Identification of a Collagenase-Inhibiting Flavonoid from Alchemilla vulgaris Using NMR-Based Metabolomics

Abstract

This paper describes the use of H NMR profiling and chemometrics in order to facilitate the selection of medicinal plants as potential sources of collagenase inhibitors. A total of 49 plants with reported ethnobotanical uses, such as the healing of wounds and burns, treatment of skin-related diseases, rheumatism, arthritis, and bone diseases, were initially chosen as potential candidates. The collagenase inhibitory activity of hydroalcoholic extracts of these plants was tested. Moreover, their phytochemical profiles were analyzed by H NMR and combined with the inhibitory activity data by an orthogonal partial least squares model. The results showed a correlation between the bioactivity and the concentration of phenolics, including flavonoids, phenylpropanoids, and tannins, in the extracts. Considering the eventual false-positive effect on the bioactivity given by tannins, a tannin removal procedure was performed on the most active extracts. After this procedure, was the most persistently active, proving to owe its activity to compounds other than tannins. Thus, this plant was selected as the most promising and further investigated through bioassay-guided fractionation, which resulted in the isolation of a flavonoid, quercetin-3---glucuronide, as confirmed by NMR and HRMS spectra. This compound showed not only a higher activity than other flavonoids with the same aglycone moiety, but was also higher than doxycycline (positive control), the only Federal Drug Administration-approved collagenase inhibitor. The approach employed in this study, namely the integration of metabolomics and bioactivity-guided fractionation, showed great potential as a tool for plant selection and identification of bioactive compounds in natural product research.

Leaves and Spiny Burs of Castanea Sativa from an Experimental Chestnut Grove: Metabolomic Analysis and Anti-Neuroinflammatory Activity

“…This workflow has already been applied successfully in several areas of research, from human diagnostics and epidemiology to the plant sciences [ 14 ]. In this latter field of study, metabolomics was successful at facilitating the identification of the active components of medicinal plants [ 15 ], studying plant ecotypes and biological features [ 16 , 17 ], and controlling food and botanical quality, both in terms of nutraceutical/biological properties and fraud detection [ 18 , 19 ].…”

Compatible and Incompatible Pollen-Styles Interaction in Pyrus communis L. Show Different Transglutaminase Features, Polyamine Pattern and Metabolomics Profiles

“…This workflow proved to be successful in several research fields, from human diagnostics and epidemiology to plant science (Wolfender et al, 2015; Anđelković et al, 2017), where it resulted particularly helpful to face the challenges posed by the complexity of natural product chemistry (Pauli et al, 2012). For instance, metabolomics has been employed to facilitate the identification of medicinal plants active principles (Gođevac et al, 2018; Mandrone et al, 2018).…”

Lady's mantle (Alchemilla vulgaris L., Rosaceae): A review of traditional uses, phytochemical profile, and biological properties

“…Namely, the activity of this compound as a collagenase inhibitor was higher than doxycycline, a Federal Drug Administration (FDA)-approved drug, used as a positive control in this study. It might be added that aside from wound or burn healing, collagenase inhibitors might be useful in the treatment of other skin-related diseases, such as dermatitis, acne, urticarial, or photoaging (Mandrone et al, 2018). Also, Vlaisavljević et al (2019) revealed amylase and tyrosinase inhibitory effects of A. vulgaris, which might be related to antidiabetic and skin-related diseases (Vlaisavljević et al, 2019).…”