Details

Autor(en) / Beteiligte

• Zhou, Ying
• Du, Zhiteng
• Wu, Qianqian
• Guo, Mi
• Chen, Zhichao
• Sun, Chenhui
• Li, Xiaobo
• Zou, Yu
• Zheng, Zhiwei
• Chen, Pan
• Cho, Won-Jea
• Cho, Young-Chang
• Chattipakorn, Nipon
• Wang, Yi
• Liang, Guang
• Tang, Qidong

Titel

Discovery of novel osthole derivatives exerting anti-inflammatory effect on DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice

Ist Teil von

• European journal of medicinal chemistry, 2024-03, Vol.268, p.116252-116252, Article 116252

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• The modification based on natural products is a practical way to find anti-inflammatory drugs. In this study, 26 osthole derivatives were synthesized, and their anti-inflammatory properties were evaluated. The preliminary activity study revealed that most osthole derivatives could effectively inhibit inflammatory cytokines IL-6 secretion in LPS stimulated mouse macrophages J774A.1. Compound 7m exhibited the most effective anti-inflammatory activity (RAW264.7 IL-6 IC50: 4.57 μM, 32 times more active than osthole) in vitro with no significant influence on cell proliferation. Additionally, the mechanistic analysis demonstrated that compound 7m could block MAPK signal transduction by inhibiting the phosphorylation of JNK and p38, thereby inhibiting the release of inflammatory cytokines. Moreover, in vivo functional investigations revealed that 7m could substantially reduce DSS-induced ulcerative colitis and LPS-induced acute lung injury, with good therapeutic effects. The pharmacokinetics and acute toxicity experiments proved the safety and reliability of 7min vivo. Overall, Compound 7m could further be studied as potential anti-inflammatory candidate. [Display omitted] •Novel osthole derivatives were designed and synthesized.•The effect was evaluated by the inhibition on pro-inflammatory cytokines release.•7m could significantly alleviate LPS-induced ALI and DSS-induced UC.•7m could play anti-inflammatory role through MAPK pathway.