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<p>Medicinal plants from the Eastern Himalayas of Northeast India are integral to traditional therapies for inflammation. This study evaluated the anti-inflammatory potential of 23 reported phytochemicals isolated from this region by targeting TNF-α, a critical mediator of autoimmune disorders. TNF-α production was induced in human peripheral blood mononuclear cells using 100&#xa0;ng/mL lipopolysaccharide for 24&#xa0;h and quantified using ELISA. The IC<sub>50</sub> was calculated by probit regression, with methotrexate as the reference standard (IC<sub>50</sub> = 1.96&#xa0;µM; 94% inhibition at 3.5&#xa0;µM). Rutin emerged as the most potent inhibitor (IC<sub>50</sub> = 2.15&#xa0;µM; 93% inhibition at 4&#xa0;µM), followed by myricitrin and quercetin-3-O-glucoside (IC<sub>50</sub> &lt; 10&#xa0;µM). Conversely, anthocyanins and punicic acid were the least effective (&gt; 300&#xa0;µM). QSAR modelling indicated that bioactivity correlates with small, planar, polyhydroxylated structures, specifically 3-O-glycosylated flavonols and ellagitannin-like polyphenols, whereas steric bulk in larger molecules diminished efficacy. Molecular docking against TNF-α (PDB: 2AZ5; Glide XP) revealed strong binding affinities for rutin (− 10.352&#xa0;kcal/mol), myricitrin (− 10.020&#xa0;kcal/mol), and quercetin-3-O-glucoside (− 10.011&#xa0;kcal/mol), driven by hydrogen bonding (TYR151, SER60, LEU120, and GLY121) and π–π stacking (TYR119). However, 100&#xa0;ns Molecular Dynamics simulations and MM-GBSA analyses identified myricitrin as the most thermodynamically stable complex, characterized by tight pocket occupancy, sustained hydrogen bonding, and reduced RMSD fluctuations. Taken together, these results imply that rutin and myricitrin are promising scaffolds for the development of anti-inflammatory drugs.</p>

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Structural insights into TNF-α inhibition by bioactive compounds found in plants of North East India: in vitro validation and in silico investigations using QSAR, molecular docking, and dynamics simulations

  • 期刊论文

  • 发表日期：

    2026年5月8日

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  • Sarbani Dey Ray,
  • Supratim Ray,
  • Bibhas Pandit,
  • Subham Ghosh,
  • Anjali Murmu,
  • Partha Pratim Roy,
  • Jagadish Singh

摘要

Medicinal plants from the Eastern Himalayas of Northeast India are integral to traditional therapies for inflammation. This study evaluated the anti-inflammatory potential of 23 reported phytochemicals isolated from this region by targeting TNF-α, a critical mediator of autoimmune disorders. TNF-α production was induced in human peripheral blood mononuclear cells using 100 ng/mL lipopolysaccharide for 24 h and quantified using ELISA. The IC50 was calculated by probit regression, with methotrexate as the reference standard (IC50 = 1.96 µM; 94% inhibition at 3.5 µM). Rutin emerged as the most potent inhibitor (IC50 = 2.15 µM; 93% inhibition at 4 µM), followed by myricitrin and quercetin-3-O-glucoside (IC50 < 10 µM). Conversely, anthocyanins and punicic acid were the least effective (> 300 µM). QSAR modelling indicated that bioactivity correlates with small, planar, polyhydroxylated structures, specifically 3-O-glycosylated flavonols and ellagitannin-like polyphenols, whereas steric bulk in larger molecules diminished efficacy. Molecular docking against TNF-α (PDB: 2AZ5; Glide XP) revealed strong binding affinities for rutin (− 10.352 kcal/mol), myricitrin (− 10.020 kcal/mol), and quercetin-3-O-glucoside (− 10.011 kcal/mol), driven by hydrogen bonding (TYR151, SER60, LEU120, and GLY121) and π–π stacking (TYR119). However, 100 ns Molecular Dynamics simulations and MM-GBSA analyses identified myricitrin as the most thermodynamically stable complex, characterized by tight pocket occupancy, sustained hydrogen bonding, and reduced RMSD fluctuations. Taken together, these results imply that rutin and myricitrin are promising scaffolds for the development of anti-inflammatory drugs.