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<p>This study employed network pharmacology and molecular docking to elucidate the anticancer mechanisms of <i>Litsea cubeba</i> against prostate cancer. Through integrative analysis, 661 shared molecular targets between <i>Litsea cubeba</i> and prostate cancer were identified, underscoring its broad therapeutic potential via multiple signaling pathways, notably AGE-RAGE, PI3K-Akt, FoxO, and specific prostate cancer cascades. Protein–protein interaction analysis highlighted key hub genes such as TP53, SRC, and STAT3, central to cancer progression. Docking studies validated these findings, revealing strong binding affinities between bioactive compounds—especially afzelin and trifolin—and pivotal proteins. Afzelin demonstrated exceptional docking scores with SRC (− 11.1&#xa0;kcal/mol) and MAPK1 (− 9.0&#xa0;kcal/mol), while trifolin showed significant interactions with EGFR (− 8.8&#xa0;kcal/mol) and HSP90AA1 (− 8.1&#xa0;kcal/mol). These interactions were stabilized by critical amino acid residues, potentially disrupting cancer-related signaling and enhancing apoptosis. Acute toxicity assessments in mice indicated that ethanol extracts of L. cubeba leaves at doses up to 5000&#xa0;mg/kg caused no mortality or overt toxicity symptoms, including neurological or gastrointestinal disturbances. Observations of stable body weights, food intake, and relative organ weights further supported the extract's safety profile. Biochemical analyses demonstrated normal urea, creatinine, and liver enzyme levels, with only a mild, non-toxic elevation of SGOT observed in female mice at the highest dose. In vitro cytotoxicity assays revealed promising anticancer activity against prostate cancer PC3 cells (IC50 of 141.2&#xa0;µg/mL). Complementary toxicity screening in zebrafish embryos confirmed minimal developmental toxicity and negligible impact on cardiac function at therapeutic concentrations, although moderate irritation potential was noted via the HET-CAM assay. Overall, this study positions <i>Litsea cubeba</i> as a viable candidate for prostate cancer therapy, highlighting its multitarget anticancer properties and favorable safety profile, warranting further experimental validation and pharmacokinetic exploration.</p>

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Anti-prostate cancer activity of Litsea cubeba ethanol extract through network pharmacology, molecular docking, and biological validation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月17日

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  • Ana Gabriela Silva Olivera,
  • Marina Andrade Rocha,
  • Princella Halim,
  • Chemayanti Surbakti,
  • Aminah Dalimunthe,
  • Alex Insandus Sitohang,
  • Fahrul Nurkolis,
  • Jicaury Roberta Pereira da Silva,
  • Estéfani Alves Asevedo,
  • Hélio Bastia Santos,
  • Ralph Gruppi Thomé,
  • Rosy Iara Maciel de Azambuja Ribeiro,
  • Rony Abdi Syahputra

摘要

This study employed network pharmacology and molecular docking to elucidate the anticancer mechanisms of Litsea cubeba against prostate cancer. Through integrative analysis, 661 shared molecular targets between Litsea cubeba and prostate cancer were identified, underscoring its broad therapeutic potential via multiple signaling pathways, notably AGE-RAGE, PI3K-Akt, FoxO, and specific prostate cancer cascades. Protein–protein interaction analysis highlighted key hub genes such as TP53, SRC, and STAT3, central to cancer progression. Docking studies validated these findings, revealing strong binding affinities between bioactive compounds—especially afzelin and trifolin—and pivotal proteins. Afzelin demonstrated exceptional docking scores with SRC (− 11.1 kcal/mol) and MAPK1 (− 9.0 kcal/mol), while trifolin showed significant interactions with EGFR (− 8.8 kcal/mol) and HSP90AA1 (− 8.1 kcal/mol). These interactions were stabilized by critical amino acid residues, potentially disrupting cancer-related signaling and enhancing apoptosis. Acute toxicity assessments in mice indicated that ethanol extracts of L. cubeba leaves at doses up to 5000 mg/kg caused no mortality or overt toxicity symptoms, including neurological or gastrointestinal disturbances. Observations of stable body weights, food intake, and relative organ weights further supported the extract's safety profile. Biochemical analyses demonstrated normal urea, creatinine, and liver enzyme levels, with only a mild, non-toxic elevation of SGOT observed in female mice at the highest dose. In vitro cytotoxicity assays revealed promising anticancer activity against prostate cancer PC3 cells (IC50 of 141.2 µg/mL). Complementary toxicity screening in zebrafish embryos confirmed minimal developmental toxicity and negligible impact on cardiac function at therapeutic concentrations, although moderate irritation potential was noted via the HET-CAM assay. Overall, this study positions Litsea cubeba as a viable candidate for prostate cancer therapy, highlighting its multitarget anticancer properties and favorable safety profile, warranting further experimental validation and pharmacokinetic exploration.