2. Academic Validation
  3. Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus

Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus

  • Plants (Basel). 2021 Mar 1;10(3):462. doi: 10.3390/plants10030462.
Hilbert D Magpantay 1,  Ivane N Malaluan 2 3,  Joe Anthony H Manzano 2 4,  Mark Tristan Quimque 2 5,  Kirstin Rhys Pueblos 2 5,  Natalija Moor 6,  Simon Budde 6,  Porferio S Bangcaya 7,  Demi Lim-Valle 8,  Hans-Martin Dahse 9,  Abbas Khan 10,  Dong-Qing Wei 10 11 12,  Grecebio Jonathan D Alejandro 13,  Allan Patrick G Macabeo 2
Affiliations

Affiliations

  • 1 Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines.
  • 2 Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines.
  • 3 Chemistry Department, College of Science, Bicol University, Rizal St., Legazpi City 4500, Philippines.
  • 4 Department of Biological Sciences, College of Science, University of Santo Tomas, España Blvd., Manila 1015, Philippines.
  • 5 Chemistry Department, College of Science, MSU-Iligan State University, Iligan City 9200, Philippines.
  • 6 Institut für Organische Chemie, Universität Regensburg, Universitätstrasse 31, D-93053 Regensburg, Germany.
  • 7 Biological Science Department, College of Teacher Education-University of Antique, Tario-Lim Memorial Campus, Tibiao, Antique 5707, Philippines.
  • 8 Clinical Microbiology Laboratory, Department of Pathology and Laboratories, Makati Medical Center, Amorsolo St., Legaspi Village, Makati City 1229, Philippines.
  • 9 Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), D-07745 Jena, Germany.
  • 10 Department of Bioinformatics and Biostatistics, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 11 State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 12 Peng Cheng Laboratory, Vanke Cloud City Phase I Bldg. 8, Xili St., Nashan District, Shenzhen 518055, China.
  • 13 Plant Sciences Laboratory, Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Blvd., Manila 1015, Philippines.
PMID: 33804446 DOI: 10.3390/plants10030462
Abstract

Phaeanthus ophthalmicus (Roxb. ex G.Don) J.Sinclair (previously known as P. ebracteolatus (Presl) Merr) is a Philippine medicinal plant occurring as evergreen shrub in the lowland forests of Luzon islands. It is used traditionally by Filipinos to treat Bacterial conjunctivitis, ulcer and wound infections. Based on previous investigations where cyclooxygenase-2 (COX-2) functions as immune-linked factor in infectious sensitivities to Bacterial pathogens by triggering pro-inflammatory immune-associated reactions, we investigated the antimicrobial and COX inhibitory activities of the extracts and tetrahydrobisbenzylisoquinoline Alkaloids of P. ophthalmicus in vitro and in silico to validate its ethnomedicinal uses. Thus, the dichloromethane-methanol (DCM-MeOH) crude extract and alkaloid extracts exhibiting Antibacterial activities against drug-resistant Bacterial strains such as methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Klebsiella pneumoniae + CRE and Pseudomonas aeruginosa + MBL afforded (+)-tetrandrine (1) and (+)-limacusine (2) as the major biologically active tetrahydrobisbenzylisoquinoline alkaloidal constituents after purification. Both tetrahydrobisbenzylisoquinoline Alkaloids 1 and 2 showed broad spectrum Antibacterial activity with strongest inhibition against the Gram-negative bacteria MβL-Pseudomonas aeruginosa Klebsiella pneumoniae + CRE. Interestingly, the alkaloid limacusine (2) showed selective inhibition against ovine COX-2 in vitro. These results were ascertained by molecular docking and molecular dynamics simulation experiments where alkaloid 2 showed strong affinity in the catalytic sites of Gram-negative Bacterial enzymes P. aeruginosa Elastase and K. pneumoniae KPC-2 carbapenemase (enzymes involved in infectivity mechanisms), and of ovine COX-2. Overall, our study provides credence on the ethnomedicinal use of the Philippine medicinal plant P. ophthalmicus as traditional plant-based adjuvant to treat Bacterial conjunctivitis and other related infections. The Antibacterial activities and selective COX-2 inhibition observed for limacusine (2) point to its role as the biologically active constituent of P. ophthalmicus. A limited number of drugs with COX-2 inhibitory properties like celecoxib also confer Antibacterial activity. Thus, tetrahydrobisbenzyl Alkaloids, especially 2, are promising pharmaceutical inspirations for developing treatments of Bacterial/inflammation-related infections.

Keywords

COX-2; Phaeanthus ophthalmicus; anti-inflammatory; antibacterial; ethnomedicinal; limacusine; medicinal plants; molecular docking; molecular dynamics simulation; tetrahydrobisbenzylisoquinoline alkaloids.

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