Deciphering the putative bioactive metabolites and the underlying mechanism of Juniperus horizontalis Moench (Creeping juniper) in the treatment of inflammation using network pharmacology and molecular docking.

El-Banna A. A., Shawky E., Celik İ., Ghareeb D. A., Abdulmalek S. A., Darwish R. S.

The Journal of pharmacy and pharmacology, cilt.76, ss.514-533, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 76
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1093/jpp/rgad101
  • Dergi Adı: The Journal of pharmacy and pharmacology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.514-533
  • Anahtar Kelimeler: Creeping juniper, anti-inflammatory, molecular docking, network pharmacology, UPLC-MS/MS
  • Erciyes Üniversitesi Adresli: Evet

Özet

Objectives To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent.Methods Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics.Key findings Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-alpha, IL-6, and IL-1 beta, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-alpha, IL-6, and IL-1B, respectively.Conclusions Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug.