Occurrence and Biological Activities of Seco-Iridoids from Jasminum L.

In this paper, the first complete review on the seco-iridoids from the genus Jasminum L. was presented. In particular, their occurrence in the genus was detailed together with their biological activities. The literature survey has clearly pointed out that only a few Jasminum species have been studied for their seco-iridoid content evidencing oleoside derivatives as main compounds. In addition, the biological studies performed on them are very scarce focusing mainly on antioxidant and anti-inflammatory assays with modest effectiveness. All these results greatly underline the need for further in-depth analyses on these compounds under both the aspects.

Nuclear magnetic resonance analysis of extra virgin olive oil: classification through secoiridoids.

BACKGROUND: Extra virgin olive oil (EVOO), a natural product with a multidisciplinary role, has been and is continuing to be studied from several points of view. Among them, its chemical analysis is of major importance and several methods have been used. Nuclear magnetic resonance (NMR) spectroscopy has inherent advantages, among them monitoring the chemical constituents without the need for a separation technique and without, for instance, possible carry-over effects. Additionally, several magnetic resonance spectroscopic techniques can provide a novel powered insight into the nature and properties of a sample under study. Moreover, -omics procedure can reveal new information and can lead to the classification of populations under study. The main objective of the present work was the possible classification of the EVOO samples based on their aldehyde content using a proposed unreferenced 1 H-NMR spectroscopic quantification method combined with a metabolomic approach. Moreover, the study of the impact of such elevated aldehyde content on several spectra regions of importance in the proton NMR spectra led to the proposal of a possible new isomer indicator. RESULTS: Univariate analysis of 12 EVOO samples showed that oleacein, oleocanthal, elenolic acid, hydroxytyrosol/hydroxytyrosol derivatives and tyrosol/tyrosol derivatives strongly differentiated two classes of EVOO: OEH (for high aldehyde EVOO content) and OE (for non-high aldehyde content). Moreover, we pointed out the 'impact' of such elevated secoiridoid and derivatives content, through their moieties' units, on a range of several resonances of the 1 H-NMR spectrum. The metabolomic approach demonstrated the classification of EVOO samples based on their secoiridoid and derivatives content. Multivariate analysis showed a strong influence on the discrimination of the EVOO classes based on the protons resonating at the aldehyde region of the 1 H-NMR spectrum; the aldehyde protons corresponding to 5S,4R-ligstrodial and 5S,4R-oleuropeindial, oleacein, oleocanthal, elenolic acid, p-HPEA-EA, 3,4-DHPEA-EA, 5S,4R- and 5S,4S-ligstrodial and the proton corresponding to a new compound were reported for the first time. This isomer compound, reported for the first time, could serve as a possible indicator for EVOO classification. CONCLUSIONS: An unreferenced quantification method was proposed and EVOO samples were classified into two classes: OEH and OE, according to their aldehyde content, gaining thus probably higher nutrient and possible pharmacological value. Moreover, we point out the 'impact' of such elevated aldehyde content on several spectral regions of the 1 H spectrum. Finally, a new compound was detected in the OEH samples and is reported for the first time. This compound could possibly be an indicator. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Biologically active secoiridoids: A comprehensive update.

Secoiridoids are natural products of cyclopentane monoterpene derivatives that are formed by splitting the rings of cyclomethene oxime compounds at C-7 and C-8, and only account for a small part of cyclic ether terpenoids. Because of the chemically active hemiacetal structure in their common basic skeleton, secoiridoids have a wide range of biological activities, such as neuroprotective, anti-inflammatory, antidiabetic, hepatoprotective, and antinociceptive activities. Phenolic secoiridoids can also act against multiple molecular targets involved in human tumorigenesis, making them potentially valuable precursors for antitumor drug development. This review provides a detailed update, covering relevant discoveries from January 2011 to December 2020, about the occurrence, structural diversity, bioactivities, and synthesis of naturally occurring secoiridoids. We aimed to resolve the lack of extensive, specific, and thorough review of secoiridoids, as well as open new areas for pharmacological investigation and better drugs based on these compounds.

Bio-Guided Isolation of Compounds from Fraxinus excelsior Leaves with Anti-Inflammatory Activity.

