2. Academic Validation
  3. Exploring the anti-inflammatory and cytotoxic effects of Valeriana tuberosa L. constituents: Integrating in vitro and in silico studies

Exploring the anti-inflammatory and cytotoxic effects of Valeriana tuberosa L. constituents: Integrating in vitro and in silico studies

  • Fitoterapia. 2025 Jul:184:106604. doi: 10.1016/j.fitote.2025.106604.
Cansel Çelik 1,  Yağmur Özhan 2,  Ceren Öztürk 1,  Zulal Sevgi Dede 3,  Tugce Citoglu 3,  Burcin Gungor 3,  Başak Aru 4,  Enise Ece Gurdal 5,  Wolfgang Sippl 6,  Hande Sipahi 2,  Mehtap Tekşen 7,  Hasan Kırmızıbekmez 8
Affiliations

Affiliations

  • 1 Department of Pharmacognosy, Faculty of Pharmacy, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Türkiye.
  • 2 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Türkiye.
  • 3 Department of Biochemistry, Faculty of Pharmacy, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Türkiye.
  • 4 Department of Immunology, Faculty of Medicine, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Türkiye.
  • 5 Department of Biopharmaceutics, Institute of Pharmacy, Martin-Luther-University of Halle-Wittenberg, 06120 Halle, Germany.
  • 6 Department of Medicinal Chemistry, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.
  • 7 Department of Biology, Faculty of Science and Letters, Aksaray University, TR- 68100, Aksaray, Türkiye.
  • 8 Department of Pharmacognosy, Faculty of Pharmacy, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Türkiye. Electronic address: [email protected].
PMID: 40345339 DOI: 10.1016/j.fitote.2025.106604
Abstract

Valeriana tuberosa L. yielded four new Iridoids, valtuberoside I-IV (1-3 and 15), along with 13 known secondary metabolites via activity-directed fractionation. Compounds were characterized by NMR and HRESIMS. EtOH extract, fractions, and isolates were evaluated for their inhibition on nitric oxide (NO) release in LPS-induced RAW 264.7 cells. Compounds 3, 4, 6, 8, 9, 11, 13, 16, and 17 exhibited anti-inflammatory activity by inhibiting the release of NO (IC50 43.44-95.71 μM), and their mode of actions were elucidated by ELISA, Western blot, qPCR, immunostaining techniques and supported by molecular modelling studies. Compounds 8, 9, 11, 13, and 17 showed significant reduction in TNF-α, IL-1β, IL-6, PGE2, and COX-2 enzyme production, while 9 and 13 decreased iNOS protein expression in RAW 264.7 cells. Compound 13 exhibited remarkable inhibition on pro-inflammatory markers, COX-2 gene expression and translocation of NF-κB to the nuclear region. Moreover, it had the most favourable interaction (ds: -6.46 kcal/mol) with iNOS in in silico analyses. The cytotoxic activities of the most active isolates against MCF-7, MDA-MB-231, U87, A172, MIA PaCa-2, PANC-1, Mahlavu, and Hep3B Cancer cell lines were assessed using CCK8 assay and their cell death mechanisms were unveiled via Apoptosis/Necrosis Assay Kit. Compound 8 had significant cytotoxic activity against MIA PaCa-2 (IC50 23.7 μM) and Hep3B (IC50 25.4 μM) Cancer cell lines, via arresting cell cycle especially in G2/M phase and triggering the apoptotic pathway. These findings indicated that 8 and 13 deserve further in vivo assays on the way to discover new potential drug leads.

Keywords

Anti-inflammatory activity; Cytotoxic activity; In silico; Iridoids; NO inhibition; Valeriana tuberosa.

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