Identification of onosma visianii roots extract and purified shikonin derivatives as potential acaricidal agents against tetranychus urticae

There is an increasing need for the discovery of reliable and eco-friendly pesticides and natural plant-derived products may play a crucial role as source of new active compounds. In this research, a lipophilic extract of Onosma visianii roots extract containing 12% of shikonin derivatives demonstrated significant toxicity and inhibition of oviposition against Tetranychus urticae mites. Extensive chromatographic separation allowed the isolation of 11 naphthoquinone derivatives that were identified by spectral techniques and were tested against Tetranychus urticae. All the isolated compounds presented effects against the considered mite and isobutylshikonin (1) and isovalerylshikonin (2) were the most active, being valuable model compounds for the study of new anti-mite agents

Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

Systemic lipopolysaccharide (LPS) induces an acute inflammatory response in the central nervous system (CNS) (\u201cneuroinflammation\u201d) characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg) in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction

Larix decidua Bark as a Source of Phytoconstituents: An LC-MS Study

Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of larch bark was performed using mixtures of ethanol/water. Furthermore, the phytochemical composition of larch bark extract was studied using LC-MS(n) methods and the main constituents were identified as flavonoids, spiro-polyphenols, and procyanidins. To confirm the identification by LC-MS semi-preparative HPLC was performed in order to isolate the main constituents and verify the structures by \ub9H-NMR. Antioxidant properties were studied using an in vitro approach combining DPPH assay and LC-MS in order to establish different roles of the various classes of phytochemicasl of the extract. DPPH activity of some of the isolated compounds was also assessed. The overall results indicate this waste material as a good source of antioxidant compounds, mainly procyanidins, whichresulted the most active constituents in the DPPH assay

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

There is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of pharmaceutical formulations. Natural Deep Eutectic Solvents (NADES) are formed by natural compounds, and can be considered as future solvents being especially useful for the preparation of nutraceuticals and food-grade extracts. In this paper various NADES were prepared using sugars, aminoacids and organic acids. Rutin (quercetin-3-O-\u3b1-l-rhamnopyranosyl-(1\u21926))-\u3b2-d-glucopyranose) was used as a model compound to study NADES. Moreover, the effect of various eutectic mixtures on rutin\u2019s water solubility was studied. Proline/glutamic acid (2:1) and proline/choline chloride (1:1) mixtures have a solubility comparable to ethanol. The proline/glutamic acid (2:1) eutectic containing rutin was used in a pharmacokinetic study in Balb/c mice while bioavailability was compared to oral dosing of water suspension. Plasmatic levels of rutin were measured by HPLC-MS/MS showing increased levels and longer period of rutin permanence in plasma of NADES treated animals. This paper reports the possible use of non-toxic NADES for pharmaceutical and nutraceutical preparations

Development of an LC-DAD-MS-Based Method for the Analysis of Hydroxyanthracene Derivatives in Food Supplements and Plant Materials

Products based on plants containing hydroxyanthracene derivatives (HADs)-such as Rheum, Cassia, and Aloe species-are widely used in food supplements or nutraceuticals due to their laxative effects. A more restricted control of HAD contents in food supplements has been implemented by EU Regulation 2021/468, in order to increase the safety of these preparations. Due to their toxicity, aloin A, aloin B, aloe emodin, emodin, and the synthetic derivative danthron have been listed as prohibited substances in food supplements, being tolerated in amounts < 1 mg kg(-1) in marketed products. In this work, we report the development of a sensitive and fast LC-DAD-MS-based procedure for the determination of these five compounds in food supplements and plant materials or extracts. The entire procedure includes a simple sample preparation step, where target analytes are concentrated by means of solvent extraction and evaporative concentration (solid samples), or by lyophilisation (liquid samples). The average LOQ of 0.10 mg/L, LOD of 0.03 mg/L, accuracy, and precision with CVs below 12.72 were obtained for the studied analytes. This method is suitable for assessing the compliance of commercial products and raw materials with EU Regulation 2021/468. Furthermore, the proposed method can represent a starting point for the development of a unique and standardised analytical approach for the determination of other HADs under the attention of EU authorities

Total phytochemical analysis of Thymus munbyanus subsp. coloratus from Algeria by HS-SPME-GC-MS, NMR and HPLC-MSn studies

In this article, we report a comprehensive characterization of volatile and polar constituents extracted from the aerial parts of Thymus munbyanus subsp. coloratus, a shrub that is used as culinary ingredient and as traditional medicine in Algeria, mainly to treat respiratory and gastrointestinal disorders and endocrine dysfunctions. Headspace solid phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was used to assess volatile constituents, whereas the phytochemical composition of solid residues obtained from extraction with solvents at diffrent polarity was obtained by an integrated Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled with tandem mass spectrometry (LC-MSn) approach. Fourty-five apolar ccompounds were identified, mainly oxygenated monoterpenes (65.8%), sesquiterpene hydrocarbons and nonoterpene hydrocarbons (18.6 and 14.5%, respectively). On the other hand, LC-MSn and NMR analyses revealed the presence of aglyconic and glycosilated flavonoids, phenylpropanoid derivatives and triterpenoid acids related to oleanolic acid, mainly in the methanol, dichloromethane and hexane extracts. Overall, these data indicate that Thymus munbyanus subsp. coloratus could be a potential source of antioxidants and bioactive compounds, and our results represent a starting point for further research on this plant species

