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<p>(Z)-4-(4-hydroxy-3-methoxybenzylidene)-3-phenylisoxazol-5(4&#xa0;H)-one (HMP) was evaluated for anti-arthritic activity using a Freund’s complete adjuvant (FCA)-induced arthritis model in Sprague–Dawley rats. Thirty-six rats were randomized into nine groups (<i>n</i> = 6). Arthritis was induced on Day 0; treatments began on Day 8 and continued for 20 days, with animals euthanized on Day 28. Paw volume was measured using digital plethysmometry, Arthritic scores was evaluated using macroscopic criteria. Blood was analyzed for hematological parameters (WBC, RBC, platelets, hemoglobin) and serum was used for biochemical markers (ALT, AST, ALP, urea, and creatinine). Prostaglandin E2 (PGE2) was quantified by ELISA, and mRNA expression of TNF-α, IL-1β, IL-6, COX-II, NF-κB and IL-4 were assessed via real-time qPCR. In silico ADMET profiling, network pharmacology, molecular docking against COX-II, TNF-α, NF-κB, IL-6 and related targets, and DFT analyses characterized HMP’s pharmacokinetic and electronic properties. HMP significantly reduced paw swelling and arthritic scores, attenuated PGE2 levels, and downregulated pro-inflammatory cytokines while upregulating anti-inflammatory IL-4. Hematological parameters were restored. Biochemical analysis indicated a favorable profile of liver and kidney function. Molecular docking revealed stable binding to TNF-α, EGFR, NFKB, STAT3 and BCL-2; DFT suggested electronic stability. These results support further preclinical development and mechanistic studies toward therapeutic application in humans. The multi-target actions and favorable ADMET profile warrant expanded safety and efficacy studies. In nutshell, HMP showed potential anti-arthritic effects.</p>

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In Vivo and In Silico Evaluation of the Anti-Arthritic Potential of an Isoxazole Derivative

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Farida Munir,
  • Aisha Mobashar,
  • Muhammad Bilal,
  • Ammara Saleem,
  • Arham Shabbir,
  • Hossam Kamli,
  • Narmeen Mehmood,
  • Amir Ali,
  • Zeeshan Akbar,
  • Humaira Nadeem,
  • Iqra Zulfiqar,
  • Sana Saleem,
  • Esmael M. Alyami,
  • Mona Alsolami,
  • Amir Bouallegue,
  • Mohammed Bourhia,
  • Gehan M. Elossaily,
  • Khalid S. Almaary

摘要

(Z)-4-(4-hydroxy-3-methoxybenzylidene)-3-phenylisoxazol-5(4 H)-one (HMP) was evaluated for anti-arthritic activity using a Freund’s complete adjuvant (FCA)-induced arthritis model in Sprague–Dawley rats. Thirty-six rats were randomized into nine groups (n = 6). Arthritis was induced on Day 0; treatments began on Day 8 and continued for 20 days, with animals euthanized on Day 28. Paw volume was measured using digital plethysmometry, Arthritic scores was evaluated using macroscopic criteria. Blood was analyzed for hematological parameters (WBC, RBC, platelets, hemoglobin) and serum was used for biochemical markers (ALT, AST, ALP, urea, and creatinine). Prostaglandin E2 (PGE2) was quantified by ELISA, and mRNA expression of TNF-α, IL-1β, IL-6, COX-II, NF-κB and IL-4 were assessed via real-time qPCR. In silico ADMET profiling, network pharmacology, molecular docking against COX-II, TNF-α, NF-κB, IL-6 and related targets, and DFT analyses characterized HMP’s pharmacokinetic and electronic properties. HMP significantly reduced paw swelling and arthritic scores, attenuated PGE2 levels, and downregulated pro-inflammatory cytokines while upregulating anti-inflammatory IL-4. Hematological parameters were restored. Biochemical analysis indicated a favorable profile of liver and kidney function. Molecular docking revealed stable binding to TNF-α, EGFR, NFKB, STAT3 and BCL-2; DFT suggested electronic stability. These results support further preclinical development and mechanistic studies toward therapeutic application in humans. The multi-target actions and favorable ADMET profile warrant expanded safety and efficacy studies. In nutshell, HMP showed potential anti-arthritic effects.