Metabolite Profiling of Colvillea racemosa via UPLC-ESI-QTOF-MS Analysis in Correlation to the In Vitro Antioxidant and Cytotoxic Potential against A549 Non-Small Cell Lung Cancer Cell Line.

In this study, flower and leaf extracts of Colvillea racemosa were considered a source of bioactive compounds. In this context, the objective of the study focused on investigating the anticancer potential as well as the phytochemical composition of both extracts. The extracts were analyzed by UPLC-ESI-QTOF-MS, and the bioactivity was tested using in vitro antioxidant assays (FRAP, DPPH, and ABTS) in addition to cytotoxic assays on non-small cell lung cancer cell line (A549). Our results clearly indicated the potent radical scavenging capacity of both extracts. Importantly, the flower extract exhibited a greater antioxidant capacity than the leaf extract. In terms of cytotoxic activity, leaf and flower extracts significantly inhibited cell viability with IC50 values of 17.0 and 17.2 µg/mL, respectively. The phytochemical characterization enabled the putative annotation of 42 metabolites, such as saccharides, phenolic acids, flavonoids, amino acids, and fatty acids. Among them, the flavonoid C-glycosides stand out due to their high relative abundance and previous reports on their anticancer bioactivity. For a better understanding of the bioactive mechanisms, four flavonoids (vitexin, kaempferol-3-O-rutinoside, luteolin, and isoorientin) were selected for molecular docking on hallmark protein targets in lung cancer as represented by γ-PI3K, EGFR, and CDK2 through in-silico studies. In these models, kaempferol-3-O-rutinoside and vitexin had the highest binding scores on γ-PI3K and CDK2, followed by isoorientin, so they could be highly responsible for the bioactive properties of C. racemosa extracts.

UHPLC-ESI-QTOF-MS metabolite profiles of different extracts from Pelargonium endlicherianum parts and their biological properties based on network pharmacological approaches.

In the present study, we aimed to investigate the chemical profiles and biological activities of different extracts (ethyl acetate, dichloromethane, ethanol, and water) of Pelargonium endlicherianum parts (aerial parts and roots). Free radical scavenging, reducing power, phosphomolybdenum, and metal chelating were assayed for antioxidant properties. To detect enzyme inhibitory properties, cholinesterase, amylase, glucosidase, and tyrosinase were chosen as target enzymes. The ethanol extract of the aerial parts contained higher amounts of total bioactive compounds (120.53 mg GAE/g-24.46 mg RE/g). The ethanol and water extracts of these parts were tentatively characterized by UHPLC-ESI-QTOF-MS and 95 compounds were annotated. In addition, the highest acetylcholiesterase (3.74 mg GALAE/g) and butyrylcholinesterase (3.92 mg GALAE/g) abilities were observed by the ethanol extract of roots. The water extract from aerial parts exhibited the most pronounced inhibitory effects on multiple cancer cell lines, especially A549 (IC50: 23.2 µg/mL) and HT-29 (IC50: 27.43 µg/mL) cells. Using network pharmacology, P. endlicherianum compounds were studied against cancer, revealing well-connected targets such as epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), AKT, receptor tyrosine-protein kinase erbB-2, and growth factor receptor bound protein 2 (GRB2) with significant impact on cancer-related pathways. The results could open a new path from natural treasure to functional applications with P. endlicherianum and highlight a new study on other uninvestigated Pelargonium species.

Diet Supplementation with Polyphenol-Rich Salicornia ramosissima Extracts Protects against Tissue Damage in Experimental Models of Cerebral Ischemia.

Strokes are the second most common cause of death worldwide and a leading cause of disability. Regular consumption of polyphenols has been shown to reduce the risk of suffering a cardiovascular event. For this reason, we have investigated the protective effect of Salicornia ramosissima, a seasonal halophyte that synthetizes high amounts of bioactive compounds, including polyphenols, in response to environmental stress. Aqueous, hydroalcoholic, and ethanolic extracts were prepared to investigate if dietary supplementation prior to ischemic challenge can prevent subsequent damage using two animal models. First, we screened the protective effect against hypoxia-reoxygenation in Drosophila melanogaster and observed that both ethanolic and hydroalcoholic extracts protected flies from the deleterious effects of hypoxia. Second, we confirmed the protective effect of S. ramosissima ethanolic extract against brain ischemia using the transient middle cerebral artery occlusion mice model. Four weeks of oral supplementation with the ethanolic extract before artery occlusion reduced infarct volume and lowered the plasma levels of the DNA peroxidant product 8-hydroxydeoxyguanosine. Phytochemical profiling of S. ramosissima ethanolic extract revealed 50 compounds. Thus, it represents a valuable source of bioactive compounds that show promising disease-modifying activities and could be further developed as an effective food supplement for the prevention or treatment of neurovascular disorders.