Inflammation is the first physiological defence mechanism against external and internal stimuli. The prolonged or inappropriate response of the immune system may lead to the persistent inflammatory response that can potentially become a basis for chronic diseases e.g., asthma, type II diabetes or cancer. An important role in the alleviation of inflammatory processes, as an adjunct to traditional pharmacological therapy, is attributed to phytotherapy, especially to raw materials with a long tradition of use, e.g., ash leaves. Despite their long-term use in phytotherapy, the specific mechanisms of action have not been confirmed in a sufficient number of biological or clinical studies. The aim of the study is a detailed phytochemical analysis of infusion and its fractions, isolation of pure compounds from the leaves of Fraxinus excelsior and evaluation of their effect on the secretion of anti-inflammatory cytokines (TNF-α, IL-6) and IL-10 receptor expression in an in vitro model of monocyte/macrophage cells isolated from peripheral blood. Methods: Phytochemical analysis was carried out by the UHPLC-DAD-ESI-MS/MS method. Monocytes/macrophages were isolated from human peripheral blood using density gradient centrifugation on Pancoll. After 24 h incubation with tested fractions/subfractions and pure compounds, cells or their supernatants were studied, respectively, on IL-10 receptor expression by flow cytometry and IL-6, TNF-α, IL-1ß secretion by the ELISA test. Results were presented with respect to Lipopolysaccharide (LPS) control and positive control with dexamethasone. Results: The infusion, 20% and 50% methanolic fractions and their subfractions, as well as their dominating compounds, e.g., ligstroside, formoside and oleoacteoside isolated from the leaves, show the ability to increase the IL-10 receptor expression on the surface of monocyte/macrophage cells, stimulated by LPS, and to decrease the secretion of pro-inflammatory cytokines, e.g., TNF-α, IL-6.

Hydrogen/Deuterium Exchange Mass Spectrometry for Probing the Isomeric Forms of Oleocanthal and Oleacin in Extra Virgin Olive Oils.

Reversed-phase liquid chromatography and electrospray ionization with Fourier-transform single and tandem mass spectrometry (RPLC-ESI-FTMS and FTMS/MS) were employed for the structural characterization of oleocanthal (OLEO) and oleacin (OLEA), two of the most important bioactive secoiridoids occurring in extra virgin olive oils (EVOOs). The existence of several isoforms of OLEO and OLEA was inferred from the chromatographic separation, accompanied, in the case of OLEA, by minor peaks due to oxidized OLEO recognized as oleocanthalic acid isoforms. The detailed analysis of the product ion tandem MS spectra of deprotonated molecules ([M-H]-) was unable to clarify the correlation between chromatographic peaks and specific OLEO/OLEA isoforms, including two types of predominant dialdehydic compounds, named Open Forms II, containing a double bond between carbon atoms C8 and C10, and a group of diasteroisomeric closed-structure (i.e., cyclic) isoforms, named Closed Forms I. This issue was addressed by H/D exchange (HDX) experiments on labile H atoms of OLEO and OLEA isoforms, performed using deuterated water as a co-solvent in the mobile phase. HDX unveiled the presence of stable di-enolic tautomers, in turn providing key evidence for the occurrence, as prevailing isoforms, of Open Forms II of OLEO and OLEA, different from those usually considered so far as the main isoforms of both secoiridoids (having a C=C bond between C8 and C9). It is expected that the new structural details inferred for the prevailing isoforms of OLEO and OLEA will help in understanding the remarkable bioactivity exhibited by the two compounds.

The Contribution of Theoretical Prediction Studies to the Antioxidant Activity Assessment of the Bioactive Secoiridoids Encountered in Olive Tree Products and By-Products.

Assessment of the antioxidant activity of different types of natural compounds is a complex research area that encompasses various in vitro tests and in vivo studies. Sophisticated modern analytical tools permit the unambiguous characterization of the compounds present in a matrix. The contemporary researcher, knowing the chemical structure of the compounds present, can carry out quantum chemical calculations that provide important physicochemical information assisting the prediction of antioxidant potential and the mechanism behind the activity of target compounds before further experimentation. The efficiency of calculations is steadily improved due to the rapid evolution of both hardware and software. It is possible, consequently, to study compounds of medium or even larger size, incorporating also models that simulate the liquid phase (solution). This review contributes to the establishment of theoretical calculations as an inherent part of the antioxidant activity assessment process, having as a case study the complex mixtures of olive bioactive secoiridoids (oleuropein, ligstroside, and related compounds). The literature indicates great variability in theoretical approaches and models used so far for only a limited number of this group of phenolic compounds. Proposals are made for standardization of methodology (reference compounds, DFT functional, basis set size, and solvation model) to facilitate comparisons and communication of findings.

