Last update 01 Nov 2024

SDF-1 x HMGB1

Last update 01 Nov 2024

Basic Info

Related Targets

SDF-1HMGB1

Drugs associated with SDF-1 x HMGB1

HBP08

Target

HMGB1 x SDF-1

Mechanism

HMGB1 inhibitors [+1]

Active Org.

Università della Svizzera Italiana

Originator Org.

Università della Svizzera Italiana

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SDF-1 x HMGB1

100 Translational Medicine associated with SDF-1 x HMGB1

0 Patents (Medical) associated with SDF-1 x HMGB1

Literatures (Medical) associated with SDF-1 x HMGB1

01 Oct 2023·European review for medical and pharmacological sciences

Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

Article

Author: Fitri, L E ; Hidayat, M ; Soeharto, S ; Handoyo, H R ; Sardjono, T W

OBJECTIVEAchilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats).MATERIALS AND METHODSThis study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation.RESULTSAfter Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels.CONCLUSIONSWe found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

01 Apr 2023·Journal of Microbiology

CXCL12/CXCR4 Axis is Involved in the Recruitment of NK Cells by HMGB1 Contributing to Persistent Airway Inflammation and AHR During the Late Stage of RSV Infection

Article

Author: Tang, Zhengzhen ; Liu, Enmei ; Yu, Guangyuan ; Chen, Sisi ; Tang, Wei

We previously showed that both high-mobility group box-1 (HMGB1) and natural killer (NK) cells contribute to respiratory syncytial virus (RSV)-induced persistent airway inflammation and airway hyperresponsiveness (AHR). Meanwhile, Chemokine (C-X-C motif) ligand 12 (CXCL12) and its specific receptor (chemokine receptor 4, CXCR4) play important roles in recruitment of immune cells. CXCL12 has been reported to form a complex with HMGB1 that binds to CXCR4 and increases inflammatory cell migration. The relationship between HMGB1, NK cells and chemokines in RSV-infected model remains unclear. An anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) was administered to observe changes of NK cells and airway disorders in nude mice and BALB/c mice. Results showed that the mRNA expression and protein levels of HMGB1 were elevated in late stage of RSV infection and persistent airway inflammation and AHR were diminished after administration of anti-HMGB1 antibodies, with an associated significant decrease in CXCR4⁺ NK cells. In addition, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 significantly suppressed the recruitment of NK cells and alleviated the airway disorders. Thus, CXCL12/CXCR4 axis is involved in the recruitment of NK cells by HMGB1, contributing to persistent airway inflammation and AHR during the late stage of RSV infection.

01 Dec 2022·Molecular Medicine

Pamoic acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia

Article

Author: De Leo, Federica ; Cigana, Cristina ; Bianchi, Marco Emilio ; Musco, Giovanna ; De Marchis, Francesco ; Bragonzi, Alessandra ; Fabris, Chantal ; Mantonico, Malisa Vittoria ; Melessike, Medede ; Quilici, Giacomo ; De Fino, Ida ; Rossi, Alice

AbstractBackgroundHigh-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear protein that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 is significantly elevated during Pseudomonas aeruginosa infections and has a clinical relevance in respiratory diseases such as Cystic Fibrosis (CF). Salicylates are HMGB1 inhibitors. To address pharmacological inhibition of HMGB1 with small molecules, we explored the therapeutic potential of pamoic acid (PAM), a salicylate with limited ability to cross epithelial barriers.MethodsPAM binding to HMGB1 and CXCL12 was tested by Nuclear Magnetic Resonance Spectroscopy using chemical shift perturbation methods, and inhibition of HMGB1·CXCL12-dependent chemotaxis was investigated by cell migration experiments. Aerosol delivery of PAM, with single or repeated administrations, was tested in murine models of acute and chronic P. aeruginosa pulmonary infection in C57Bl/6NCrlBR mice. PAM efficacy was evaluated by read-outs including weight loss, bacterial load and inflammatory response in lung and bronco-alveolar lavage fluid.ResultsOur data and three-dimensional models show that PAM is a direct ligand of both HMGB1 and CXCL12. We also showed that PAM is able to interfere with heterocomplex formation and the related chemotaxis in vitro. Importantly, PAM treatment by aerosol was effective in reducing acute and chronic airway murine inflammation and damage induced by P. aeruginosa. The results indicated that PAM reduces leukocyte recruitment in the airways, in particular neutrophils, suggesting an impaired in vivo chemotaxis. This was associated with decreased myeloperoxidase and neutrophil elastase levels. Modestly increased bacterial burdens were recorded with single administration of PAM in acute infection; however, repeated administration in chronic infection did not affect bacterial burdens, indicating that the interference of PAM with the immune system has a limited risk of pulmonary exacerbation.ConclusionsThis work established the efficacy of treating inflammation in chronic respiratory diseases, including bacterial infections, by topical delivery in the lung of PAM, an inhibitor of HMGB1.

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