Medicinal Plants from Ancient Tradition as a Source for Matrix Proteases Inhibitors. Study of Correlation between Biological Activity and Phytochemical Profile

Considering the crucial involvement of matrix metalloproteinases’ (MMPs) misregulated activity in the pathogenesis of several degenerative diseases, this class of enzymes has been considered a highly active set of targets for the design of new therapeutic agents. However, the scant success of synthetic MMP inhibitors, largely due to the disappointing results obtained in both clinical and preclinical studies, makes medicinal plants a valuable source of new active compounds able to modulate MMPs activity. In this work, a consistent number of plants, selected on the base of an ethnobotanical research, were tested as inhibitors of collagenase, the founding member of the MMPs family. 1H-NMR-based metabolomic analysis combined with multivariate data treatment (PLS and OPLS) was used to correlate the biological activity to the phytochemical profiles, suggesting tannins as an important class of collagenase inhibitors. Thus, a tannin-removal procedure was developed, which allowed to prove this hypothesis and to identify another class of active metabolites, the glucuronide-conjugated flavonoids (especially quercetin-3-O-β-glucoronide), whose the plant Alchemilla vulgaris was found to be a good source. In another stage of the project, different varieties of tea were investigated as collagenase inhibitors, finding black tea samples particularly potent. Then, an OPLS model was developed with the aim of correlating the biological activity to the UV-Vis spectra of teas, showing that a high activity was related to absorption values in the range 350-440 nm. A subsequent fractionation of the most active tea sample was carried out, and this approach allowed to corroborate the results obtained by the metabolomic analysis. Considering that the absorbance measurement of an extract represents a cheap and simple procedure, the proposed method can be suitable, for instance, to select the best tea variety to be developed as an anti-wrinkles cosmetic or food supplement

Plant Secondary Metabolites: An Opportunity for Circular Economy

Moving toward a more sustainable development, a pivotal role is played by circular economy and a smarter waste management. Industrial wastes from plants offer a wide spectrum of possibilities for their valorization, still being enriched in high added-value molecules, such as secondary metabolites (SMs). The current review provides an overview of the most common SM classes (chemical structures, classification, biological activities) present in different plant waste/by-products and their potential use in various fields. A bibliographic survey was carried out, taking into account 99 research articles (from 2006 to 2020), summarizing all the information about waste type, its plant source, industrial sector of provenience, contained SMs, reported bioactivities, and proposals for its valorization. This survey highlighted that a great deal of the current publications are focused on the exploitation of plant wastes in human healthcare and food (including cosmetic, pharmaceutical, nutraceutical and food additives). However, as summarized in this review, plant SMs also possess an enormous potential for further uses. Accordingly, an increasing number of investigations on neglected plant matrices and their use in areas such as veterinary science or agriculture are expected, considering also the need to implement "greener" practices in the latter sector

Editorial : Pathoblockers and antivirulence agents of plant-origin for the management of multidrug resistant pathogens

Given the huge diversity of flora and ecosystems in the world, plants likely represent significant sources of bioactive compounds and, consequently, they have been extensively explored for new drug discoveries. Among their bioactivities, plant metabolites, which are the most powerful and promising elements of plants, have been shown to possess antimicrobial potential. It is well known that plant extracts act as antibacterial and antifungal agents (Anand et al., 2019; Mandrone et al., 2019; Adeosun et al., 2022), but they are also a valuable source of anti-virulence compounds with unique mechanism of action targeting pathogenicity or virulence. In addition, some phytochemicals, despite not being directly microbial inhibitors by themselves, show antibiotic adjuvant activity or bio-enhancing activity to attain bactericidal synergism (Patil et al., 2011; Dudhatra et al., 2012); moreover, they serve as reducing and stabilizing agents for the effective synthesis of plant-based metal nanoparticles, improving the antibacterial properties of these nanomaterials (Guleria et al., 2022).http://www.frontiersin.org/Microbiologyam2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-15:Life on lan

Metabolomic analysis and bioactivities of Arbutus unedo leaves harvested across the seasons in different natural habitats of Sardinia (Italy)

