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Peer-reviewedCC BY 4.0Molecules

Bioactivity-Guided Isolation of Cytoprotective Metabolites from Two Verbascum Species Reveals Differential Modulation of Cigarette Smoke-Induced Inflammation and Oxidative Stress

  • Gulin Renda1,2
  • Nurdan Yazici1
  • Rengin Reis3
  • Elif Nur Barut4
  • Burak Barut5
  • Icim Gokkaya6,7
  • Elif Oz3,8
  • Manar M. Amin9,10
  • Yeter Yesil Canturk11
11 affiliations
  1. 1Department of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Türkiye
  2. 2Trabzon Teknokent, Farmakodental Health Products, Trabzon 61080, Türkiye
  3. 3Department of Toxicology, Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Türkiye
  4. 4Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Türkiye
  5. 5Department of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Türkiye
  6. 6Department of Pharmaceutical Botany, Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Türkiye
  7. 7Institute of Health Sciences, Ankara University, Ankara 06290, Türkiye
  8. 8Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul 34126, Türkiye
  9. 9Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
  10. 10Department of Pharmacology, Graduate School of Health Sciences, Karadeniz Technical University, Trabzon 61080, Türkiye
  11. 11Department of Pharmaceutical Botany, Faculty of Pharmacy, Istanbul University, Istanbul 34126, Türkiye
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Abstract

Verbascum species are traditionally used for respiratory disorders and are rich sources of iridoid glycosides, phenylethanoid glycosides, and triterpenoid saponins. However, V. kurdicum and V. longipedicellatum have not previously been investigated phytochemically or biologically. This study aimed to identify their bioactive constituents and characterize their protective effects against cigarette smoke extract (CSE)-induced bronchial epithelial injury. Bioactivity-guided fractionation of 50% methanol extracts yielded twelve compounds identified by NMR. Cytoprotective potential was evaluated in BEAS-2B cells, and selected compounds were investigated for effects on IL-6, IL-8, HO-1, TLR4 expression and downstream effectors (MyD88 and NF-κB), GSH, 8-OHdG levels, and SOD activity. Ajugol exhibited the strongest cytoprotective activity and significantly restored viability following CSE exposure. Ajugol, aucubin, and 1-O-caffeoyl-β-D-glucopyranose were selected for mechanistic evaluation. Aucubin and 1-O-caffeoyl-β-D-glucopyranose significantly reduced CSE-induced IL-6 release, while all three suppressed IL-8, with ajugol producing the greatest effect. Ajugol also attenuated TLR4 upregulation and reduced 8-OHdG levels and the CSE-induced increase in SOD activity, whereas MyD88, total NF-κB, p-NF-κBSer536, and GSH were not significantly improved. These findings provide the first phytochemical and biological characterization of both species and identify ajugol as a promising lead against CSE-induced bronchial epithelial damage.

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Cite

BibTeXRIS
BibTeX
@article{renda2026bioactivityguided,
  title = {{Bioactivity-Guided Isolation of Cytoprotective Metabolites from Two Verbascum Species Reveals Differential Modulation of Cigarette Smoke-Induced Inflammation and Oxidative Stress}},
  author = {Gulin Renda and Nurdan Yazici and Rengin Reis and Elif Nur Barut and Burak Barut and Icim Gokkaya and Elif Oz and Manar M. Amin and Yeter Yesil Canturk},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31213818},
  url = {https://www.mdpi.com/1420-3049/31/21/3818},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Bioactivity-Guided Isolation of Cytoprotective Metabolites from Two Verbascum Species Reveals Differential Modulation of Cigarette Smoke-Induced Inflammation and Oxidative Stress
AU  - Gulin Renda
AU  - Nurdan Yazici
AU  - Rengin Reis
AU  - Elif Nur Barut
AU  - Burak Barut
AU  - Icim Gokkaya
AU  - Elif Oz
AU  - Manar M. Amin
AU  - Yeter Yesil Canturk
PY  - 2026
DA  - 2026/10/22
JO  - Molecules
DO  - 10.3390/molecules31213818
UR  - https://www.mdpi.com/1420-3049/31/21/3818
AB  - Verbascum species are traditionally used for respiratory disorders and are rich sources of iridoid glycosides, phenylethanoid glycosides, and triterpenoid saponins. However, V. kurdicum and V. longipedicellatum have not previously been investigated phytochemically or biologically. This study aimed to identify their bioactive constituents and characterize their protective effects against cigarette smoke extract (CSE)-induced bronchial epithelial injury. Bioactivity-guided fractionation of 50% methanol extracts yielded twelve compounds identified by NMR. Cytoprotective potential was evaluated in BEAS-2B cells, and selected compounds were investigated for effects on IL-6, IL-8, HO-1, TLR4 expression and downstream effectors (MyD88 and NF-κB), GSH, 8-OHdG levels, and SOD activity. Ajugol exhibited the strongest cytoprotective activity and significantly restored viability following CSE exposure. Ajugol, aucubin, and 1-O-caffeoyl-β-D-glucopyranose were selected for mechanistic evaluation. Aucubin and 1-O-caffeoyl-β-D-glucopyranose significantly reduced CSE-induced IL-6 release, while all three suppressed IL-8, with ajugol producing the greatest effect. Ajugol also attenuated TLR4 upregulation and reduced 8-OHdG levels and the CSE-induced increase in SOD activity, whereas MyD88, total NF-κB, p-NF-κBSer536, and GSH were not significantly improved. These findings provide the first phytochemical and biological characterization of both species and identify ajugol as a promising lead against CSE-induced bronchial epithelial damage.
SN  - 1420-3049
ER  -