Natural Compound and Cellular Mode of Action

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Chemical and Molecular Sciences".

Deadline for manuscript submissions: closed (20 December 2022) | Viewed by 2509

Special Issue Editor

Special Issue Information

Dear Colleagues,

Although natural products are already used in many applications, a central challenge of natural product research is to evaluate the mode of action of natural products more precisely. This requires sophisticated new methods for identifying the molecular mechanism of action in various living systems, from which new applications can be evaluated. The effect of single pure substances needs to be investigated, as well as the effect of synergisms of chemically pure compounds in order to understand the enhanced effect of, for example, plant extracts in comparison to the pure substance. This Special Issue welcomes reviews and original manuscripts that investigate and describe novel methods or results of mode of action analysis of natural products starting from chemically pure compounds (i.e., not natural extracts) and, based on these, initiate and stimulate applied research for novel uses of natural products. Technical, pharmaceutical, and agricultural applications are all invited.

Dr. Martin Gruhlke
Guest Editor

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Keywords

  • natural compound
  • mode of action
  • drug research
  • synergism
  • pure compound

Published Papers (2 papers)

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Research

25 pages, 6131 KiB  
Article
COX2-Inhibitory and Cytotoxic Activities of Phytoconstituents of Matricaria chamomilla L.
by Assia I. Drif, Bharathi Avula, Ikhlas A. Khan and Thomas Efferth
Appl. Sci. 2023, 13(15), 8935; https://doi.org/10.3390/app13158935 - 03 Aug 2023
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Abstract
Chamomile tea is a popular beverage and herbal remedy with various health benefits, including antioxidant and antimicrobial activities and beneficial effects on metabolism. In this study, we investigated the inhibitory activities of secondary metabolites from Matricaria chamomile L. against COX2, an enzyme involved [...] Read more.
Chamomile tea is a popular beverage and herbal remedy with various health benefits, including antioxidant and antimicrobial activities and beneficial effects on metabolism. In this study, we investigated the inhibitory activities of secondary metabolites from Matricaria chamomile L. against COX2, an enzyme involved in inflammation and linked to cancer development. The cytotoxicity of the compounds was also evaluated on a panel of 60 cancer cell lines. Myricetin, one of the COX2-inhibiting and cytotoxic compounds in chamomile tea, was further studied to determine a proteomic expression profile that predicts the sensitivity or resistance of tumor cell lines to this compound. The expression of classical mechanisms of anticancer drug resistance did not affect the responsiveness of cancer cells to myricetin, e.g., ATP-binding cassette (ABC) transporters (ABCB, ABCB5, ABCC1, ABCG2), tumor suppressors (p53, WT1), and oncogenes (EGFR, RAS), whereas significant correlations between myricetin responsiveness and GSTP expression and cellular proliferation rates were observed. Additionally, Kaplan–Meier survival time analyses revealed that high COX2 expression is associated with a worse survival prognosis in renal clear cell carcinoma patients, suggesting a potential utility for COX2 inhibition by myricetin in this tumor type. Overall, this study provides insight into the molecular modes of action of chamomile secondary metabolites and their potential as cancer-preventive or therapeutic agents. Full article
(This article belongs to the Special Issue Natural Compound and Cellular Mode of Action)
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12 pages, 2026 KiB  
Article
Mode of Action of the Natural Product Allicin in a Plant Model: Influence on the Cytoskeleton and Subsequent Shift in Auxin Localization
by Ulrike Noll, Miriam Schreiber, Monika Hermanns, Christopher A. Mertes, Alan J. Slusarenko and Martin C. H. Gruhlke
Appl. Sci. 2022, 12(22), 11470; https://doi.org/10.3390/app122211470 - 11 Nov 2022
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Abstract
Allicin is a defense substance produced by garlic cells when they are injured. It is a redox-active thiosulfinate showing redox-activity with a broad range of dose-dependent antimicrobial and biocidal activity. It is known that allicin efficiently oxidizes thiol-groups, and it has been described [...] Read more.
Allicin is a defense substance produced by garlic cells when they are injured. It is a redox-active thiosulfinate showing redox-activity with a broad range of dose-dependent antimicrobial and biocidal activity. It is known that allicin efficiently oxidizes thiol-groups, and it has been described as a redox toxin because it alters the redox homeostasis in cells and triggers oxidative stress responses. Allicin can therefore be used as a model substance to investigate the action of thiol-specific prooxidants. In order to learn more about the effect of allicin on plants, we used pure synthetized allicin, and studied the influence of allicin on organelle movement in Tradescantia fluminensis as a cytoskeleton-dependent process. Furthermore, we investigated cytoplasmic streaming in sterile filaments of Tradescantia fluminensis, organelle movement using transgenic Arabidopsis with organelle-specifics GFP-tags, and effects on actin and tubulin in the cytoskeleton using GFP-tagged lines. Tubulin and actin were visualized by GFP-tagging in transgenic lines of Arabidopsis thaliana to visualize the influence of allicin on the cytoskeleton. Since auxin transport depends on recycling and turnover of the PIN protein involving cytoskeletal transport to and from the membrane localization sites, auxin distribution in roots was investigated using of transgenic PIN1–GFP, PIN3–GFP, DR5–GFP and DII–VENUS Arabidopsis reporter lines. Allicin inhibited cytoplasmic streaming in T. fluminensis, organelle movement of peroxi-somesperoxisomes, and the Golgi apparatus in a concentration-dependent manner. It also destroyed the correct root tip distribution of auxin, which probably contributed to the observed inhibition of root growth. These observations of the disruption of cytoskeleton-dependent transport processes in plant cells add a new facet to the mechanism of action of allicin as a redox toxin in cells. Full article
(This article belongs to the Special Issue Natural Compound and Cellular Mode of Action)
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