Potential anti-inflammatory effect of anti-HMGB1 in animal models of ICH by downregulating the TLR4 signaling pathway and regulating the inflammatory cytokines along with increasing HO1 and NRF2

• Published in: European journal of pharmacology 2022-01, Vol.915, p.174694, Article 174694
• Main Authors: Xu, Ji, Firouz, Sahar Mashayekhi, Farrokhian, Mina, Ghoreishizadeh, Shadi, Merza Mohamad, Talar Ahmad, Rostami, Amirabbas, Tamjididfar, Rozita, Akbari, Morteza, Shomali, Navid, Zamiri, Reza Eghdam, Shotorbani, Siamak Sandoghchian, Shahi, Ali Sadeghian
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - metabolism; Cytokines - metabolism; Disease Models, Animal; Down-Regulation - drug effects; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; HMGB1; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; HO1; ICH; Inflammation Mediators - metabolism; Male; Membrane Proteins; Mice; Microglia - drug effects; Microglia - metabolism; NF-E2-Related Factor 2 - metabolism; NRF2; Signal Transduction - drug effects; TLR4; Toll-Like Receptor 4 - metabolism
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174694

Intracerebral hemorrhage (ICH) is a severe clinical problem without effective treatment; the leading cause is neuroinflammation. High-mobility group box one protein (HMGB1) is an abundant protein in the cell nucleus of most mammalian cells, which exerts its function by binding to chromatin. The present study focused on the therapeutic effect of anti-HMGB1 on ICH via the downregulation of inflammatory pathways. The ICH mice models were created by collagenase IV injection in the striatum of mice. Then, mice were received different medications and divided into three groups: anti-HMGB1, anti-Toll-like receptor 4 (TLR4), and non-treated ICH groups. Cerebrospinal fluid (CSF) was obtained, and ELISA was carried out to determine the levels of inflammatory agents. Microglial cells were isolated from the cerebral hemispheres, and then Real-Time PCR and western blot were performed. The results showed that the anti-inflammatory effects of anti-HMGB1 were tremendous than anti-TLR4. Overall, the results showed that anti-HMGB1 had a more reducer effect on pro-inflammatory cytokines release (***P