A biochemical perspective on the fate of virgin olive oil phenolic compounds in vivo.

The chemistry of the phenolic compounds found in virgin olive oil (VOO) is very complex due, not only to the different classes of polyphenols that can be found in it, but, above all, due to the existence of a very specific phenol class found only in oleaceae plants: the secoiridoids. Searching in the Scopus data base the keywords flavonoid, phenolic acid, lignin and secoiridoid, we can find a number of 148174, 79435, 11326 and 1392 research articles respectively, showing how little is devote to the latter class of compounds. Moreover, in contrast with other classes, that include only phenolic compounds, secoiridoids may include phenolic and non-phenolic compounds, being the articles concerning phenolic secoiridoids much less than the half of the abovementioned articles. Therefore, it is important to clarify the structures of these compounds and their chemistry, as this knowledge will help understand their bioactivity and metabolism studies, usually performed by researchers with a more health science's related background. In this review, all the structures found in many research articles concerning VOO phenolic compounds chemistry and metabolism was gathered, with a special attention devoted to the secoiridoids, the main phenolic compound class found in olives, VOO and olive leaf.

New Affordable Methods for Large-Scale Isolation of Major Olive Secoiridoids and Systematic Comparative Study of Their Antiproliferative/Cytotoxic Effect on Multiple Cancer Cell Lines of Different Cancer Origins.

Olive oil phenols (OOPs) are associated with the prevention of many human cancers. Some of these have been shown to inhibit cell proliferation and induce apoptosis. However, no systematic comparative study exists for all the investigated compounds under the same conditions, due to difficulties in their isolation or synthesis. Herein are presented innovative methods for large-scale selective extraction of six major secoiridoids from olive oil or leaves enabling their detailed investigation. The cytotoxic/antiproliferative bioactivity of these six compounds was evaluated on sixteen human cancer cell lines originating from eight different tissues. Cell viability with half-maximal effective concentrations (EC50) was evaluated after 72 h treatments. Antiproliferative and pro-apoptotic effects were also assessed for the most bioactive compounds (EC50 ≤ 50 µM). Oleocanthal (1) showed the strongest antiproliferative/cytotoxic activity in most cancer cell lines (EC50: 9−20 µM). The relative effectiveness of the six OOPs was: oleocanthal (1) > oleuropein aglycone (3a,b) > ligstroside aglycone (4a,b) > oleacein (2) > oleomissional (6a,b,c) > oleocanthalic acid (7). This is the first detailed study comparing the bioactivity of six OOPs in such a wide array of cancer cell lines, providing a reference for their relative antiproliferative/cytotoxic effect in the investigated cancers.

Comparative Evaluation of the Phytochemical Profiles and Antioxidant Potentials of Olive Leaves from 32 Cultivars Grown in China.

Olives (Olea europaea L.) are a significant part of the agroindustry in China. Olive leaves, the most abundant by-products of the olive and olive oil industry, contain bioactive compounds that are beneficial to human health. The purpose of this study was to evaluate the phytochemical profiles and antioxidant capacities of olive leaves from 32 cultivars grown in China. A total of 32 phytochemical compounds were identified using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, including 17 flavonoids, five iridoids, two hydroxycinnamic acids, six triterpenic acids, one simple phenol, and one coumarin. Specifically, olive leaves were found to be excellent sources of flavonoids (4.92-18.29 mg/g dw), iridoids (5.75-33.73 mg/g dw), and triterpenic acids (15.72-35.75 mg/g dw), and considerable variations in phytochemical content were detected among the different cultivars. All tested cultivars were classified into three categories according to their oil contents for further comparative phytochemicals assessment. Principal component analysis indicated that the investigated olive cultivars could be distinguished based upon their phytochemical profiles and antioxidant capacities. The olive leaves obtained from the low-oil-content (<16%) cultivars exhibited higher levels of glycosylated flavonoids and iridoids, while those obtained from high-oil-content (>20%) cultivars contained mainly triterpenic acids in their compositions. Correspondingly, the low-oil-content cultivars (OL3, Frantoio selection and OL14, Huaou 5) exhibited the highest ABTS antioxidant activities (758.01 ± 16.54 and 710.64 ± 14.58 mg TE/g dw, respectively), and OL9 (Olea europaea subsp. Cuspidata isolate Yunnan) and OL3 exhibited the highest ferric reducing/antioxidant power assay values (1228.29 ± 23.95 mg TE/g dw and 1099.99 ± 14.30 mg TE/g dw, respectively). The results from this study may be beneficial to the comprehensive evaluation and utilization of bioactive compounds in olive leaves.

