Metabolite and bioactivity profiling of natural and elicitor-enhanced Crocus sativus L. extracts as a biotechnological source of antioxidants: in silico targeting of oxidative stress-related enzymes

Çetinkaya S., Haydaroğlu Ü. S., GÖK H. N., Nartop P., Bahtiyarca R., Özbek F., ...Daha Fazla

Plant Cell, Tissue and Organ Culture, cilt.162, sa.3, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 162 Sayı: 3
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s11240-025-03171-7
  • Dergi Adı: Plant Cell, Tissue and Organ Culture
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Compendex, Environment Index, Food Science & Technology Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Crocus sativusL, Molecular docking, Oxidative stress, Protein-protein interaction, Safranal, Secondary metabolite
  • Gazi Üniversitesi Adresli: Evet

Özet

Saffron (Crocus sativus L.) is a valuable medicinal plant known for its rich content of apocarotenoids with potent antioxidant activity. Although stigma-derived metabolites are well-documented, the potential of in vitro cultures for sustainable metabolite production remains underexplored. This study compared natural saffron stigma extracts with elicitor-treated suspension cultures (salicylic acid and methyl jasmonate) in terms of metabolite production, antioxidant activity, and molecular interactions. HPLC results showed that natural KM stigmas had the highest crocin content (135.6 mg/g), while SM yielded the highest safranal (2.1992 ± 0.0252 mg/g) and crocetin (0.0356 ± 0.0002 mg/g) levels. SA 100 µM and combined SA + MeJA 50 µM elicitation significantly enhanced antioxidant capacity (DPPH up to 64.6%, MCA up to 40.1%). Despite lower crocin levels in cultures, antioxidant activity was comparable or superior to natural extracts. In silico analyses revealed strong binding affinities of crocin (vina score − 10.9 kcal/mol) to oxidative stress-related enzymes, but SwissADME indicated poor bioavailability due to high polarity. However, this drawback could potentially be addressed through formulation strategies such as nanoparticle encapsulation or lipid-based delivery systems. In contrast, safranal exhibited high oral bioavailability and BBB permeability, highlighting its pharmacokinetic advantage. In conclusion, this study demonstrated that elicitor-supported production strategies in saffron cell suspension cultures of C. sativus L. represent a promising biotechnological alternative to natural stigmas for the production of antioxidant bioactive, especially safranal. The antioxidant activities and interactions of the obtained extracts with target proteins supported the potential of saffron-derived compounds for therapeutic applications. These findings highlight the potential of elicitor-induced saffron cell cultures as sustainable biofactories for pharmacologically favorable antioxidants like safranal, offering an effective alternative to conventional stigma-based production.