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<p><i>Solanum mauritianum</i> Scop. (SM) is a medicinal plant with ethnopharmacological relevance, noted for its diverse secondary metabolites. Despite its traditional use in inflammatory conditions, its mechanistic anti-inflammatory potential remains unexplored. This study investigates the molecular effects of SM leaf ethyl acetate extract (SMLE) on key inflammatory signalling pathways.&#xa0;Quantitative, qualitative and GC-MS mediated identification of phytoconstituents in SMLE was carried out. Preliminary screening for SMLE was carried out using DPPH, nitric oxide scavenging and protein denaturation assays. In vitro anti-inflammatory effect of SMLE was evaluated in PMA-activated THP-1 cells. FACS, RT-PCR, and ELISA were performed to measure intracellular ROS and proinflammatory cytokine expression (IL-6, IL-1β, TNF-α), respectively. Molecular docking of quercetin, a key SMLE compound, was studied. A change in DNA promoter methylation of IL-6 was performed using RFLP.&#xa0;Phenolics, alkaloids, and terpenoids were identified in SMLE, and GC-MS analysis revealed 24 compounds. A flavonoid, quercetin, was isolated and characterised from the extract. SMLE was biocompatible with both THP-1 and human PBMNCs. In PMA-activated THP-1 cells, SMLE reduced intracellular ROS by 83% compared to H₂O₂ controls and significantly (P &lt; 0.001) downregulated IL-6 (2.3-fold ± 0.05), IL-1β (1.2-fold ± 0.05), and TNF-α (1.2-fold ± 0.08) expression at transcript and protein levels. Docking showed strong binding of quercetin to NOX2 (–8.72 kcal/mol). SMLE also maintained CpG methylation status at the IL-6 promoter region.&#xa0;Biocompatible SMLE downregulates inflammation in activated monocytes, potentially by binding to NOX2 and preventing ROS-mediated activation of the IL-6 gene promoter. Its strong in vitro anti-inflammatory efficacy, combined with low cytotoxicity, highlights SMLE as a promising candidate for anti-inflammatory therapeutics. By preserving CpG methylation at the IL-6 promoter, SMLE may offer an epigenetic means of limiting IL-6-driven chronic inflammation, which is clinically relevant in conditions such as atherosclerosis, arthritis, and other inflammatory disorders.</p>

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Solanum mauritianum Scop. Leaf Extract Attenuates ROS-Mediated Inflammation and Prevents IL-6 Promoter Demethylation in Activated Monocytes

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Aswathy Karanath-Anilkumar,
  • Muhammad Sadiq,
  • Suganya Ganesan,
  • Shiek S. S. J. Ahmed,
  • Ganesh Munuswamy-Ramanujam

摘要

Solanum mauritianum Scop. (SM) is a medicinal plant with ethnopharmacological relevance, noted for its diverse secondary metabolites. Despite its traditional use in inflammatory conditions, its mechanistic anti-inflammatory potential remains unexplored. This study investigates the molecular effects of SM leaf ethyl acetate extract (SMLE) on key inflammatory signalling pathways. Quantitative, qualitative and GC-MS mediated identification of phytoconstituents in SMLE was carried out. Preliminary screening for SMLE was carried out using DPPH, nitric oxide scavenging and protein denaturation assays. In vitro anti-inflammatory effect of SMLE was evaluated in PMA-activated THP-1 cells. FACS, RT-PCR, and ELISA were performed to measure intracellular ROS and proinflammatory cytokine expression (IL-6, IL-1β, TNF-α), respectively. Molecular docking of quercetin, a key SMLE compound, was studied. A change in DNA promoter methylation of IL-6 was performed using RFLP. Phenolics, alkaloids, and terpenoids were identified in SMLE, and GC-MS analysis revealed 24 compounds. A flavonoid, quercetin, was isolated and characterised from the extract. SMLE was biocompatible with both THP-1 and human PBMNCs. In PMA-activated THP-1 cells, SMLE reduced intracellular ROS by 83% compared to H₂O₂ controls and significantly (P < 0.001) downregulated IL-6 (2.3-fold ± 0.05), IL-1β (1.2-fold ± 0.05), and TNF-α (1.2-fold ± 0.08) expression at transcript and protein levels. Docking showed strong binding of quercetin to NOX2 (–8.72 kcal/mol). SMLE also maintained CpG methylation status at the IL-6 promoter region. Biocompatible SMLE downregulates inflammation in activated monocytes, potentially by binding to NOX2 and preventing ROS-mediated activation of the IL-6 gene promoter. Its strong in vitro anti-inflammatory efficacy, combined with low cytotoxicity, highlights SMLE as a promising candidate for anti-inflammatory therapeutics. By preserving CpG methylation at the IL-6 promoter, SMLE may offer an epigenetic means of limiting IL-6-driven chronic inflammation, which is clinically relevant in conditions such as atherosclerosis, arthritis, and other inflammatory disorders.