HO-1 Pathways

Article

Author: Bae, Jong-Sup ; Kim, Nayeon ; Kim, Chaeyeong

Cornuside (CNS), found in the fruit of Cornus officinalis Seib, is a natural bisiridoid glucoside that possesses therapeutic effects by suppressing inflammation. This study aimed to determine whether CNS could inhibit the inflammatory response induced by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVECs) and mice, as well as to decipher the mechanisms. After activating HUVECs with LPS, the cells were treated with CNS. Cells were then isolated for protein or mRNA assays to analyze signaling and inflammatory molecules. In addition, mice received an intraperitoneal injection of LPS, followed by an intravenously administered dose of CNS. CNS inhibited cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions induced by LPS. CNS decreased phosphorylated signal transducer and activator of transcription 1 (STAT1)-1 by promoting HO-1 expression, inhibiting nuclear factor (NF)-[Formula: see text]B-luciferase activity, and decreasing COX-2/prostaglandin E2 (PGE2) and iNOS/NO. Furthermore, CNS treatment in LPS-activated HUVECs increased the nuclear translocation of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and combined Nrf2 to anti-oxidant response elements and decreased IL-1[Formula: see text] production. Reduced iNOS/NO expression by CNS was restored when HO-1 RNAi inhibited heme oxygenase-1 (HO-1). After CNS treatment in vivo, iNOS levels in lung tissue and tumor necrosis factor (TNF)-[Formula: see text] expression in the bronchoalveolar lavage fluid were significantly decreased. The results indicated that CNS increased HO-1 expression, reduced LPS-activated NF-[Formula: see text]B–luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, all of which contributed to the inhibition of STAT-1 phosphorylation. Thus, CNS can be a potential new substance for treating inflammatory disorders.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis