Natural essential oils as a new therapeutic tool in colorectal cancer.

Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC.

Solanum linnaeanum Leaves: Chemical Profiling of VOCs and Effects on Seed Germination and Early Growth of Monocots and Dicots.

Some Solanaceae plants are a rich source of sesquiterpenoid phytoalexins with allelopathic potential. Powder and aqueous extract obtained from the leaves of Solanum linnaeanum Hepper & P.M.L. Jaeger were used to treat the seeds of three target species (Lolium multiflorum Lam., Sinapis alba L. and Trifolium incarnatum L.). Both matrices were evaluated along with untreated controls to determine their toxicity on germination and seedling growth. The results revealed that the pre-emergence treatments were able to be very effective against all three species in the filter paper test by inhibiting the germination up to 100 %. The effectiveness was reduced by the interaction with soil. Despite this, significant data were obtained, albeit different according to the applied matrix. In general, L. multiflorum was the most sensitive to both the action of the leaf powder and aqueous extract while S. alba was found to be the most resistant to powder activity and T. incarnatum had the strongest response to the extract. For the first time, SPME-GC/MS technique was used to characterize the volatile chemical profile of S. linnaeanum leaves. The analyses highlighted the presence of different classes of compounds including terpenoids and sesquiterpenoids potentially useful in the fight against noxious plants both in natural and cultivated ecosystems.

Detection of Volatiles by HS-SPME-GC/MS and Biological Effect Evaluation of Buddha's Hand Fruit.

The present work aimed to chemically characterize and evaluate the antiradical power and biological effects of Citrus medica var. sarcodactylus essential oil (EO) and hydrolate (Hy) from exocarp as well as methanol extracts, from both exocarp and mesocarp (EEX and MEX). The whole fresh fruit was also investigated by SPME-GC/MS to describe its volatile composition. EO and Hy were analyzed by GC/MS and HS-GC/MS techniques, respectively. Limonene and γ-terpinene were found to be the most abundant compounds both in the fresh parts of the fruit and in the EO, while α-terpineol and terpinen-4-ol were in the Hy. The extracts were also rich in furan and coumarin derivatives. A good antiradical activity of all samples except Hy was detected both against ABTS·+ than DPPH·, removed up to about 50%. The antibacterial activity against Bacillus cereus and Escherichia coli was evaluated by microwell dilution method to determine MIC and MBC values. EEX and MEX showed efficacy at very high concentrations against both tested bacteria. The MIC value of EO against B. cereus was 0.5% v/v, while Hy was not able to inhibit the bacterial growth at the tested concentrations. Cytotoxicity investigated on the HL60 leukemia cell line by MTT assay provided an EC50 of 1.24% v/v for EO. Interesting activity of Hy was also observed.

Tryptophan Derivatives by Saccharomyces cerevisiae EC1118: Evaluation, Optimization, and Production in a Soybean-Based Medium.

Given the pharmacological properti es and the potential role of kynurenic acid (KYNA) in human physiology and the pleiotropic activity of the neurohormone melatonin (MEL) involved in physiological and immunological functions and as regulator of antioxidant enzymes, this study aimed at evaluating the capability of Saccharomyces cerevisiae EC1118 to release tryptophan derivatives (dTRPs) from the kynurenine (KYN) and melatonin pathways. The setting up of the spectroscopic and chromatographic conditions for the quantification of the dTRPs in LC-MS/MS system, the optimization of dTRPs' production in fermentative and whole-cell biotransformation approaches and the production of dTRPs in a soybean-based cultural medium naturally enriched in tryptophan, as a case of study, were included in the experimental plan. Variable amounts of dTRPs, with a prevalence of metabolites of the KYN pathway, were detected. The LC-MS/MS analysis showed that the compound synthesized at highest concentration is KYNA that reached 9.146 ± 0.585 mg/L in fermentation trials in a chemically defined medium at 400 mg/L TRP. Further experiments in a soybean-based medium confirm KYNA as the main dTRPs, whereas the other dTRPs reached very lower concentrations. While detectable quantities of melatonin were never observed, two MEL isomers were successfully measured in laboratory media.

A Comparative Study of the Chemical Composition by SPME-GC/MS and Antiradical Activity of Less Common Citrus Species.

Citrus secondary metabolites, such as terpene compounds, are very important for human health due to their bioactivity including anti-inflammatory, anti-cancer, and antioxidant effects. In this work, for the first time, the volatile chemical composition of peels and juices from four different Citrus species (C. junos, Citrus × aurantium, C. aurantium 'Bizzarria' and C. medica 'Florentina', commonly known as Yuzu jeune, Oni Yuzu, Bizzarria orange and Florence cedar, respectively) was investigated by Solid-Phase Microextraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS) technique and the antiradical activity was also examined. The results showed that limonene and γ-terpinene were the main volatile substances detected both in the juices and in the peels, followed by other minority compounds responsible for the phyto-complex of the unique aromas which characterize each individual analyzed Citrus species. Principal component analysis (PCA), performed on volatile compounds, showed both some correlation as well as a clear separation between the juice and the peel of each species. Among them, Oni Yuzu juice was found to be the richest in total polyphenols and flavonoids while its capacity to scavenge ABTS•+ and DPPH• radicals was similar to that of Yuzu Jeune and Bizzarria orange.

Antimicrobial Activity and Synergy Investigation of Hypericum scabrum Essential Oil with Antifungal Drugs.

The chemical composition of Lebanese Hypericum scabrum essential oil (EO) was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GG-MS). Its antimicrobial activity was evaluated by determining its minimal inhibitory concentrations (MICs) against a Gram-negative and a Gram-positive bacterium, one yeast, and five dermatophytes. H. scabrum EO was most active on filamentous fungi (MIC values of 32-64 µg/mL). Synergy within the oil was investigated by testing each of the following major components on Trichophyton rubrum: α-pinene, limonene, myrcene, ß-pinene and nonane, as well as a reconstructed EO. The antifungal activity of the natural oil could not be reached, meaning that its activity might be due, in part, to minor constituent(s). The interactions between H. scabrum EO and commercially available antifungals were assessed by the checkerboard test. A synergistic effect was revealed in the combination of the EO with amphotericin B.

Characterization of the Biogenic Volatile Organic Compounds (BVOCs) and Analysis of the PR1 Molecular Marker in Vitis vinifera L. Inoculated with the Nematode Xiphinema index.

Upon pathogen attack, plants very quickly undergo rather complex physico-chemical changes, such as the production of new chemicals or alterations in membrane and cell wall properties, to reduce disease damages. An underestimated threat is represented by root parasitic nematodes. In Vitis vinifera L., the nematode Xiphinema index is the unique vector of Grapevine fanleaf virus, responsible for fanleaf degeneration, one of the most widespread and economically damaging diseases worldwide. The aim of this study was to investigate changes in the emission of biogenic volatile organic compounds (BVOCs) in grapevines attacked by X. index. BVOCs play a role in plant defensive mechanisms and are synthetized in response to biotic damages. In our study, the BVOC profile was altered by the nematode feeding process. We found a decrease in ß-ocimene and limonene monoterpene emissions, as well as an increase in α-farnesene and α-bergamotene sesquiterpene emissions in nematode-treated plants. Moreover, we evaluated the PR1 gene expression. The transcript level of PR1 gene was higher in the nematode-wounded roots, while in the leaf tissues it showed a lower expression compared to control grapevines.

Editorial to the Special Issue "Biological and Pharmacological Activity of Plant Natural Compounds".

Plant natural products are a valuable source of compounds with a healthy potential effect on living organisms, including animals and humans [...].

LC-MS/MS-Based Profiling of Tryptophan-Related Metabolites in Healthy Plant Foods.

Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier "indolome" to collect all metabolites in the Tryptophan pathway. In addition, Tryptophan-rich plant sources can be used as substrates for the fermentation by yeast strains to produce pharmacologically active metabolites, such as Melatonin. To pursue this technological development, we have developed a UHPLC-MS/MS method to monitor 14 Tryptophan, Tryptamine, amino-benzoic, and pyridine metabolites. In addition, different extraction procedures to improve the recovery of Tryptophan and its derivatives from the vegetal matrix were tested. We investigated soybeans, pumpkin seeds, sesame seeds, and spirulina because of their botanical diversity and documented healthy effects. Four different extractions with different solvents and temperatures were tested, and water extraction at room temperature was chosen as the most suitable procedure to extract the whole Tryptophan metabolites pattern (called by us "indolome") in terms of ease, high efficiency, short time, low cost, and sustainability. In all plant matrices, Tryptophan was the most abundant indole compound, while the pattern of its metabolites was different in the diverse plants extracts. Overall, 5-OH Tryptamine and Kynurenine were the most abundant compounds, despite being 100-1000-fold lower than Tryptophan. Melatonin was undetected in all extracts, but sesame showed the presence of a Melatonin isomer. The results of this study highlight the variability in the occurrence of indole compounds among diverse food plants. The knowledge of Tryptophan metabolism in plants represents a relevant issue for human health and nutrition.

Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice.

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-ß, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H1). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-ß and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.

Soil Application of Effective Microorganisms (EM) Maintains Leaf Photosynthetic Efficiency, Increases Seed Yield and Quality Traits of Bean (Phaseolus vulgaris L.) Plants Grown on Different Substrates.

