Scholarlink

Objective (s) <p>Despite the established epidemiological synergy between <i>Porphyromonas gingivalis</i>-induced periodontitis and oral squamous cell carcinoma (OSCC), a critical gap remains in developing single-agent therapeutics that simultaneously neutralize bacterial virulence and suppress host oncogenic signaling. This study aimed to comprehensively evaluate Curcumin 4'-O-β-D-gentiobioside (COG) as a novel, dual-pathway phytochemical intervention targeting the keystone virulence factor RgpB while concurrently disrupting OSCC progression networks.</p> Materials and methods <p>A multi-modal computational approach was used, including network pharmacology, molecular docking, molecular dynamics simulations, and ADMET profiling. Anti-aging activity was predicted through pharmacological activity modeling.</p> Results <p>Network pharmacology identified Curcumin 4'-O-β-D-gentiobioside (COG; PubChem CID: 46926100) targeting hub genes (TNF, IL6, EGFR, AKT1), enriching immune regulation, apoptosis, and oxidative stress pathways (FDR &lt; 0.05). Docking revealed strong binding to RgpB (XP GScore: − 9.867&#xa0;kcal/mol), supported by hydrogen bonds and π-stacking. Molecular dynamics confirmed stability (RMSD: 1.0–1.5&#xa0;Å; ΔG =  − 14&#xa0;kcal/mol). COG downregulated pro-inflammatory (CXCL10, MAPK8) and oncogenic (MDM2, BCL2L1) mediators, while enhancing ER stress response (KDELC1, ATF4). ADMET analysis predicted high absorption, negligible neurotoxicity, and no hepatotoxicity/genotoxicity. Predicted anti-aging activities included senolytic, antioxidant, and NF-κB inhibition.</p> Conclusion(s) <p>These results position COG as a promising dual-agent that concurrently neutralizes RgpB virulence, disrupts chronic inflammation, and suppresses OSCC progression, addressing a critical unmet need in oral disease therapeutics.&#xa0;These findings warrant in vivo validation for translation into oral disease therapeutics.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Computational discovery of curcumin 4′-O-β-D-gentiobioside as a dual anti-virulence and anti-cancer agent

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月17日

查看全文
  • Nada H. Aljarba,
  • Sayan Chakraborty,
  • Aniruddha Chatterjee,
  • Ashok Kumar Bishoyi,
  • R. Roopashree,
  • Daniel Ejim Uti,
  • Esther Ugo Alum

摘要

Objective (s)

Despite the established epidemiological synergy between Porphyromonas gingivalis-induced periodontitis and oral squamous cell carcinoma (OSCC), a critical gap remains in developing single-agent therapeutics that simultaneously neutralize bacterial virulence and suppress host oncogenic signaling. This study aimed to comprehensively evaluate Curcumin 4'-O-β-D-gentiobioside (COG) as a novel, dual-pathway phytochemical intervention targeting the keystone virulence factor RgpB while concurrently disrupting OSCC progression networks.

Materials and methods

A multi-modal computational approach was used, including network pharmacology, molecular docking, molecular dynamics simulations, and ADMET profiling. Anti-aging activity was predicted through pharmacological activity modeling.

Results

Network pharmacology identified Curcumin 4'-O-β-D-gentiobioside (COG; PubChem CID: 46926100) targeting hub genes (TNF, IL6, EGFR, AKT1), enriching immune regulation, apoptosis, and oxidative stress pathways (FDR < 0.05). Docking revealed strong binding to RgpB (XP GScore: − 9.867 kcal/mol), supported by hydrogen bonds and π-stacking. Molecular dynamics confirmed stability (RMSD: 1.0–1.5 Å; ΔG =  − 14 kcal/mol). COG downregulated pro-inflammatory (CXCL10, MAPK8) and oncogenic (MDM2, BCL2L1) mediators, while enhancing ER stress response (KDELC1, ATF4). ADMET analysis predicted high absorption, negligible neurotoxicity, and no hepatotoxicity/genotoxicity. Predicted anti-aging activities included senolytic, antioxidant, and NF-κB inhibition.

Conclusion(s)

These results position COG as a promising dual-agent that concurrently neutralizes RgpB virulence, disrupts chronic inflammation, and suppresses OSCC progression, addressing a critical unmet need in oral disease therapeutics. These findings warrant in vivo validation for translation into oral disease therapeutics.

Graphical Abstract