2. Academic Validation
  3. Diclofenac and eugenol hybrid with enhanced anti-inflammatory activity through activating HO-1 and inhibiting NF-κB pathway in vitro and in vivo

Diclofenac and eugenol hybrid with enhanced anti-inflammatory activity through activating HO-1 and inhibiting NF-κB pathway in vitro and in vivo

  • Eur J Med Chem. 2023 Nov 5;259:115669. doi: 10.1016/j.ejmech.2023.115669.
Wei Wang 1,  Shou-Kai Wang 1,  Qi Wang 1,  Zhe Zhang 1,  Bo Li 1,  Zi-Dan Zhou 1,  Jian-Feng Zhang 1,  Chao Lin 1,  Ting-Xiao Chen 1,  Zhen Jin 1,  You-Zhi Tang 2
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
  • 2 Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address: youzhitang@scau.edu.cn.
PMID: 37517204 DOI: 10.1016/j.ejmech.2023.115669
Abstract

A series of diclofenac hybrid molecules were synthesized and evaluated for their NO-inhibitory ability in LPS-induced RAW 264.7 macrophage cells. Among them, compound 1 showed the highest NO-inhibitory ability (approximately 66%) and no significant cytotoxicity. Compound 1 exhibited superior NF-κB-inhibitory ability compared to diclofenac through the activation of Nrf2/HO-1 signaling pathway in RAW 264.7. 20 mg/kg compound 1 resulted in remarkable colitis improvement in dextran sulfate sodium (DSS)-induced mice model by up-regulating HO-1 and down-regulating phosphorylation level of NF-κB p65. Moreover, 50 mg/kg dose of compound 1 showed a lower ulcerogenic potential compared to diclofenac in rats. The diclofenac-eugenol hybrid (compound 1) may serve as a novel anti-inflammatory agent based on its role in inhibiting the NF-κB signaling pathway and activating HO-1 expression with no toxicity in vitro and in vivo.

Keywords

Anti-inflammation; Diclofenac-eugenol hybrid; Gastric ulcer; Heme oxygenase-1; NF-κB p65; Ulcerative colitis.

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