Extra Virgin Olive Oil Secoiridoids Modulate the Metabolic Activity of Dacarbazine Pre-Treated and Treatment-Naive Melanoma Cells.

Nowadays, many individuals, whether healthy or diagnosed with disease, tend to expose themselves to various easily accessible natural products in hopes of benefiting their health and well-being. Mediterranean populations have traditionally used olive oil not only in nutrition but also in cosmetics, including skincare. In this study, the phenolic profile-composed of twelve compounds altogether, including the secoiridoids oleocanthal (OCAL) and oleacein (OCEIN)-of extra virgin olive oil (EVOO) from autochthonous cultivars from Croatia was determined using 1H qNMR spectroscopy and HPLC-DAD analysis, and its biological activity was investigated in melanoma cell lines. The EVOO with the highest OCEIN content had the strongest anti-cancer activity in A375 melanoma cells and the least toxic effect on the non-cancerous keratocyte cell line (HaCaT). On the other hand, pure OCAL was shown to be more effective and safer than pure OCEIN. Post-treatment with any of the EVOO phenolic extracts (EVOO-PEs) enhanced the anti-cancer effect of the anti-cancerous drug dacarbazine (DTIC) applied in pre-treatment, while they did not compromise the viability of non-cancerous cells. The metastatic melanoma A375M cell line was almost unresponsive to the EVOO-PEs themselves, as well as to pure OCEIN and OCAL. Our results demonstrate that olive oils and/or their compounds may have a potentially beneficial effect on melanoma treatment. However, their usage can be detrimental or futile, especially in healthy cells, due to inadequately applied concentrations/combinations or the presence of resistant cells.

Exploitation of virgin olive oil by-products (Olea europaea L.): phenolic and volatile compounds transformations phenomena in fresh two-phase olive pomace ('alperujo') under different storage conditions.

BACKGROUND: Much effort has recently been spent for re-using virgin olive oil by-products as nutraceutical ingredients for human diet thanks to their richness in bioactive phenols, but their management is not easy for producers. We aimed to provide useful information for a better management of fresh olive pomace before drying, by studying the phenolic and volatile compounds transformations phenomena of fresh olive pomace stored under different conditions planned to simulate controlled and uncontrolled temperature conditions in olive oil mills. RESULTS: The evolution of the phenolic and volatile compounds was studied by high-performance liquid chromatography-diode array detector mass spectrometry (HPLC-DAD-MS) and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS). The phenolic profile varied rapidly during storage: the verbascoside content decreased about 70% after 17 days even at 4 °C, while the content of simple phenols such as hydroxytyrosol and caffeic acid increased over time. The low temperature was able to slow down these phenomena. A total of 94 volatile organic compounds (VOCs) were detected in the fresh olive pomace, with a prevalence of lipoxygenase (LOX) VOCs (78%), mainly aldehydes (19 490.9 µg kg-1 ) despite the higher number of alcohols. A decrease in LOX volatiles and a quick development of the ones linked to off-flavors (carboxylic acids, alcohols, acetates) were observed, in particular after 4 days of storage at room temperature. Only storage at 4 °C allowed these phenomena to be slowed down. CONCLUSION: To preserve the natural phenolic phytocomplex of fresh olive pomace before drying and to avoid off-flavors development, storage in open containers must be avoided and a short storage in cold rooms (7-10 days) is to be preferred. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Therapeutic potential of plant iridoids in depression: a review.

CONTEXT: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. OBJECTIVE: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication. METHODS: The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with in vivo or in vitro experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression. RESULTS: Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression. DISCUSSION AND CONCLUSIONS: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

Two bi-functional cytochrome P450 CYP72 enzymes from olive (Olea europaea) catalyze the oxidative C-C bond cleavage in the biosynthesis of secoxy-iridoids - flavor and quality determinants in olive oil.

