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Biological & pharmaceutical bulletin

Biological & pharmaceutical bulletin

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ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury

Published:1 January 2024 DOI: 10.1248/bpb.b23-00603 PMID: 39477466
Ce Dai,?Xiaohe Wang,?Rui Liu,?Weilu Gao,?Hui Zhang,?Zongsheng Yin,?Zhenfei Ding

Abstract

Spinal cord injury (SCI), a public health problem caused by mechanical injury, leads to secondary excessive inflammatory reactions and long-term damage to neurological function. ACY1215 is a highly selective histone deacetylase 6 (HDAC6) inhibitor and reportedly has anti-inflammatory effects; however, its regulatory role in SCI has not been studied. The purpose of this study was to explore the role of ACY1215 in preventing inflammation, inhibiting astrogliosis, enhancing remyelination and preserving axons after spinal cord injury and further exploring the possible cellular signaling pathways involved. First, lipopolysaccharide (LPS) was utilized to stimulate rat astrocytes in vitro. Quantitative RT (qRT)-PCR and Western blotting showed that ACY1215 inhibited the expression of glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) in LPS-activated astrocytes. In addition, Western blotting results showed that ACY1215 could inhibit the signal transduction pathway of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). In vivo, ACY1215 could exert anti-inflammatory effects by inhibiting the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Moreover, ACY1215 repaired spinal cord injury by reducing the formation of glial scars and promoting remyelination and nerve recovery. In summary, ACY1215 can inhibit the NF-κB and STAT3 signaling pathways in astrocytes, reduce inflammation and ameliorate SCI. Our results provide a novel strategy for the treatment of SCI.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ACY-1215 1316214-52-4 C24H27N5O3 196 suppliers $19.00-$2395.30
ACY-1215 1316214-52-4 C24H27N5O3 196 suppliers $19.00-$2395.30
ACY-1215 1316214-52-4 C24H27N5O3 196 suppliers $19.00-$2395.30
ACY-1215 1316214-52-4 C24H27N5O3 196 suppliers $19.00-$2395.30

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