Selectivity Tuning by Natural Deep Eutectic Solvents (NADESs) for Extraction of Bioactive Compounds from Cytinus hypocistis-Studies of Antioxidative, Enzyme-Inhibitive Properties and LC-MS Profiles.

In the present study, the extracts of Cytinus hypocistis (L.) L using both traditional solvents (hexane, ethyl acetate, dichloromethane, ethanol, ethanol/water, and water) and natural deep eutectic solvents (NADESs) were investigated in terms of their total polyphenolic contents and antioxidant and enzyme-inhibitive properties. The extracts were found to possess total phenolic and total flavonoid contents in the ranges of 26.47-186.13 mg GAE/g and 0.68-12.55 mg RE/g, respectively. Higher total phenolic contents were obtained for NADES extracts. Compositional differences were reported in relation to antioxidant potential studied by several assays (DPPH: 70.19-939.35 mg TE/g, ABTS: 172.56-4026.50 mg TE/g; CUPRAC: 97.41-1730.38 mg TE/g, FRAP: 84.11-1534.85 mg TE/g). Application of NADESs (choline chloride-urea 1:2, a so-called Reline) allowed one to obtain the highest number of extracts having antioxidant potential in the radical scavenging and reducing assays. NADES-B (protonated by HCl L-proline-xylitol 5:1) was the only extractant from the studied solvents that isolated a specific fraction without chelating activity. Reline extract exhibited the highest acetylcholinesterase inhibition compared to NADES-B and NADES-C (protonated by H2SO4 L-proline-xylitol 5:1) extracts, which showed no inhibition. The NADES extracts were observed to have higher tyrosinase inhibitory properties compared to extracts obtained by traditional organic solvents. Furthermore, the NADES extracts were relatively better inhibitors of the diabetic enzymes. These findings provided an interesting comparison in terms of total polyphenolic content yields, antioxidant and enzyme inhibitory properties (cholinesterase, amylase, glucosidase, and tyrosinase) between traditional solvent extracts and NADES extracts, used as an alternative. While the organic solvents showed better antioxidant activity, the NADES extracts were found to have some other improved properties, such as higher total phenolic content and enzyme-inhibiting properties, suggesting functional prospects for their use in phytonutrient extraction and fractionation. The obtained results could also be used to give a broad overview of the different biological potentials of C. hypocistis.

A Prospective of Multiple Biopharmaceutical Activities of Procyanidins-Rich Uapaca togoensis Pax Extracts: HPLC-ESI-TOF-MS Coupled with Bioinformatics Analysis.

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.

Recovery of Bioactive Compounds from Pomegranate (Punica granatum L.) Peel Using Pressurized Liquid Extraction.

Pressurized liquid extraction (PLE) is a clean and environmentally friendly alternative for the recovery of bioactive compounds from fruit by-products. Herein we focused on PLE for the extraction of bioactive compounds from pomegranate peel using a combination of pressurized water and ethanol. The main aim was to determine the optimal PLE conditions, i.e., ethanol percentage and process temperature, to obtain a pomegranate peel extract (PPE) with maximum total phenolic content (TPC), punicalagin content, and antimicrobial activity (AMA). The experimental design was conducted using a central composite design with axial points. Response surface methodology was applied to optimize the response variables using the desirability function. Multiple response optimization indicated a process temperature of 200 °C and ethanol of 77% as optimal conditions. The TPC and the punicalagin content of PPE-PLE obtained under optimal conditions were 164.3 ± 10.7 mg GAE/g DW and 17 ± 3.6 mg/g DW, respectively. Our findings support the efficacy of PLE on TPC recovery but not in punicalagin recovery. The AMA against S. aureus was 14 mm. The efficacy of PPE-PLE in food applications must continue to be studied in order to achieve adequate information on its potential for developing new food additives.