EM (effective microorganisms) is a biofertilizer consisting of a mixed culture of potentially beneficial microorganisms. In this study, we investigated the effects of EM treatment on leaf in vivo chlorophyll a fluorescence of photosystem II (PSII), yield, and macronutrient content of bean plants grown on different substrates (nutrient rich substrate vs. nutrient poor sandy soil) in controlled environmental conditions (pot experiment in greenhouse). EM-treated plants maintained optimum leaf photosynthetic efficiency two weeks longer than the control plants, and increased yield independent of substrate. The levels of seed nutritionally-relevant molecules (proteins, lipids, and starch) were only slightly modified, apart from the protein content, which increased in plants grown in sandy soil. Although EM can be considered a promising and environmentally friendly technology for sustainable agriculture, more studies are needed to elucidate the mechanism(s) of action of EM, as well as its efficacy under open field conditions.

Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective.

Synergy is a process in which some substances cooperate to reach a combined effect that is greater than the sum of their separate effects. It can be considered a natural "straight" strategy which has evolved by nature to obtain more efficacy at low cost. In this regard, synergistic effects may be observed in the interaction between herbal products and conventional drugs or biochemical compounds. It is important to identify and exploit these interactions since any improvement brought by such kind of process can be advantageously used to treat human disorders. Even in a complex disease such as cancer, positive synergistic plant-drug interactions should be investigated to achieve the best outcomes, including providing a greater benefit to patients or avoiding adverse side effects. This review analyzes and summarizes the current knowledge on the synergistic effects of plant-drug interactions with a focus on anticancer strategies.

Rice allelopathy in weed management - An integrated approach.

The intensive use of pesticides with low biodegradability and high persistence in soil, surface and ground waters, represents a considerable environmental risk, especially under high weed pressure conditions. Furthermore, the number of herbicide-resistant weeds is increasing. Against this background, the investigation of alternative weed control strategies has taken on considerable importance. Among these, allelopathy as a negative effect of one plant on another due to the direct or indirect (including microorganisms) release of chemicals in the environment can be a useful tool for the integrated management of weeds in agroecosystems. In particular, the paddies have been considered in this work by reviewing the data both on rice allelopathy and rice weed agronomic control methods developed to improve the crop yield.

Tagetes spp. Essential Oils and Other Extracts: Chemical Characterization and Biological Activity.

Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties on the basis of their use in folk medicine. Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders, as well as muscular pain, across the world. Furthermore, these plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The phytochemical composition of the extracts of different Tagetes species parts are reported in this work. These compounds exhibit antioxidant, antiinflammatory, and enzyme inhibitory properties. Cultivation and the factors affecting the chemical composition of Tagetes species are also covered. In the current work, available literature on Tagetes species in traditional medicine, their application as a food preservative, and their antimicrobial activities are reviewed.

Chemical Profile, Antioxidant and Antibacterial Activities of Achillea moschata Wulfen, an Endemic Species from the Alps.

Aerial parts of Achillea moschata Wulfen (Asteraceae) growing wild in the Italian Rhaetian Alps were investigated to describe, for the first time, their phenolic content, as well as to characterize the essential oil. Inspection of the metabolic profile combining HPLC-DAD and ESI-MS/MS data showed that the methanol extract contained glycosylated flavonoids with luteolin and apigenin as the main aglycones. Among them, the major compound was 7-O-glucosyl apigenin. Caffeoyl derivates were other phenolics identified. The essential oil obtained by steam distillation and investigated by GC/FID and GC/MS showed camphor, 1,8-cineole, and bornylacetate as the main constituents. The antioxidant capacity of three different extracts with increasing polarity and of the essential oil was evaluated by employing ABTS·+ and DPPH· radical scavenging assays. The methanolic extract was the only significantly effective sample against both synthetic radicals. All samples were also tested against Gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa) bacterial species using the disk diffusion assay. The non-polar extracts (dichloromethane and petroleum ether) and the essential oil possessed a broad spectrum of antimicrobial activity expressed according to inhibition zone diameter (8-24 mm).

Phytochemical analysis and allelopathic potential of essential oil of yarrow (Achillea spp.) ecotypes against redroot pigweed (Amaranthus retroflexus L.).

