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<p><i>Garcinia latissima</i><?tk 2?><?tk 2?> Miq. has been traditionally used by local communities in Indonesia for wound healing and to relieve itching. A phytochemical investigation of the stem bark of <i>G. latissima</i> led to the isolation of 12 tocotrienol and triterpenoid derivatives, including two previously undescribed metabolites, <i>δ</i>-(<i>E</i>)-deoxy-amplexichromanoyl acetate (<b>1</b>) and (20<i>S</i>,24<i>S</i>)-20,24-epoxylanostane-3<i>β</i>,25-diol (<b>2</b>), whose structures were elucidated using HRESIMS and NMR spectroscopic analyses. Among the isolates, (20<i>R</i>)-eupha-8,25-diene-3<i>β</i>,24<i>ξ</i>-diol (<b>11</b>) suppressed nitric oxide production in LPS-stimulated RAW 264.7 cells by more than 60% at concentrations of 10 and 50 µM, without significant cytotoxicity (cell viability &gt; 80%). It also reduced the release of several inflammatory mediators, particularly MCP-1, as determined by a membrane antibody array. ELISA confirmed a significant decrease in MCP-1 levels, up to 2.3- and 2.8-fold at 3 and 24&#xa0;h, respectively, following pre-treatment with compound <b>11</b> at 50 µM. Molecular docking and molecular dynamics simulations indicated a strong binding affinity of compound <b>11</b> to MD2, TAK1, and NF-κB1, key proteins in the TLR-4 signaling pathway, with predicted affinities higher than those of reference ligands. ADMET analysis further suggested favorable drug-like properties, including high predicted oral bioavailability and minimal toxicity. These findings suggest that compound <b>11</b> has promising anti-inflammatory potential, warranting further experimental studies to elucidate its mechanism of action and to validate its effects in additional inflammation-related bioassays.</p>

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Discovery of anti-inflammatory compounds from the stem bark of Garcinia latissima through in vitro and in silico approaches

  • 期刊论文

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  • 发表日期：

    2025年11月26日

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  • Edwin R. Sukandar,
  • Nitchakan Darai,
  • Jaruwan Chatwichien,
  • Sutthida Wongsuwan,
  • Sutin Kaennakam,
  • Thitiporn Pattarakankul,
  • Retno Purbowati,
  • Taslim Ersam,
  • Kowit Hengphasatporn,
  • Yasuteru Shigeta,
  • Patipark Kueanjinda,
  • Tanapat Palaga,
  • Santi Tip-pyang,
  • Warinthorn Chavasiri,
  • Thanyada Rungrotmongkol,
  • Chanat Aonbangkhen

摘要

Garcinia latissima Miq. has been traditionally used by local communities in Indonesia for wound healing and to relieve itching. A phytochemical investigation of the stem bark of G. latissima led to the isolation of 12 tocotrienol and triterpenoid derivatives, including two previously undescribed metabolites, δ-(E)-deoxy-amplexichromanoyl acetate (1) and (20S,24S)-20,24-epoxylanostane-3β,25-diol (2), whose structures were elucidated using HRESIMS and NMR spectroscopic analyses. Among the isolates, (20R)-eupha-8,25-diene-3β,24ξ-diol (11) suppressed nitric oxide production in LPS-stimulated RAW 264.7 cells by more than 60% at concentrations of 10 and 50 µM, without significant cytotoxicity (cell viability > 80%). It also reduced the release of several inflammatory mediators, particularly MCP-1, as determined by a membrane antibody array. ELISA confirmed a significant decrease in MCP-1 levels, up to 2.3- and 2.8-fold at 3 and 24 h, respectively, following pre-treatment with compound 11 at 50 µM. Molecular docking and molecular dynamics simulations indicated a strong binding affinity of compound 11 to MD2, TAK1, and NF-κB1, key proteins in the TLR-4 signaling pathway, with predicted affinities higher than those of reference ligands. ADMET analysis further suggested favorable drug-like properties, including high predicted oral bioavailability and minimal toxicity. These findings suggest that compound 11 has promising anti-inflammatory potential, warranting further experimental studies to elucidate its mechanism of action and to validate its effects in additional inflammation-related bioassays.