Harnessing Saussurea lappa for Anti-leishmanial, Anti-toxoplasmic, and Anti-bacterial Activity: Molecular and Computational Insights

Indian Journal of Pharmaceutical Education and Research

  • Manal Mohamed Elhassan Taha1Health Research Centre, Jazan University, Jazan, SAUDI ARABIA.
  • Siddig Ibrahim Abdelwahab1Health Research Centre, Jazan University, Jazan, SAUDI ARABIA.
  • Muruganantham Bharathi2Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, INDIA.
  • Waleed S. Koko3Department of Biology, College of Science, Qassim University, Qassim, SAUDI ARABIA.
  • Ibrahim S. Al Nasr3Department of Biology, College of Science, Qassim University, Qassim, SAUDI ARABIA.
  • Tariq A. Khan4Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Qassim, SAUDI ARABIA.
  • Mohamed Eltaib Elmobark5Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Jazan, SAUDI ARABIA.
  • Zia ur Rehman1Health Research Centre, Jazan University, Jazan, SAUDI ARABIA.
  • Sivakumar S. Moni5Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Jazan, SAUDI ARABIA.
  • Syam Mohan6Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences., 7School of Health Sciences, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, INDIA.
  • Bassem Oraibi1Health Research Centre, Jazan University, Jazan, SAUDI ARABIA.
  • Hassan Ahmad Alfaifi8Pharmaceutical Care Administration, Jeddah Second Health Cluster, Ministry of Health, Jeddah, SAUDI ARABIA.
  • Dina Abdulrahman Ismail Albadawi9Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, SAUDI ARABIA.
  • Ahmed Ali Jerah10Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, SAUDI ARABIA.
  • Yasir Babiker11Department of Surgery, Faculty of Medicine, Jazan University, Jazan, SAUDI ARABIA.
  • Saleh M Abdullah10Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, SAUDI ARABIA.
  • Ibrahim Abdel Aziz Ibrahim12Department of Pharmacology and Toxicology, Umm Al-Qura University, Makkah, SAUDI ARABIA.
  • Abdullah Farasani1Health Research Centre, Jazan University, Jazan, SAUDI ARABIA., 10Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan, SAUDI ARABIA.

Volume 59 Issue 4 Pages 1429-1443

DOI: 10.5530/ijper.20251782

Abstract

Objectives: Saussurea lappa Clark has shown preliminary promise in various biological contexts. This study investigates the antileishmanial, antitoxoplasmic, and antibacterial activities of methanolic extracts from S. lappa roots, focusing on key active components, Dehydrocostuslactone (DHL) and Dihydrodehydrocostus Lactone (DDHL). Materials and Methods: Bioassays were conducted to assess the extract's efficacy against Leishmania major, Toxoplasma gondii, Staphylococcus aureus, and Klebsiella pneumoniae, with cytotoxicity tested on Vero cells using the MTT assay. Molecular docking analyses explored the binding interactions of DHL and DDHL with critical targets, such as pteridine reductase and squalene synthase in L. major; (acyl-carrier-protein) S-malonyltransferase and DNA gyrase in S. pyogenes; and carbapenemase and DNA gyrase in K. pneumoniae. Results: The extract exhibited moderate antileishmanial activity against Leishmania major promastigotes (IC50: 14.7 µg/mL, SI: 1.2) and amastigotes (IC50: 17.2 µg/mL, SI: 1.18), with lower potency compared to Amphotericin B. However, its high toxicity to host macrophages (CC50: 20.3 µg/mL) limits further potential. It showed poor antitoxoplasmal activity (IC50: 14.7 µg/mL, SI: 0.394) and was toxic to Vero cells (CC50: 5.8 µg/mL). Antibacterial assays revealed concentration-dependent inhibition zones against Streptococcus pyogenes (24±1.7 mm at 250 µg/mL) and Klebsiella pneumoniae (37±1.7 mm at 250 µg/mL). Molecular docking showed strong interactions of DHL with Pteridine reductase (-7.1 kcal/mol) and DDHL with Carbapenemase (-7.9 kcal/mol). Both compounds exhibited favorable ADMET profiles, including high oral absorption, suggesting potential as therapeutic agents for further investigation and active compound isolation. Conclusion: These findings highlight the potential of S. lappa as a therapeutic agent and underscore the need for additional preclinical research to further validate and develop its antimicrobial applications.

Keywords

  • Saussurea lappa
  • Antimcrobial
  • Molecular docking
  • Leishmania major
  • ADMET
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