Comprehensive Analysis of Antioxidant Compounds from Lippia citriodora and Hibiscus sabdariffa Green Extracts Attained by Response Surface Methodology.

Phenolic compounds have shown to have a high bioactive potential against various pathologies, postulating as an interesting alternative to manage some diseases. In this sense, both Lippia citriodora and Hibiscus sabdariffa are two botanical sources with a demonstrated high bioactive potential, in which their antioxidant capacity stands out. In this work, the optimization of the extraction conditions for the recovery of phytochemicals from L. citriodora leaves and H. sabdariffa calyces has been carried out using Response Surface Methodologies (RSM) considering their total polar compounds measured by HPLC-ESI-TOF/MS and Folin-Ciocalteu assay, and its antioxidant capacity evaluated by Ferric Reducing Antioxidant Power (FRAP) and Trolox Equivalent Antioxidant Capacity (TEAC) assays. The results showed that to maximize the antioxidant capacity in H. sabdariffa, a moderate temperature and high ethanol percentage are needed, while a low temperature and a high percentage of ethanol are needed in L. citriodora. In addition, with the results obtained in the multiple response analysis, it is possible to affirm the importance of this type of analysis to develop functional ingredients, taking into account both total content of phenolic compounds and their bioactivity. Furthermore, as confirmed in this study, these analyses can be extrapolated in different techniques and in different matrices, with phenolic compounds from different families being important to develop new high added value products for food, pharmaceutical or cosmetic industries.

LC-MS and Spectrophotometric Approaches for Evaluation of Bioactive Compounds from Peru Cocoa By-Products for Commercial Applications.

Peru is one of the main areas where there are large cocoa crops with special relevance to the economy of this country. In fact, cocoa is a major, economically important, international crop which has been linked to several benefits, such as anti-allergenic, anti-atherogenic, anti-inflammatory, anti-microbial, anti-oxidant, anti-thrombotic, cardioprotective and vasodilatory properties, relating to its bioactive compound content. However, in cocoa industrial processing, several residues or wastes, which are commonly discarded generating a negative impact on the environment, are produced in large amounts. Some of the cocoa by-products, which go underutilized, could be a good source of bioactive compounds with high utility for the development of innovative products in nutraceutical, medical or pharmaceutical industries. For this reason, the aim of this study is to qualitatively determine the phytochemical composition of husk and bean extracts from different cocoa-growing areas and processes from Peru by high performance liquid chromatography coupled to mass spectrometry. Furthermore, we aim to evaluate their phenolic and flavan-3-ol contents and antioxidant capacities for the purpose of highlighting the potential of cocoa by-products from these cultivars as functional ingredients. In total, 49 chemical compounds were detected in the analyzed extracts. Comparing both husks and beans, bean extracts were characterized by high content in flavonoids whereas husk extracts had a higher content of phenolic acids. The presence of these compounds together with the bioactivity results suggest that these matrices may be further studied for their revaluation in the development of high added-value products in nutraceutical, medical, and pharmaceutical industries.

The Beneficial Effects of Lippia Citriodora Extract on Diet-Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition.

SCOPE: Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well-characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. METHODS: Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg-1 ). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium-dependent vasodilator response to acetylcholine. RESULTS: LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. CONCLUSION: The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.

Characterization of a new blackberry cultivar BRS Xingu: Chemical composition, phenolic compounds, and antioxidant capacity in vitro and in vivo.

The cultivar BRS Xingu was launched by EMBRAPA in 2015 with the intention of presenting higher productivity. Due to the lack of studies on this cultivar, the objective was to present the physical-chemical, centesimal, and phenolic composition of the BRS Xingu blackberry, its antioxidant capacity, protection against ROS generation, and compare it with other commercialized cultivars such as Guarani, Tupy, and Xavante. The BRS Xingu was prominent regarding anthocyanin and condensed tannin content and superior to the other cultivars. Moreover, BRS Xingu presented higher antioxidant capacity, protection of C. elegans from ROS generation, and soluble solid content when compared to Tupy, which is the most cultivated variety in the world. In the new cultivar, five anthocyanins, five phenolic acids, and ten non-anthocyanin flavonoids were identified. BRS Xingu is presented as an alternative blackberry with potential for industrialization and in natura consumption.