Discovery of potential ovicidal natural products using metabolomics

Abstract

Plant extracts are a potential source of new compounds for nematode control and may be an excellent alternative for the control gastrointestinal nematodes that are resistant to conventional anthelmintics. However, research involving natural products is a complex process. The main challenge is the identification of bioactive compounds. Online analytical techniques with universal detectors, such as high-performance liquid chromatography-mass spectrometry (HPLC-MS), together with metabolomics could enable the fast, accurate evaluation of a massive amount of data, constituting a viable option for the identification of active compounds in plant extracts. This study focused on the evaluation of the ovicidal activity of ethanol extracts from 17 plants collected from the Pantanal wetland in the state of Mato Grosso do Sul, Brazil, against eggs of Haemonchus placei using the egg hatchability test. The ethanol extracts were obtained using accelerated solvent extraction. The data on ovicidal activity, mass spectrometry and metabolomics were evaluated using HPLC-DAD-MS, partial least squares regression analysis (PLS-DA) and a correlation map (univariate correlation analyses) to detect compounds that have a positive correlation with biological activity. Among the ten metabolites with the best correlation coefficients, six were phenylpropanoids, two were triterpene saponins, one was a brevipolide, and one was a flavonoid. Combinations of metabolites with high ovicidal action were also identified, such as phenylpropanoids combined with the triterpene saponins and the flavonoid, flavonoids combined with iridoid and phenylpropanoids, and saponins combined with phenylpropanoid. The positive correlation between classes of compounds in plants belonging to different genera and biological activity (as previously identified in the literature) reinforces the robustness of the statistical data and demonstrates the efficacy of this method for the selection of bioactive compounds without the need for isolation and reevaluation. The proposed method also enables the determination of synergism among the classes, which would be impracticable using traditional methods. The present investigation demonstrates that the metabolomic technique was efficient at detecting secondary metabolites with ovicidal activity against H. placei. Thus, the use of metabolomics can be a tool to accelerate and simplify bioprospecting research with plant extracts in veterinary parasitology.

Phytochemical Study of Aerial Parts of Leea asiatica

“…The current study demonstrated the presence of triterpenoids, including oleanolic acid, ursolic acid, the representative pentacyclic triterpenes, and their derivatives ( 1 – 8 ). The anthelmintic activity of L. asiatica is thought to be exerted by triterpenoids because several reports demonstrated that oleanolic acid and ursolic acid possessed anthelmintic activity [39,40], and saponins were also associated with the ovicidal action of the plant extract [41]. Thus, this study supports the evidence for clarifying the anthelmintic effect of L. asiatica .…”

In Vitro Anthelmintic Activity of Saponins from Medicago spp. Against Sheep Gastrointestinal Nematodes

“…Moreover, the EC 90 and EC 50 values found for the most active saponins in this study are similar to those reported for other active plant compounds [33]. These results are in agreement with previously reported data, confirming a high ovicidal activity of saponins from Medicago spp.…”

“…The saponins aescin and digitonin [17] and saponin fractions contained in Zizyphus joazeiro [16], Phytolacca icosandra [34] and Agave sisalana [18] showed 'in vitro' ovicidal activity against the nematodes of small ruminants. Similarly, the 'in vitro' ovicidal action of Combretum molle against eggs of H. contortus from sheep and of Ipomoea chiliantha, Tocoiena formosa and Aspilia latissima against the eggs of Haemonchus placei from cattle, have been attributed to their saponin content [33,35]. Biological effects of saponins are normally ascribed to their specific interaction with the cell membrane, causing changes in the cell permeability [20,36,37].…”

Exhaustive extraction of cyclopeptides from Amanita phalloides: Guidelines for working with complex mixtures of secondary metabolites

“…The results of our work add to a growing body of literature demonstrating the use of ASE for the extraction of many classes of secondary metabolites (Borges et al, 2019; Ligor et al, 2018; Widelski et al, 2018). To the best of our knowledge, this is the first report on exhaustive extraction of cyclopeptides and other metabolites from Amanita samples.…”

“…Furthermore, the extraction is a fully controlled process, which eliminates the problem of batch to batch variability caused by changing extraction conditions. Thus, ASE is a fast, efficient, and more environmentally friendly approach and has been proven to be a reliable and reproducible extraction technique for numerous types of natural matrices (Borges et al, 2019; Ligor, Ratiu, Kielbasa, Al‐Suod, & Buszewski, 2018; Widelski et al, 2018).…”