Background: Arbutus unedo L. is a wild tree of Mediterranean regions used as food and in traditional medicine and important for afforestation programs. There is no detailed information available on the variation of A. unedo leaves metabolome across the seasons. The leaves were analyzed by Proton nuclear magnetic resonance (1 H NMR)-based metabolomics, comparing samples harvested across the seasons and in ten different natural habitats of Sardinia (Italy). Results: Multivariate analysis showed the impact of seasonal variation on the metabolome: glucose and quinic acid increased in summer, while in spring sucrose was accumulated. β-Arbutin, the main known active principle of A. unedo, generally reached the highest concentration in autumn. In winter, O-β-methylglucose, γ-aminobutyric acid (GABA), flavonols (quercetin-3-O-α-rhamnoside, myricetin-3-O-α-rhamnoside, kaempferol-3-O-α-rhamnoside), catechin, and gallocatechin increased. Characteristic metabolomic features were found also for samples collected in different locations. For instance, trees growing at the highest altitude and exposed to lower temperatures produced less flavonols and catechins. The only sample collected on trees growing on limestones, dolomites, and dolomitic limestones type of soil showed generally the highest content of arbutin. The highest phenolics content was found during spring, while samples collected on flowering branches in winter were the ones with the highest flavonoid content. The antioxidant activity was also variated, ranging from 1.3 to 10.1 mg of Trolox equivalents (TE)/mL of extract, and it was positively correlated to both total phenolics and flavonoid content. Winter samples showed the lowest antibacterial activity, while summer and autumn ones exhibited the highest activity (IC50 values ranging from 17.3 to 42.3 µg/mL against Staphylococcal species). Conclusion: This work provides 1 H-NMR fingerprinting of A. unedo leaves, elucidating the main metabolites and their variations during seasons. On the basis of arbutin content, autumn could be considered the balsamic period of this taxon. Samples collected in this season were also the most active ones as antibacterial. Moreover, an interesting metabolomic profile enriched in catechins and flavonols was observed in leaves collected in winter on flowering branches which were endowed with high antioxidant potential

Metabolomics and genetics of reproductive bud development in Ficus carica var. sativa (edible fig) and in Ficus carica var. caprificus (caprifig): similarities and differences

In figs, reproductive biology comprises cultivars requiring or not pollination, with female trees (edible fig) and male trees (caprifig) bearing different types of fruits. Metabolomic and genetic studies may clarify bud differentiation mechanisms behind the different fruits. We used a targeted metabolomic analysis and genetic investigation through RNA sequence and candidate gene investigation to perform a deep analysis of buds of two fig cultivars, ‘Petrelli’ (San Pedro type) and ‘Dottato’ (Common type), and one caprifig. In this work, proton nuclear magnetic resonance (1H NMR-based metabolomics) has been used to analyze and compare buds of the caprifig and the two fig cultivars collected at different times of the season. Metabolomic data of buds collected on the caprifig, ‘Petrelli’, and ‘Dottato’ were treated individually, building three separate orthogonal partial least squared (OPLS) models, using the “y” variable as the sampling time to allow the identification of the correlations among metabolomic profiles of buds. The sampling times revealed different patterns between caprifig and the two edible fig cultivars. A significant amount of glucose and fructose was found in ‘Petrelli’, differently from ‘Dottato’, in the buds in June, suggesting that these sugars not only are used by the ripening brebas of ‘Petrelli’ but also are directed toward the developing buds on the current year shoot for either a main crop (fruit in the current season) or a breba (fruit in the successive season). Genetic characterization through the RNA-seq of buds and comparison with the literature allowed the identification of 473 downregulated genes, with 22 only in profichi, and 391 upregulated genes, with 21 only in mammoni

Berberine and Tinospora cordifolia exert a potential anticancer effect on colon cancer cells by acting on specific pathways

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial-mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial-mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity

Supplementary data for the article: Ivanović, S.; Mandrone, M.; Simić, K.; Ristić, M.; Todosijević, M.; Mandić, B.; Gođevac, D. GC-MS-Based Metabolomics for the Detection of Adulteration in Oregano Samples. Journal of the Serbian Chemical Society 2021, 86 (12), 1195–1203. https://doi.org/10.2298/JSC210809089I.

Supplementary material for: [https://doi.org/10.2298/JSC210809089I]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/5035