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<p>Inflammation-driven disorders such as rheumatoid arthritis require safer and more effective therapeutic alternatives to conventional immunosuppressive drugs. In this study, we purified and identified a soil-derived fungal isolate. Its anti-inflammatory and anti-arthritic potential was evaluated using integrated chemical, biological, and computational approaches. Morphological characteristics combined with 18&#xa0;S rRNA gene sequencing confirmed the isolate as <i>Penicillium chrysogenum</i> (GenBank accession: PV110187.1), validating its taxonomic identity for downstream investigations. Gas chromatography–mass spectrometry (GC–MS) profiling of the methanolic extract revealed a chemically diverse metabolome dominated by polyunsaturated fatty acid esters and terpenoid constituents. The most abundant constituents were methyl 5,8,11,14-eicosatetraenoate (43.21%), caryophyllene oxide (17.68%), and docosahexaenoic acid methyl ester (6.84%). Additionally, several other known anti-inflammatory metabolites—including costunolide, reynosin, lupeol, and valerenol—were also identified in the extract. In vitro evaluation demonstrated potent inhibition of heat-induced protein denaturation, with an IC₅₀ value of 10.07 ± 0.07&#xa0;µg/mL, supporting strong anti-inflammatory activity. The IC₅₀ value guided the selection of rational in vivo doses. These were subsequently validated using a complete Freund’s adjuvant-induced arthritis model. Administration of the fungal extract at 10, 20, and 40&#xa0;mg/kg significantly alleviated paw swelling in a dose-dependent manner. The highest dose exhibited efficacy comparable to methotrexate. Histopathological analyses confirmed marked preservation of joint cartilage, synovial architecture, and muscle integrity. Extract treatment restored the cytokine balance by significantly suppressing the pro-inflammatory cytokines IFN-γ, IL-1β, and IL-17. Conversely, levels of the anti-inflammatory cytokine IL-4 were markedly enhanced. Besides, biochemical assessments demonstrated hepatic and renal safety. Molecular docking studies supported these findings, revealing strong binding affinities of key metabolites to the JAK2 receptor. Therefore, these results support the potential of <i>P. chrysogenum</i> extract as a biologically active anti-inflammatory preparation, pending additional mechanistic and translational studies.</p>

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Harnessing Penicillium chrysogenum metabolites for immune modulation and anti-inflammatory activity: chemical profiling, in vivo validation, and computational insights

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Ahmed Sadoun,
  • Hussien H. Elshikh,
  • Mahmoud M. Elaasser,
  • Mohammed Yosri,
  • Alsayed E. Mekky

摘要

Inflammation-driven disorders such as rheumatoid arthritis require safer and more effective therapeutic alternatives to conventional immunosuppressive drugs. In this study, we purified and identified a soil-derived fungal isolate. Its anti-inflammatory and anti-arthritic potential was evaluated using integrated chemical, biological, and computational approaches. Morphological characteristics combined with 18 S rRNA gene sequencing confirmed the isolate as Penicillium chrysogenum (GenBank accession: PV110187.1), validating its taxonomic identity for downstream investigations. Gas chromatography–mass spectrometry (GC–MS) profiling of the methanolic extract revealed a chemically diverse metabolome dominated by polyunsaturated fatty acid esters and terpenoid constituents. The most abundant constituents were methyl 5,8,11,14-eicosatetraenoate (43.21%), caryophyllene oxide (17.68%), and docosahexaenoic acid methyl ester (6.84%). Additionally, several other known anti-inflammatory metabolites—including costunolide, reynosin, lupeol, and valerenol—were also identified in the extract. In vitro evaluation demonstrated potent inhibition of heat-induced protein denaturation, with an IC₅₀ value of 10.07 ± 0.07 µg/mL, supporting strong anti-inflammatory activity. The IC₅₀ value guided the selection of rational in vivo doses. These were subsequently validated using a complete Freund’s adjuvant-induced arthritis model. Administration of the fungal extract at 10, 20, and 40 mg/kg significantly alleviated paw swelling in a dose-dependent manner. The highest dose exhibited efficacy comparable to methotrexate. Histopathological analyses confirmed marked preservation of joint cartilage, synovial architecture, and muscle integrity. Extract treatment restored the cytokine balance by significantly suppressing the pro-inflammatory cytokines IFN-γ, IL-1β, and IL-17. Conversely, levels of the anti-inflammatory cytokine IL-4 were markedly enhanced. Besides, biochemical assessments demonstrated hepatic and renal safety. Molecular docking studies supported these findings, revealing strong binding affinities of key metabolites to the JAK2 receptor. Therefore, these results support the potential of P. chrysogenum extract as a biologically active anti-inflammatory preparation, pending additional mechanistic and translational studies.