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<p>Honey contains a diverse range of phenolic compounds that contribute to its functional properties; however, comparative data linking bee species, geographical origin, and quantitative phenolic profiles of Indonesian honeys remain limited. Accordingly, this study compared six honeys: three from <i>Apis mellifera</i> (Subang, Batang, Pasuruan) and three from <i>Heterotrigona itama</i> (Tanggamus, Banjar, Kapuas Hulu), examining whether species and origin influence composition, function, and relevance for bioresearch. The product quality was evaluated toward SNI 8664:2018; quantified TPC and TFC; assessed antioxidant activity (DPPH, ABTS, FRAP), antibacterial properties (agar-well diffusion), and anti-inflammatory effects (BSA denaturation); characterized targeted phenolics using UPLC–MS/MS; and conducted in silico docking studies on CDK2 (which promotes cancer cell proliferation) and Chk1 (DNA-damage checkpoint) with ADME, brief molecular dynamics, and MM-PBSA analysis. Every sample fulfilled the freshness requirements; darker honeys had lower pH and greater Pfund, and higher TPC/TFC values coincided with stronger antioxidant responses. <i>H. itama</i> Tanggamus (H1) had the highest TPC/TFC and the strongest antioxidant response (DPPH IC<sub>50</sub> 10.08&#xa0;mg mL<sup>− 1</sup>), whereas <i>A. mellifera</i> Batang (A2) had the lowest. The honey samples analyzed exhibited more pronounced antibacterial properties against <i>S. aureus</i> compared to <i>E. coli</i>, as evidenced by a larger zone of inhibition ranging from 9.7 to 18.6&#xa0;mm. Specific honey samples also showed measurable anti-inflammatory effects, with IC₅₀ values of 5.24&#xa0;mg mL⁻¹ for H1 and 6.38&#xa0;mg mL⁻¹ for A3. UPLC-MS/MS analysis revealed an increase in taxifolin and benzoic acid derivatives in stingless bee honey. Furthermore, in silico analysis identified 6-phenylisoquinoline from <i>A. mellifera</i> honey harvested in Subang as a potential activator of CDK2/Chk1. Overall, both the type of honey and its geographic origin had a significant impact on the phenolic composition and associated bioactivity. It underscores the importance of confirming the source and highlights the necessity for various quantification techniques and additional cell-based validation. <i>S. aureus</i> exhibited more antibacterial activity than <i>E. coli</i> (9.7–18.6&#xa0;mm), and anti-inflammatory activity followed suit (H1 IC<sub>50</sub> 5.24&#xa0;mg mL<sup>− 1</sup>; A3 6.38&#xa0;mg mL<sup>− 1</sup>). In stingless-bee honeys, UPLC-MS/MS revealed the enrichment of taxifolin and benzoic-acid derivatives, while in silico study revealed 6-phenylisoquinoline from <i>A. mellifera</i> Subang to be a CDK2/Chk1 engager. Species and region structured phenolic profiles and bioactivity, supporting origin verification and motivating orthogonal quantification and cell-based validation.</p>

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Comparative study of Apis mellifera and Heterotrigona itama honeys from different Indonesian regions on bioactivities, quantitative phenolic profiles, and in silico target engagement

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Yelin Adalina,
  • Gusnia Meilin Gholam,
  • Bima Putra Pratama,
  • Dimas Andrianto,
  • Kanti Dewi Rizqiani,
  • Reny Sawitri,
  • Kusmiati Kusmiati,
  • Rohmah Pari,
  • Saefudin Saefudin,
  • Efrida Basri,
  • Totok Kartono Waluyo

摘要

Honey contains a diverse range of phenolic compounds that contribute to its functional properties; however, comparative data linking bee species, geographical origin, and quantitative phenolic profiles of Indonesian honeys remain limited. Accordingly, this study compared six honeys: three from Apis mellifera (Subang, Batang, Pasuruan) and three from Heterotrigona itama (Tanggamus, Banjar, Kapuas Hulu), examining whether species and origin influence composition, function, and relevance for bioresearch. The product quality was evaluated toward SNI 8664:2018; quantified TPC and TFC; assessed antioxidant activity (DPPH, ABTS, FRAP), antibacterial properties (agar-well diffusion), and anti-inflammatory effects (BSA denaturation); characterized targeted phenolics using UPLC–MS/MS; and conducted in silico docking studies on CDK2 (which promotes cancer cell proliferation) and Chk1 (DNA-damage checkpoint) with ADME, brief molecular dynamics, and MM-PBSA analysis. Every sample fulfilled the freshness requirements; darker honeys had lower pH and greater Pfund, and higher TPC/TFC values coincided with stronger antioxidant responses. H. itama Tanggamus (H1) had the highest TPC/TFC and the strongest antioxidant response (DPPH IC50 10.08 mg mL− 1), whereas A. mellifera Batang (A2) had the lowest. The honey samples analyzed exhibited more pronounced antibacterial properties against S. aureus compared to E. coli, as evidenced by a larger zone of inhibition ranging from 9.7 to 18.6 mm. Specific honey samples also showed measurable anti-inflammatory effects, with IC₅₀ values of 5.24 mg mL⁻¹ for H1 and 6.38 mg mL⁻¹ for A3. UPLC-MS/MS analysis revealed an increase in taxifolin and benzoic acid derivatives in stingless bee honey. Furthermore, in silico analysis identified 6-phenylisoquinoline from A. mellifera honey harvested in Subang as a potential activator of CDK2/Chk1. Overall, both the type of honey and its geographic origin had a significant impact on the phenolic composition and associated bioactivity. It underscores the importance of confirming the source and highlights the necessity for various quantification techniques and additional cell-based validation. S. aureus exhibited more antibacterial activity than E. coli (9.7–18.6 mm), and anti-inflammatory activity followed suit (H1 IC50 5.24 mg mL− 1; A3 6.38 mg mL− 1). In stingless-bee honeys, UPLC-MS/MS revealed the enrichment of taxifolin and benzoic-acid derivatives, while in silico study revealed 6-phenylisoquinoline from A. mellifera Subang to be a CDK2/Chk1 engager. Species and region structured phenolic profiles and bioactivity, supporting origin verification and motivating orthogonal quantification and cell-based validation.