This study will contribute to the knowledge of plant allelopathy and its application in weed management, as well as to the valuation of medicinal and neglected plant species. An allelopathy experiment was conducted to introduce Achillea spp. as an effective species on the red root pigweed (Amaranthus retroflexus L.). The allelopathic effect of dry material from the flower, leaf and stem of Tanacetum polycephalum L. and 9 Achillea spp. (Achillea santolina L., A. millefolium L., A. nobilis L., A. conferta DC., A. vermicularis Trin., A. beibersteinii Afan., A. talagonica Boiss., A. tenuifolia Lam., A. aleppica DC.) applied to the soil on the growth of redroot pigweed seedling was tested. Five different ratios of aerial dry material of different species as residues (at 0, 10, 20, 40, and 50 g kg-1 dry weight) were used in the pots. Achillea residual had a significant effect on the growth of redroot pigweed. Achillea vermicolaris and A. aleppica were the most effective species at stopping the growth of redroot pigweed, reducing its dry matter by 90% at 0.07 and 0.02 g kg-1 dry weight, respectively. Based on the results of GC/MS analyses, 152 different compounds were found in the essential oil of Achillea spp. The possible relationship between allelochemicals and seedling investigation by partial least squares regression between effective doses for controlling redroot pigweed and allelochemical compounds of Achillea species. Result showed that cis-Menth-2-en-1-ol, α-Terpinyl, propionate and Bornyl acetate had the most effect on inhibiting the growth of redroot pigweed. Our research revealed that the Achillea genus has a lot of potential as a bioherbicide. This means that its leftovers or mulch could be used as a good cover crop to control redroot pigweed.

Yet another in vitro evidence that natural compounds introduced by diet have anti-amyloidogenic activities and can counteract neurodegenerative disease depending on aging.

A major issue in Alzheimer's disease (AD) research is to find some new therapeutic drug which decrease Amyloid-beta (Aß) aggregation. From a therapeutic point of view the major question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. Natural compounds are capable of binding to different targets implicated in AD and exert neuroprotective effects. Aim of this study was to evaluate the in vitro inhibition of Aß1-42 fibrillogenesis in presence of Gallic acid, Rutin, Melatonin and ProvinolsTM . We performed the analysis with Transmission and Scanning Electron Microscopy, and with X-ray microanalysis. Samples treated with Rutin, that arises from phenylalanine via the phenylpropanoid pathway, show the best effective result obtained because a significantly fibril inhibition activity is detectable compared to the other compounds. Melatonin shows a better inhibitory activity than ProvinolsTM and Gallic acid at the considered concentrations.

Antibacterial Potential of Essential Oils and Silver Nanoparticles against Multidrug-Resistant Staphylococcus pseudintermedius Isolates.

Staphylococcus pseudintermedius is an emergent zoonotic agent associated with multidrug resistance (MDR). This work aimed to describe the antibacterial activity of four essential oils (EOs) and silver nanoparticles (AgNPs) against 15 S. pseudintermedius strains isolated from pyoderma. The four EOs, namely Rosmarinus officinalis (RO), Juniperus communis (GI), Citrus sinensis (AR), and Abies alba (AB), and AgNPs were used alone and in combination to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). All strains were MDR and methicillin-resistant. Among the antibiotic cohort, only rifampicin, doxycycline, and amikacin were effective. EOs' chemical analysis revealed 124 compounds belonging to various chemical classes. Of them, 35 were found in AR, 75 in AB, 77 in GI, and 57 in RO. The monoterpenic fraction prevailed over the sesquiterpenic in all EOs. When EOs were tested alone, AB showed the lowest MIC followed by GI, AR, and RO (with values ranging from 1:128 to 1:2048). MBC increased in the following order: AB, AR, GI, and RO (with values ranging from 1:512 to 1:2048). MIC and MBC values for AgNPs were 10.74 mg/L ± 4.23 and 261.05 mg/L ± 172.74. In conclusion, EOs and AgNPs could limit the use of antibiotics or improve the efficacy of conventional therapies.

Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity.

Although polyphenols represent the paradigm of the health-promoting effects ascribed to grape products, recently, attention has been paid to dietary melatonin, significantly present in Mediterranean foods. In this work, we measured melatonin, its isomers, stilbenes (trans- and cis-resveratrol and their glucosides, piceids) and total polyphenols in some different grape products (red, white and dessert wines, grape juices and Modena balsamic vinegars) of distinct Italian areas. We also evaluated their antiradical activity by DPPH(·) and ABTS(·+) assays. For indoleamine analysis, the separation was carried out on a 1.7-µm C18 BEH column and the detection performed by means of mass spectrometry with electrospray ionization in positive ion mode with multiple reaction monitoring. The confirmation of the peak identity was accomplished by injection into the high-resolution system (Orbitrap) using accurate mass measurements (error below 1.0 ppm). Mass spectrometry analyses revealed, for the first time, the presence of melatonin in dessert wines and balsamic vinegars, as well as the occurrence of three different melatonin isomers in grape products.