HMGB1 Review: Anti-inflammatory mechanism based on HMGB1-TLR4-NF-kB signaling pathway

HMGB1 pathway

Cerebrovascular disease is a serious threat to human health, is the world’s death, disabling one of the major diseases. Cerebrovascular disease is more common in ischemic, accounting for about 80%, because of its complex pathogenesis, special parts, the current lack of effective treatment. Puerarin (Pue) is a flavonoid compound that has a definite effect on cardiovascular and cerebrovascular diseases because of its low oral bioavailability (only 5% -6%), although partly through the blood-brain barrier, In the brain concentration is very low, so the clinical application is very limited. Acetyl puerarin has a neuroprotective effect, which can significantly reduce the cerebral infarct volume and improve neurological function in rats with cerebral ischemia-reperfusion injury. The results of this study show that acetylpuerarin (AP) is a puerarin acetylated derivative. Defects in the treatment of ischemic encephalopathy showed a good application prospects. But the distribution of acetyl puerarin in the brain tissue how the body through which form of work? There is no literature reported. Nanoparticles (nanoparticles, NP) are commonly used in brain preparations. The preparation process is simple, the drug release is stable, can prevent the drug is degraded or P-glycoprotein (P-glycoprotein, P-gp) pumped cells, with sustained-release effect, drug protection, improve drug efficacy, reduce drug toxicity The advantage is a good carrier for brain-targeted preparations. As a carrier for the preparation of nanoparticles, polylactic acid-glycolic acid (PLGA), because it can be biodegradable to lactic acid and glycolic acid, the final metabolism of water and carbon dioxide, non-toxic to the human body, no accumulation, and FDA approved for Clinical research. In this study, one of the purposes of this study was to study the in vivo process of acetyl puerarin and its distribution in brain tissue on the basis of PLGA as carrier, and to study the distribution of acetyl puerarin Brain targeting of PLGA nanoparticles and its protective effect on cerebral ischemia – reperfusion injury. Inflammatory response is one of the important mechanisms of ischemic brain injury, ischemia and reperfusion early production of cytokines (such as IL-1 TNF-a, etc.) and adhesion molecules (such as ICAM-1, VCAM-1, etc.) The basis of ischemic injury to inflammatory lesions.

Therefore, timely and effective anti-inflammatory treatment can help to alleviate the degree of cerebral ischemia-reperfusion injury. High mobility group box 1 (HMGB1) is a class of non-histone chromosome-binding proteins that are widely conserved in the nucleus of eukaryotic cells. In recent years, a large number of studies confirmed that HMGB1 can be used as inflammatory cytokines involved in inflammatory response. HMGB1 can be secreted by necrotic cells or stimulated by monocytes / macrophages to the extracellular domain, and is associated with advanced glycation end products (RAGE) and Toll-like (Toll-like receptors, TLRs), the final activation of NF-kB, mediated inflammatory response. HMGB1 and its receptors are widely expressed in the central nervous system and play an important role in the regulation of inflammation, apoptosis and blood-brain barrier permeability. In cerebral ischemic injury, due to cerebrovascular occlusion, rapid decline in cerebral blood flow, leading to ischemic core area of acute necrosis, and peripheral tissue (ie, ischemic penumbra) also experienced inflammation, free radicals, excitatory amino acid toxicity , Intracellular Ca2 + overload, energy metabolism, apoptosis and other pathophysiological processes, to promote nerve cells, glial cells and cerebral vascular endothelial cells release HMGB1, and HMGB1 can aggravate glutamate and glucose oxygen deprivation of nerve damage , Promote iNOs, COX-2, IL-1 and TNF-a and other inflammatory mediators release, promote nerve cell death. It can be seen that HMGB1 is an association with early excitotoxicity after cerebral ischemia and subsequent inflammatory injury.

Check HMGB1 knowledge base and HMGB1 ELISA kit review

Reference:

1: Ma C, Wang Y, Dong L, Li M, Cai W. Anti-inflammatory effect of resveratrol
through the suppression of NF-kB and JAK/STAT signaling pathways. Acta Biochim
Biophys Sin (Shanghai). 2015 Mar;47(3):207-13. doi: 10.1093/abbs/gmu135. Epub
2015 Feb 3. PubMed PMID: 25651848.


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