A novel paracetamol derivative alleviates lipopolysaccharide-induced neuroinflammation.

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Tác giả: Santosh Kumar Adla, Kristiina M Huttunen, Aaro Jalkanen, Adéla Králová, Ahmed B Montaser, Jaana Rysä, Janne Tampio

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : European journal of pharmacology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 556904

Neuroinflammation has been implicated as a pathological contributor to several neurodegenerative disorders. Increasing evidence suggests that paracetamol (PCM, acetaminophen) has unappreciated anti-neuroinflammatory properties. However, PCM possesses hepatotoxicity in higher dosages, which are needed for achieving therapeutic concentrations in the brain. To lessen this effect and improve drug efficacy, PCM was in this study converted into an L-type amino acid transporter 1 (LAT1)-utilizing derivative and tested whether this LAT1-mediated delivery approach could enhance the relief of neuroinflammation, using both in vitro and in vivo lipopolysaccharide (LPS)-stimulated models. The gained results confirmed the derivative's improved transport into mouse primary astrocytes, immortalized microglia (BV2), and human immortalized microglia (SV40) via LAT1. In the LPS-stimulated BV2 model, the derivative effectively reduced the prostaglandin E
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