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<p>Rheumatoid arthritis (RA) is a chronic, complex systemic inflammatory disease characterized by synovial inflammation, hyperplasia, angiogenesis, cartilage and bone destruction. Research into naturally derived herbal medicine has gained significant interest. We endeavored in our study to evaluate phytochemicals, phenolic and flavonoid content and multi-modal anti-arthritic and immunomodulatory effect of ethanolic extract of <i>Colchicum luteum</i> (EECL). GC-MS analysis reported 40 phytocompounds, Pentanoic acid (6.77%), cis-vaccenic acid (7.03%), Di-isopropylethylamine (6.46%) and morpholine (19.44%) with highest peak. In vitro egg albumin assay surpassed protein denaturation in concentration dependant manner. In CFA induced arthritis model, 100, 200 and 400&#xa0;mg/kg EECL demonstrated dose-dependent significant effects (<i>p</i> &lt; 0.05) in paw diameter, arthritic score, body weight, and organs weight. Histopathological analysis showed marked reduction in inflammation, pannus development and blood cell infiltration. Hematological, biochemical, and oxidative marker were normalized in treatment groups as compared to arthritic control (<i>p</i> &lt; 0.05). The extract persuasively down-regulated the COX-2, PGE2, IL-1β, IL-6, NF-κβ, and TNF-α, and up-regulated the mRNA expression of I-κB, IL-4, and IL-10. Moreover, Phytocompounds were screened following the Lipinski rule and drug bioavailability properties. PPI network construction evaluated PTGS2, PPARG PTGS1, ALOX5, ESR1, PTGES, NR3C1, PTPRC, MAPK1 and PLA2G4A as common targets of RA. GO and Kegg pathway analysis revealed <i>C. luteum</i> involved in eicosanoid biosynthesis, prostaglandin synthesis, inflammatory responses and arachidonic acid metabolism. Molecular docking analysis demonstrated strong binding affinity of 2-ethylacridine with the COX-2 active site, indicating its potential inhibitory activity against inflammatory mediators. Furthermore, MD simulation confirmed the stability of the ligand COX-2 complex, supporting the reliability of docking results and reinforcing the anti-inflammatory potential of <i>C. luteum</i>. This study provides novel approach that rationalizes <i>C. luteum</i> corms traditional use in arthritis treatment and supports its phytotherapeutic application.</p> Graphical abstract <p></p>

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Multi-target modulation of inflammatory pathways by Colchicum luteum in rheumatoid arthritis through experimental and in silico evidence

  • 期刊论文

  • 发表日期：

    2026年3月27日

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  • Iqra Farzeen,
  • Salma Sultana,
  • Sana Inam,
  • Asma Ashraf

摘要

Rheumatoid arthritis (RA) is a chronic, complex systemic inflammatory disease characterized by synovial inflammation, hyperplasia, angiogenesis, cartilage and bone destruction. Research into naturally derived herbal medicine has gained significant interest. We endeavored in our study to evaluate phytochemicals, phenolic and flavonoid content and multi-modal anti-arthritic and immunomodulatory effect of ethanolic extract of Colchicum luteum (EECL). GC-MS analysis reported 40 phytocompounds, Pentanoic acid (6.77%), cis-vaccenic acid (7.03%), Di-isopropylethylamine (6.46%) and morpholine (19.44%) with highest peak. In vitro egg albumin assay surpassed protein denaturation in concentration dependant manner. In CFA induced arthritis model, 100, 200 and 400 mg/kg EECL demonstrated dose-dependent significant effects (p < 0.05) in paw diameter, arthritic score, body weight, and organs weight. Histopathological analysis showed marked reduction in inflammation, pannus development and blood cell infiltration. Hematological, biochemical, and oxidative marker were normalized in treatment groups as compared to arthritic control (p < 0.05). The extract persuasively down-regulated the COX-2, PGE2, IL-1β, IL-6, NF-κβ, and TNF-α, and up-regulated the mRNA expression of I-κB, IL-4, and IL-10. Moreover, Phytocompounds were screened following the Lipinski rule and drug bioavailability properties. PPI network construction evaluated PTGS2, PPARG PTGS1, ALOX5, ESR1, PTGES, NR3C1, PTPRC, MAPK1 and PLA2G4A as common targets of RA. GO and Kegg pathway analysis revealed C. luteum involved in eicosanoid biosynthesis, prostaglandin synthesis, inflammatory responses and arachidonic acid metabolism. Molecular docking analysis demonstrated strong binding affinity of 2-ethylacridine with the COX-2 active site, indicating its potential inhibitory activity against inflammatory mediators. Furthermore, MD simulation confirmed the stability of the ligand COX-2 complex, supporting the reliability of docking results and reinforcing the anti-inflammatory potential of C. luteum. This study provides novel approach that rationalizes C. luteum corms traditional use in arthritis treatment and supports its phytotherapeutic application.

Graphical abstract