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Peer-reviewedCC BY 4.0Molecules

Immunomodulatory and Antioxidant Activities of Pinus sylvestris L. Xylem Sap: Modulation of NK-92 Cell Receptors and Cytotoxic Function

  • Hasan Uğur Öncel1
  • Işık Neslişah Korkut2
  • Ahmet Beyatli3
  • Ömer Faruk Bayrak4
  • Serap Kuruca5
5 affiliations
  1. 1Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Gedik University, Istanbul 34913, Türkiye
  2. 2Department of Physiology, Faculty of Medicine, Istanbul University, Turgut Özal Millet Str., Istanbul 34093, Türkiye
  3. 3Department of Medicinal and Aromatic Plants, Hamidiye Vocational School of Health Services, University of Health Sciences, Istanbul 34668, Türkiye
  4. 4Department of Medical Genetics, Faculty of Medicine, Yeditepe University, Istanbul 34718, Türkiye
  5. 5Department of Physiology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34408, Türkiye
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Abstract

This study investigated the phytochemical profile, antioxidant capacity, and immunomodulatory properties of Pinus sylvestris xylem sap harvested from the Kastamonu region of Türkiye during the early spring active sap-flow period. Quantitative screening demonstrated significant polyphenolic density, with total phenolic (39.65 ± 2.12 mg GAE/g) and flavonoid contents (21.48 ± 3.11 mg Catechin/g) reflecting a high relative accumulation of mobile, hydrophilic flavonoids. Targeted LC-MS/MS analysis further revealed the presence of several phenolic and flavonoid-related compounds, with catechin as the predominant compound in the directly extracted sample, while epicatechin and epigallocatechin were among the major compounds detected following acid hydrolysis. The sap exhibited consistent, robust antioxidant activity across DPPH (43.52 ± 2.76 mg TE/g), ABTS (41.64 ± 2.17 mg TE/g), and FRAP (39.21 ± 1.95 mg TE/g) assays, indicating multi-pathway radical scavenging and electron-donating capacities in cell-free chemical models. While direct exposure yielded concentration-dependent cytotoxicity against tumor lines (IC50 values: 7.6–12.5 µg/mL), subtoxic conditioning (1 µg/mL) and substantially enhanced NK-92-mediated lysis of target cancer cells, most prominently against MCF-7 breast carcinoma. Flow cytometric analysis revealed that xylem sap treatment selectively upregulated surface expression of CD16 (from 0.00% to 15.93%) and CD57 on NK-92 cells without altering baseline CD56. Furthermore, sap stimulation triggered a concentration-dependent surge in IFN-γ production and elevated cytotoxic responses in lymphocytes isolated from both healthy controls (n = 5) and breast cancer patients (n = 5). These findings indicate that conifer xylem sap represents in vitro immunomodulatory properties and enhances NK-92 cell-mediated cytotoxic responses in cell culture models.

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Cite

BibTeXRIS
BibTeX
@article{oncel2026immunomodulatory,
  title = {{Immunomodulatory and Antioxidant Activities of Pinus sylvestris L. Xylem Sap: Modulation of NK-92 Cell Receptors and Cytotoxic Function}},
  author = {Hasan Uğur Öncel and Işık Neslişah Korkut and Ahmet Beyatli and Ömer Faruk Bayrak and Serap Kuruca},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31203581},
  url = {https://www.mdpi.com/1420-3049/31/20/3581},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Immunomodulatory and Antioxidant Activities of Pinus sylvestris L. Xylem Sap: Modulation of NK-92 Cell Receptors and Cytotoxic Function
AU  - Hasan Uğur Öncel
AU  - Işık Neslişah Korkut
AU  - Ahmet Beyatli
AU  - Ömer Faruk Bayrak
AU  - Serap Kuruca
PY  - 2026
DA  - 2026/10/01
JO  - Molecules
DO  - 10.3390/molecules31203581
UR  - https://www.mdpi.com/1420-3049/31/20/3581
AB  - This study investigated the phytochemical profile, antioxidant capacity, and immunomodulatory properties of Pinus sylvestris xylem sap harvested from the Kastamonu region of Türkiye during the early spring active sap-flow period. Quantitative screening demonstrated significant polyphenolic density, with total phenolic (39.65 ± 2.12 mg GAE/g) and flavonoid contents (21.48 ± 3.11 mg Catechin/g) reflecting a high relative accumulation of mobile, hydrophilic flavonoids. Targeted LC-MS/MS analysis further revealed the presence of several phenolic and flavonoid-related compounds, with catechin as the predominant compound in the directly extracted sample, while epicatechin and epigallocatechin were among the major compounds detected following acid hydrolysis. The sap exhibited consistent, robust antioxidant activity across DPPH (43.52 ± 2.76 mg TE/g), ABTS (41.64 ± 2.17 mg TE/g), and FRAP (39.21 ± 1.95 mg TE/g) assays, indicating multi-pathway radical scavenging and electron-donating capacities in cell-free chemical models. While direct exposure yielded concentration-dependent cytotoxicity against tumor lines (IC50 values: 7.6–12.5 µg/mL), subtoxic conditioning (1 µg/mL) and substantially enhanced NK-92-mediated lysis of target cancer cells, most prominently against MCF-7 breast carcinoma. Flow cytometric analysis revealed that xylem sap treatment selectively upregulated surface expression of CD16 (from 0.00% to 15.93%) and CD57 on NK-92 cells without altering baseline CD56. Furthermore, sap stimulation triggered a concentration-dependent surge in IFN-γ production and elevated cytotoxic responses in lymphocytes isolated from both healthy controls (n = 5) and breast cancer patients (n = 5). These findings indicate that conifer xylem sap represents in vitro immunomodulatory properties and enhances NK-92 cell-mediated cytotoxic responses in cell culture models.
SN  - 1420-3049
ER  -