Olive (Olea europaea) is an important crop in Europe, with high cultural, economic and nutritional significance. Olive oil flavor and quality depend on phenolic secoiridoids, but the biosynthetic pathway of these iridoids remains largely uncharacterized. We discovered two bifunctional cytochrome P450 enzymes, catalyzing the rare oxidative C-C bond cleavage of 7-epi-loganin to produce oleoside methyl ester (OeOMES) and secoxyloganin (OeSXS), both through a ketologanin intermediary. Although these enzymes are homologous to the previously reported Catharanthus roseus secologanin synthase (CrSLS), the substrate and product profiles differ. Biochemical assays provided mechanistic insights into the two-step OeOMES and CrSLS reactions. Model-guided mutations of OeOMES changed the product profile in a predictable manner, revealing insights into the molecular basis for this change in product specificity. Our results suggest that, in contrast to published hypotheses, in planta production of secoxy-iridoids is secologanin-independent. Notably, sequence data of cultivated and wild olives point to a relation between domestication and OeOMES expression. Thus, the discovery of this key biosynthetic gene suggests a link between domestication and secondary metabolism, and could potentially be used as a genetic marker to guide next-generation breeding programs.

Potential Uses of Olive Oil Secoiridoids for the Prevention and Treatment of Cancer: A Narrative Review of Preclinical Studies.

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and characterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed.

Characterization of the Phenolic Fingerprint of Kolovi Extra Virgin Olive Oils from Lesvos with Regard to Altitude and Farming System Analyzed by UHPLC-QTOF-MS.

Extra virgin olive oil (EVOO) is recognized for its nutritional virtues and the beneficial health effects deriving from its hydrophilic fraction (phenolic acids, phenolic alcohols, flavonoids, and secoiridoids). The phenolic compounds of EVOOs possess multiple biological properties such as antioxidant, antimicrobial, anticarcinogenic, and anti-inflammatory properties, among others. Considering that EVOOs produced in Greece are recognized as high-quality products due to their rich phenolic content, it is imperative to characterize Greek monovarietal EVOOs and ensure that their uniqueness is closely linked to their botanical and territorial origin. In this work, an ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) analytical method combined with target and suspect screening was used to characterize monovarietal EVOOs of the Kolovi variety from Lesvos, and thereby establish their phenolic fingerprint. Overall, 25 phenols were determined, and the total quantification and semi-quantification results ranged between 251 and 1230 mg/kg, highlighting the high phenolic content of the Kolovi variety from the island of Lesvos in the North Aegean.

Chemical Profile, Cytotoxic Activity and Oxidative Stress Reduction of Different Syringa vulgaris L. Extracts.

Syringa vulgaris L. (common lilac) is one of the most popular ornamental species, but also a promising not comprehensively studied source of bioactive compounds with important therapeutic potential. Our study was designed to characterize the chemical composition and to assess the antioxidant and cytotoxic properties of ethanolic extracts obtained from S. vulgaris L. flowers, leaves, bark, and fruit. The chemical profile of the ethanolic extracts was investigated using chromatographic (HPLC-DAD-ESI+, GC-MS) and spectral (UV-Vis, FT-IR) methods, while the protective effect against free radicals was evaluated in vitro by different chemical assays (DPPH, FRAP, CUPRAC). The cytotoxic activity was tested on two tumoral cell lines, HeLa, B16F10, using the MTT assay. Significant amounts of free or glycosylated chemical components belonging to various therapeutically important structural classes, such as phenyl-propanoids (syringin, acteoside, echinacoside), flavonoids (quercetin, kaempferol derivatives) and secoiridoids (secologanoside, oleuropein, 10-hydroxy oleuropein, demethyloleuropein, syringalactone A, nuzhenide, lingstroside) were obtained for the flowers, leaves and bark extracts, respectively. Furthermore, MTT tests pointed out a significant cytotoxic potential expressed in a non-dose-dependent manner toward the tumoral lines. The performed methods underlined that S. vulgaris extracts, in particular belonging to flowers and leaves, represent valuable sources of compounds with antioxidant and antitumoral potential.

Bioactive Secoiridoids in Italian Extra-Virgin Olive Oils: Impact of Olive Plant Cultivars, Cultivation Regions and Processing.

In the last two decades, phenolic compounds occurring in olive oils known as secoiridoids have attracted a great interest for their bioactivity. Four major olive oil secoiridoids, i.e., oleuropein and ligstroside aglycones, oleacin and oleocanthal, were previously characterized in our laboratory using reversed-phase liquid chromatography with electrospray ionization-Fourier transform-mass spectrometry (RPLC-ESI-FTMS). The same analytical approach, followed by multivariate statistical analysis (i.e., Principal Component Analysis), was applied here to a set of 60 Italian extra-virgin olive oils (EVOO). The aim was to assess the secoiridoid contents as a function of olive cultivars, place of cultivation (i.e., different Italian regions) and olive oil processing, in particular two- vs. three-phase horizontal centrifugation. As expected, higher secoiridoid contents were generally found in olive oils produced by two-phase horizontal centrifugation. Moreover, some region/cultivar-related trends were evidenced, as oleuropein and ligstroside aglycones prevailed in olive oils produced in Apulia (Southern Italy), whereas the contents of oleacin and oleocanthal were relatively higher in EVOO produced in Central Italy (Tuscany, Lazio and Umbria). A lower content of all the four secoiridoids was generally found in EVOO produced in Sicily (Southern Italy) due to the intrinsic low abundance of these bioactive compounds in cultivars typical of that region.

