Molecular Modes of Action of Defensive Secondary Metabolites

Wink, Michaël; Schimmer, Oskar; Roberts, Jeremy A.; Evan, David; McManus, Michael T.; Rose, Jocelyn K. C.

doi:10.1002/9781119312994.apr0418

Cited by 17 publications

(15 citation statements)

References 318 publications

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“…In cell cycle analysis, reference drugs colchicine and vinblastine were shown to induce G2/M arrest, which agrees with the literature that they depolymerize microtubules or prevent tubulin assembly by binding to colchicine domain and vinca domain, respectively (Kavallaris, 2010; Wink, 2007; Wink & Schimmer, 2010). Colchicine and vinblastine alter the dynamic of mitotic spindles during mitosis, which triggers the cell cycle checkpoint and thus arrests the cell cycle at G2/M phase (Jordan & Wilson, 2004; Wink, 2016).…”

Section: Discussionsupporting

confidence: 87%

Cucurbitacins: elucidation of their interactions with the cytoskeleton

Wang

Tanaka

Peixoto

2017

PeerJ

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Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and actin filaments were studied in living cells (Hela and U2OS) and in vitro using GFP markers, immunofluorescence staining and in vitro tubulin polymerization assay. Cucurbitacin B, E and I apparently affected microtubule structures in living cells and cucurbitacin E inhibited tubulin polymerization in vitro with IC50 value of 566.91 ± 113.5 µM. Cucurbitacin E did not affect the nucleation but inhibited the growth phase and steady state during microtubule assembly in vitro. In addition, cucurbitacin B, E and I all altered mitotic spindles and induced the cell cycle arrest at G2/M phase. Moreover, they all showed potent effects on actin cytoskeleton by affecting actin filaments through the depolymerization and aggregation. The interactions of cucubitacin B, E and I with microtubules and actin filaments present new insights into their modes of action.

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Section: Discussionsupporting

confidence: 87%

Cucurbitacins: elucidation of their interactions with the cytoskeleton

Wang

Tanaka

Peixoto

2017

PeerJ

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“…Of all the plant secondary metabolites, phenolic compounds show the highest level of bioactivity against parasitic worms. Phenolic compounds inhibit proteins and include flavonoids, coumarins, and condensed tannins (Wink and Schimmer 2010). Condensed tannins have received the most attention, and international research programs such as the EU-wide Legume-Plus initiative have sought to develop new breeds of tanninenriched lucerne and sainfoin (http:// legumeplus.eu/).…”

Section: Perspec Vesmentioning

confidence: 99%

“…Plants naturally produce over 60,000 chemical compounds to deter herbivores, to destroy microbial pathogens, and to communicate with other organisms like pollinators (Wink 2010). Before the creation of synthetic anthelmintics by drug companies in the mid-20 th century, humans relied on plants to control livestock intestinal parasites (Corley and Godley 2011).…”

Section: Introductionmentioning

confidence: 99%

Plant-Based Solutions to Global Livestock Anthelmintic Resistance

French

2018

EBL

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Anthelmintic resistance in livestock is increasing globally. Livestock intestinal parasites now develop resistance to synthetic anthelmintics within 2–10 years, collectively costing billions of dollars annually in lost revenue around the world. Over-reliance on commercial drugs and dips and changes in livestock management practices are key drivers of this trend. To date, current research has focused on identifying new anthelmintics from bacterial and fungal sources or even synthesizing new drugs that target parasite metabolism or reproduction. Plant-derived anthelmintics are a promising alternative, yet to date major research funders and scientists have overlooked this option. Until the mid-20th century, rural communities relied on plant-based methods of controlling livestock parasites. These methods include feeding livestock specific medicinal plants and trees, grazing livestock on herbal leys, and changing where livestock grazed based on ecological factors (e.g., flooding) that increased parasite burdens. Many historic texts and ethnological accounts record the ethnobotanical knowledge of rural communities and the plants they used to control livestock intestinal parasites. Some traditions persist today yet the farmers, graziers, and shepherds who hold this knowledge are rapidly disappearing and with them perhaps a potential long-term solution to anthelmintic resistance. This short perspective piece will cover recent research using ethnobotanical data as a means to identifying potential new anthelmintics; the morphological, physiological, and metabolic effect of plant secondary metabolites on parasites; and an overview of “best practices” which can reduce bias in assessments of plant bioactivity and increase reproducibility of test results. This will hopefully bring recent advances in ethnobiology, chemistry, and ecology to new audiences, and, potentially, spark new interest in using medicinal plants to improve livestock health.

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“…Some SMs such as pyrrolizidine alkaloids and furanocoumarins are both lipophilic, aromatic and planar which allows them to intercalate or alkylate DNA, thereby causing mutations and even cancer and show substantial antibacterial, antifungal, antiviral and cytotoxic properties (van Wyk and Wink, 2015;Wink and Schimmer, 2010;Schmeller et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Procavia capensis hyraceum used in traditional medicine for modulation of mutagen-induced genotoxicity

Asita¹,

Rantsâ€TMo²,

Magama³

et al. 2018

J. Med. Plants Res.

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Hyraceum (HM) is used in traditional medicine in Southern Africa. Three concentrations of HM (mg/ml in distilled water) (0.0156, 0.03125 and 0.0625) were assessed for cytotoxicity (CT), genotoxicity (GT) and modulation of cyclophosphamide (CP)-and ethyl methanesulfonate (EMS)-induced GT using the Allium cepa assay following 24 h treatment. CP (1.00 mg/ml) and EMS (0.0375 mg/ml) were not cytotoxic but genotoxic. HM (0.03125, 0.0625 mg/ml) and its mixtures with CP or EMS induced significant reduction (p <0.05) of the mitotic index (MI) and were adjudged cytotoxic. HM alone and its mixtures with CP or EMS induced statistically significant genotoxicity (p < 0.05). Mixture of HM (0.016 mg/ml) with CP was not significantly more genotoxic than CP alone (ME 0.57). Each mixture of HM (0.03125, 0.0625 mg/ml) with CP was insignificantly less genotoxic than CP alone with modulatory effect (ME) of -0.14 and -0.01, respectively, which suggested no interaction between HM and CP. Mixtures of HM with EMS induced positive and significant (>2-fold) MEs and each mixture was significantly (p < 0.05) more genotoxic than HM or EMS alone which indicated a synergistic interaction. Sticky chromosomes, chromosome laggards, chromosome fragments, anaphase and telophase bridges, binucleate interphase cells were observed.

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Molecular Modes of Action of Defensive Secondary Metabolites

Cited by 17 publications

References 318 publications

Cucurbitacins: elucidation of their interactions with the cytoskeleton

Cucurbitacins: elucidation of their interactions with the cytoskeleton

Plant-Based Solutions to Global Livestock Anthelmintic Resistance

Evaluation of Procavia capensis hyraceum used in traditional medicine for modulation of mutagen-induced genotoxicity

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