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Unravelling the wound healing ability and mode of action of pyridine carboxamide oxime using Caenorhabditis elegans as potential prescreen wound model.

Authors
  • Pooranachithra, Murugesan1
  • Bhaskar, James Prabhanand2
  • Murali, Deepa2
  • Das, Shibendu Sekhar2
  • JebaMercy, Gnanasekaran1
  • Krishnan, Venkateswaran2
  • Balamurugan, Krishnaswamy3
  • 1 Department of Biotechnology, Science Campus, Alagappa University, Karaikudi 630 003, Tamil Nadu, India. , (India)
  • 2 ITC Life Sciences & Technology Centre, Peenya Industrial Area, Phase 1, Bangalore 560058, Karnataka, India. , (India)
  • 3 Department of Biotechnology, Science Campus, Alagappa University, Karaikudi 630 003, Tamil Nadu, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Life sciences
Publication Date
Oct 15, 2019
Volume
235
Pages
116859–116859
Identifiers
DOI: 10.1016/j.lfs.2019.116859
PMID: 31513816
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In the current scenario of ethical issues related to animal usage in research, the present study was intended to explore the proficient utility of nematode, Caenorhabditis elegans as wound model in preliminary screening of wound healing therapeutics. In this study, a new wounding protocol and quantitative assessment strategies for various healing parameters [survival, Reactive Oxygen Species (ROS), calcium signals, F-actin dynamics, new collagen synthesis and wound induced anti-microbial peptides] were developed and used for preliminary screening of wound healing actives from natural sources. Wound healing ability of positive lead Tridax procumbens (TP) and its major phytocompounds [Octa decenoic acid (ODA), Pyridine carboxamide oxime, known as Nicotinamide (NA) and Dimethyl Benz[c]acridine (DMB)] were assessed using C. elegans wound model and cell lines scratch wound healing assay. Mode of action of active lead was elucidated using metabolome analysis coupled with MALDI-MS followed by molecular docking. From the four tested methanolic extracts, TP was chosen as positive lead compared to control, Benzalkonium chloride (BKC) based on survival and new collagen synthesis analyses. Results indicated that the wound healing ability of TP was majorly contributed by NA. Further, it was found that NA acts in chloromethyl nicotinamide derivative form by interacting with the known wound healing biomarker, glycogen synthase kinase 3 (GSK-3) to exert wound healing ability. The study evidenced that C. elegans, could be a reliable wound model for high-throughput screening of wound healing actives and to identify their possible mode of action. Copyright © 2019 Elsevier Inc. All rights reserved.

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