Epigenetic Modifications Induced by Olive Oil and Its Phenolic Compounds: A Systematic Review.

Many studies demonstrated that olive oil (especially extra virgin olive oil: EVOO) phenolic compounds are bioactive molecules with anti-cancer, anti-inflammatory, anti-aging and neuroprotective activities. These effects have been recently attributed to the ability of these compounds to induce epigenetics modifications such as miRNAs expression, DNA methylation and histone modifications. In this study, we systematically review and discuss, following the PRISMA statements, the epigenetic modifications induced by EVOO and its phenols in different experimental systems. At the end of literature search through "PubMed", "Web of Science" and "Scopus", 43 studies were selected.Among them, 22 studies reported data on miRNAs, 15 on DNA methylation and 13 on histone modification. Most of the "epigenomic" changes observed in response to olive oil phenols' exposure were mechanistically associated with the cancer preventive and anti-inflammatory effects. In many cases, the epigenetics effects regarding the DNA methylation were demonstrated for olive oil but without any indication regarding the presence or not of phenols. Overall, the findings of the present systematic review may have important implications for understanding the epigenetic mechanisms behind the health effects of olive oil. However, generally no direct evidence was provided for the causal relationships between epigenetics modification and EVOO health related effects. Further studies are necessary to demonstrate the real physiological consequences of the epigenetics modification induced by EVOO and its phenolic compounds.

Optimization of salicylic acid and chitosan treatment for bitter secoiridoid and xanthone glycosides production in shoot cultures of Swertia paniculata using response surface methodology and artificial neural network.

BACKGROUND: In this study, response surface methodology (RSM) and artificial neural network (ANN) was used to construct the predicted models of linear, quadratic and interactive effects of two independent variables viz. salicylic acid (SA) and chitosan (CS) for the production of amarogentin (I), swertiamarin (II) and mangiferin (III) from shoot cultures of Swertia paniculata Wall. These compounds are the major therapeutic metabolites in the Swertia plant, which have significant role and demand in the pharmaceutical industries. RESULTS: Present study highlighted that different concentrations of SA and CS elicitors substantially influenced the % yield of (I), (II) and (III) compounds in the shoot culture established on modified ½ MS medium (supplemented with 2.22 mM each of BA and KN and 2.54 mM NAA). In RSM, different response variables with linear, quadratic and 2 way interaction model were computed with five-factor-three level full factorial CCD. In ANN modelling, 13 runs of CCD matrix was divided into 3 subsets, with approximate 8:1:1 ratios to train, validate and test. The optimal enhancement of (I) (0.435%), (II) (4.987%) and (III) (4.357%) production was achieved in 14 days treatment in shoot cultures of S. paniculata elicited by 9 mM and 12 mg L- 1 concentrations (SA) and (CS). CONCLUSIONS: In optimization study, (I) show 0.170-0.435%; (II) display 1.020-4.987% and (III) upto 2.550-4.357% disparity with varied range of SA (1-20 mM) and CS (1-20 mg L- 1). Overall, optimization of elicitors to promote secoiridoid and xanthone glycoside production with ANN modeling (r2 = 100%) offered more significant results as compared to RSM (r2 = 99.8%).

Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice.

Previously we conducted a phytochemical study on the seeds of Fraxinus excelsior and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of Fraxinus mandshurica seeds have not been studied. In the present study, we investigated the secoiridoid compounds in F. mandshurica seed extract (FM) using column chromatography, 1H-NMR, 13C-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect of FM on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from FM and identified. The total content of secoiridoids in FM reached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 µM. After obese mice were administrated with FM at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, FM could attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice. FM could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes, Bacteroidia, S24-7 and Allobaculum), and reducing the proportion of obesogenic gut microbiota (Firmicutes and Dorea). This study suggests that F. mandshurica seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.