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<p>Diabetic peripheral neuropathy (DPN) remains refractory to current single-target pharmacotherapies, warranting multi-target interventions. This study investigated the neuroprotective potential of methanolic fruit extracts from <i>Garcinia pedunculata</i> (MEGP) and <i>Garcinia lanceifolia</i> (MEGL) using integrated chemoinformatics–systems pharmacology–cell biology approaches. GC–MS profiling identified 11 (MEGP) and 20 (MEGL) bioactive compounds. Target prediction revealed 2359 compound-associated proteins, with 270 significantly overlapping with DPN-associated genes (<i>p</i> &lt; 0.001). Network analysis identified TNF and AKT1 as key hubs, with GO/KEGG enrichment highlighting critical pathways including PI3K-Akt, MAPK, JAK-STAT, and Wnt/β-catenin involved in neuronal survival and inflammation. Molecular docking demonstrated notable binding affinities: 12-hydroxy-14-methyl-oxa-cyclotetradec-6-en-2-one with AKT1 (ΔG = − 7.1&#xa0;kcal/mol) and benzofuran acetic acid derivative with TNF (ΔG = − 6.5&#xa0;kcal/mol). In vitro validation using high glucose-stressed SH-SY5Y cells (1000&#xa0;µg/mL, 1&#xa0;h) showed significant cytoprotection with MEGP (50&#xa0;µg/mL) and MEGL (100&#xa0;µg/mL) pre-treatment, restoring cell viability to 75–78% (<i>p</i> &lt; 0.001), reducing ROS levels by ~ 60%, and decreasing apoptotic cell counts by 30–40%. MEGP demonstrated superior neuroprotective efficacy across all assays. These findings reveal that MEGP and MEGL exert multi-targeted neuroprotective effects through TNF and AKT1-centered signaling networks, highlighting their polypharmacological potential for DPN therapy and emphasizing conservation needs for these bioactive-rich endangered species.</p>

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Neuroprotective potential of Garcinia extracts against diabetic peripheral neuropathy: GC–MS profiling, network pharmacology, molecular docking, and in vitro studies

  • 期刊论文

  • 发表日期：

    2025年11月22日

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  • Arpita Paul,
  • Mohit Kumar,
  • Diksheeta Sharma,
  • Kevser Kübra Kırboğa,
  • Mithun Rudrapal,
  • Pritom Chowdhury,
  • Pronobesh Chattopadhyay,
  • Md. Kamaruz Zaman

摘要

Diabetic peripheral neuropathy (DPN) remains refractory to current single-target pharmacotherapies, warranting multi-target interventions. This study investigated the neuroprotective potential of methanolic fruit extracts from Garcinia pedunculata (MEGP) and Garcinia lanceifolia (MEGL) using integrated chemoinformatics–systems pharmacology–cell biology approaches. GC–MS profiling identified 11 (MEGP) and 20 (MEGL) bioactive compounds. Target prediction revealed 2359 compound-associated proteins, with 270 significantly overlapping with DPN-associated genes (p < 0.001). Network analysis identified TNF and AKT1 as key hubs, with GO/KEGG enrichment highlighting critical pathways including PI3K-Akt, MAPK, JAK-STAT, and Wnt/β-catenin involved in neuronal survival and inflammation. Molecular docking demonstrated notable binding affinities: 12-hydroxy-14-methyl-oxa-cyclotetradec-6-en-2-one with AKT1 (ΔG = − 7.1 kcal/mol) and benzofuran acetic acid derivative with TNF (ΔG = − 6.5 kcal/mol). In vitro validation using high glucose-stressed SH-SY5Y cells (1000 µg/mL, 1 h) showed significant cytoprotection with MEGP (50 µg/mL) and MEGL (100 µg/mL) pre-treatment, restoring cell viability to 75–78% (p < 0.001), reducing ROS levels by ~ 60%, and decreasing apoptotic cell counts by 30–40%. MEGP demonstrated superior neuroprotective efficacy across all assays. These findings reveal that MEGP and MEGL exert multi-targeted neuroprotective effects through TNF and AKT1-centered signaling networks, highlighting their polypharmacological potential for DPN therapy and emphasizing conservation needs for these bioactive-rich endangered species.