Chemical Characterization and Cytotoxic and Antioxidant Activity Evaluation of the Ethanol Extract from the Bulbs of Pancratium maritimun Collected in Sicily

P. maritimum L., belonging to the Amaryllidaceae family, is a species that grows on beaches and coastal sand dunes mainly on both sides of the Mediterranean Sea and Black Sea, the Middle East, and up to the Caucasus region. It has been largely investigated due to its several interesting biological properties. With the aim of providing new insights into the phytochemistry and pharmacology of this species, the ethanolic extract of the bulbs from a local accession, not previously studied, growing in Sicily (Italy), was investigated. This chemical analysis, performed by mono- and bi-dimensional NMR spectroscopy, as well as LC-DAD-MSn, allowed to identify several alkaloids, three of which were never detected in the genus Pancratium. Furthermore, the cytotoxicity of the preparation was assessed in differentiated human Caco-2 intestinal cells by trypan blue exclusion assay, and its antioxidant potential was evaluated using the DCFH-DA radical scavenging method. The results obtained demonstrate that P. maritimum bulbs’ extract exerts no cytotoxic effect and is able to remove free radicals at all the concentrations tested

Oviposition inhibitory activity of the Mexican sunflower Tithonia diversifolia (Asteraceae) polar extracts against the two-spotted spider mite Tetranychus urticae (Tetranychidae)

The Mexican sunflower (Tithonia diversifolia, Asteraceae) is an invasive shrub of agricultural and non-agricultural lands in tropical countries. Besides extensive utilizations in the traditional medicine, mainly to treat malaria, the plant is believed to have a great potential in agriculture of developing countries as a green biomass to produce fertilizer, fodder and biopesticides. The plant is known to produce tagitinins, which are sesquiterpene lactones with a bitter taste endowed with toxicity against several insects such as mosquitoes, aphids, and beetles. Here, we evaluated the potential of T. diversifolia against the two-spotted spider mite Tetranychus urticae (Tetranychidae), which is one of the most economically important arthropod pests worldwide. The leaf methanolic extract and its ethyl acetate fraction were tested for acute and chronic toxicity and for oviposition inhibitory effects. The chemical composition of the extracts was analyzed by HPLC-MSn and NMR. The main constituents were flavonoid derivatives, phenylpropanoids and sesquiterpene lactones. Among the latter, tagitinin C and tagitinin A were the major compounds. In acute toxicity assays, mortality did not exceed 50% even for the highest tested dose of 150 \u3bcg cm-3. However, in chronic toxicity assays, on day 5 from application, the methanolic extract LD50 was 41.3 \u3bcg cm-3 while LD90 was 98.7 \u3bcg cm-3. Furthermore, both T. diversifolia extracts inhibited oviposition in T. urticae. The ethyl acetate extract was the most active oviposition inhibitor, with an ED50 value of 44.3 \u3bcg cm-3 and an ED90 of 121.5 \u3bcg cm-3. Overall, the good yield rate of the extract and the high crop yield highlighted good prospects of using the extract from this plant for the development of oviposition inhibitors against mite

Microbial inactivation efficiency of supercritical CO2drying process

Conventional drying of spices, as hot air treatment, often needs an additional downstream inactivation step to decrease the microbial load of the dried product and improve its microbial safety and microbial quality. In this regard, the present work explored the possibility to dry and decontaminate food in a single step using supercritical carbon dioxide (scCO(2)) as a drying agent. A case study was focused on the drying of herbs and the antimicrobial effects were evaluated on the naturally present microbiota. For this purpose, experiments were carried out on coriander leaves using a high pressure vessel at 10 MPa, at two different temperatures (40 and 50 degrees C) with drying time of 0 and 150 min to establish the influence of each parameter on the microbial inactivation. Yeasts and molds appeared to be the least resistant to scCO(2) as they could never be detected after the treatment (<2 log CFU/g). Mesophilic bacteria were also significantly reduced, up to 4 log CFU/g, but remained above the limit of quantification. The quality of the dried product was comparable with the quality of air-dried samples in terms of phenolic constituents. Overall, the results indicated that scCO(2) drying was a promising green drying technique combining both drying and microbial inactivation in a single step with a relevant impact on safety and costs

Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs). The results showed that most of derivatives totally inhibit PDK1 and PDK4. Molecular docking analysis was executed to predict the possible binding mode of these derivatives using ligand-based homology modeling technique. Evaluation of the capability of new triazines to inhibit the cell growth in 2D and 3D KRAS-wild-type (BxPC-3) and KRAS-mutant (PSN-1) PDAC cell line, was carried out. The results showed the capacity of the new derivatives to reduce cell growth with a major selectivity against KRAS-mutant PDAC PSN-1 on both cell models. These data demonstrated that the new triazine derivatives target PDK1 enzymatic activity and exhibit cytotoxic effects on 2D and 3D PDAC cell models, thus encouraging further structure manipulation for analogs development against PDA